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dermal fillers, hyaluronic acid, injections, nose, rhinoplasty, Dermatology, and RL1-803

Dong Li,1 Jiaming Sun,2 Yuguang Zhang,3 Xiaojun Wang,4 Songlin Yang,5 Candice Harvey,6 Lijuan Zhang7 1Department of Plastic Surgery, Peking University Third Hospital, Beijing, People’s Republic of China; 2Depatment of Plastic Surgery, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Plastic Surgery, Shanghai 9th People’s Hospital, Shanghai, People’s Republic of China; 4Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 5Department of Plastic Surgery Shanghai 6th People’s Hospital, Shanghai, People’s Republic of China; 6Clinical Development, Allergan Aesthetics, an AbbVie Company, Marlow, UK; 7Clinical Development, Allergan Aesthetics, an AbbVie Company, Beijing, People’s Republic of ChinaCorrespondence: Dong Li, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 10 8226 6699, Fax +86 10 8226 6116, Email lidong9@sina.comPurpose: Soft tissue filler injection is less invasive than surgical approaches for facial aesthetic improvement. This study evaluated the safety and effectiveness of the soft tissue filler VYC-20L (Juvéderm Voluma® XC) for improvement of volume and aesthetic appearance of the nose in Chinese subjects.Patients and Methods: In a prospective, multicenter, no-treatment–controlled study in China, adult subjects were randomized 3:1 to receive VYC-20L (treatment group) or have optional treatment delayed by 24 weeks (control group). The treatment group received VYC-20L on day 1 plus optional touch-up at week 8 for suboptimal improvement. The primary effectiveness measure was mean change in nose area volume from baseline to week 24 by digital analysis of three-dimensional (3D) images. Multiple secondary effectiveness and safety measures were assessed.Results: Of 164 subjects randomized, 162 were treated, and 157 comprised the modified intent-to-treat population (mean age, 31 years; 94% female). In the treatment group, mean VYC-20L volume injected was 1.18 mL (initial treatment) and 0.67 mL (touch-up; n = 46 [38.3%]). VYC-20L achieved significantly larger changes in nose area volume than control at week 24 (2.032 vs ‒0.005 cm3, respectively; p < 0.0001) and greater improvements on the Global Aesthetic Improvement Scale (investigator and subject), Nose Satisfaction Scale, and other 3D measures. No treatment-related adverse events occurred. Most injection site responses were mild/moderate, resolving within 14 days. Mean initial/touch-up treatment procedural pain ratings were less than 3 (0‒10 scale; higher = worse pain).Conclusion: VYC-20L is safe and effective for nose augmentation in Chinese adults.Keywords: dermal fillers, hyaluronic acid, injections, nose, rhinoplasty

apolipoprotein e, carotid atherosclerosis, gene polymorphism, blood lipids, Therapeutics. Pharmacology, and RM1-950

Wenbing Ma,1,2,* Liting Zhang,1,* Lei Luo,1 Suya Zhang,1,* Shuang Yang,1 Hongping Yao,1 Lei Zhang,1 Xiaoyun Lu,2 Weiyi Feng1 1Department of Pharmacology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiyi Feng, Department of Pharmacology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel/Fax +86-029-85323242, Email fengweiyi@mail.xjtu.edu.cn Xiaoyun Lu, Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, People’s Republic of China, Tel/Fax +86-029-82668463, Email luxy05@xjtu.edu.cnBackground: The apolipoprotein E (ApoE) genetic variation may be involved in the development of Carotid Atherosclerosis (CAS) disease. So far, few data are available on the role of ApoE isoforms in CAS. The association between this ApoE genotype and CAS remains controversial. The aim of this study was to investigate ApoE gene polymorphism in relation to CAS and the relationships between ApoE gene polymorphism and plasma lipid levels in the ShaanXi Han populations.Patients and methods: The study group enrolled 399 CAS participants and 399 non-CAS controls. ApoE gene polymorphisms were determined by Polymerase chain reaction and hybridization.Results: The ϵ3/ϵ4 genotype and ϵ4 allele in patients with CAS were significantly higher than control participants. In stratified analyses by age and sex, the elevated risk conferred by ɛ4 allele was evident in adults under 60 years old, but not in adults over 60 years old, females and males. ϵ4 carriers had significantly elevated ApoB and ApoB/ApoA and decreased ApoE levels than ϵ2 carriers in CAS patients. After adjusting for confounding factors, hypertension, ApoA-I, low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and ϵ4 allele were significant independent risk factor for CAS. ApoE-ϵ4 allele was associated with a nearly 1.5-fold increased risk of CAS.Conclusion: This study provides convincing evidence that ϵ4 allele, hypertension, ApoA-I, LDL-C and TG levels are independent risk factor for CAS in the ShaanXi Han populations. ApoE polymorphism was associated with CAS and this association was partly mediated through blood lipids. Also, the clinical use of genomic data may become useful in optimizing individual preventative and therapeutic strategies.Keywords: apolipoprotein E, carotid atherosclerosis, gene polymorphism, blood lipids

gastric cancer, aloin, pharmacological mechanisms, network pharmacology, experimental verification, Therapeutics. Pharmacology, and RM1-950

Jia Gao,1,* Sifu Yang,2,* Guanqun Xie,3 Jieli Pan,4 Feiye Zhu4 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Medical Oncology Department, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, 310014, People’s Republic of China; 3College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 4Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jieli Pan; Feiye Zhu, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email panjieli_zj@163.com; zhufeiye@163.comPurpose: This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification.Methods: Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments.Results: A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway.Conclusion: This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.Keywords: gastric cancer, Aloin, pharmacological mechanisms, network pharmacology, experimental verification

chronic obstructive pulmonary disease, screening questionnaire, gender, spirometry, roc curve, Diseases of the respiratory system, and RC705-779

Shuang Yang,1,2,* Xin Yin,3,* Yanan Zhang,4 Hanwei Zhao,4 Zixuan Zheng,2 Junqing Li,2 Xiaoying Hu,1 Juan Xie,2 Zhijun Jie,2 Na Wang,3 Jindong Shi2 1Department of General Medicine, Jiangchuan Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 4Department of General Medicine, Zhuanqiao Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jindong Shi, Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China, Tel +86 18918168579, Email shijindong@5thhospital.com Na Wang, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 13564748559, Email na.wang@fudan.edu.cnPurpose: To evaluate the screening efficacy of a self-designed questionnaire for chronic obstructive pulmonary disease (COPD) and the potential gender disparity in its efficacy.Patients and Methods: A screening questionnaire, the COPD Screening Questionnaire-Minhang (COPD-MH), was designed with reference to the self-scored COPD population screener (COPD-PS) and the COPD screening questionnaire (COPD-SQ), incorporating characteristics of the local population in Shanghai, China. The revised questionnaire included only five questions. Each question scored 0– 4, with a highest total score of 20. The COPD-PS and COPD-SQ comprised 5 and 7 questions, respectively. Their scoring criteria were not consecutive integers and, thus, not easily counted. The COPD-MH focused on symptoms, and each item was set the same answers for convenience. Screening for COPD was conducted among residents over 40 years old in a community in Shanghai using the three aforementioned questionnaires. Each participant also received spirometry tests. A receiver operator characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to assess the validity of each questionnaire.Results: A total of 1197 community residents in Minhang District completed the screening. A total of 1023 participants were finally included in analysis with a detected prevalence of 12.4% for COPD. The best cut-off values for the COPD-PS, COPD-SQ, and COPD-MH were 4, 16, and 7 points, respectively. The AUCs for these three questionnaires were > 0.5, but the sensitivity of the COPD-MH was higher than those of the COPD-PS and COPD-SQ. The sensitivity of COPD-MH was 80.77% for males and 77.5% for females. The COPD-MH had higher diagnostic efficiency and higher sensitivity with gender-specific cut-off values.Conclusion: The COPD-MH is comparable to and less time-consuming than the existing screening methods for COPD. Gender-related factors affect the optimal cut-off values of the COPD screening questionnaire, and rectifying this can improve the practical screening efficacy.Keywords: chronic obstructive pulmonary disease, screening questionnaire, gender, spirometry, ROC curve

Medicine and Science

Abstract Sexual dysfunction (SD) is prevalent in patients with mental health disorders and can significantly impair their quality of life. Early recognition of SD in a clinical setting may help patients and clinicians to optimize treatment options of SD and/or other primary diagnoses taking SD risk into account and may facilitate treatment compliance. SD identification is often overlooked in clinical practice; we seek to explore whether patients with a high risk of SD can be identified at the individual level by assessing known risk factors via a machine learning (ML) model. We assessed 135 subjects referred to a tertiary mental health clinic in a Western Canadian city using health records data, including age, sex, physician’s diagnoses, drug treatment, and the Arizona Sexual Experiences Scale (ASEX). A ML model was fitted to the data, with SD status derived from the ASEX as target outcomes and all other variables as predicting variables. Our ML model was able to identify individual SD cases—achieving a balanced accuracy of 0.736, with a sensitivity of 0.750 and a specificity of 0.721—and identified major depressive disorder and female sex as risk factors, and attention deficit hyperactivity disorder as a potential protective factor. This study highlights the utility of SD screening in a psychiatric clinical setting, demonstrating a proof-of-concept ML approach for SD screening in psychiatric patients, which has marked potential to improve their quality of life.

cerebral small vessel diseases, enlarged perivascular spaces, motor, gait, balance, physical performance, Geriatrics, and RC952-954.6

Shuna Yang, Xuanting Li, Wei Qin, Lei Yang, Wenli Hu Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wenli Hu, Email wenlihu3366@126.comBackground and Objective: Motor dysfunction is common in the elderly, and is associated with adverse consequences. Enlarged perivascular spaces in basal ganglia (BG-EPVSs) are considered an MRI marker of cerebral small-vessel diseases. However, the consequences of BG-EPVSs are largely unknown. In the present study, we aimed to explore the association between large numbers of BG-EPVSs and motor performance.Methods: We prospectively recruited elderly individuals in the Neurology Department of our hospital from December 1, 2020 to January 31, 2022. Participants with > 20 BG-EPVSs on the unilateral side of the slice containing the most EPVSs were classified as the BG-EPVS group (n=99) and the rest as controls (n=193). Motor performance was assessed by quantitative gait analysis, Tinetti test, timed up-and-go (TUG) test, and the Short Physical Performance Battery (SPPB). Spearman correlation analysis and multivariate linear regression analysis were performed to investigate the association between BG-EPVSs and motor performance.Results: Compared with the control group, the BG-EPVS group had lower gait speed and cadence, shorter stride length, longer TUG duration, and lower Tinetti gait test, Tinetti balance test, and SPPB scores (P< 0.01). Spearman correlation analysis showed that BG-EPVSs were negatively related to gait speed, gait cadence, stride length, and Tinetti gait test, Tinetti balance test, and SPPB scores (ρ= – 0.539 to – 0.223, P< 0.001) and positively related to TUG duration (ρ=0.397, P< 0.001). Regression analysis indicated that BG-EPVSs were an independent risk factor of lower gait speed, shorter stride length, poor balance, and poor general physical performance after adjusting for confounders (β= – 0.313 to – 0.206, P< 0.01).Conclusion: Large numbers of BG-EPVSs were independently related to poor gait, balance, and general physical performance in elderly individuals, which provides information about the consequences of BG-EPVSs and risk factors for motor dysfunction.Keywords: cerebral small-vessel diseases, enlarged perivascular spaces, motor, gait, balance, physical performance

opioid use disorder, patient reported outcomes, patient-centred care, medication for opioid use disorder, Medicine (General), and R5-920

Nitika Sanger,1,* Balpreet Panesar,2,* Michael Dennis,3 Tea Rosic,4 Myanca Rodrigues,4 Elizabeth Lovell,5 Shuling Yang,3 Mehreen Butt,6 Lehana Thabane,4,7 Zainab Samaan4,5 1Medical Science Graduate Program, McMaster University, Hamilton, Ontario, Canada; 2Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada; 3Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; 4Health Research Methodology Graduate Program, McMaster University, Hamilton, Ontario, Canada; 5Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada; 6Accelerated Nursing Program, McMaster University, Hamilton, Ontario, Canada; 7Centre for Evaluation of Medicines, Programs for Assessment of Technology in Health (PATH) Research Institute, McMaster University, Hamilton, Ontario, Canada*These authors contributed equally to this workCorrespondence: Zainab Samaan, Health Research Methodology Graduate Program, McMaster University, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada, Tel +1 905-522-1155 ext. 35448, Fax +1 905-381-5629, Email samaanz@mcmaster.caIntroduction: Patient centred care is needed now more than ever in the treatment of opioid use disorder. Trials, policy makers, and service providers have most often used treatment retention and opioid urine screens as measures of treatment effectiveness. However, patients receiving medication for opioid use disorder treatment (MOUD) may prioritise the use of different ways to assess treatment success.Objective: The aim of this review is to synthesize literature examining the self-reported goals patients would like to achieve in MOUD for opioid use disorder.Methods: We searched MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception until April 30th, 2021. No restrictions were placed on language, age, or type of MOUD. A qualitative synthesis is presented given that a meta-analysis was not possible.Results: The search yielded a total of 21,082 records from which 8 met criteria for inclusion in the qualitative synthesis. We identified a total of 43 patient-reported treatment goals from the 8 studies. Twelve domains were created from the 43 goals reported. These domains cover a range of important areas for patients’ goals related to living a normal life, physical health, mental health, treatment, and substance use specific areas.Conclusion: This review highlights several patient goals that they would like to achieve during treatment for opioid use disorder that are not commonly considered as markers of treatment effectiveness. Goals related to health, living a normal life, and overall substance use concerns by patients should be taken into consideration by clinical trialists, researchers, policy makers, service providers, patients, and communities engaged in developing and tailoring treatment plans for opioid use disorder.Systematic Review Registration: PROSPERO CRD42018095553.Keywords: opioid use disorder, patient reported outcomes, patient-centred care, medication for opioid use disorder

viral infections, duplex bilateralis, herpes zoster, immunological tests, bad mood, Infectious and parasitic diseases, and RC109-216

Tianhang Yu,1 Jikai Song,2 Xin Chen,1 Jin Li,1 Shuang Yang,1 Jie Yang1 1Department of Dermatology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 2Zhejiang Provincial People’s Hospital, Qingdao University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jie Yang, Tel +8618832506999, Email yjj1971321@163.comAbstract: Herpes zoster (HZ) is usually distributed on one side of the body; HZ duplex bilateralis is very rare with only 0.1% of all HZ cases. The occurrence of HZ duplex bilateralis is associated with abnormal immune function. In this report, we present a case of a 47-year-old woman who had no major health issues developed HZ duplex bilateralis after an adverse life event and extreme depression one month ago. HZ related symptoms were controlled after patient received antiviral, analgesic, and nerve-nourishing treatment in our hospital.Keywords: viral infections, duplex bilateralis, herpes zoster, immunological tests, bad mood

hair, trichoscopy, histopathology, Dermatology, and RL1-803

Danchen Hu,1– 4 Ping Tu,1– 4 Shuxia Yang1– 4 1Department of Dermatology, Peking University First Hospital, Beijing, 100034, People’s Republic of China; 2National Clinical Research Center for Skin and Immune Diseases, Beijing, 100034, People’s Republic of China; 3Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, 100034, People’s Republic of China; 4NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, 100034, People’s Republic of ChinaCorrespondence: Shuxia Yang, Department of Dermatology, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Tel + 86-13661345723, Email yangshuxia@bjmu.edu.cnBackground: Collecting data on hair counts helps dermatologists diagnose hair diseases more accurately. Quantitative trichoscopy analysis and pathologic examination are two common ways to evaluate hair parameters.Purpose: The study aims to compare the effect of quantitative trichoscopy analysis and pathologic examination in hair counting and quantify the hair density of average Chinese people.Methods: Trichoscopy was performed in four scalp regions with a total of twenty-three volunteers without alopecia: frontal, vertex, occipital, and parietal. Hair density parameters were recorded. A 4-mm punch biopsy was performed in the occipital area, and all specimens were transversely sectioned serially and observed to calculate the hair densities.Results: The average hair density, hairs per follicle unit, and vellus hair ratio from quantitative trichoscopy analysis in the occipital region were 163.07± 28.17/cm2, 1.87± 0.25 and 6.60± 3.95%, lower than those from biopsy significantly (214.97± 48.73/cm2, 2.24± 0.30 and 10.48± 6.43%). The hair shaft diameter measured by quantitative trichoscopy analysis was 74.52± 8.02μm, higher than that by histopathologic examination (68.65± 8.00μm) (p< 0.05).Conclusion: Quantitative trichoscopy is a noninvasive, quick, and convenient way to evaluate hair density. Histopathologic examination is an invasive way but provides more accurate data. The data obtained from trichoscopy and pathological examination are different to some extent, which cannot be substituted entirely for each other. This study established the reference for hair density in the adult Chinese population.Keywords: hair, trichoscopy, histopathology

Arthrodesis, Fusion, First metatarsophalangeal joint, Hallux abducto valgus, Hallux rigidus, Systematic review, Diseases of the musculoskeletal system, and RC925-935

Abstract Background First metatarsophalangeal joint arthrodesis is commonly performed for symptomatic end-stage hallux rigidus. It has been postulated to produce good results in the literature. Various fixation techniques offer differences in union rates, complications and functional outcomes, stirring debates about which produces the best outcomes for patients. Therefore, this review aims to synthesise and compare the outcomes of modern fixation techniques used for first metatarsophalangeal joint (FMPJ) arthrodesis. Methods The electronic database searched were PubMed, CINAHL, Cochrane Library, and Google Scholar. The critical appraisal skills programme tool for cohort study was used. The interventions consisted of screw(s), plate(s), and staple(s). Studies comprising outdated fixation techniques such as suture, metallic wire, external fixation, Rush rods or Steinmann pins were excluded. Participants were adults over 18 years, undergoing FMPJ arthrodesis in the UK. Studies with the population consisting primarily of revision cases, patients with rheumatoid arthritis or diabetes were excluded. Results Seven UK studies included 277 feet and a 95.7% overall union rate at a mean union time of 83.5 days. Staples had the highest union rate of 98.2% at mean union time of 84 days, followed by plates (95.2%, 92 days), and finally screws (94.9%, 71 days). The overall complication incidence is 5.8%. All of the fixation techniques produced good functional outcomes postoperatively. Conclusions Whilst staple techniques showed the highest union rate, plating techniques are preferable over screws or staples for better results across several outcome measures, including reduced complication incidence, stability, early ambulation, and good functional outcome. The Manchester-Oxford Foot Questionnaire and EuroQol-5Dimensional are recommended as measurement tools to assess functional outcomes following FMPJ arthrodesis.

impacted ureteral calculi, holmium laser ureteroscopic lithotripsy, systemic inflammatory response syndrome, risk factors, drug resistance, sensitivity, Medicine (General), and R5-920

Quangang Yuan,1,* Jiang Guo,2,* Long He,1 Qiulin Chen,1 Xianhong Zou,1 Siming Yang,1 Zhenyang Zhang1 1Department of Urology, Chongqing Hechuan Hongren Hospital, Chongqing, 401520, People’s Republic of China; 2Department of Urology, Anyue People’s Hospital of Ziyang City, Ziyang City, Sichuan Province, 642300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenyang Zhang, Tel/Fax +86 23-67710675, Email urinaryzhang@163.comObjective: To investigate the risk factors, pathogen distribution, and drug resistance of systemic inflammatory response syndrome (SIRS) after holmium laser ureteroscopic lithotripsy for impacted ureteral calculi (HLULIUC).Patients and Methods: The clinical data of 293 patients with HLULIUC in our hospital from October 2017 to February 2021 were retrospectively collected, including age, BMI, stone size, operation time, urine routine, urine culture, basic illness, complete blood count, liver and kidney function, etc. Patients were divided into SIRS and non-SIRS groups according to whether they had SIRS or not. Then the differences in clinical data, blood and urine bacterial culture results, and drug resistance between the two groups were analyzed.Results: The incidence of SIRS after HLULIUC was 17.75%. Logistic regression analysis showed that the risk factors of SIRS after HLULIUC include ureteral calculi≥ 1cm (OR=2.839, 95% CI=1.341– 5.647, P=0.021), long operation time (OR=4.534, 95% CI=2.597– 12.751, P=0.017), diabetes mellitus (OR=3.137, 95% CI=1.142– 7.319, P=0.012), increased preoperative C-reactive protein (OR=1.864, 95% CI=1.05– 4.347, P=0.032), and positive urine leukocytes (OR=3.514, 95% CI=1.7237– 9.734, P=0.007) and culture (OR=6.034, 95% CI=3.097– 15.751, P< 0.001) before operation. The main pathogens causing SIRS after HLULIUC were Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa. The pathogenic bacteria are sensitive to drugs including piperacillin/tazobactam, meropenem, tigecycline, teicoplanin, vancomycin, and imipenem. The resistance rates to quinolones (such as levofloxacin) and to the second- and third-generations of cephalosporins were as high as 52.94%– 90.19%.Conclusion: Ureteral calculi≥ 1cm, long operation time, diabetes, increased C-reactive protein, and preoperative positive urine leukocytes and culture are independent risk factors of SIRS after HLULIUC. Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa are the main pathogenic bacteria for SIRS after HLULIUC. The pathogenic bacteria are sensitive to drugs, including piperacillin/tazobactam, meropenem, tigecycline, teicoplanin, vancomycin, and imipenem.Keywords: impacted ureteral calculi, holmium laser ureteroscopic lithotripsy, systemic inflammatory response syndrome, risk factors, drug resistance, sensitivity

free triiodothyronine, mild cognitive impairment, insulin resistance, type 2 diabetes mellitus, Specialties of internal medicine, and RC581-951

Haoqiang Zhang,1– 3,* Shufang Yang,2,4,* Wenwen Zhu,1,2 Tong Niu,1,2 Zheng Wang,1,2 Ke An,1,2 Zuoling Xie,1,2 Pin Wang,2 Xi Huang,1,2 Chenchen Wang,1,2 Haiyan Shangguan,2 Yang Yuan,1 Shaohua Wang1 1Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, People’s Republic of China; 4Department of Endocrinology, Taizhou People’s Hospital, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaohua Wang; Yang Yuan, Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Tel +86-25-83262815 ; +86-13814003661, Fax +86-25-83285132, Email gyjwsh@126.com; yang_yuan000@sina.comPurpose: We aim to determine the role of free triiodothyronine (FT3), the main active ingredient of thyroid hormones (THs), in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI).Patients and Methods: A total of 255 T2DM patients without diagnosed thyroid diseases were recruited and divided into MCI group and healthy cognition group. Neuropsychological functions were observed by multidimensional cognitive function scales in including MoCA, Digit Span Test (DST), Verbal Fluency Test (VFT), Clock drawing test (CDT), Trail Making Test (TMT) A and B, Instantaneously Recalled Auditory Verbal Learning Test (AVLT-IR), Delayed Recalled Auditory Verbal Learning Test (AVLT-DR) and Logical Memory Test (LMT). Correlation and logistic regression analyses were performed to explore the association between FT3 and diabetic cognitive dysfunction.Results: Compared with 147 normal cognition patients, 108 MCI patients exhibited lower FT3 and higher HOMA-IR. FT3 level was not only positively correlated with MoCA scores, but DST, VFT and LMT, while negatively associated with TMTB. Furthermore, there is a negative association between FT3 and HOMA-IR. Logistic regression showed that decreased FT3 is a risk factor of MCI in T2DM patients. Although FT3 is not the risk factor of MCI after homeostasis model assessment of insulin resistance (HOMA-IR) was entered as an independent variable, lower FT3 is associated with VFT and LMT adjusted by age, education, BMI, DM duration, HBP duration, smoking, HbA1c and HOMA-IR.Conclusion: Lower FT3 levels may involve in MCI, especially for executive function and scene memory in T2DM patients without diagnosed thyroid diseases.Keywords: free triiodothyronine, mild cognitive impairment, insulin resistance, type 2 diabetes mellitus

pain, fatigue, sleep disturbance, anxiety, depression, Medicine (General), and R5-920

Xiaofang Dong,1 Sen Yang,2 Yuanli Guo,1 Peihua Lv,1 Yanjin Liu1 1Neurology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Orthopedics Department, The Seventh People’s Hospital of Zhengzhou, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Yanjin Liu, Neurology Department, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13523548732, Email luomeiruxue139@sina.com; liu-yanjin@126.comPurpose: To identify latent classes of acute stroke patients with distinct experiences with the symptom clusters of depression, anxiety, fatigue, sleep disturbance, and pain symptoms and assess, if the selected variables determine a symptom-cluster experience in acute stroke patients.Participants and Methods: A sample of 690 participants were collected from July 2020 to December 2020 in a cross-sectional descriptive study. Latent class analysis was conducted to distinguish different clusters of acute stroke participants who experienced five patient-reported symptoms. Furthermore, multinomial logistic regression was selected to verify the influencing indicators of each subgroup, with selected socio-demographic variables, clinical characteristics, self-efficacy, and perceived social support as independent variables and the different latent classes as the dependent variable.Results: Three latent classes, named “all high symptom,” “high psychological disorder,” and “all low symptom,” were identified, accounting for 9.6%, 26.3%, and 64.1% of symptom clusters, respectively. Patients in the “all high symptom” and “high psychological disorder” classes reported significantly lower quality of life (F=40.21, p < 0.05). Female gender, younger age, higher National Institutes of Health Stroke Scale scores, and lower self-efficacy and perceived social support were risk factors associated with the “high psychological disorder” class. Younger patients with lower self-efficacy and perceived social support were more likely to be in the “all high symptom” class.Conclusion: This study identified latent classes of acute stroke patients that can be used in predicting symptom-cluster experiences following a stroke. Also, the ability to characterize subgroups of patients with distinct symptom experiences helps identify high-risk patients. Focusing on symptom clusters in clinical practice can inspire us to create effective targeted interventions for subgroups of stroke patients suffering from the same symptom cluster.Keywords: pain, fatigue, sleep disturbance, anxiety, depression

retrospective analyze, cervical spondylosis, anterior cervical discectomy and fusion, cervical sagittal balance parameters, fusion devices., Medicine (General), and R5-920

Zihan Wei, Ying Zhang, Sizhen Yang, Chenhui Cai, Jiawen Ye, Hao Qiu, Xu Hu, Yiyun Qu, Xuan Wen, Tongwei Chu Department of Orthopedics, Xinqiao Hospital of Chongqing, Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Tongwei Chu, Department of Orthopedics, Xinqiao Hospital of Chongqing, Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel/Fax +8613708388336, Email chtw@sina.comObjective: To compare the cervical sagittal balance parameters and clinical efficacy of three fusion devices after short-segment anterior cervical discectomy and fusion.Patients and Methods: Retrospectively analyzed 516 patients with cervical spondylosis who underwent surgery at our hospital from May 2013 to May 2019. All patients had complete data and were divided into three groups according to the selected fusion cage. Neck and upper limb pain were assessed by the visual analog scale (VAS) score. Neurological function was evaluated by the modified Japanese Orthopedics Society (mJOA) score. Also, the curvature of the cervical spine and the occurrence of dysphagia were observed.Results: There were no significant differences in the general information, thoracic inlet angle, T1 slope, or surgical data among the groups (p> 0.05). There were significant differences in the scores between pre- and postoperatively in the different groups (p< 0.05). There were no significant differences in the C2-C7 Cobb angle or C2-C7 sagittal vertebral axis before the operation among the groups (p> 0.05). There was a significant difference in the correction and loss of correction among the groups postoperatively and on follow-up (p> 0.05). Dysphagia was less likely in the Zero-P VA fusion group than in the other two groups.Conclusion: Different fusion instruments can relieve the symptoms. In the Prodisc-C Vivo group, no significant improvement in cervical sagittal balance was achieved. A good effect on improving sagittal balance was observed in both the Zero-P VA fusion and Skyline anterior cervical titanium plate groups, but a better effect on preventing dysphagia was observed in the Zero-PVA fusion group.Keywords: retrospective analyze, cervical spondylosis, anterior cervical discectomy and fusion, cervical sagittal balance parameters, fusion devices

glucagon-like peptide-1, diabetes mellitus, alzheimer’s disease, parkinson's disease, cognition., Therapeutics. Pharmacology, and RM1-950

Dihe Cheng, Shuo Yang, Xue Zhao, Guixia Wang Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Guixia Wang; Xue Zhao, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China, Tel +86 15843081103 ; +86 18744014213, Email gwang168@jlu.edu.cn; xuezhao@jlu.edu.cnAbstract: Recent clinical guidelines have emphasized the importance of screening for cognitive impairment in older adults with diabetes, however, there is still a lack of understanding about the drug therapy. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are widely used in the treatment of type 2 diabetes and potential applications may include the treatment of obesity as well as the adjunctive treatment of type 1 diabetes mellitus in combination with insulin. Growing evidence suggests that GLP-1 RA has the potential to treat neurodegenerative diseases, particularly in diabetes-related Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here, we review the molecular mechanisms of the neuroprotective effects of GLP-1 RA in diabetes-related degenerative diseases, including AD and PD, and their potential effects.Keywords: glucagon-like peptide-1, diabetes mellitus, Alzheimer’s disease, Parkinson’s disease, cognition

hiv-1, genotype, integrase strand transfer inhibitor, pre-treatment drug resistance mutation, beijing, Therapeutics. Pharmacology, and RM1-950

Fengting Yu,1,2,* Qun Li,1,2,* Linghang Wang,1,2 Hongxin Zhao,1,2 Hao Wu,3 Siyuan Yang,1,2 Yunxia Tang,1,2 Jiang Xiao,1,2 Fujie Zhang1,2 1Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People’s Republic of China; 3Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fujie Zhang, Clinical and Research Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86 10 84322581, Email treatment@chinaaids.cnIntroduction: Integrase strand transfer inhibitors (INSTIs) are important drugs that are currently used as the first line treatment for HIV-1 patients. The aim of this study was to characterize HIV-1 INSTI mutations among ART-naive patients in Beijing from 2019– 2021.Methods: 865 ART-naive patients were enrolled in this study between January 2019 and June 2021 in Beijing. The amplification of the entire pol gene containing the reverse transcriptase, protease and integrase regions was performed using a validated In-house SBS method. HIV-1 subtypes and circulating recombinant forms (CRFs) were determined using the COMET online tool (http://comet.retrovirology.lu). Stanford HIV-1 drug resistance database (HIVdb version 8.9) was used to analyze the mutations.Results: 865 HIV-1 pol sequences were successfully amplified and sequenced. Among them, no major INSTI-related mutations were identified, but 12 polymorphic accessory mutations were found. Two patients have E138A and G163R mutations respectively and both could cause low-level resistance to RAL and EVG. Furthermore, one patient having S230R mutation resulted in low-level resistance to RAL, EVG, DTG and BIC.Conclusion: The prevalence of INSTIs mutations remains low, which demonstrated that INSTIs have good applicability currently in our city. Nevertheless, it is very important to monitor the INSTI-related mutations in Beijing.Keywords: HIV-1, genotype, integrase strand transfer inhibitor, pre-treatment drug resistance mutation, Beijing

polygenic risk score, apnea-hypopnea index, single nucleotide polymorphisms, discriminatory accuracy, Psychiatry, RC435-571, Neurophysiology and neuropsychology, and QP351-495

Juan Li,1,2 Qianwen Lv,1 Haili Sun,1 Yunyun Yang,1,3 Xiaolu Jiao,1,3 Song Yang,1 Huahui Yu,1,3 Yanwen Qin1,3 1Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, 100029, People’s Republic of China; 2Emergency Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, People’s Republic of ChinaCorrespondence: Yanwen Qin, Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-10-64456529, Fax +86-10-64456095, Email qinyanwen@vip.126.com; qinyanwen@ccmu.edu.cnPurpose: Obstructive sleep apnea (OSA) is a common chronic polygenic disease. Multiple genetic markers associated with OSA have been identified by genome-wide association studies. Here, we aimed to construct a polygenic risk score (PRS) and examine the association with the presence of OSA in a Chinese Han Population.Patients and Methods: This study included 1057 individuals who were genotyped for nine susceptibility loci from three genes (ADIPOQ, PPARG, and TNF), from which each individual’s PRS was calculated by summing the number of risk alleles. The associations between PRS and OSA were determined by logistic regression analyses. Model discrimination was assessed by a receiver operating characteristic (ROC) curve using bootstrapping with 1000 resamples.Results: The subjects included 874 with OSA and 183 controls. A higher PRS was associated with an increased apnea-hypopnea index (AHI). The PRS was an important risk factor for the development of OSA (OR = 1.237 per SD, P = 0.030). Subjects with higher PRS had a 2.88-fold (95% CI: 1.393– 5.955, P = 0.004) and 5.402-fold (95% CI: 2.311– 12.624, P< 0.001) greater risk for having OSA and moderate-to-severe OSA, respectively, compared with those with lower genetic risk. More importantly, compared with determination of risk based solely on clinical factors, addition of the PRS increased discriminatory accuracy for both OSA (AUC from 0.75 to 0.78, P = 0.02) and moderate-to-severe OSA (AUC from 0.80 to 0.83, P = 0.02).Conclusion: Our study suggests that the PRS is independently associated with AHI and OSA. Combining PRS with conventional risk factors could improve the discrimination of OSA.Keywords: polygenic risk score, apnea-hypopnea index, single nucleotide polymorphisms, discriminatory accuracy

thyroid hormone receptor, c3h mice, hair cycle, pclaf, wnt/beta-catenin pathway, hedgehog pathway, Dermatology, and RL1-803

Peiqiu Zhu,1– 5 Weiwei Deng,1– 5 Jin Yu,1– 5 Shuxia Yang1– 5 1Department of Dermatology and Venereology, Peking University First Hospital, Beijing, People’s Republic of China; 2Research Center for Medical Mycology, Peking University, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, People’s Republic of China; 4National Clinical Research Center for Skin and Immune Diseases, Beijing, People’s Republic of China; 5NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, People’s Republic of ChinaCorrespondence: Shuxia Yang; Jin Yu, Tel +86 83573103 ; +86 83573075, Email yangshuxia@bjmu.edu.cn; yujin676@126.comBackground: Thyroxine is important to maintain the normal operation of the body. Both clinical and experimental results show thyroxine is closely related to hair growth, the mechanism of which is not fully understood.Purpose: Investigate the effect of thyroxine receptor agonist, TDM10842, for dorsal hair growth in C3H mice and explore its underlying mechanism.Methods: Depilated mice were applied with the TDM10842, vehicle of this drug and without any materials on dorsal skin. RNA‐sequencing (RNA‐seq) was employed to identify the change in gene expression of skin tissues. Quantitative real-time PCR (rt-PCR) and immunoblotting were conducted to validate key differentially expressed genes (DEGs) between different groups.Results: The TDM group showed early induction of anagen. 857, 782, and 276 differentially expressed genes were identified between 3 groups. As a critical DEG in group TDM, Pclaf was positively related to the motivation of Wnt/beta-catenin and Hedgehog signaling pathways, with a high expression of Ki67 and cyclinD1.Conclusion: TDM10842 accelerates the anagen entrance and the potential mechanism might be the activation of Wnt/beta-catenin and Hedgehog pathways. Pclaf serves as a critical molecule involved in pathway activation, and cyclinD1 is an important effector protein downstream of the pathways.Keywords: thyroid hormone receptor, C3H mice, hair cycle, Pclaf, Wnt/beta-catenin pathway, Hedgehog pathway

microbiota, acute respiratory distress syndrome, corticosteroid, hematologic neoplasms, Pathology, RB1-214, Therapeutics. Pharmacology, and RM1-950

Jiawei Shen,1,* Yan Hu,2,* Jie Lv,1 Huiying Zhao,1 Bin Wang,1 Shuguang Yang,1 Anqi Du,1 Shuang Liu,2 Youzhong An1 1Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Peking University International Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youzhong An, Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China, Email bjicu_bmc@163.comObjective: In this study, we aim to classify hematological patients with the pneumonia-associated acute respiratory syndrome (ARDS) into different groups that were characterized by distinct early responsiveness to corticosteroids, describe the microbiota signatures of the non-responders and responders, and compare the prognosis of the two groups.Methods: Hematological patients with ARDS were included and treated with mechanical ventilation and corticosteroid. According to the early improvement to the corticosteroid therapy, patients were classified as non-responders and responders. The lung microbiota signatures and the outcomes of the non-responders and responders were compared.Results: Fifty patients were included in this study. Twenty-eight patients were classed as non-responders and 22 as responders. Compared to the non-responders, responders had higher serum levels of IL-6, IL-8, TNF-α and CRP, their lung microbiota was with lower alpha diversity and enriched with virus species. The responders had an overall higher ventilator free days than the non-responders [4 (0– 6) vs 6 (0– 10), p=0.034], for survivors the difference was more significant [5 (3– 6) vs 8 (3– 10), p=0.012]. Survival analysis showed that there was no difference in survival rate between the two groups over time (Log-rank p=0.073). When non-responders were stratified into subgroups of patients with infection or co-infection, those non-responders with co-infection had significantly lower survival rate than other patients (Log-rank p= 0.028).Conclusion: For hematological patients with pneumonia-associated ARDS, the responders of corticosteroids had higher ventilator free days at day 28 than the non-responders. The microbiota signatures were distinct in the two groups. The non-responders with coinfections had the lowest survival rate when compared to the non-responders with no coinfections and the responders.Keywords: microbiota, acute respiratory distress syndrome, corticosteroid, hematologic neoplasms

network pharmacology, molecular docking, rheumatoid arthritis, sidaxue (sx), vegf/pi3k/akt signaling pathway, tnf-α signaling pathway, il/nf-κb signaling pathway, Therapeutics. Pharmacology, and RM1-950

Ning Wu,1,* Taohua Yuan,1,* ZhiXin Yin,1 Xiaotian Yuan,1 Jianfei Sun,1 Zunqiu Wu,1 Qilong Zhang,1 Carl Redshaw,2 Shenggang Yang,1 Xiaotian Dai3 1Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Chemistry, University of Hull, Hull, Yorkshire, HU6 7RX, UK; 3Department of Mathematics and Statistics, University of Calgary, Calgary, AB, Canada*These authors contributed equally to this workCorrespondence: Shenggang Yang, Guizhou Medical University, Guiyang, Guizhou, 550025, People’s Republic of China, Tel/Fax +86 13158000576, Email yangshenggang2021@126.com Xiaotian Dai, Department of Mathematics and Statistics, University of Calgary, Calgary, AB, T2N 1N4, Canada, Tel/Fax +1 435 754 4980, Email xiaotian.dai@uCalgary.caPurpose: This study aimed to investigate the molecular mechanisms of Compound Sidaxue (SX), a prescription of Chinese Miao medicine, in treating rheumatoid arthritis (RA) using network pharmacology and in vivo experimental approaches.Methods: Network pharmacology was adopted to detect the active components of four Traditional Chinese herbal medicine (TCM) of SX, and the key targets and signaling pathways in the treatment of RA were predicted, and the key components and targets were screened for molecular docking. The predicted targets and pathways were validated in bovine type II collagen and incomplete Freund’s adjuvant emulsifier-induced rat RA model.Results: In this study, we identified 33 active components from SX, predicted to act on 44 RA-associated targets by network pharmacology. PPI network demonstrated that TNF-α, VEGF-A, IL-2, IL-6, AKT, PI3K, STAT1 may serve as the key targets of SX for the treatment of RA. The main functional pathways involving these key targets include PI3K-AKT signaling pathway, TNF signaling pathway, NF-κB signaling pathway. Molecular docking analysis found that the active components β-amyrin, cajanin, eleutheroside A have high affinity for TNF-α, VEGFA, IL-2, AKT, and PI3K, etc. SX can improve joint swelling in Collagen-induced arthritis (CIA) rats, reduce inflammatory cell infiltration and angiogenesis in joint synovial tissue, and down-regulate IL-2, IL-6, TNF-α, VEGF, PI3K, AKT, p-AKT, NF-κBp65, the expression of p-NF-κBp65, STAT1, and PTGS2 are used to control the exacerbation of inflammation and alleviate the proliferation of synovial pannus, and at the same time play the role of cartilage protection to achieve the effect of treating RA.Conclusion: Through a network pharmacology approach and animal study, we predicted and validated the active compounds of SX and their potential targets for RA treatment. The results suggest that SX can markedly alleviate CIA rat by modulating the VEGF/PI3K/AKT signaling pathway, TNF-α signaling pathway, IL/NF-κB signaling pathway.Keywords: network pharmacology, molecular docking, rheumatoid arthritis, Sidaxue, VEGF/PI3K/AKT signaling pathway, TNF-α signaling pathway, IL/NF-κB signaling pathway