ObjectiveTo investigate the effects of the combination of components from Tripterygii Radix et Rhizoma and Chuanxiong Rhizoma on rheumatoid arthritis fibroblast-like synoviocytes （RA-FLSs） and the underlying mechanism. MethodsRA-FLSs were grouped as follows： blank control， positive control （methotrexate）， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma. The cell-counting kit-8 （CCK-8） assay was employed to the cell proliferation， invasion， and apoptosis. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， reactive oxygen species （ROS）， and malondiadehyde （MDA） in cells were measured. Western blot was employed to determine the protein levels of nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB） p65， phosphorylated inhibitory subunit of NF-κBα （p-IκBα）， cysteinyl aspartate-specific protease-3 （Caspase-3）， and B-cell lymphoma 2 （Bcl-2）. Real-time PCR was employed to determine the mRNA levels of Nrf2， HO-1， and NF-κB p65. ResultsThe cells in the groups of positive control， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma were treated with 2.50 mg·L^-1 methotrexate， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol， 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol + 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， respectively. Compared with the blank control group， drug administration reduced the proliferation and invasion and increased the apoptosis of cells （P<0.01）， lowered the levels of TNF-α， IL-6， ROS， and MDA （P<0.01）， up-regulated the mRNA and protein levels of Caspase-3， Nrf2， and HO-1 （P<0.01）， and down-regulated the mRNA and protein levels of Bcl-2， NF-κB p65， and p-IκBα （P<0.01）. Compared with the Tripterygii Radix et Rhizoma components group， the combination of components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma inhibited the proliferation and invasion （P<0.05） and promoted the apoptosis of RA-FLSs， up-regulated the mRNA levels of Nrf2 and HO-1 and protein levels of Nrf2 and Caspase-3 （P<0.05）， and down-regulated the protein levels of NF-κB p65 and p-IκBα （P<0.05）. ConclusionThe combination of components from Chuanxiong Rhizoma and Tripterygii Radix et Rhizoma can inhibit the proliferation and invasion and promote the apoptosis of RA-FLSs and alleviate oxidative stress and inflammation by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 pathway， and regulating the expression of Bcl-2/Caspase-3.

Thrombocytopenia is a common complication during the treatment of malignant tumors. It can lead to insufficient doses of chemotherapy drugs or delayed chemotherapy, shorten patients’ survival time, and affect prognosis. Thrombocytopenia has two types: cancer treatment-induced thrombocytopenia and tumor-associated immune thrombocytopenia. The latter is relatively rare, and its pathogenesis may be related to immune dysregulation. Current studies have shown that gene polymorphism and methylation are involved in tumor-associated immune thrombocytopenia. The pathogenesis and treatment of tumor-associated immune thrombocytopenia are discussed in this article.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Background Heavy metals may play an important role in environmental risk factors associated disorders of activities of daily living (ADL) in older adults. Objective To investigate the associations between plasma levels of six heavy metals (zinc, arsenic, cadmium, lead, manganese, and copper) and ADL disorders in older adults. Methods A cross-sectional survey was conducted from 2018 to 2019 among 1412 rural elderly people in Gongcheng Yao Autonomous County, Guangxi Zhuang Autonomous Region. The plasma metal concentrations were detected by inductively coupled plasma mass spectrometry (ICP-MS), and subsequently classified into three groups (T1-T3) based on tertiles, with the T1 group as the reference. The samples were assessed for ADL disorders using the ADL scale. Logistic regression and restricted cubic spline model (RCS) were used to estimate the odds ratio (OR) and 95% confidence interval (CI) to assess the associations between heavy metals and the prevalence of reporting ADL disorders. Results The mean age of the study population was (68.52 ± 5.92) years, 825 (58.4%) female and 587 (41.6%) male. Of these, 372 (26.34%) subjects reported ADL disorders, and most of them were female (74.30%). The results of logistic regression showed that the participants in the cadmium T2 group (0.15-0.25 µg·L⁻¹) had a higher risk of ADL disorders compared to the T1 group (≤0.15 μg·L⁻¹) (OR=1.552, 95%CI: 1.086, 2.134). After stratification by sex, the relative risk of ADL disorders was lower in the plasma copper T3 group (>1019.58 µg·L⁻¹) compared to the T1 group (≤868.12 μg·L⁻¹) in men (OR=0.481, 95%CI: 0.232, 0.998). The relative risk of ADL disorders was higher in the plasma cadmium T2 group (0.15-0.25 µg·L⁻¹) compared to the T1 group (≤0.15 μg·L⁻¹) in women (OR=1.758, 95%CI: 1.182, 2.616). The RCS results showed that the risk of ADL disorders in men was nonlinearly associated with copper (P_nonlinear=0.011, P_overall<0.05). Conclusion High levels of cadmium are positively associated with the risk of reporting ADL disorders, while high levels of copper are negatively associated with the risk of reporting ADL disorders in men.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:A SARS-CoV-2 pseudovirus(PsV)system was established for neutralizing antibody evaluation and virus entry inhibitor screening.Methods:Lentiviral vector plasmids psPAX2,pCDH-Luc and SARS-CoV-2 Spike(S)protein expres-sion plasmids were co-transfected,and harvested pseudoviral supernatant was used to infect ACE2-293T cells.Protein content of p24 was determined to reflect titer of PsV,and expression of S protein in PsV was detected by Western blot.Neutralization capacity of an S protein monoclonal antibody was evaluated using original strain,D614G,Gamma,Delta,Omicron PsV.Two reported virus entry inhibitors,chloroquine and carrageenin,were used to detect effect on entry of Omicron PsV.Results:Lentiviral vector successfully incorporated S protein.Western blot results showed that S protein mutated at 665Y showed a different cleavage form(90 kD)than wild-type full-length S protein(180 kD).Titer of PsV packaged by three plasmids system was higher.Ratio of S protein expression plasmid,transfer plasmid and packaging plasmid at 1∶3∶3 was optimum condition for viral packaging.Titer of PsV packaged under this condi-tion was over 20 ng/ml.PsV could effectively infect ACE2-293T cells,and double reporter gene GFP and firefly luciferase were expressed obviously,whose chemiluminescence values reached 106.Monoclonal antibodies of S protein effectively neutralized four types of PsVs,but neutralization of original strain was 10～30 times greater than that of variant PsV.Virus entry inhibitors,chloroquine and ι-carrageenan significantly inhibited entry of Omicron PsV.Conclusion:SARS-CoV-2 PsV infection system we conducted can simu-late entry of SARS-CoV-2 successfully.Effective pharmacodynamic evaluation of neutralizing antibodies and virus entry inhibitors can be performed efficiently by the system,which can provide a technical platform for evaluation of neutralizing antibody of SARS-CoV-2 and screening of virus entry inhibitors,and would benefit R&D of anti-SARS-CoV-2 drugs.

Objective To investigate the expression of Member RAS Oncogene Family(RAB10)in pancreatic cancer(PAAD)and its effects on the proliferation,migration,invasion and apoptosis of SW1990 cells(human pancreatic cancer cells).Methods The expression of RAB1 0 mRNA in PAAD tissues wasanalyzed by the cancer gene database GEPIA(Gene Expression Profiling Interactive Analysis)and TCGA(The Cancer Genome Atlas).Cox regression analysis was used to detect relationship between RAB10 mRNA expression and the prognosis of pan-creatic cancer patients.We targeted small interfering RNA(R4B10-siRNA)targeting RAB10 as the silence group,and constructed an overexpression plasmid(RAB10-OE)for overexpression of RAB10 as the overexpression group.The effects of silencing and overexpressionweredetected by Q-PCR;protein expression levelsweredetected by West-ern blot.EdUcellproliferation test,wound healing test,Transwelltestand flow cytometry test were used to determine the effects of RAB10 on the proliferation,migration,invasion and apoptosis of SW1990 pancreatic cancer cells.Re-sults RAB10 mRNA expression in PAAD tissues was higher than that innormal pancreatic tissues(P＜0.05).The results of EdUcellproliferation testshowed that the proliferation rate of SW1990 cells in the RAB10-OE group was higher thanthat in the control group,and the proliferation rate of SW1990 cells in the RAB10-siRNA group was lower than that inthe control group(P＜0.05).The results of the Transwell test and wound healing test showed that the invasion rate and mobility rate of RAB10-OE group were higher thanthose of the control group,and the mobility and invasion rate of RAB10-siRNA group were lower than those of the control group(P＜0.05).The re-sults of flow cytometry test showed that the apoptosis rate was lower in the RAB10-OE group than the control group,and the apoptosis rate in the RAB10-siRNA group was higher than the control group(P＜0.05).The median sur-vival time of RAB10 high expression group was significantly lower than that of RAB10 low expression group(P＜0.05).Cox regression analysis showed that clinical grade,T stage,M stage and RAB10 mRNA expression were re-lated to survival and prognosis of pancreatic cancerpatients(P＜0.05).Multivariate Cox regression analysis showed that the expression level of RAB10 mRNA was the independent risk factor affecting the prognosis of pancre-atic cancer patients(P＜0.05).Conclusion RAB10 is highly expressed in PAAD tissues and RAB10 can pro-mote the proliferation of pancreatic cancer cells,accelerate the ability to invade and migrate,and inhibit the apop-tosis of pancreatic cancer cells.RAB10 is an independent risk factor for survival prognosis in patients with pancreat-ic cancer.

Objective To explore the therapeutic effect of lignans extracted from Eucommia Ulmoides Oliver on diabetes encephalopathy(DE)rats and the effects on nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods A rat model of DE was established,and 48 successfully established DE rats were randomly divided into model group,and low-and high-dose lignans groups(200 and 400 mg/kg),and metformin(200 mg/kg)group,with 12 rats in each group.Another 12 healthy rats served as control group.Each group of rats was giv-en corresponding drug intervention once a day for 6 consecutive weeks.Cognitive and memory abilities,serum levels of IL-6,TNF-α,MDA and SOD,and mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were measured in all groups.Pathological changes of the hippocampus were observed after HE staining.Results Compared with the control group,significantly longer escape latency and increased serum levels of IL-6,TNF-α and MDA,while lower times of crossing original platform,shorter residence duration of original platform quadrant,decreased serum SOD level,and reduced mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were observed in the model group(all P＜0.05).Low-and high-dose lignans treatment reversed all above indica-tors when compared with model group(P＜0.05).What's more,the effects of high-dose lignans treatment were more significant than low-dose treatment in escape latency,serum levels of IL-6,TNF-α and MDA,times through the original platform,residence duration of the original platform quadrant,serum SOD level,and mRNA Nrf2 and HO-1 in the hippocampus(6.07±0.70 vs 4.76± 0.52,30.96±2.96 s vs 23.49±2.60 s,77.02±6.51 U/ml vs 61.71±6.75 U/ml,0.69±0.06 vs 0.49± 0.05,0.74±0.07 vs 0.57±0.06,P＜0.05).Conclusion Eucommia lignans can improve the cogni-tive ability,enhance the antioxidant capacity,inhibit inflammatory response and protect the hippo-campus of DE rats,and the mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Objective:To investigate the association of polymorphisms at the matrix metalloproteinase(MMP)-3-1612 position of the promotor region with the inflammatory response and oxidative stress in elderly patients with cerebral ischemic stroke.Methods:In this retrospective study, 129 elderly patients with cerebral infarction diagnosed and treated in our hospital between March 2019 and March 2021 were enrolled as the study group, and 110 healthy subjects were selected as the control group.Polymorphisms of the MMP-3-1612 position in the promotor region, the inflammatory response and oxidative stress were examined using appropriate parameters and the associations between them were analyzed. Results:Compared with the control group, the proportions of patients with hypertension, diabetes, and smoking history in the study group were significantly higher( χ2=16.05, 17.19, 14.19, all P<0.05), and the levels of fasting blood glucose, low-density lipoprotein, and homocysteine were also significantly higher( t=6.22, 3.64, 2.69, all P<0.05).Meanwhile, compared with patients carrying the MMP-3-5A/6A or the MMP-3-6A/6A genotype, the levels of serum inflammatory markers such as high mobility group box-1 protein(HMGB1), fractalkine(FKN), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)and interleukin-17(IL-17)in patients carrying the MMP-3 gene 5A/5A genotype were significantly higher(all P<0.05).In addition, the expression of serum oxidative stress-related molecules Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid-2 related factor2(Nrf2), antioxidant response element(ARE), quinone oxidoreductase 1(NQO1), and heme oxygenase-1(HO-1)was also significantly increased(all P<0.05), but there was no difference in these markers between patients carrying the MMP-3-5A/6A genotype and patients carrying the MMP-3-6A/6A genotype( P>0.05).Patients carrying the 5A/5A genotype and the 6A/6A genotype exhibited only one 97 bp band and one 120 bp band, respectively, while the patients carrying the 5A/6A genotype exhibited two 97 bp bands and two 120 bp bands.There was no statistical difference in the number of patients carrying the 5A/6A genotype in the cerebral infarction group compared with the control group( P>0.05), and the number of patients carrying the 5A/5A genotype in the cerebral infarction group was higher than that in the control group(69% or 53.49% vs.35% or 31.82%, χ2=11.34, P<0.05).Polymorphisms of the MMP-3 gene had a positive correlation with the risk of stroke( r=0.25, P<0.05). MMP-3-1612 gene polymorphism( OR=7.21, 95% CI: 1.13-1.83, P=0.01), elevated blood glucose( OR=1.27, 95% CI: 1.18-2.06, P<0.001), high homocysteine( OR=1.05, 95% CI: 1.08-1.58, P<0.01), hypertension( OR=5.414, 95% CI: 1.140-4.46, P<0.01), elevated low-density lipoprotein( OR=4.03, 95% CI: 1.03-2.35, P=0.02), coronary heart disease( OR=1.17, 95% CI: 1.47-3.19, P<0.01)and diabetes( OR=8.52, 95% CI: 1.32-4.71, P<0.01)were risk factors for cerebral infarction. Conclusions:In elderly patients with cerebral infarction, polymorphisms of the MMP-3-1612 position in the promotor region is closely related to the risk of cerebral ischemic stroke, the inflammatory response and oxidative stress.MMP-3 gene polymorphisms are risk factors for stroke.

Objective:To explore any effect of transcranial magnetic stimulation and peripheral magnetic stimulation of the mylohyoid muscle on dysphagia among stroke survivors.Methods:Sixty stroke survivors with dysphagia were randomly divided into a control group, a peripheral magnetic stimulation group, a central magnetic stimulation group, and a central + peripheral magnetic stimulation group, each of 15. In addition to routine swallowing training, the subjects were given the appropriate magnetic stimulation daily, five times a week for two weeks. Before and after the intervention, swallowing was evaluated using the Functional Oral Intake Scale (FOIS), Penetration-Aspiration Scale (PAS) and a functional dysphagia scale (FDS).Results:The average FDS, PAS, and FOIS scores of all four groups had improved significantly after the treatment. Improvement significantly greater than in the control group was observed in the average FOIS, FDS and PAS scores of the other three groups. The peripheral + central magnetic stimulation group showed the greatest average improvement.Conclusion:Combining mylohyoid muscle magnetic stimulation with magnetic stimulation of the cerebral cortex can significantly relieve dysphagia. It is more effective than conventional swallowing rehabilitation or either magnetic stimulation alone.