BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

Objective To investigate the effect of closed-chain exercise training on hemiplegic shoulder pain and shoulder joint sta-bility in stroke patients,and to explore the relationship between hemiplegic shoulder pain and shoulder joint sta-bility.Methods A total of 52 stroke patients with hemiplegic shoulder pain in Jiangsu Province Hospital from October,2020 to January,2023 were selected,and were randomly divided into control group(n=26)and experimental group(n=26).Both groups received conventional rehabilitation therapy,while the experimental group additionally under-went closed-chain exercise training for shoulder joint.Pain severity and motor function were assessed using Visu-al Analog Scale(VAS)and Fugl-Meyer Assessment-Upper Extremities(FMA-UE)before and after intervention.Musculoskeletal ultrasound was used to measure acromion-greater tuberosity distance(AGT),acromion-lesser tu-berosity distance(ALT),acromiohumeral distance(AHD)and supraspinatus thickness(SST)to evaluate shoulder joint stability.Correlation analysis was conducted on the improvements in shoulder pain and shoulder joint stabil-ity in the experimental group.Results Two cases in the control group and two in the experimental group dropped down.Both groups showed signifi-cant improvements in VAS and FMA-UE scores after intervention(|t|>5.214,P<0.001),and the scores im-proved more in the experimental group than in the control group(|t|>2.087,P<0.05).The experimental group also showed significant improvements in AGT,ALT,AHD and SST(|t|>4.187,P<0.001),with AGT,ALT and AHD being superior to those in the control group(|t|>2.155,P<0.05).The difference of VAS score in the exper-imental group was correlated with the difference of FMA-UE,AGT and ALT after intervention(r>0.434,P<0.05).Conclusion Closed-chain shoulder exercise training can significantly improve shoulder joint stability while alleviating shoulder pain,and effectively enhancing upper limb function in stroke patients with hemiplegic shoulder pain.Hemiplegic shoulder pain is correlated with shoulder joint stability.

Objective:To investigate the relationship between different types of tea intake and COVID-19 infection.Methods:Data were retrieved from a genome-wide association study(GWAS),involving 447 485,and 64 949 people for single nucleotide polymorphisms(SNPs).Two-sample Mendelian randomization(MR)analysis was used to investigate the relationship of different types of tea intake with four subgroups of COVID-19 infected population,including COVID-19 infected population versus general population,COVID-19 hospitalized population versus general population,COVID-19 hospitalized population versus non-hospitalized population,and very severe respiratory confirmed population versus general population.Inverse-variance weighted(IVW)method was used as the main method of causal analysis.MR Egger intercept was used for pleiotropy test,and Cochran's Q-statistic was used for heterogeneity test.Results:Compared to the general population,tea intake decreased the incidence of COVID-19 in the infection population(IVW method,OR=0.806,95%CI:0.651-0.999),and the hospitalized population(IVW method,OR=0.533,95%CI:0.369-0.770).Additionally,the underlying pleiotropy was not found following the MR-Egger regression intercept(MR intercept=-0.002,P=0.667),and the Cochran's Q-statistic showed no heterogeneity(Q-statistic=52.712,P=0.057).Compared to the general population,the underlying pleiotropy in the hospitalized patients was not found by MR-Egger regression intercept(MR intercept=-0.001,P=0.909),and the Cochran's Q-statistic showed no heterogeneity(Q-statistic=25.214,P=0.945).However,green tea and herbal tea had no effect on COVID-19 infection.Conclusions:Overall tea intake reduces the risk of COVID-19 infection in the general population compared to COVID-19 infected and hospitalized populations,while green tea and herbal tea have no protective effect against COVID-19 infection.

Objective:To investigate the relationship between different types of tea intake and COVID-19 infection.Methods:Data were retrieved from a genome-wide association study(GWAS),involving 447 485,and 64 949 people for single nucleotide polymorphisms(SNPs).Two-sample Mendelian randomization(MR)analysis was used to investigate the relationship of different types of tea intake with four subgroups of COVID-19 infected population,including COVID-19 infected population versus general population,COVID-19 hospitalized population versus general population,COVID-19 hospitalized population versus non-hospitalized population,and very severe respiratory confirmed population versus general population.Inverse-variance weighted(IVW)method was used as the main method of causal analysis.MR Egger intercept was used for pleiotropy test,and Cochran's Q-statistic was used for heterogeneity test.Results:Compared to the general population,tea intake decreased the incidence of COVID-19 in the infection population(IVW method,OR=0.806,95%CI:0.651-0.999),and the hospitalized population(IVW method,OR=0.533,95%CI:0.369-0.770).Additionally,the underlying pleiotropy was not found following the MR-Egger regression intercept(MR intercept=-0.002,P=0.667),and the Cochran's Q-statistic showed no heterogeneity(Q-statistic=52.712,P=0.057).Compared to the general population,the underlying pleiotropy in the hospitalized patients was not found by MR-Egger regression intercept(MR intercept=-0.001,P=0.909),and the Cochran's Q-statistic showed no heterogeneity(Q-statistic=25.214,P=0.945).However,green tea and herbal tea had no effect on COVID-19 infection.Conclusions:Overall tea intake reduces the risk of COVID-19 infection in the general population compared to COVID-19 infected and hospitalized populations,while green tea and herbal tea have no protective effect against COVID-19 infection.

Objective To summarize the experience in carotid endarterectomy(CEA)for the treatment of carotid artery stenosis,in order to decrease postoperative complications and enhance clinical efficacy.Methods The clinical data of 64 cases receiving surgical treatment for carotid artery stenosis from January 2022 to December 2024 were analyzed retrospectively.Clinical data including age,gender,condition of underlying diseases,degree of carotid artery stenosis,degree of coronary artery stenosis,cerebral blood flow before operation,characteristics of carotid plaques before operation,usage of antiplatelet drugs during perioperative period,usage of carotid shunt during operation,intraoperative carotid artery occlusion time,operation time,postoperative complications and follow-up results were collected.Results All 64 patients underwent CEA successfully.Among them,14 cases underwent shunt during operation,48 cases received single antiplatelet therapy during perioperative period and 16 cases received dual antiplatelet therapy.The median operation time was 161.50(138.00,186.50)min,the clamping time was(28.42±10.72)min.The incidence of postoperative complications included 1 case of incisional infection(1.56%),1 case of incisional hematoma(1.56%),1 case of internal carotid artery occlusion(1.56%),1 case of cerebral hypoperfusion(1.56%).There were no cerebral infarction,no cerebral hyperperfusion,no cardiac events and no brain nerve injury.There was no one case of postoperative complications in the patients who underwent shunt during operation.All patients were followed up for 3～38 months.Among them,there were 2 cases of stroke and there was no death during the fellow-up period.The clamping time was significantly shorter in shunting group than in non-shunting group[(18.43±6.64)min vs.(31.22±9.98)min,P<0.05)],there were no significant differences in remaining clinical data between two groups(P>0.05).The degree of carotid artery stenosis was more severe in the dual antiplatelet group than in the single antiplatelet group[on operation side(χ2=-2.377,P<0.05),on contralaternal side(χ2=-2.261,P<0.05)],there were no significant differences in remaining clinical data between two groups(P>0.05).Conclusions CEA is an effective treatment for carotid artery stenosis,shunting during CEA is safe.Meticulous perioperative management and operative procedures could help to reduce the rate of postoperative complications.

Objective To investigate the predictive value of triglyceride glucose-body mass index(TyG-BMI),serum triglyceride-to-high-density lipoprotein cholesterol ratio(TG/HDL-C),and metabolic score for insulin resistance(METS-IR)for fatty pancreatic disease(FPD).Methods A total of 240 patients with FPD treated in The First Affiliated Hospital of Zhengzhou University from January 2020 to November 2023 were included as the case group,while 480 healthy subjects who underwent healthy checks in the same period were randomly selected as the control group.General clinical data and laboratory indicators were collected.The Mann-Whitney U test and chi-square test were used to compare non-normally distributed continuous variables,and categorical variables between groups,respectively.A binary logistic regression model was used to assess the relationship between TyG-BMI,TG/HDL-C,and METS-IR and FPD.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive diagnostic value of those simplified insulin resistance indicators for FPD in the general population and different sex populations.Results Age,BMI,systolic blood pressure,diastolic blood pressure,fasting plasma glucose,uric acid,alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transferase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,TyG-BMI,TG/HDL-C,and METS-IR in the case group were significantly higher than those in the control group(all P<0.05).The case group had significantly higher proportions of individuals with hypertension,diabetes,and fatty liver disease than the control group(all P<0.05).The high-density lipoprotein cholesterol level was significantly lower in the case group than in the control group(P<0.05).The multivariable Logistic regression analysis showed that after adjusting for various influencing factors,TyG-BMI,TG/HDL-C,and METS-IR remained as independent risk factors for the development of FPD,with the odds ratios(95%confidence intervals)being 1.027(1.018-1.037),6.964(2.022-23.989),and 1.184(1.123-1.248),respectively.In the ROC curve analysis,the AUCs of METS-IR and TyG-BMI were 0.823 and 0.803,respectively,with their sensitivities being 76.3%and 75.8%,specificities being 74.6%and 71.7%,and optimal cut-off values being 34.86 and 196.70,respectively;the next were BMI(AUC=0.758)and TG/HDL-C(AUC=0.734);in the sex-stratified analysis,the AUC values of METS-IR were highest in both the male and female subgroups,which were 0.834 and 0.810,respectively.Conclusion TyG-BMI,TG/HDL-C,and METS-IR show good predictive value for the development of FPD,in which METS-IR is more excellent.

AIM:To investigate the potential effect of Dabuyuan Jian(DBYJ)on peroxisome proliferator-acti-vated receptor γ(PPARγ)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory proteins in mice with mild cognitive impairment(MCI),and to explore the mechanism of DBYJ in improving the learning and memory ability of MCI mice.METHODS:Forty C57BL/6 male mice were randomly divided into 5 groups,including negative control(NC)group,D-galactose(D-Gal)group,D-Gal+DBYJ group,D-Gal+GW9662(PPARγ inhibitor)group and D-Gal+GW9662+DBYJ group,with 8 mice each.The mice in NC group were subcutaneously injected with 0.9%saline solution on the back of the neck for 8 weeks,while those in the remaining 4 groups were subcutaneously injected with D-Gal(100 mg·kg-1·d-1)on the back of the neck for 8 weeks to establish the MCI model.From week 5 to week 8,the mice in D-Gal+GW9662 and D-Gal+DBYJ+GW9662 groups were intraperitoneally injected with GW9662(1 mg·kg-1·d-1).From week 5,the mice in D-Gal+DBYJ and D-Gal+DBYJ+GW9662 groups were treated with DBYJ(13.2 g/kg)by gavage,while those in the re-maining 3 groups were administered an equal volume of purified water for 4 weeks.The Morris water maze(including posi-tioning navigation experiment and space exploration experiment)was used to assess the learning and memory ability of the mice.The structural integrity of the hippocampus of the mice was assessed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate damage to hippocampal neurons in mice,and Western blot was applied to detect the protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),PPARγ,P65 and phosphorylated P65(p-P65)in the hippocampus of the mice.RESULTS:Compared with NC group,the escape latency of the mice in D-Gal+D-Gal and D-Gal+GW9662 groups significantly increased(P＜0.01),while the number of platform crossing and the duration of staying in the target quadrant within 60 s significantly decreased(P＜0.01).The number of neurons in the CA3 region remarkably decreased(P＜0.01),and pyramidal cell disarrangement and neuronal shrinkage were observed.The levels of TNF-α,IL-1β and p-P65 were up-regulated,while the expression of PPARγ was down-regulated(P＜0.05).Compared with D-Gal group,the escape latency of the mice in D-Gal+DBYJ group significantly decreased(P＜0.01),while the number of plat-form crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.01).The number of neurons in the CA3 region increased(P＜0.01),the pyramidal cells were more neatly arranged,and the cytoarchitec-ture was intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regu-lated(P＜0.05).Compared with D-Gal+GW9662 group,significantly decreased escape latency was observed in D-Gal+DBYJ+GW9662 group(P＜0.01),and the number of platform crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.05).The number of neurons in the CA3 region increased(P＜0.01),the pyrami-dal cells were arranged more neatly,and the cytoarchitecture was relatively intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regulated(P＜0.05).The effects shown in D-Gal+DBYJ+GW9662 group were inferior to those in D-Gal+DBYJ group,indicating that the therapeutic effect of DBYJ was inhibited after the addition of GW9662.CONCLUSION:Dabuyuan Jian improves the learning and memory ability of MCI mice,and the mechanism may be related to the expression of key proteins in the PPARγ/NF-κB signaling pathway.

Objective To investigate the effect of closed-chain exercise training on hemiplegic shoulder pain and shoulder joint sta-bility in stroke patients,and to explore the relationship between hemiplegic shoulder pain and shoulder joint sta-bility.Methods A total of 52 stroke patients with hemiplegic shoulder pain in Jiangsu Province Hospital from October,2020 to January,2023 were selected,and were randomly divided into control group(n=26)and experimental group(n=26).Both groups received conventional rehabilitation therapy,while the experimental group additionally under-went closed-chain exercise training for shoulder joint.Pain severity and motor function were assessed using Visu-al Analog Scale(VAS)and Fugl-Meyer Assessment-Upper Extremities(FMA-UE)before and after intervention.Musculoskeletal ultrasound was used to measure acromion-greater tuberosity distance(AGT),acromion-lesser tu-berosity distance(ALT),acromiohumeral distance(AHD)and supraspinatus thickness(SST)to evaluate shoulder joint stability.Correlation analysis was conducted on the improvements in shoulder pain and shoulder joint stabil-ity in the experimental group.Results Two cases in the control group and two in the experimental group dropped down.Both groups showed signifi-cant improvements in VAS and FMA-UE scores after intervention(|t|>5.214,P<0.001),and the scores im-proved more in the experimental group than in the control group(|t|>2.087,P<0.05).The experimental group also showed significant improvements in AGT,ALT,AHD and SST(|t|>4.187,P<0.001),with AGT,ALT and AHD being superior to those in the control group(|t|>2.155,P<0.05).The difference of VAS score in the exper-imental group was correlated with the difference of FMA-UE,AGT and ALT after intervention(r>0.434,P<0.05).Conclusion Closed-chain shoulder exercise training can significantly improve shoulder joint stability while alleviating shoulder pain,and effectively enhancing upper limb function in stroke patients with hemiplegic shoulder pain.Hemiplegic shoulder pain is correlated with shoulder joint stability.

Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.