BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

BACKGROUND:Lifespan of prosthetic joint was being influenced by periprosthetic infection after total hip arthroplasty. Combination of debridement,antibiotics,and implant retention with the replacement of assembled components represents a novel approach in the management of acute prosthetic joint infection after total hip arthroplasty.OBJECTIVE:To observe the efficacy of debridement,antibiotics,and implant retention combined with the replacement of assembled components in the treatment of acute prosthetic joint infection after total hip arthroplasty.METHODS:Twenty-two patients with acute prosthetic joint infection after initial total hip arthroplasty at the Department of Orthopedics,Huangshi Central Hospital,China,between July 2018 and February 2022 were enrolled. The infection time of all patients was less than 3 weeks after the initial arthroplasty. Intraoperative joint fluid extraction and bacterial culture of infected synovium proved to be acute stage infection. They were treated using debridement,antibiotics,and implant retention combined with the replacement of assembled components. Infections were assessed using leukocyte count,erythrocyte sedimentation rate,and C-reactive protein levels before,3 and 6 months after surgery. Improvements in hip joint function were evaluated using Harris hip score. Pain relief was assessed using visual analog scale score. Paired sample t-test was used to analyze the improvement of each index before and after operation.RESULTS AND CONCLUSION:(1) One patient died of non-periprosthesis infection and was subsequently lost to follow-up,which was excluded. The remaining 21 patients received clinical follow-up,and the follow-up time was more than 1 year,with a mean follow-up time of (19.52±3.88) months. Among them,20 patients were successfully treated with surgery and 1 patient failed,and the infection control rate was 95％. (2) The levels of leukocyte count,erythrocyte sedimentation rate,and C-reactive protein were lower in 3 and 6 months after surgery (P<0.05);Harris hip function scores were higher than those before surgery (P<0.05);pain visual analog scale scores were lower than those before surgery (P<0.05),and the differences were significant (P<0.05). (3) It is indicated that debridement,antibiotics,and implant retention combined with the replacement of assembled components after total hip arthroplasty in patients with acute prosthetic joint infection can effectively control prosthetic joint infection,improve hip function,and relieve hip pain caused by infection.

Objective To investigate the learning curve of real-life vaginal delivery,including its difficult steps and influencing factors,to optimize the future training of vaginal delivery for residents in department of obstetrics and gynecology.Methods From 25 Sep 2020 to 12 Mar 2022,OBGYN residents without previous experiences in vaginal delivery were prospectively enrolled in Obstetrics and Gynecology Hospital,Fudan University.Residents performed normal vaginal delivery under the supervision of senior obstetricians and midwives.The performance score(PS)of vaginal delivery and its 9 steps were evaluated via a questionnaire fulfilled by the supervisor once each delivery was finished.Logistic regression models were performed for univariate and multivariate analyses to evaluate the factors that might be correlated with the PS.Results Eventually,233 deliveries performed by 60 residents were analyzed.Results showed that more than 10 deliveries were needed for 70%of residents to obtain minimal competence of vaginal delivery.Perineal protection,delivery of the fetal head,delivery of the fetal shoulders and repair of episiotomy or laceration were found to be the most difficult steps,which required more practices to achieve minimal competence level.Univariate analyses showed the delivery experience,the times of observation/simulation/training,and humanistic care skills might influence the total PS(P<0.05).However,only delivery experience(OR=1.43,95%CI:1.22-1.67)and the times of observation(OR=1.02,95%CI:1.00-1.04)were found to be independently correlated with the total PS in multivariate analyses.Conclusion More than 10 real-life practices were required to achieve the minimal competence of normal vaginal delivery.Enhancing the training on the four difficult steps of vaginal delivery might improve the learning efficiency when delivery opportunities are limited.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

Objective:To explore and analyze the correlation between the expression of mismatch repair(MMR)protein and programmed death ligand 1(PD-L1)in colorectal cancer(CRC)tissue and clinical pathological characteristics.Methods:The study period were from July 2021 to December 2024,200 cases of colorectal cancer patients treated in our hospital were selected as the research subjects.Collected all patient lesion tissue samples(lesion group)and adjacent tissue samples(located ≥5 cm from the tumor edge,adjacent group),and used the immunohistochemistry(IHC)method to detect the expression of Mismatch repair(MMR)(MLH1,MSH2,MSH6,and PMS2)protein and PD-L1 protein.Investigated the clinical and pathological characteristics of patients and conducted correlation analysis.Results:The positive rates of dMMR and pMMR protein expression in the lesion group were 39.00％and 70.00％,respectively,while those in the adjacent cancer group were 11.00％and 89.00％,respectively.There were significant difference compared between the lesion group and the adjacent cancer group(P＜0.05).The positive rate of PD-L1 protein expression in the lesion group were 25.00％,while that in the adjacent cancer group were 80.00％.The expression of PD-L1 protein in the lesion group were significantly lower than that in the adjacent cancer group(P＜0.05).There were significant differences in the positive rates of MMR and PD-L1 protein expression among patients with different histological differentiation,clinical stages,and lymph node metastasis(P＜0.05),while there were no significant differences in the positive rates of MMR and PD-L1 protein expression among patients of different genders,ages,and disease sites(P＞0.05).Spearman analysis showed there were correlation between the expression of MMR and PD-L1 proteins in colorectal cancer tissues and clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis(P＜0.05).Conclusion:Low expression of MMR and PD-L1 proteins are commonly observed in colorectal cancer tissues.The expression of MMR and PD-L1 proteins in colorectal cancer tissues are correlated with clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis.

Objective:To observe the effect of modified autologous skull defect repair in patients with traumatic brain injury and its influence on neurological function and living ability.Methods:104 patients with traumatic brain injury who were admitted to our hospital from March 2022 to August 2024 were included,they were divided into Group A[37 cases,poly ether ether ketone(PEEK)skull defect repair],Group B(35 cases,traditional titanium mesh skull defect repair),and Group C(32 cases,modified autologous skull defect repair).Perioperative indicators,neurological function,activity of daily living,quality of life,satisfaction,and incidence of postoperative complications were compared among three groups.Results:There were no differences in the operation time,operation blood loss and postoperative hospital stay among the three groups(P＞0.05).The hospitalization costs of Group A,Group B and Group C decreased successively(P＜0.05).Activity of Daily Living(ADL)scores at 3 and 6 months after surgery increased among three groups,while National Institutes of Health Stroke Scale(NIHSS)scores decreased(P＜0.05).There was no significant difference in physiological function,social function,psychological function,and material life among the three groups at 6 months after surgery(P＞0.05).The overall satisfaction rate in Group C was higher than that of Group A and Group B(P＜0.05).The overall incidence of complications in Group C was lower than that in Group A and Group B(P＜0.05).Conclusion:PEEK,traditional titanium mesh,and modified autologous skull are used in skull defect repair,operation time,operation blood loss and postoperative hospital stay are comparable,they can also reduce neurological function damage,improve living ability,and enhance the quality of life of patients,however,PEEK is relatively expensive,the satisfaction of traditional titanium mesh is low,andincidence of postoperative complications are relatively high.

Objective:To observe the effect of modified autologous skull defect repair in patients with traumatic brain injury and its influence on neurological function and living ability.Methods:104 patients with traumatic brain injury who were admitted to our hospital from March 2022 to August 2024 were included,they were divided into Group A[37 cases,poly ether ether ketone(PEEK)skull defect repair],Group B(35 cases,traditional titanium mesh skull defect repair),and Group C(32 cases,modified autologous skull defect repair).Perioperative indicators,neurological function,activity of daily living,quality of life,satisfaction,and incidence of postoperative complications were compared among three groups.Results:There were no differences in the operation time,operation blood loss and postoperative hospital stay among the three groups(P＞0.05).The hospitalization costs of Group A,Group B and Group C decreased successively(P＜0.05).Activity of Daily Living(ADL)scores at 3 and 6 months after surgery increased among three groups,while National Institutes of Health Stroke Scale(NIHSS)scores decreased(P＜0.05).There was no significant difference in physiological function,social function,psychological function,and material life among the three groups at 6 months after surgery(P＞0.05).The overall satisfaction rate in Group C was higher than that of Group A and Group B(P＜0.05).The overall incidence of complications in Group C was lower than that in Group A and Group B(P＜0.05).Conclusion:PEEK,traditional titanium mesh,and modified autologous skull are used in skull defect repair,operation time,operation blood loss and postoperative hospital stay are comparable,they can also reduce neurological function damage,improve living ability,and enhance the quality of life of patients,however,PEEK is relatively expensive,the satisfaction of traditional titanium mesh is low,andincidence of postoperative complications are relatively high.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.