BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

Objective To evaluate the predictive value of triglyceride-glucose body mass index(TyG-BMI),atherogenic index of plasma(AIP),and postprandial glucose excursion(PPGE)for sarcopenia in patients with type 2 diabetes mellitus(T2DM).Methods An observational cohort trial was conducted on 590 hospitalized T2DM patients(322 males and 268 females)admitted to Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University between January 2023 and December 2024.General demographic data and key metabolic indicators,including fasting plasma glucose(FPG),postprandial 2-hour plasma glucose(PPG),triglyceride(TG)were collected,and then TyG-BMI,AIP,and PPGE were calculated.Based on the Asian Working Group for Sarcopenia(AWGS)2019 criteria,they were divided into a sarcopenia group(n=140)and a non-sarcopenia group(n=450).After 1∶1 propensity score matching(PSM),102 patients with sarcopenia were matched with 102 without.Differences in metabolic indicators FPG,PPG,TyG-BMI,AIP and PPGE were compared between the 2 groups.Spearman correlation analysis was conducted to assess correlations of these indicators with sarcopenia.Conditional logistic regression analysis was performed to identify independent risk factors,and receiver operating characteristic(ROC)curves were plotted to assess predictive performance.An external validation cohort consisting of 192 T2DM patients from Department of Endocrinology of Jiangbei Branch of First Affiliated Hospital of Army Medical University between January 2023 and December 2024 was included to validate the prediction model.Results After PSM,the baseline data of the 2 groups was balanced(P>0.05).The sarcopenia group showed higher levels of PPG,AIP,and PPGE,but lower TyG-BMI value than the non-sarcopenia group(all P=0.001).Spearman correlation analysis revealed that the TyG-BMI was negatively correlated(r=-0.404,P=0.001),whereas AIP and PPGE were positively correlated with concomitant sarcopenia(r=0.280,P=0.001;r=0.372,P=0.001)in the T2DM patients.Conditional logistic regression analysis identified AIP(OR=14.367)and PPGE(OR=1.245)as independent risk factors,while TyG-BMI(OR=0.966)as independent protective factors.ROC curve analysis revealed that the area under the curve(AUC)of the combined model of TyG-BMI,AIP and PPGE in predicting sarcopenia was 0.918,and the AUC value was 0.954 in external validation,with good sensitivity and specificity.Conclusion TyG-BMI,AIP,and PPGE are important metabolic predictors in T2DM patients with sarcopenia.Their combination has good screening value for sarcopenia,and can be applied in external prediction for T2DM patients.

ObjectiveTo analyze the characteristics and influencing factors of elderly hospitalized patients with carbapenem-resistant gram-negative bacillus (CRO) infection in the intensive care unit (ICU) of a gradeⅡ level A general hospital in Yangpu District of Shanghai, and to provide scientific basis for the prevention and control of hospital-acquired CRO infection in such hospitals. MethodsThe clinical data of elderly ICU patients (age ≥60 years) from January 2019 to December 2023 were retrospectively collected. A total of 122 cases with hospital-acquired CRO infection were used as the case group, and a total of 68 cases with carbapenem-sensitive gram-negative (CSO) infection were used as the control group. The clinical characteristics of the two groups were analyzed, and univariate analysis and logistic regression analysis were performed for screening for possible influencing factors on hospital-acquired CRO infection. ResultsThe main pathogens of CRO infection were carbapenem-resistant Acinetobacter baumannii (CRAB) (53 cases, 43.44%) and carbapenem-resistant Klebsiella pneumoniae (CRKP) (46 cases, 37.70%), and 17 patients (13.93%) had more than two types of CRO infection. Among the CRO infection, the main sites were lower respiratory tract infection (58 cases, 47.54%), ventilator-associated pneumonia (21 cases, 17.21%), and catheter-associated urinary tract infections (16 cases, 13.11%). The incidence rate of poor prognosis was higher in the CRO infection group (54.10%) than that in the CSO infection group (36.76%) (P=0.021). The results of univariate analysis showed that male, history of hospitalization within three months, chronic respiratory disease, hypoproteinemia, anemia, and history of invasive procedures prior to infection, including indwelling central venous catheter, invasive mechanical ventilation, urinary catheter, gastric tube placement and parenteral nutrition, in addition, heparin anticoagulation, the use of broad-spectrum penicillin, third-generation cephalosporins, fluoroquinolones, carbapenems, carbapenems combined with fluoroquinolones, carbapenems combined with glycopeptides, use of ≥3 antibiotics and long time of antibiotic use prior to infection were all associated with the CRO infection (P<0.05). The results of logistic regression analysis showed that use of carbapenems (OR=7.739, 95%CI: 2.226‒26.911), ≥3 types of antibiotics (OR=6.307, 95%CI: 1.674‒23.754), invasive mechanical ventilation (OR=4.082, 95%CI: 1.795‒9.281), urinary catheter (OR=3.554, 95%CI: 1.074‒11.758), and comorbid hypoproteinemia (OR=4.741, 95%CI: 2.039‒11.022) and diabetes (OR=3.245, 95%CI: 1.344‒7.839) were positively correlated with the risk of CRO infection. ConclusionConcurrent use of carbapenems with multiple other antibiotics, as well as the use of invasive mechanical ventilation, urinary catheter, and comorbid hypoproteinemia and diabetes, may be associated with an increased influencing of CRO infection. More attention should be paid to the prevention and control of infection in elderly patients with the above-mentioned risk factors, and active screening of drug-resistant bacteria should be strengthened. Besides, the rational use of broad-spectrum antibiotics such as carbapenems, avoiding unnecessary invasive operations, and paying attention to patient nutrition and blood glucose control all can reduce the incidence of CRO infection and help to improve clinical outcomes.

Objective:To investigate whether deltoid ligament (DL) injury produces axial-plane rotational instability of the ankle in patients with chronic ankle instability (CAI).Methods:A retrospective study was conducted to analyze the 33 patients with CAI who had been treated at Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University between January 2023 and December 2024. The cohort consisted of 17 males and 16 females with an age of (31.5±9.9) years. The patients were assigned into 2 groups based on the presence of DL injury: a lateral chronic ankle instability (LCAI) group ( n=17) and a rotational ankle instability (RAI) group ( n=16). Barefoot natural walking trials were performed in all patients. Three-dimensional kinematic data were synchronously collected using an optical motion capture system (12 cameras) and force plates. A lower extremity model was constructed to obtain shank axial rotation (internal/external rotation) and rear-foot inversion/eversion angles. Continuous relative phase (CRP) analysis was employed to assess shank-rearfoot movement coupling. The mean absolute relative phase (MARP) and deviation phase (DP) were calculated. Results:There was no statistically significant difference in the clinical baseline data between the 2 groups, indicating comparability ( P>0.05). Throughout the gait cycle, no significant differences were found in shank rotation angles or rear-foot eversion angles between the RAI group and the LCAI group. However, CRP analysis revealed that during the early stance phase (initial contact and loading response), shank-rearfoot coupling was significantly lower in the RAI group than in the LCAI group. In the early stance phase, the CRP values in the RAI group were significantly higher than those in the LCAI group. The CRP curve changes in the RAI group were consistently higher in the standce phase of the entire gait cycle than those in the LCAI group, and the peak value of the CRP curve was larger in the RAI group. Concurrently, the RAI group exhibited significantly higher MARP and DP values than the LCAI group (27.48°±14.54° versus 15.21°±9.56°; 26.02°±11.73° versus 17.83°±9.82°) (both P<0.05). Conclusion:DL injury significantly damages the axial rotational stability of the ankle joint and significantly exacerbates the mechanical instability of the ankle joint in CAI patients.

Objective To investigate the distribution of carbapenem-resistant genes and their drug susceptibility in vitro on carbapen-em-resistant Enterobacter cloacae(CRECC)in Taizhou area,and provide evidence for effective anti-infective treatment in clinical prac-tice.Methods Forty-seven strains of CRECC isolated from Enze Hospital,Taizhou Enze Medical Center(Group)and Luqiao Reha-bilitation Hospital during January 2015 and November 2022 were retrospectively analyzed.The enzyme types and resistance genes of carbapenemase were detected by the NG-Test Carba 5 and Carba-R Xpert,respectively,and the susceptibility of CERCC to common drugs was tested in vitro.Results Among 47 strains of CRECC,27 were detected to produce carbapenemase,including 24 producing New Delhi metallo-β-lactamase(NDM)type,1 producing both Klebsiella pneumoniae carbapenemase(KPC)and NDM types,and 2 producing imipenemase(IMP)type.One strain belonged to NDM genotype but no NDM enzyme type was detected.The CRECC strains had the highest sensitivity to polymyxin B(95.7%),followed by tigecycline(93.6%),fosfomycin(61.7%),and ceftazidime/avibac-tam(40.4%).In addition,the CRECC strains producing carbapenemase were more sensitive to polymyxin B,fosfomycin and aztreo-nam than those without producing carbapenemase.Conclusion The CRECC strains in Taizhou area are mainly NDM type,which has high sensitivity to polycolistin B,tigecycline and fosfomycin.NG-Test Carba 5 can not cover some strains that do not produce carbapen-emase or carry mutations in carbapenemase.

Objective To investigate the distribution of carbapenem-resistant genes and their drug susceptibility in vitro on carbapen-em-resistant Enterobacter cloacae(CRECC)in Taizhou area,and provide evidence for effective anti-infective treatment in clinical prac-tice.Methods Forty-seven strains of CRECC isolated from Enze Hospital,Taizhou Enze Medical Center(Group)and Luqiao Reha-bilitation Hospital during January 2015 and November 2022 were retrospectively analyzed.The enzyme types and resistance genes of carbapenemase were detected by the NG-Test Carba 5 and Carba-R Xpert,respectively,and the susceptibility of CERCC to common drugs was tested in vitro.Results Among 47 strains of CRECC,27 were detected to produce carbapenemase,including 24 producing New Delhi metallo-β-lactamase(NDM)type,1 producing both Klebsiella pneumoniae carbapenemase(KPC)and NDM types,and 2 producing imipenemase(IMP)type.One strain belonged to NDM genotype but no NDM enzyme type was detected.The CRECC strains had the highest sensitivity to polymyxin B(95.7%),followed by tigecycline(93.6%),fosfomycin(61.7%),and ceftazidime/avibac-tam(40.4%).In addition,the CRECC strains producing carbapenemase were more sensitive to polymyxin B,fosfomycin and aztreo-nam than those without producing carbapenemase.Conclusion The CRECC strains in Taizhou area are mainly NDM type,which has high sensitivity to polycolistin B,tigecycline and fosfomycin.NG-Test Carba 5 can not cover some strains that do not produce carbapen-emase or carry mutations in carbapenemase.

Objective:To investigate whether deltoid ligament (DL) injury produces axial-plane rotational instability of the ankle in patients with chronic ankle instability (CAI).Methods:A retrospective study was conducted to analyze the 33 patients with CAI who had been treated at Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University between January 2023 and December 2024. The cohort consisted of 17 males and 16 females with an age of (31.5±9.9) years. The patients were assigned into 2 groups based on the presence of DL injury: a lateral chronic ankle instability (LCAI) group ( n=17) and a rotational ankle instability (RAI) group ( n=16). Barefoot natural walking trials were performed in all patients. Three-dimensional kinematic data were synchronously collected using an optical motion capture system (12 cameras) and force plates. A lower extremity model was constructed to obtain shank axial rotation (internal/external rotation) and rear-foot inversion/eversion angles. Continuous relative phase (CRP) analysis was employed to assess shank-rearfoot movement coupling. The mean absolute relative phase (MARP) and deviation phase (DP) were calculated. Results:There was no statistically significant difference in the clinical baseline data between the 2 groups, indicating comparability ( P>0.05). Throughout the gait cycle, no significant differences were found in shank rotation angles or rear-foot eversion angles between the RAI group and the LCAI group. However, CRP analysis revealed that during the early stance phase (initial contact and loading response), shank-rearfoot coupling was significantly lower in the RAI group than in the LCAI group. In the early stance phase, the CRP values in the RAI group were significantly higher than those in the LCAI group. The CRP curve changes in the RAI group were consistently higher in the standce phase of the entire gait cycle than those in the LCAI group, and the peak value of the CRP curve was larger in the RAI group. Concurrently, the RAI group exhibited significantly higher MARP and DP values than the LCAI group (27.48°±14.54° versus 15.21°±9.56°; 26.02°±11.73° versus 17.83°±9.82°) (both P<0.05). Conclusion:DL injury significantly damages the axial rotational stability of the ankle joint and significantly exacerbates the mechanical instability of the ankle joint in CAI patients.

ObjectiveTo observe the clinical efficacy of Shengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome. MethodA total of 90 patients suffering from carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome were randomly divided into a control group and an observation group， with 45 cases in each group. The control group was treated with polymyxin B， and the observation group was treated with Shengmaisan combined with polymyxin B. The treatment course of both groups was seven days. The infection-related indicators ［white blood cell （WBC） count， procalcitonin （PCT）， neutrophil apolipoprotein （HNL）］， inflammatory factors ［interleukin-6 （IL-6）， serum chemokine ligand 2 （CXCL2）］， and T lymphocyte subpopulations （CD3⁺， CD4⁺， CD8⁺， and CD4⁺/ CD8⁺ value）， acute physiological and chronic health Ⅱ （APACHE Ⅱ） score before and after treatment， as well as bacterial clearance rate and 28-day survival rate after treatment were observed. Result① The experiment was completed， and 81 cases were included， including 41 cases in the observation group and 40 cases in the control group. The general data of the two groups were comparable. ② The bacterial clearance rate of the observation group and the control group was 75.6% （31/41） and 52.5% （21/40）， respectively， and the observation group was higher than the control group （χ²=4.7， P<0.05）. ③ The WBC count， PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group and the control group all decreased after treatment （P<0.05）. Except for the WBC count， the PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group were lower than those of the control group （P<0.05）. ④ The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were increased after treatment （P<0.05）， and CD8⁺ was decreased （P<0.05）. In the control group， only CD3⁺ value was increased （P<0.05）. The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were higher than those in the control group， and the value of CD8⁺ was lower than that in the control group （P<0.05）. ⑤ The 28-day survival rate in the observation group was higher than that in the control group （χ²=4.3， P<0.05）. ConclusionShengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome can better clear bacteria， control infection， reduce the level of inflammatory factors， regulate the immune state of the body， and improve the short-term prognosis.

Objective To investigate the value of novel coagulation and fibrinolysis markers in the diag-nosis and prognosis of septic coagulation disease (SIC).Methods A total of 153 patients with sepsis admitted and treated in this hospital from July 2022 to March 2023 were retrospectively analyzed.According to the SIC diagnostic criteria issued by the International Society of Thrombosis and Hemostasis (ISTH) in 2017,the pa-tients were divided into the SIC group (n=55) and the general sepsis group (the SA group,n=98).The basic data and follow up situation of the patients were collected.The multivariate logistic regression was adopted to analyze the influencing factors of SIC occurrence in the patients with sepsis.The receiver operating character-istic (ROC) curve was used to analyze the predictive efficiency of the related indicators for the SIC occurrence in the patients with sepsis.The included 66 patients with sepsis from April to July 2023conducted the verifica-tion.The Kaplan-Meier survival curve was used to analyze the survival situation of the patients.Results The acute physiological and chronic health status scoring system (APACHEⅡ) score,assessment of sequential or-gan failure (SOFA) score,prothrombin time (PT),PLT,D-dimer (D-D),thrombin antithrombin complex-Ⅲ (AT-Ⅲ),tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC),thrombomodulin (TM) had statistical differences between the two groups (P<0.05).The multivariate logistic regression anal-ysis showed that PT,PLT,D-D,t-PAIC and TM were the independent influencing factors for the SIC occur-rence in the patients with sepsis (P<0.05).The combined detection of PT,PLT,D-D,t-PAIC and TM could increase the predictive efficiency[area under the curve (AUC)=0.914].This model had good fitting goodness (x2=12.593,P=0.127);the verification group showed that it had good predictive efficiency (AUC=0.888),and this model had good fitting goodness (x2=7.996,P=0.333).The median overall survival time in the t-PAIC<19.27 μg/mL group was longer than that in the t-PAIC≥19.27 μg/mL group,which in the TM<16.11 TU/mL group was longer than that in the TM≥16.11 TU/mL group (P<0.05).Conclusion The model con-structed based on the influencing factors has good predictive efficiency for the SIC occurrence in the patients with sepsis.t-PAIC and TM have high value for the prognosis judgment in the patients with sepsis.