The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Objective:To explore the relationship between the prognostic nutritional index(PNI)and the prevalence of coronary heart disease(CHD)in adults.Methods:A cross-sectional analysis was conducted based on the 2017-2020 National Health and Nutrition Examination Survey(NHANES)database.A total of 12,141 adult participants were initially included and divided into CHD group and control group according to the disease status questionnaire.PNI was calculated using serum albumin level and lymphocyte count.Multivariable logistic regression was applied to explore the association between PNI and the prevalence of CHD in adults.Subgroup analysis was conducted to assess whether this association remained consistent across different populations.A restricted cubic spline model was con-structed to clarify the dose-response relationship between PNI and CHD prevalence in adults.Results:Among the 3,894 adult participants,200(5.14％)had CHD.The PNI level in CHD patients was significantly lower than that of the control group[(49.20±8.59)vs.(51.57±4.80),P＜0.001].Multivariable logistic regression analysis showed that,after adjustment for sex,age,race,marital status,body mass index(BMI),hypertension,diabetes and family history of cardiovascular disease,an increase in PNI was still independently associated with a lower prev-alence of CHD(odds ratio[OR]=0.92,95％CI 0.89～0.94,P＜0.001).The dose-response relationship indica-ted a negative linear correlation between PNI and CHD prevalence(P＜0.001).Subgroup analysis showed that the association between PNI and CHD differed significantly across BMI,hypertension and diabetes subgroups(P for in-teraction＜0.05 or＜0.01).Conclusion:Increasing PNI was significantly associated with a lower prevalence of CHD in adults,and this association was more pronounced in specific high-risk populations,such as those with obe-sity,hypertension,and diabetes.Our findings suggest that maintaining good nutritional status is of great significance in reducing the risk of CHD.

Objective:To compare the efficacy of arthroscopic figure-of-eight transtibial tension-reducing technique combined with interference screw fixation versus interface screw fixation alone in the treatment of anterior cruciate ligament (ACL) rupture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 43 patients with ACL rupture admitted to Taihe Hospital between January 2022 and October 2023, including 24 males and 19 females, aged 17-61 years [(38.0±12.6)years]. Based on the tibial fixation method, 20 patients were treated with interference screw fixation alone (interference screw group) and 23 patients with figure-of-eight transtibial tension-reduction technique combined with interference screw fixation (figure-of-eight tension-reduction combined with interference screw group). An Endobutton suspension plate was used in femoral fixation in both groups. The following parameters were compared between the two groups: operative duration and graft diameter; coronal and sagittal tibial tunnel measurements by MRI within 72 hours postoperatively and at the last follow-up; knee range of motion, visual analogue scale (VAS) scores, International Knee Documentation Committee (IKDC) scores, and Lysholm scores preoperatively, at 1 month postoperatively, and at the last follow-up; perioperative complication rates.Results:All the patients were followed up for 11-28 months [(14.1±3.4)months]. There were no significant differences in operative duration or graft diameter between the two groups ( P>0.05). No significant differences were observed in coronal or sagittal tibial tunnel measurements between the two groups within 72 hours postoperatively ( P>0.05). Whereas at the last follow-up, the coronal and sagittal tibial tunnel measurements in the figure-of-eight tension-reduction combined with interference screw group were (11.6±0.7)mm and (11.7±1.1)mm, significantly lower than (13.5±0.6)mm and (13.4±1.9)mm in the interference screw group ( P<0.01). Preoperative knee range of motion, IKDC scores, Lysholm scores, and VAS scores showed no significant differences between the two groups ( P>0.05). At 1 month postoperatively and at the last follow-up, the figure-of-eight tension-reduction combined with interference screw group demonstrated significantly greater knee range of motion [100.0(95.0, 100.0)° and 130.0(120.0, 135.0)°], compared with 72.5(60.0, 95.0)° and 120.0(105.0, 133.3)° in the interference screw group ( P<0.05). VAS scores at 1 month postoperatively and at the last follow-up were 2.0(2.0, 2.0)]points and 1.0(1.0, 1.0)points in the figure-of-eight tension-reduction combined with interference screw group, significantly lower than 3.0(2.3, 4.0)points and 2.0(1.0, 2.0)points in the interference screw group ( P<0.05). IKDC scores at 1 month postoperatively and at the last follow-up were (58.8±5.7)points and (72.4±6.7)points in the figure-of-eight tension-reduction combined with interference screw group, significantly higher than (51.1±5.2)points and (67.4±7.9)points in the interference screw group ( P<0.05). Lysholm scores at 1 month postoperatively and at the last follow-up were (58.9±12.7)points and (89.1±6.0)points in the figure-of-eight tension-reduction combined with interference screw group, significantly higher than (41.2±15.0)points and (78.3±12.3)points in the interference screw group ( P<0.05). No perioperative complications were observed in either group. Conclusion:Compared with interface screw fixation alone, arthroscopic figure-of-eight transtibial tension-reduction technique combined with interference screw fixation for ACL rupture can enhance graft stability, restore knee joint range of motion, alleviate pain, and improve knee function recovery.

OBJECTIVE: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). METHODS: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. RESULTS: C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. CONCLUSION We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Humans ; Colorectal Neoplasms/diagnosis* ; Cyclin-Dependent Kinase 4/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/genetics* ; Aged ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective:To explore the relationship between the prognostic nutritional index(PNI)and the prevalence of coronary heart disease(CHD)in adults.Methods:A cross-sectional analysis was conducted based on the 2017-2020 National Health and Nutrition Examination Survey(NHANES)database.A total of 12,141 adult participants were initially included and divided into CHD group and control group according to the disease status questionnaire.PNI was calculated using serum albumin level and lymphocyte count.Multivariable logistic regression was applied to explore the association between PNI and the prevalence of CHD in adults.Subgroup analysis was conducted to assess whether this association remained consistent across different populations.A restricted cubic spline model was con-structed to clarify the dose-response relationship between PNI and CHD prevalence in adults.Results:Among the 3,894 adult participants,200(5.14％)had CHD.The PNI level in CHD patients was significantly lower than that of the control group[(49.20±8.59)vs.(51.57±4.80),P＜0.001].Multivariable logistic regression analysis showed that,after adjustment for sex,age,race,marital status,body mass index(BMI),hypertension,diabetes and family history of cardiovascular disease,an increase in PNI was still independently associated with a lower prev-alence of CHD(odds ratio[OR]=0.92,95％CI 0.89～0.94,P＜0.001).The dose-response relationship indica-ted a negative linear correlation between PNI and CHD prevalence(P＜0.001).Subgroup analysis showed that the association between PNI and CHD differed significantly across BMI,hypertension and diabetes subgroups(P for in-teraction＜0.05 or＜0.01).Conclusion:Increasing PNI was significantly associated with a lower prevalence of CHD in adults,and this association was more pronounced in specific high-risk populations,such as those with obe-sity,hypertension,and diabetes.Our findings suggest that maintaining good nutritional status is of great significance in reducing the risk of CHD.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.