Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.

Objective:To explore the association between the metabolic score for insulin resistance (METS-IR) and metabolic dysfunction-associated fatty liver disease (MAFLD), and to compare the diagnostic ability of METS-IR with the fatty liver index (FLI) and hepatic steatosis index (HSI) for MAFLD.Methods:This cross-sectional study enrolled 551 individuals participating in community health screenings in Suzhou between September and November 2022. Data collected included basic demographics, clinical indicators, and iLivTouch? (FibroTouch FT5000, Wuxi Hisky Medical Technologies, China) transient elastography results. Participants were categorized into non-MAFLD ( n=218) and MAFLD ( n=333) groups based on an ultrasound attenuation parameter (UAP) cutoff of 244 dB/m measured by iLivTouch. Logistic regression and restricted cubic spline (RCS) analyses were employed to assess the relationship between METS-IR and MAFLD. The diagnostic value of METS-IR was evaluated using receiver operating characteristic (ROC) curves. DeLong′s test was used to compare the diagnostic performance of the different indices. Results:Among the 551 participants, the prevalence of MAFLD diagnosed by transient elastography was 60.4% (333/552). Compared to the non-MAFLD group, the MAFLD group had significantly higher levels of BMI, SBP, DBP, HbA1c, FPG, 2hPG, TC, TG, LDL-C, ALT, AST, GGT, SUA, liver stiffness measurement (LSM), METS-IR, FLI, and HSI, while HDL-C levels were lower (all P<0.05). The MAFLD group also had a higher prevalence of males, overweight/obesity, smoking, hypertension, pre-diabetes, dyslipidemia, hyperuricemia, metabolic syndrome, and antihypertensive medication use (all P<0.05). Multivariate logistic regression analysis, after adjusting for gender, age, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, hyperuricemia, ALT, AST, and GGT, demonstrated that METS-IR, FLI, and HSI remained significantly associated with an increased risk of MAFLD ( OR=1.148, 1.042, 1.270, respectively; all P<0.001). The areas under the ROC curve for METS-IR, FLI, and HSI in diagnosing MAFLD were 0.733 (95% CI: 0.691-0.774), 0.727 (95% CI: 0.685-0.770), and 0.677 (95% CI: 0.632-0.722), respectively. The sensitivities were 57.40%, 62.20%, and 48.30%; specificities were 78.00%, 72.90%, and 78.40%; and optimal cutoff values were 38.526, 35.225, and 35.386, respectively. DeLong′s test indicated no significant difference in diagnostic performance between METS-IR and FLI ( P=0.722). However, both METS-IR and FLI demonstrated significantly better diagnostic performance than HSI ( P=0.008 and P=0.018, respectively). Conclusion:METS-IR is significantly associated with MAFLD and effectively identifies MAFLD in community settings. Its diagnostic performance is comparable to FLI and superior to HSI.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.

Objective:To explore the association between the metabolic score for insulin resistance (METS-IR) and metabolic dysfunction-associated fatty liver disease (MAFLD), and to compare the diagnostic ability of METS-IR with the fatty liver index (FLI) and hepatic steatosis index (HSI) for MAFLD.Methods:This cross-sectional study enrolled 551 individuals participating in community health screenings in Suzhou between September and November 2022. Data collected included basic demographics, clinical indicators, and iLivTouch? (FibroTouch FT5000, Wuxi Hisky Medical Technologies, China) transient elastography results. Participants were categorized into non-MAFLD ( n=218) and MAFLD ( n=333) groups based on an ultrasound attenuation parameter (UAP) cutoff of 244 dB/m measured by iLivTouch. Logistic regression and restricted cubic spline (RCS) analyses were employed to assess the relationship between METS-IR and MAFLD. The diagnostic value of METS-IR was evaluated using receiver operating characteristic (ROC) curves. DeLong′s test was used to compare the diagnostic performance of the different indices. Results:Among the 551 participants, the prevalence of MAFLD diagnosed by transient elastography was 60.4% (333/552). Compared to the non-MAFLD group, the MAFLD group had significantly higher levels of BMI, SBP, DBP, HbA1c, FPG, 2hPG, TC, TG, LDL-C, ALT, AST, GGT, SUA, liver stiffness measurement (LSM), METS-IR, FLI, and HSI, while HDL-C levels were lower (all P<0.05). The MAFLD group also had a higher prevalence of males, overweight/obesity, smoking, hypertension, pre-diabetes, dyslipidemia, hyperuricemia, metabolic syndrome, and antihypertensive medication use (all P<0.05). Multivariate logistic regression analysis, after adjusting for gender, age, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, hyperuricemia, ALT, AST, and GGT, demonstrated that METS-IR, FLI, and HSI remained significantly associated with an increased risk of MAFLD ( OR=1.148, 1.042, 1.270, respectively; all P<0.001). The areas under the ROC curve for METS-IR, FLI, and HSI in diagnosing MAFLD were 0.733 (95% CI: 0.691-0.774), 0.727 (95% CI: 0.685-0.770), and 0.677 (95% CI: 0.632-0.722), respectively. The sensitivities were 57.40%, 62.20%, and 48.30%; specificities were 78.00%, 72.90%, and 78.40%; and optimal cutoff values were 38.526, 35.225, and 35.386, respectively. DeLong′s test indicated no significant difference in diagnostic performance between METS-IR and FLI ( P=0.722). However, both METS-IR and FLI demonstrated significantly better diagnostic performance than HSI ( P=0.008 and P=0.018, respectively). Conclusion:METS-IR is significantly associated with MAFLD and effectively identifies MAFLD in community settings. Its diagnostic performance is comparable to FLI and superior to HSI.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To explore the association between the variability of triglyceride glucose index (TyG) and the risk of type 2 diabetes mellitus(T2DM).Methods:This study was a retrospective cohort study. A total of 22 929 community-dwelling elderly (aged≥60 years) who received annual health check-ups in Kunshan city of Suzhou Municipality during 2014 to 2021 were enrolled in the study. Fasting triglycerides and blood glucose were measured during annual physical check-ups and the TyG was calculated, the standard deviation of TyG measurements in three consecutive physical check-ups was used as the indicatior of TyG long-term variability. According to the quartile of TyG long-term variability, the study subjects were divided into four groups, namely Q 1 (0-0.14), Q 2 (>0.14-0.22), Q 3 (>0.22-0.33), Q 4 (>0.33-1.90). The outcome variable was the occurrence of T2DM. The relationship between TyG variability and T2DM incidence was analyzed by multivariate Cox regression. Results:In the study cohort 11 518 (50.2%) were females and the mean age was (67.42±5.35) years. By the end of follow-up, 2 934 cases of new T2DM were diagnosed, with an oveall incidence rate of 12.8%. After adjusting for multiple confounders and average TyG, long-term variability of TyG was significantly associated with T2DM risk ( HR=1.83, 95% CI: 1.51-2.20). The risk of T2DM in Q 4 group was significantly higher than that in Q 1 group ( HR=1.33, 95% CI: 1.19-1.47). Kaplan-Meier survival curve showed that long-term variability of TyG was significantly correlated with the cumulative risk of T2DM incidence ( P<0.001). Conclusions:TyG variability is an independent risk factor for T2DM, suggesting that attention should be paid not only to specific time-point TyG levels but also to TyG fluctuation for early identification of T2DM risk.

Multimorbidity is significantly associated with life quality decline, disability, and increased mortality risk. Additionally, it leads to greater consumption of healthcare resources, presenting substantial challenges to healthcare systems globally. To better assess the burden of multimorbidity, its impact on patient health outcomes and healthcare services, and to explore the underlying mechanisms in its development, this paper summarizes the existing methods used for measuring and analyzing multimorbidity in research and practice, including disease count, disease-weighted indices, multimorbidity pattern recognition (such as disease association analysis, clustering analysis, and network analysis) and longitudinal methods to provide references for the accurate assessment of the prevalence of multimorbidity and its changes and improve the validity and universality of research findings.

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Objective:To survey the status quo and influencing factors of contracted family doctor pay services in urban communities of Suzhou city.Methods:This study was a cross-sectional study. A questionnaire survey on the status quo and influencing factors of contracted family doctor pay services was conducted from July to October 2022 among 750 residents from 40 communities of 4 subdistricts in Suzhou Gusu District, selected by stratified random sampling method. A self-designed questionnaire was used for the survey, which included demographic information, status quo of pay services among residents and factors influencing the service contracting. Chi-square test and binary logistic regression were used to analyze the influencing factors of contracted family doctor pay services.Results:A total of 750 questionnaires were distributed, with 720 valid ones returned at a recovery rate of 96.0%. Among the 720 residents, 370 (51.4%) were female, and 300 (41.7%) were between the age of 35 and 60 years old. There were 71 residents who had contracted pay services with a contracting rate of 9.9% (71/720), and the renewal rate was 80.3% (57/71). The top 3 reasons for signing the contract were health guidance (67.6%, 48/71), medical counselling (63.4%, 45/71) and 3 free consultations (57.7%, 41/71). The top 3 reasons for not signing a contract were not needing services (49.9%, 324/649), not knowing about contracted services (41.9%, 272/649) and rarely visiting the community health service center (25.6%, 166/649). Age ( χ2=21.072), marital status ( χ2=10.969), knowing the family doctor team ( χ2=145.954), knowing the family doctor contract system ( χ2=133.981), knowing the content and the rights of the contracted services ( χ2=132.905), using primary medical institutions as first choice for common and chronic diseases ( χ2=13.532), multiple comorbid chronic diseases ( χ2=30.024), being agreed by family members ( χ2=46.258), signing contract in family members ( χ2=108.833) or relatives and friends ( χ2=47.492), and experience in community health service centers ( χ2=26.116) were significantly associated with the contract signing (all P<0.05). Logistic regression analysis showed that knowing family doctor team well ( OR=23.13,95% CI:5.05-105.97) or very well( OR=95.28,95% CI: 10.71-847.68); having ≥3 chronic diseases compared to no chronic diseases ( OR=5.60, 95% CI: 1.88-16.75, P<0.05); contracting agreed by family members compared to not agreed ( OR=2.66, 95% CI: 1.03-6.84, P<0.05); signing contract in family members compared to not signing ( OR=4.42, 95% CI:2.05-9.55, P<0.05) were independent influencing factors of signing contract of family doctor pay services. Conclusions:The rate of contracted of family doctor pay services in Gusu District of Suzhou City is relatively low. Knowing the family doctor team, having multiple comorbid chronic diseases, agreement among family members, and signing contract in family members are influencing factors of contracted family doctor pay services.