Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

Objective:To examine the interaction between gender and the visceral adiposity index (VAI) in relation to the risk of type 2 diabetes mellitus (T2DM).Methods:This retrospective cohort study utilized data from the public Dryad database derived from the NAGALA (NAFLD in the Gifu Area, Longitudinal Analysis) project (1994-2016). Participants were stratified into quartiles based on VAI levels. A multivariate Cox proportional hazards regression model was employed to evaluate whether VAI independently predicts T2DM risk. Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves were constructed for each VAI quartile. Subgroup analyses were conducted to examine associations across age and body mass index categories. Both multiplicative and additive interaction effects between gender and VAI were assessed. Additionally, gender-specific Cox models were fitted to further explore these associations.Results:A total of 15 453 participants [8 419 males and 7 034 females; mean age, (43.7±8.9) years] were included, with a median follow-up duration of 5.39 years. During follow-up, 373 participants (2.4%) developed T2DM. After adjustment for potential confounders, higher VAI levels were independently associated with increased T2DM risk ( HR=1.16; 95% CI 1.11-1.21), consistent with the results across VAI quartiles. Kaplan-Meier analysis revealed a significant trend of increasing T2DM incidence across VAI quartiles ( P<0.001). The area under the ROC curve for VAI in predicting T2DM at 3, 5, and 10 years was 0.755, 0.735, and 0.696, respectively. Sensitivity analyses showed that elevated VAI was associated with increased T2DM risk across all age and body mass index subgroups (all P<0.05). Regarding interaction analysis, the HR (95% CI) for the multiplicative interaction between VAI and gender was 1.22 (1.19-1.26). The relative excess risk of interaction was -1.08 (95% CI -2.96 to -0.06), the attributable proportion of interaction was -0.54 (95% CI -1.35 to -0.01), and the synergy index was 0.48 (95% CI 0.26-0.91), indicating a negative additive interaction. Using low-VAI women as the reference group, the risk of T2DM in high-VAI women was higher ( HR=2.53, 95% CI 1.59-4.02) compared to high-VAI men ( HR=2.01, 95% CI 1.49-2.72). In gender-specific analyses, increasing VAI remained significantly associated with elevated T2DM risk after adjustment in both females ( HR=1.43, 95% CI 1.21-1.68) and males ( HR=1.16; 95% CI 1.11-1.22), with consistent findings across VAI quartiles. Conclusions:VAI and gender demonstrated multiplicative and additive interaction in relation to T2DM risk. The association between increasing VAI and T2DM risk was more pronounced in women than in men.

Objective:To examine the interaction between gender and the visceral adiposity index (VAI) in relation to the risk of type 2 diabetes mellitus (T2DM).Methods:This retrospective cohort study utilized data from the public Dryad database derived from the NAGALA (NAFLD in the Gifu Area, Longitudinal Analysis) project (1994-2016). Participants were stratified into quartiles based on VAI levels. A multivariate Cox proportional hazards regression model was employed to evaluate whether VAI independently predicts T2DM risk. Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves were constructed for each VAI quartile. Subgroup analyses were conducted to examine associations across age and body mass index categories. Both multiplicative and additive interaction effects between gender and VAI were assessed. Additionally, gender-specific Cox models were fitted to further explore these associations.Results:A total of 15 453 participants [8 419 males and 7 034 females; mean age, (43.7±8.9) years] were included, with a median follow-up duration of 5.39 years. During follow-up, 373 participants (2.4%) developed T2DM. After adjustment for potential confounders, higher VAI levels were independently associated with increased T2DM risk ( HR=1.16; 95% CI 1.11-1.21), consistent with the results across VAI quartiles. Kaplan-Meier analysis revealed a significant trend of increasing T2DM incidence across VAI quartiles ( P<0.001). The area under the ROC curve for VAI in predicting T2DM at 3, 5, and 10 years was 0.755, 0.735, and 0.696, respectively. Sensitivity analyses showed that elevated VAI was associated with increased T2DM risk across all age and body mass index subgroups (all P<0.05). Regarding interaction analysis, the HR (95% CI) for the multiplicative interaction between VAI and gender was 1.22 (1.19-1.26). The relative excess risk of interaction was -1.08 (95% CI -2.96 to -0.06), the attributable proportion of interaction was -0.54 (95% CI -1.35 to -0.01), and the synergy index was 0.48 (95% CI 0.26-0.91), indicating a negative additive interaction. Using low-VAI women as the reference group, the risk of T2DM in high-VAI women was higher ( HR=2.53, 95% CI 1.59-4.02) compared to high-VAI men ( HR=2.01, 95% CI 1.49-2.72). In gender-specific analyses, increasing VAI remained significantly associated with elevated T2DM risk after adjustment in both females ( HR=1.43, 95% CI 1.21-1.68) and males ( HR=1.16; 95% CI 1.11-1.22), with consistent findings across VAI quartiles. Conclusions:VAI and gender demonstrated multiplicative and additive interaction in relation to T2DM risk. The association between increasing VAI and T2DM risk was more pronounced in women than in men.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To explore the relationship between insomnia and osteoporosis.Methods:Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio ( OR) and 95% confidence interval ( CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran′s Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results:The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% ( OR=1.007, 95% CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs ( Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10 -5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results ( P=0.059), and radial MR did not detect any outliers. Conclusion:Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

Objective To explore the mechanism of Yangxue Qingnao Granules(Siwu Decoction modified)in the treatment of hypertension based on network pharmacology and molecular docking.Methods The chemical composition analysis results of Yangxue Qingnao Granules in the early stage of the research group were used as the basis for the screening of active compounds.The oral bioavailability≥30%and drug-likeness≥0.18 were used as the screening conditions,and the blood components were supplemented in combination with the literature.TCMSP,chemical professional database and SWISS database were used to predict the targets of potential active compounds of Yangxue Qingnao Granules.Hypertension-related targets were obtained through GeneCards and DiGSeE databases.The intersection of the targets related to hypertension disease and the targets of the potential active compounds of Yangxue Qingnao Granules(common targets)is the potential target of Yangxue Qingnao Granules for the treatment of hypertension.The potential targets were matched with the potential active compounds of Yangxue Qingnao Granules to obtain the antihypertensive active compounds of Yangxue Qingnao Granules.PPI analysis was performed on the potential targets of serum brain granules in the treatment of hypertension through the STRING database,and the core targets were screened according to the degree value.The David database was used to analyze the GO function and KEGG pathway enrichment of the core targets.The core targets with the top six degrees were selected as the docking target proteins,and molecular docking verification was performed with the antihypertensive active compounds.Results A total of 32 potential active compounds,161 active compound targets and 1 539 hypertension-related targets were obtained.After intersection,88 potential targets(common targets)of Yangxue Qingnao Granules in the treatment of hypertension were obtained,involving 29 antihypertensive active compounds.PPI analysis screened 14 core targets:PPARG,ACHE,IL4,CCL2,JUN,NOS3,APP,IL1B,CAT,PTGS2,CASP3,TP53,TNF,IL6,involving 158 GO entries and 13 signaling pathways.Five key active ingredients,chlorogenic acid,rosmarinic acid,paeoniflorin catechinic acid and aloe emodin,were obtained by molecular docking,which were combined with PTGS2,CASP3,TNF,CAT,TP53 and IL6,respectively.Conclusion Yangxue Qingnao Granules may act on core targets such as PTGS2 and CASP3 through key active components such as chlorogenic acid and rosmarinic acid,regulate key pathways such as TNF signaling pathway,MAPK signaling pathway and Toll-like receptor signaling pathway,and play a role in the treatment of hypertension through anti-inflammatory effects.

Objective: Diabetic retinopathy (DR) is the retinal consequence of chronic progressive diabetic microvascular leakage and occlusion. Non-proliferating diabetic retinopathy (NPDR) is the early stage of DR. It eventually occurs to some degree in all patients with diabetes mellitus. In recent years, many clinical trials have shown that Compound Danshen Dripping Pill (CDDP) may be associated with the improvement of NPDR symptoms. The aim of this study was to quantitatively summarize the association between CDDP and the therapeutic effects of NPDR. Methods: It was conducted that a systematic literature search of PubMed, Web of Science, CNKI, VIP and Wanfang Data updated in June 2020 with the following search terms: “diabetic retinopathy” or “retinopathy” or “DR” or “NPDR”, in combination with “Compound Danshen Dripping Pill” or “Salvia miltiorrhiza” or “Danshen”. Risk ratio (RR) and weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between treatment and control groups. The sensitivity analyses were undertaken by removing each individual study when high heterogeneity appeared. Subgroup analysis, Meta-regression, and publication bias analysis were also conducted. The strength of evidence was evaluated with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Results: Twenty-six RCTs involving 2047 subjects were included to conduct a Meta-analysis after screening the studies, extracting the data, and assessing the study quality. The Stata15.0 software was utilized for processing. Meta-analysis indicated that curative effects of treatment group with CDDP was significantly better than control [RR = 0.54, 95% CI (0.40, 0.73); moderate-quality evidence]. In addition, the results showed that CDDP was significantly associated with improving retinal hemorrhages [WMD = −0.62, 95% CI (−0.78, −0.46); low-quality evidence], the vision [WMD = 0.14, and 95% CI (0.09, 0.19), low-quality evidence], fundus fluorescence angiography [RR = 0.37 and 95% CI (0.23, 0.60); low-quality evidence], reduction of retinal microaneurysm [WMD = −3.74 and 95% CI (−4.38, −3.11); moderate-quality evidence], hemangioma volume [WMD = −3.15, 95%CI (−3.45, −2.85); moderate-quality evidence], macular thickness [WMD = −5.52, 95%CI = (−64.27, −48.78); low-quality evidence], mean defect [WMD = −1.65 and 95% CI (−1.95, −1.34); very low-quality evidence], fasting blooding glucose [WMD = −0.95, 95% CI (−1.19, −0.70); low-quality evidence), hemoglobin A1c [WMD = −0.62, 95% CI (−0.93, −0.30); low-quality evidence], high sensitive C reaction protein [WMD = −5.66, 95% CI (−8.01, −3.31); low-quality evidence]. Sensitivity, subgroup, and Meta-regression analyses were also assessed. Conclusion: The study demonstrated that CDDP has beneficial clinical effects for treating NPDR and improve the vision. Moreover, it indicated that oral CDDP in NPDR patients led to significant regulation of serum level of fasting blooding glucose, hemoglobin A1c and high sensitive C reaction protein, which was associated with the pathogenesis of NPDR. However, high-quality and large randomized clinical trials will be needed to prove the consequence in future.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.