Objective To investigate the influencing factors associated with the comorbidity of inflammatory bowel disease (IBD) and depression. Methods A case-control study was conducted based on the ^“Healthcare Big Data Platform^” of a tertiary class-A comprehensive hospital in Shandong Province. IBD comorbid with depression was served as the case group and IBD without depression was served as the control group. Propensity score matching (PSM) was performed by matching the case group with the control group in a ratio of 1:2 according to the age and gender of the patients. Conditional logistic regression model was used to explore the influencing factors associated with the comorbidity of IBD and depression. Results A total of 405 patients with IBD were enrolled in this study, including 270 patients without depression and 135 patients comorbid with depression. The results of conditional logistic regression showed that the use of immunosuppressants (OR=2.84, 95% CI: 1.00-8.07) and glucocorticoids (OR=2.05, 95% CI: 1.17-3.58), dementia (OR=5.20, 95% CI:1.59-17.05), cardiovascular disease (OR=3.58, 95% CI: 1.84-6.98) and cancer (OR=2.63, 95% CI: 1.16-5.95) were associated with the comorbidity of depression and IBD. Conclusion Attention should be paid to the use of immunosuppressants and glucocorticoids in the population of IBD comorbid with depression, and the coexistence of physical diseases such as dementia, cardiovascular disease and cancer. Early prevention and targeted treatment measures should be taken for high-risk populations to reduce their risk of depression and improve their quality of life and health.

This study aimed to investigate the therapeutic effect of Yindan Pinggan capsules (YDPG) on intrahepatic cholestasis (IHC) through animal experiments, while utilizing network pharmacology and molecular docking techniques to explore its potential mechanisms. Initially, the therapeutic effect of YDPG on an α-naphthylisothiocyanate (ANIT)-induced IHC mouse model was assessed through liver function tests, routine blood tests, and liver pathology analysis. Subsequently, network pharmacology tools were employed to predict the active components, core targets, and signaling pathways of YDPG. Molecular docking technology was employed to verify the binding activity of key active components of YDPG with core targets, followed by protein immunoblotting to validate the key targets. Results showed that YDPG significantly improved liver function abnormalities and hepatocyte damage in IHC mice. Network pharmacology analysis revealed that 94 active components in YDPG were associated with 396 targets for the treatment of IHC, and were significantly enriched in pathways such as the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, lipid metabolism, and bile secretion. Molecular docking results showed good binding activity between key active components of YDPG and core targets of the PI3K-AKT signaling pathway. Further protein immunoblotting confirmed that YDPG could reduce the phosphorylation levels of PI3K and AKT proteins, core targets of the PI3K-AKT pathway in liver tissue. These findings suggest that YDPG may alleviate biological processes such as oxidative stress and inflammatory responses by regulating the PI3K-AKT signaling pathway, thereby improving liver damage in IHC mice and exerting a therapeutic effect on IHC. This experiment has been approved by the Animal Experiment Ethics Committee of Jinan University (ethical approval number: IACUC-20241011-09).

[Objective] : To systematically evaluate the overall efficacy of external application of traditional Chinese medicine (EA-TCM) in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain (CIBP). [Methods] : We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems. It included four Chinese databases [Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP) ], six English databases (Scopus, Embase, Web of Science, PubMed, Cochrane Library, and OpenGrey), and two registration systems (Chinese Clinical Trial Registry and ClinicalTrials.gov). The timeframe for the literature search extended from the inception of each database to December 31, 2023. Meta-analysis was performed using RevMan (v5.4.1), and the outcome indicators (pain relief rate, analgesic duration, quality of life, pain intensity, breakthrough pain frequency, and adverse reactions) were graded using GRADE profiler (v3.6). [Results] : According to the established inclusion and exclusion criteria, a total of 43 studies was deemed eligible, involving 3 142 participants with CIBP. The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone, the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate [risk ratio (RR) = 1.32, 95% confidence interval (CI): 1.24 to 1.41, P < 0.000 01], analgesic duration [mean difference (MD) = 1.33, 95% CI: 0.97 to 1.69, P < 0.000 01], and quality of life (MD = 5.66, 95% CI: 4.88 to 6.44, P < 0.000 01). Furthermore, the combined therapy significantly reduced pain intensity (MD = – 1.00, 95% CI: – 1.19 to – 0.80, P < 0.000 01), breakthrough pain frequency (MD = – 0.43, 95% CI: – 0.51 to – 0.36, P < 0.000 01), and adverse reactions (RR = 0.60, 95% CI: 0.53 to 0.68, P < 0.000 01) in CIBP patients. Based on the GRADE assessment, the level of evidence varied from low to moderate. [Conclusion] EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life. Additionally, the EA-TCM can effectively reduce the incidence of adverse reactions associated with three-step analgesic therapy.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

With the rapid advancement of refractive surgery, small incision lenticule extraction(SMILE)has become a mainstream procedure due to its biomechanical advantage in preserving the integrity of the anterior elastic layer and epithelium. However,postoperative stromal tissue removal and stress redistribution may still compromise corneal biomechanical stability, potentially affecting long-term corneal stability and visual quality. This review focuses on the mechanisms underlying biomechanical changes after SMILE, summarizing recent findings on corneal thinning, reduced mechanical strength, and stress remodeling, and their impact on corneal morphology and visual quality. It further explores potential contributors to postoperative ectasia, increased higher-order aberrations(HOAs), and visual fluctuations, highlighting individual variability and current controversies in the literature. Moreover, current evidence on adjunctive strategies such as corneal cross-linking(CXL)in enhancing biomechanical strength, reducing complications, and improving optical quality was analyzed. Finally, optimal timing for CXL, threshold values of biomechanical metrics, and the role of individualized preoperative assessment and postoperative management was discussed, aiming to provide a theoretical and clinical basis for improving safety and visual outcomes following SMILE.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.