ObjectiveTo investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication. MethodsA retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria. ResultsA total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ²=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ²=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria. ConclusionZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.

Insomnia is a prevalent disorder characterized by difficulties in falling asleep or maintaining sleep.Chronic insomnia can severely impair physical and mental health,as well as quality of life.The traditional Chinese medicine(TCM)theory,"all the eleven zang organs depend on the gallbladder,"is derived from the chapter of Discussion on Six-Plus-Six System and the Manifestations of Organs of Plain Questions.It highlights the pivotal role of the gallbladder in maintaining visceral function.The gallbladder governs decision-making and plays a central role in sleep regulation by modulating spleen-stomach transportation and transformation,dispersing qi movement throughout the body,harmonizing yin and yang,and modulating ying and wei systems.Research has demonstrated that bile acids correspond closely with the gallbladder's TCM functions of"governing the earth zang"and"regulating the eleven zang organs,"serving as a crucial material basis for gallbladder physiology.Dysregulation of bile acid metabolism may contribute to insomnia through multiple pathways,including gastrointestinal dysfunction,disruption of gut microbiota balance,induction of neuroinflammation,and circadian rhythm disturbances.This study proposes that bile acid metabolism disorder may constitute a key pathological mechanism linking gallbladder dysfunction—according to TCM theory—to insomnia.Based on clinical experience,novel therapeutic strategies are proposed under the framework of"regulating the gallbladder to tranquilize mind",including the use of gallbladder-related materials,prioritized application of liver-regulating herbs,and implementation of a sleep rhythm reconstruction protocol.

Insomnia is a prevalent disorder characterized by difficulties in falling asleep or maintaining sleep.Chronic insomnia can severely impair physical and mental health,as well as quality of life.The traditional Chinese medicine(TCM)theory,"all the eleven zang organs depend on the gallbladder,"is derived from the chapter of Discussion on Six-Plus-Six System and the Manifestations of Organs of Plain Questions.It highlights the pivotal role of the gallbladder in maintaining visceral function.The gallbladder governs decision-making and plays a central role in sleep regulation by modulating spleen-stomach transportation and transformation,dispersing qi movement throughout the body,harmonizing yin and yang,and modulating ying and wei systems.Research has demonstrated that bile acids correspond closely with the gallbladder's TCM functions of"governing the earth zang"and"regulating the eleven zang organs,"serving as a crucial material basis for gallbladder physiology.Dysregulation of bile acid metabolism may contribute to insomnia through multiple pathways,including gastrointestinal dysfunction,disruption of gut microbiota balance,induction of neuroinflammation,and circadian rhythm disturbances.This study proposes that bile acid metabolism disorder may constitute a key pathological mechanism linking gallbladder dysfunction—according to TCM theory—to insomnia.Based on clinical experience,novel therapeutic strategies are proposed under the framework of"regulating the gallbladder to tranquilize mind",including the use of gallbladder-related materials,prioritized application of liver-regulating herbs,and implementation of a sleep rhythm reconstruction protocol.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective:To discuss the molecular association pattern of Shenling Baizhu Powder for type 2 diabetes (T2DM) and ulcerative colitis through network pharmacology method based on the theory of "treating different diseases with same method" in TCM.Methods:The TCMSP and ETCM Chinese medicine chemical composition databases were used to obtain the chemical composition and predict the targets of Shenling Baizhu Powder. The OMIM, GeneCards, DrugBank and TTD disease databases were used to obtain the disease targets of T2DM and ulcerative colitis. The intersection targets of chemical composition of Shenling Baizhu Powder, T2DM and ulcerative colitis were obtained by Bioinformatics platform. Cytoscape 3.8.2 software was used to map the "Chinese materia medica-component-target" network and "effective component- intersection target" network. The GO enrichment analysis and KEGG pathway analysis of the intersection targets were performed with the STRING platform. The intersection target protein-protein interaction network was constructed by STRING database, and core targets were obtained using the CytoNCA plugin of Cytoscape 3.8.2 software. AutodockTools software was applied to validate the molecular docking between the core chemical components and the core targets of Shenling Baizhu Powder.Results:Totally 176 chemical components of Shenling Baizhu Powder, 226 corresponding targets, 11 478 T2DM targets, 4 857 Ulcerative targets of ulcerative colitis, and 162 intersection targets of medicinal chemistry components and diseases were obtained. 1 789 related biological processes, 163 molecular functions, 92 cell constituents, and 192 signaling pathways were obtained by GO enrichment analysis and KEGG pathway analysis. The signaling pathways were mainly about AGE-RAGE, TNF, IL-17,MAPK, PI3K-Akt signaling pathways, etc. The core components of Shenling Baizhu Powder were mainly sitosterol, luteolin, kaempferol, naringenin, beta-carotene, etc. The core targets were EGFR, ALB, IL1B, CASP3, ESR1, VEGFA, PTGS2, TNF, IL6, MYC, AKT 1, JUN, TP53, etc. The core chemical components had tight correlation with the core targets by the molecular docking.Conclusions:By acting on core targets such as TNF, IL1B, IL6, AKT1, VRGFA, PTGS2, MYC, JUN, TP53, and regulating IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, etc., Shenling Baizhu Powder improves tissue inflammation damage, mucosal barrier damage, immune regulation imbalance, intestinal flora dysbiosis, insulin resistance, apoptosis, oxidative stress and other biological processes. Therefore Shenling Baizhu Powder can treat T2DM and ulcerative colitis with the same method.

Sodium taurocholate cotransporting polypeptide (NTCP) is not only an important transporter for bile acid absorption into the liver, but also a functional receptor for HBV and HDV, and extensive studies have been performed for its structure, function, gene characteristics, and expression and regulation mechanisms. NTCP is also associated with chronic viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, primary biliary cholangitis, and hepatocellular carcinoma. This article elaborates on the role of NTCP in various hepatobiliary diseases, so as to provide new direction for the diagnosis and treatment of related diseases.

Hepatocellular carcinoma (HCC) is a type of tumor with a high incidence rate, a low rate of early diagnosis, and poor prognosis, and its development and progression involve many factors. As an important organelle in cells, mitochondria is the "energy factory" of cells and is one of the main sites for the production of reactive oxygen species in vivo, and it also participates in the regulation of cell apoptosis. There are varying degrees of changes in mitochondrial membrane, oxidation respiratory chain, mitochondrial dynamics, mitochondrial DNA, and mitochondrial calcium homeostasis during the development and progression of HCC, and such changes may affect the progression of HCC. This article systematically elaborates on the association between mitochondria and HCC, so as to provide a new direction for the diagnosis and treatment of HCC.

ObjectiveTo investigate the clinical effect and safety of transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) in the treatment of advanced primary liver cancer. MethodsA total of 186 patients with advanced primary liver cancer who were treated in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to June 2019 were enrolled and divided into study group and control group using a random number table, with 93 patients in each group. Both groups of patients underwent TACE, and the patients in the study group were treated with ultrasound-guided percutaneous MWA. The two groups were compared in terms of clinical outcome and complications. Quantitative real-time PCR was used to measure the serum level of microRNA-202 (miR-202), ELISA was used to measure the serum levels of fragile histidine triad (FHIT) and P16 protein, and the changes in the above three indices at 3 months after treatment were compared. The two-independent-samples t test was used for comparison of continuous data between two groups, and the paired t-test was used for comparison within one group before and after treatment; The chi-square testwas used for comparison of categorical data between groups. ResultsThe study group had a significantly higher objective response rate than the control group (47.32% vs 27.96%, χ2=7.422, P=0.006), and there was no significant difference in disease control rate between the two groups(P＞0.05). Both groups had significant increases in the serum levels of miR-202, FHIT, and P16 protein at 3 months after treatment (all P＜0.05), and compared with the control group, the study group had significantly higher serum levels of miR-202 (0.84±0.14 vs 0.58±017, t=11.385, P＜0.001), FHIT (1126.35±73.05 pg/ml vs 762.87±56.71 pg/ml, t=37.904, P＜0.001), and P16 protein (52.86±651 pg/ml vs 39.06±5.37 pg/ml, t=15.770, P＜0.001). ConclusionUltrasound-guided MWA in addition to TACE can improve the short-term response of patients with advanced primary liver cancer and increase the serum levels of miR-202, FHIT, and P16 protein, with relatively high safety.

Objective To develop an method for detecting the characteristic chromatograms of Qihong decoction by high-performance liquid chromatography coupled with diode arry and evaporative light-scattering detectors (HPLC-DAD-ELSD). Methods The determination was carried out with Venusil MP-C18 (250 mm × 4.6 mm, 5 μm) column,using acetonitrile-0.2％ formic acid as mobile phase with gradient elution at a flow rate of 1.0 ml/min and detected at the wave length 254 nm, 290 nm, 365 nm. The drift tube temperature for ELSD was set at 70 ℃, and the nebulizing gas flow rate was 2.8 L/min. Results There were 34 chemical compositions in characteristic chromatograms of Qihong decoction. Among them, 16 peaks came from Polygoni Orientalis Fructus, 17 from Astagali Radix, respectively. A total of 18 chemical constituents were identified. Conclusions The method was simple, steady and reliable which could be applied to the quality control of Qihong decoction.