Patients with chronic cholestatic liver diseases face numerous challenges in the detection， assessment， and management of suspected drug-induced liver injury （DILI）， and in particular， it is difficult to distinguish cholestatic DILI from the progression of underlying cholestatic liver diseases clinically and histologically. Currently， there is a lack of related research and management guidelines for DILI with chronic cholestatic liver diseases. This article discusses the potential risks， causality， and classification criteria for chronic cholestatic liver diseases with DILI， in order to improve the understanding of such diseases among clinicians and provide a reference for prevention， treatment， and management strategies.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Prostate cancer is one of the most common male malignancies in many parts of the world and also the fifth leading cause of cancer death among men worldwide.At present,the commonly used clinical screening methods for prostate cancer are serum prostate-specific antigen(PSA)and transrectal ultrasound guided puncture biopsy.However,the above two diagnostic methods have some related problems such as over-diagnosis caused by false negative and false positive.Metabolomics is an important component of systems biol-ogy,which recognizes minor changes in certain molecular metabolites during tumorigenesis and development.This article reviewed how to use the method of metabolomics to find the metabolites of the three major sub-stances in the patients with prostate cancer and the changes of related metabolic pathways to provide the new ideas for the clinical diagnosis of prostate cancer.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective:To explore the changes in early postpartum pelvic floor muscle strength following the implementation of the new labor process.Methods:This retrospective cohort study selected 1 834 primiparous women with singleton, full-term pregnancies who delivered at Peking University First Hospital from February 2011 to March 2016 and had a pelvic floor re-examination 6-8 weeks postpartum. Out of these, 738 cases who followed the old labor process before 2014 were categorized as the old process group, and 1 096 cases who followed the new labor process after 2014 were categorized as the new process group. Basic data, childbirth information, and postpartum pelvic floor muscle strength of the two groups were compared. Data were statistically analyzed using t-test, Chi-square test, Mann-Whitney U test, Wilcoxon rank-sum test, and ordered multicategory logistic regression to assess the impact of the new and old labor process and other factors on pelvic floor muscle strength. Results:The total duration of labor, as well as the duration of the first, second, and third stages of labor, were longer in the new process group than in the old process group [549.0 min (360.0-768.0 min) vs. 482.5 min (328.0-635.0 min), 465.0 min (297.5-672.5 min) vs. 420.0 min (285.0-555.0 min), 42.0 min (24.0-74.0 min) vs. 27.0 min (18.0-45.0 min), with Z-value of－5.72,－3.95, and－9.28, all P<0.05). The rates of vaginal delivery and labor analgesia were higher in the new process group [72.1% (790/1 096) vs. 67.2% (496/738), χ2=7.41; 67.4% (739/1 096) vs. 53.4% (394/738), χ2=36.82; both P<0.05]. There were no statistically significant differences in the comparison of Class Ⅰ and Class Ⅱ muscle strength grades between the two groups (all P>0.05). Conclusion:There was no significant decline in early postpartum pelvic floor muscle strength following the implementation of the new labor process standards.

Objective:To evaluate the feasibility and safety of a novel transjugular intrahepatic portosystemic shunt (TIPS) puncture set for transjugular intrahepatic portal puncture in swine.Methods:Thirteen domestic swine were randomly divided into experimental group ( n=7) and control group ( n=6) and received transjugular intrahepatic portal puncture with the novel puncture set and the R?sch-Uchida Transjugular Liver Access Set (RUPS-100), respectively. Three swines in each group were randomly selected and sacrificed immediately after the procedure and the rest were sacrificed 1 week later. The intraoperative technical success rate, puncture attempts, procedure time, fluoroscopy time, vital signs and occurrence of complications related to the procedure as well as the changes of liver and kidney function before, immediately after and 1 week after the procedure were compared between two groups. Independent sample t test, paired t test, Mann-Whitney U test, chi-square test or Fisher′s exact test were performed to compare the differences between groups. Results:The technical success rate was 100% for both groups. No significant difference in portal puncture attempts [2.0 (1.0, 5.0) vs. 2.0(1.0, 5.5), P>0.999], procedure time [(47.7±20.6) vs. (52.5±28.0)min, P=0.729] and fluoroscopy time [(725.1±489.2) vs. (763.7±562.4)s, P=0.897] was observed between two groups. In addition, no significant difference of the major liver and kidney function between two groups before, immediately after and 1 week after procedure ( P>0.05 at all time points). No significant difference of the major liver and kidney function change in two groups during perioperative period was identified (all P>0.05). Furthermore, no significant difference of non-target puncture occurrence was observed between two groups ( P>0.999). In the meantime, no significant difference of occurrence of small hematomas around hepatic hilar was discovered among swine sacrificed immediately after procedure between two groups ( P>0.999). No other major complications were identified in either group. Conclusion:The novel TIPS puncture set is feasible and safe to perform transjugular intrahepatic portal puncture in swine.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Objective:To prepare cisplatin-loaded anti-progastrin-releasing peptide (ProGRP) monoclonal antibody targeted nanobubbles, and to explore the proliferation inhibition effect and anti-cancer molecular mechanism of them on small cell lung cancer (SCLC).Methods:The cisplatin targeted nanobubbles were prepared by thin film hydrating method, and the physicochemical property were explored. The subcutaneous xenograft tumor models of SCLC in 10 nude mice were established, and the ultrasound molecular targeting development effect of cisplatin targeted nanobubbles was analyzed by using blank nanobubbles as control. Another 24 tumor-bearing nude mouse models were established and randomly divided into four groups: blank nanobubbles group, cisplatin group, cisplatin nanobubbles group, cisplatin targeted nanobubbles group. The tumor inhibition rate was calculated. The effect on SCLC proliferation was detected by CCK8 method. RT-PCR and Western blotting methods were used to detect SCLC proliferation related genes the P53, Rb, c-myc protein and mRNA expression level of change, the molecular regulatory mechanism was analyzed.Results:The cisplatin targeted nanobubbles were successfully prepared. The particle size was (467.3±42.3)nm, the structure was stable. The cisplatin targeted nanobubbles had a good effect of ultrasonic molecular development in SCLC xenograft.Compared with the control group, the proliferation of SCLC cells was significantly inhibited by cisplatin targeted nanobubbles. The RT-PCR and Western blotting analysis showed that compared with the control group, the mRNA and protein levels of the proliferation-related gene P53 and Rb in the cisplatin targeted nanovesicles group were significantly up-regulated, and the mRNA and protein levels of c-myc were significantly down-regulated (all P<0.05). Conclusions:The cisplatin targeted nanobubbles can inhibit the proliferation of SCLC, and may be used as a new potential targeted drug for the treatment of SCLC.