Biliary tract cancer (BTC) is a rare group of malignancies that develop from the epithelial lining of the biliary tree and have a poor prognosis. Although chemotherapy is the standard of care for patients with advanced BTC in China, its clinical benefits are moderate. In recent years, the approval of targeted therapies and immunotherapies has provided new avenues for the management of advanced BTC. Nonetheless, the increasing number of personalized medicine approaches has created a challenge for clinicians choosing individualized treatment strategies based on tumor characteristics. In this article, we discuss recent progress in implementing precision medicine approaches for advanced BTC in China and examine genomic profiling studies in Chinese patients with advanced BTC. We also discuss the challenges and opportunities of using precision medicine approaches, as well as the importance of considering population-specific factors and tailoring treatment approaches to improve outcomes for patients with BTC. In addition to providing a comprehensive overview of current and emerging precision medicine approaches for the management of advanced BTC in China, this review article will support clinicians outside of China by serving as a reference regarding the role of patient- and population-specific factors in clinical decision-making for patients with this rare malignancy.
Humans ; Precision Medicine/methods* ; Biliary Tract Neoplasms/genetics* ; China ; Molecular Targeted Therapy ; Immunotherapy/methods*

Objective To investigate the correlation between the combined assessment of preoperative 5-factor modified frailty index(mFI-5)and Naples prognostic score(NPS)with overall survival in patients with unresectable hepatocellular carcinoma(uHCC)following interventional therapy.Methods A retrospective cohort study enrolled 292 patients with uHCC who underwent interventional therapy at the Department of Hepatobiliary Pancreatic Surgery of the Second Affiliated Hospital in Army Medical University from October 2017 to December 2021.Patients were stratified into high-risk and low-risk groups based on mFI-5(≥1),NPS(≥3),and CONUT(≥4)scores.Propensity score matching(PSM)was performed to balance baseline characteristics(post-matching n=186).The primary endpoint was overall survival(OS),analyzed using Kaplan-Meier curves with log-rank tests.The predictive performance of combined indicators was evaluated by receiver operating characteristic(ROC)curves,and prognostic factors were assessed via Cox regression analysis.Results After PSM,baseline characteristics(including age,tumor markers,and treatment-related parameters)showed no significant differences between the two groups.Survival analysis demonstrated a 2.252-fold higher risk of death in the mFI-5 plus NPS high-risk group(95%CI:1.60～3.18,P<0.001).The combination of mFI-5 and NPS scores yielded an area under curve(AUC)of 0.718 for predicting 3-year overall survival,significantly outperforming either index alone(P=0.007).Multivariable Cox regression analysis identified that dual positivity for mFI-5 and NPS(HR=1.46;95%CI:1.01～2.11,P=0.044),portal vein tumor thrombosis(HR=1.49;95%CI:1.03～2.16,P=0.035),tumor diameter>5 cm(HR=2.01;95%CI:1.27～3.17,P=0.003),Barcelona clinic liver cancer(BCLC)stage C disease(HR=2.05;95%CI:1.37～3.07,P<0.001)were independent predictors of poor prognosis.Postoperative combination targeted therapy and immunotherapy was associated with significantly reduced mortality risk(HR=0.57;95%CI:0.39～0.81,P=0.002).Conclusion The combination of mFI-5 and NPS scores is significantly associated with overall survival in patients with unresectable hepatocellular carcinoma(uHCC)undergoing locoregional therapy,providing a validated tool for clinical risk stratification and personalized treatment planning.

It is the hotspot that studying the interplay and mechanism between intestinal flora metabolites and diseases.Deoxycholic acid, one of the intestinal flora metabolites, is one of the most abundant secondary bile acids in human intestinal tract, which is corelated with many diseases, while the mechanisms remain unclear.The imbalance of deoxycholic acid is connected with the intestinal flora disorder and high fat diet, which could result in several immunoreaction and inflammatory reaction.In this review, the interaction between deoxycholic acid and digestive diseases in children, such as non-alcoholic fatty liver disease, inflammatory bowel disease and irritable bowel syndrome, is discussed to explore their related mechanism, so as to clarify the direction of further study on the influence of intestinal microbiota metabolites deoxycholic acid on the human body.

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

OBJECTIVE：To estab lish“TCM Data Analysis Platform Based on Strategy Pattern ”（TCMDP），and to analyze the medication rules of TCM prescription against primary hepatic carcinoma （PHC），so as to provide reference for TCM prescription screening. METHODS ：According to the idea of strategy pattern ，TCMDP software was developed ，and the frequency statistics，association，clustering，classification and other methods and the different algorithms covered were encapsulated. Effective TCM prescriptions against PHC were collected and screened from 4 tertiary-grade class-A hospitals in Nanchang city and CNKI ， PubMed. A database of prescriptions for PHC （PDOPHC）was established ，and TCM prescriptions in the data base were put into TCMDP. Clustering algorithm modified by CMC-DD ，modified WD-Get Rules algorithm after merging depth and width search and frequency statistics were used to analyze the distribution of prescription syndrome. Taking phlegm-blood stasis syndrome type （TYPHC）as example ，data mining was carried out on drug efficacy category ，four properties ，five flavors and channel tropism ， drug property combination ，key couplet medicines and key drug combination. RESULTS ：A total of 907 TCM prescriptions against PHC were collected ，mainly involving 10 syndrome types ，such as phlegm-blood stasis syndrome ，deficiency of the vital essential and blood stasis syndrome and liver and spleen blood stasis syndrome. TCM related to TYPHC commonly used in pre- scriptions were tonifying deficiency medicine ， phlegm-re- solving medicine ，promoting blood circulation and removing blood stasi s medicine ，etc．Four properties were mostly cold ，warm and calm ；the five flavors were most ly swe et，bitter and pungent ；channel tropism were mostly spleen ，liver，stomach， lung，heart and kidney ；drug combination were mostly warming-sweet-spleen ，warming-pungent-spleen and cold-bitter-liver ，etc.； there were 36 couplet medicines with frequency ≥30 times；there were 31 strong association rules and 8 key drug combinations in the prescriptions. WD-Get Rules results showed that in the TCM prescriptions against PHC ，Atractylodes macrocephala ，Codonopsis pilosula，Poria cocos and Glycyrrhiza uralensis were in the key position. They were often combined with many kinds of drugs ， which were related to the effect of Sijunzi decoction on strengthening Qi and tonifying spleen. CMC-DD results showed that therapy for TYPHC focused on strengthening the spleen and stomach ，replenishing Qi and blood ；and at the same time ，it treated TYPHC with phlegm-blood stasis syndrome from multiple angles ，such as soothing the liver and regulating Qi ，eliminating phlegm ，clearing heat and detoxification ，promoting blood circulation and nourishing Yin. CONCLUSIONS ：Clinical treatment of TYPHC mainly adopts the methods of invigorating the spleen and replenishing Qi ，soothing the liver and regulating Qi ，promoting blood circulation and removing blood stasis ，which conforms to the medication principle of “strengthening the body and eliminating pathogenic factors”. The application of TCMDP can realize the data mining and analysis of TCM in multi-level and multi-directional way ， which provides a new and effective way for the mining and research of compatibility rules of TCM prescriptions.

Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qua-litative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ke-toconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation pro-ducts, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.

Objective:To establish a method for the content determination of two ingredients in ktoconazole and clobetasol propio -nate cream.Methods:HPLC was performed on a Kromasil C 18 column (250 mm ×4.6 mm, 5 μm) with the mobile phase of metha-nol-sodium acetate with gradient elution at a flow rate of 1.0 ml· min-1 .The detection wavelength was 239 nm, the column tempera-ture was 30℃and the injection volume was 10 μl.Results:The linear range was 160.30-1282.40 μg· ml-1 for ketoconazole (r=1.0000) and 4.03-32.24μg· ml-1 for clobetasol propionate (r=1.0000).The average recoveries were 100.9％(RSD=0.52％, n=9) and 100.2％(RSD=0.56％,n=9), respectively.Conclusion:The method is accurate with good specificity and high sensi-tivity, which can be used for the detection of ketoconazole and clobetasol propionate .

Objective To observe the effect of excretory/secretory products from Trichinella spiralis adult worms(AES)on cecal ligation and puncture(CLP)?induced sepsis in mice. Methods Forty?eight BALB/c mice were randomly divided into 3 groups:a sham operation group(PBS+sham group,Group A),a CLP?induced sepsis group(PBS+CLP group,Group B)and an AES treatment group(AES+ CLP group,Group C). The mice of each group were intraperitoneally injected with 25 μg of AES or PBS only as a control in a total volume of 200μl. Eight mice from each group were selected randomly for survival analy?sis of 96 hours. The other 8 mice in each group were observed for pathological changes in the lung,liver and kidney tissues by HE staining 12 h after CLP,and then determined for the detection of cytokines including TNF?α,IL?1β,IL?6,IL?10 and TGF? βin the sera by ELISA. Results The difference among the survival rates of mice in the 3 groups was statistically significant (χ2=21.16,P<0.05). Compared to Group A(100%),the survival rate of mice in Group B(0)decreased significantly(P<0.05),and also the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group B increased signifi?cantly after CLP. Compared with the mice in group B,the survival rate of those in Group C(70%)increased significantly(P<0.05),and the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group C decreased significantly after the treatment with AES. The differences among the levels of pro?inflammatory cytokines TNF?α(F=27.11,P<0.05),IL?1β(F=18.75,P<0.05)and IL?6(F=100.93,P<0.05)in the sera of the mice in the three groups were statistically signifi?cant. Compared with the mice in Group A,the levels of the 3 cytokines of those in Group B increased significantly(all P <0.05). However,after the treatment with AES,the levels of the pro?inflammatory cytokines of those in Group C decreased signifi?cantly(all P<0.05). The differences among the levels of immunoregulatory cytokines IL?10(F=10.88,P<0.05)and TGF?β(F=11.37,P<0.05)in the sera of the mice in the three groups were also statistically significant. Compared with the mice in Group B,the levels of IL?10 and TGF?β of those in Group C were higher after treatment with AES(both P<0.05). Conclu?sion T. spiralis AES has a therapeutic potential for alleviating sepsis induced by CLP in mice.