Ductular reaction （DR） refers to the adaptive pathological changes that occur after hepatobiliary injury， and it is essentially a repair response involving the proliferation， fibrosis， and inflammation of biliary epithelial cell （BEC）. With the understanding of the biological function of BEC， the potential value of DR in disease prognosis and treatment has gradually become a research hotspot. This article systematically reviews the molecular mechanism of DR， its potential as a therapeutic target， and future development directions， as well as novel therapies suggested by targeting these molecular mechanisms， in order to provide a new direction for overcoming current bottlenecks in the treatment of bile duct diseases.

Objective To construct a decision support education program for the family members of patients with advanced cancer and to investigate its application effects,so as to improve understanding and acceptance of hospice care for family members of advanced cancer patients.Methods Using the Ottawa Decision Support Framework as a theoretical guide,the program was initially drafted based on a literature review,qualitative interview and expert consultation.From September 2023 to January 2024,a convenience sampling method was used to select patients' families in a tertiary-level hospital in Tianjin as the research subjects,and they were randomly divided into an experimental group and a control group.The experimental group received the decision support education program in addition to routine care,while the control group received routine care.Family members' knowledge about hospice,the scores on the Death Attitude Profile Scale,and their willingness to choose hospice care were compared before and after the interventions.Results The program finally included 4 first-level items,15 second-level items,and 59 third-level items.During the program implementation phase,4 cases withdrew from the study,resulting in 46 cases in the experimental group and 47 cases in the control group.After intervention,the experimental group had higher scores on hospice knowledge and positive attitude towards death than the control group,while scores on negative attitude towards death were lower(P＜0.05);their willingness to choose hospice care for themselves and for the patients was higher than that of the control group(P＜0.05).Conclusion The hospice care decision support education program is scientific,feasible and practical,which can improve the knowledge of hospice care of the family members,improve their attitude towards death,and ultimately improve their willingness to choose hospice care.

Objective To construct a decision support education program for the family members of patients with advanced cancer and to investigate its application effects,so as to improve understanding and acceptance of hospice care for family members of advanced cancer patients.Methods Using the Ottawa Decision Support Framework as a theoretical guide,the program was initially drafted based on a literature review,qualitative interview and expert consultation.From September 2023 to January 2024,a convenience sampling method was used to select patients' families in a tertiary-level hospital in Tianjin as the research subjects,and they were randomly divided into an experimental group and a control group.The experimental group received the decision support education program in addition to routine care,while the control group received routine care.Family members' knowledge about hospice,the scores on the Death Attitude Profile Scale,and their willingness to choose hospice care were compared before and after the interventions.Results The program finally included 4 first-level items,15 second-level items,and 59 third-level items.During the program implementation phase,4 cases withdrew from the study,resulting in 46 cases in the experimental group and 47 cases in the control group.After intervention,the experimental group had higher scores on hospice knowledge and positive attitude towards death than the control group,while scores on negative attitude towards death were lower(P＜0.05);their willingness to choose hospice care for themselves and for the patients was higher than that of the control group(P＜0.05).Conclusion The hospice care decision support education program is scientific,feasible and practical,which can improve the knowledge of hospice care of the family members,improve their attitude towards death,and ultimately improve their willingness to choose hospice care.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Objective To explore the clinical characteristics and genetic mechanisms of patients with Mucolipidosis Ⅲα/β caused by GNPTAB gene mutations.Methods A retrospective analysis was conducted on the clinical data and genetic tests of a confirmed case of Mucolipidosis Ⅲα/β.Various protein prediction tools were used to generate protein models of the wild type and mutant GNPTAB proteins,and computational biology tools were employed to elucidate the differences in protein structure and function between the wild type and mutant variants.Results The patient in this case mainly presented with joint deformities and short stature.Genetic sequencing revealed compound heterozygous mutations in the GNPTAB gene,c.2715+1G＞A and c.1582T＞C;the missense mutation c.1582T＞C has not been reported in the literature.By constructing and analyzing three-dimensional models of the mutants,it was found that the c.2715+1G＞A mutation alters the overall structure of the protein,leading to the loss of protein function,while the c.1582T＞C mutation affects the interaction between the subunit of N-acetylglucosamine-1-phosphate transferase and its ligand.Conclusions This case of MLⅢα/β results from a mutation in the GNPTAB gene,including a missense mutation c.1582T＞C that has not been previ-ously reported,which expands the spectrum of pathogenic mutations of this gene.Through computational analysis of the protein variants resulting from the GNPTAB gene mutation,the understanding of their structure-function relationship has been elaborated,revealing the molecular mechanisms behind the onset of ML Ⅲα/β disease.

Objective To explore the clinical characteristics and genetic mechanisms of patients with Mucolipidosis Ⅲα/β caused by GNPTAB gene mutations.Methods A retrospective analysis was conducted on the clinical data and genetic tests of a confirmed case of Mucolipidosis Ⅲα/β.Various protein prediction tools were used to generate protein models of the wild type and mutant GNPTAB proteins,and computational biology tools were employed to elucidate the differences in protein structure and function between the wild type and mutant variants.Results The patient in this case mainly presented with joint deformities and short stature.Genetic sequencing revealed compound heterozygous mutations in the GNPTAB gene,c.2715+1G＞A and c.1582T＞C;the missense mutation c.1582T＞C has not been reported in the literature.By constructing and analyzing three-dimensional models of the mutants,it was found that the c.2715+1G＞A mutation alters the overall structure of the protein,leading to the loss of protein function,while the c.1582T＞C mutation affects the interaction between the subunit of N-acetylglucosamine-1-phosphate transferase and its ligand.Conclusions This case of MLⅢα/β results from a mutation in the GNPTAB gene,including a missense mutation c.1582T＞C that has not been previ-ously reported,which expands the spectrum of pathogenic mutations of this gene.Through computational analysis of the protein variants resulting from the GNPTAB gene mutation,the understanding of their structure-function relationship has been elaborated,revealing the molecular mechanisms behind the onset of ML Ⅲα/β disease.

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Objective To understand the quality of life in patients with pulmonary tuberculosis within three years after treatment， determine its related factors， and make suggestions for improving the short-term quality of life in patients with pulmonary tuberculosis after treatment. Methods A telephone survey was used to investigate registered tuberculosis patients in Shanghai in 2018 using the short form 12 （SF-12） and the chronic obstructive pulmonary disease （COPD） assessment test questionnaire （CAT）. Results A total of 975 patients with pulmonary tuberculosis who had completed the treatment were included in the study. The total physiological score was determined to be 49.18±10.25， and the total psychological score was 50.27±8.03 （t=5.62，P<0.000 1）. The average CAT score was 13.31±6.08. Multivariate linear regression analysis showed that quality of life was positively associated with high educational level， high monthly family income， and frequent physical exercise， whereas negatively associated with comorbidities， low self-care ability， and changing jobs. Conclusion We should pay more attention to the patients with pulmonary tuberculosis coexistent with COPD and other lung diseases. Measures should be implemented for the improvement in the quality of life， including providing financial support， encouraging regular exercise， and improving lung function.

Deciphering the metabolites of multiple components in herbal medicine has far-reaching significance for revealing pharmacodynamic ingredients.However,most chemical components of herbal medicine are secondary metabolites with low content whose in vivo metabolites are close to trace amounts,making it difficult to achieve comprehensive detection and identification.In this paper,an efficient strategy was proposed:herb-derived metabolites were predicted according to the structural characteristics and metabolic reactions of chemical constituents in Corydalis Rhizoma and chemical structure screening tables for metabolites were conducted.The fragmentation patterns were summarized from represen-tative standards combining with specific cleavage behaviors to deduce structures of metabolites.Ion abundance plays an important role in compound identification,and high ion abundance can improve identification accuracy.The types of metabolites in different biological samples were very similar,but their ion abundance might be different.Therefore,for trace metabolites in biological samples,we used the following two methods to process:metabolites of high dose herbal extract were analyzed to char-acterize those of clinical dose herbal extracts in the same biological samples;cross-mapping of different biological samples was applied to identify trace metabolites based on the fact that a metabolite has different ion abundance in different biological samples.Compared with not using this strategy,44 more metabolites of clinical dose herbal extract were detected.This study improved the depth,breadth,and accuracy of current methods for herb-derived metabolites characterization.

Objective To summarize the pathogenesis,diagnosis and treatment of aplasia cutis congenita (ACC) in China.Methods We reviewed and summarized all published ACC cases in China in the past four decades from China National Knowledge Internet(CNKI),Wan-Fang Medical Database and VIP database.Results Totally,258 cases were included,consisting of 144 males,95 females and 19 of unknown gender.Fifteen cases reported family history,16 had maternal morbidity during pregnancy,17 exposed to maternal medication or toxic material.Skin lesions of ACC occurred on the scalp (39 cases,15.1％),trunk (8 cases,3.1％) or limbs (107 cases,41.5％) and sometimes were manifested as multiples skin defects (104 cases,40.3％).Eighty-nine cases (38.4％) were presented with isolated skin defect,and 169 (61.6％) were complicated by other abnormalities or congenital defects.Totally,235(91.1％) cases were treated conservatively,15 cases with dural defect,skull defect or defect area ＞ 10％ underwent dermatoplasty,and the other eight cases refused any treatment.Among the 248 cases being followed up,233 (93.95％) healed after treatment for one week to four months,three had scar contracture,four developed joint contracture,and eight (3.2％) died of hemorrhage or infection.Conclusions ACC is a congenital skin defect which might involve skin,bone and multiple parts of the body,often complicated with other abnormalities.Superficial and small skin defect maybe managed conservatively,while for patients with bone exposure or defect,large area skin defect,surgical management is recommended.Appropriate management can ensure good outcomes in most cases.