Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

With reference to the teaching reform of standardized training cases based on organ systems, a teaching case writing team has been established, integrating the teaching experts in basic medicine, clinical medicine, humanities medicine, and other fields. Through collective lesson preparation and discussion, non-fictional comprehensive scenario writing techniques have been used based on organ systems and oriented by competency development, and the teaching cases for postgraduate students were written on the basis of real cases, which lays a solid foundation for the hierarchical and progressive cultivation and improvement of the quality of competency cultivation for postgraduate students through case teaching based on organ systems.

By identifying and analyzing the problems and difficulties in the implementation process of student stratification, goal stratification, practice stratification, and assessment stratification in standardized residency training, this article proposes to fully leverage the main role of professional bases in hierarchical and progressive teaching for standardized residency training and strengthen the specific responsibilities of professional base teaching groups in discussing hierarchical and progressive teaching plans, evaluation standards, and assessments. It is also necessary to scientifically implement student stratification, achieve consistent stratification goals, strengthen the training of hierarchical and progressive teaching concepts and teaching abilities for teachers, enhance the ability for homogeneous and hierarchical evaluation, and develop countermeasures that combine stage training goal process evaluation with dynamic personalized teaching by mentors, so as to provide a useful reference for further promoting the reform of standardized residency training using a hierarchical and progressive teaching model.

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.

Bilirubin has good anti-inflammatory， antioxidant and immunomodulatory effects， but its poor water solubility and low bioavailability greatly limit its clinical application. Researchers have developed bilirubin into various nanoparticles， which effectively eliminate the limitation of low solubility of bilirubin with the advantage of dosage form， so that they can maximize its pharmacological activities such as anti-inflammatory， anti-oxidation and immune regulation. Bilirubin nanoparticles have great application potential in a variety of gastrointestinal diseases， liver and kidney diseases， skin diseases， autoimmune diseases， islet transplantation and targeted therapy of tumors （both as a direct anti-tumor drug and as a drug delivery system）. The study of bilirubin nanoparticles will promote the clinical application of bilirubin and the development of related new drugs.

By searching the literature on the application of entrustable professional activities in college education in China and globally, this article comprehensively analyzes the concept of entrustable professional activities, the development of evaluation items, the effectiveness of clinical application, the problems to be improved, and research prospects, so as to provide a useful reference for the reform and evaluation of competency-oriented medical education in China and the application of entrustable professional activities that can be repeated and promoted in clinical teaching.

Objective:To analyze the syndrome differentiation medication law of TCM in treating overactive bladder (OAB) based on data mining techniques.Methods:The articles about the treatment of OAB with TCM were collected from China National Knowledge Infrastructure (CNKI), Wanfang database, Chongqing VIP database and SinoMed. A prescription database for OAB was established. Methods such as frequency statistics, association rule analysis, clustering analysis, and factor analysis were used to analyze the medication law of the prescriptions.Results:The results showed that a total of 91 prescriptions were included, involving 134 kinds of Chinese materia medica. Five drugs were with a usage frequency of >30%. The top 4 categories with medication frequency were herbs for tonifying deficiency, herbs for inducing diuresis and draining dampness, herbs for relieving exterior syndrome and herbs for regulating qi. The properties of the included herbs were characterized by mild and warm, and the tastes were mainly sweet, pungent and bitter. The majority of meridian tropism was kidney meridian, supplemented by spleen, liver and lung meridians. The association rule analysis showed eight high-relevance medicine pairs, and four new candidate prescriptions were summarized after the clustering analysis, and six common factors were extracted by factor analysis.Conclusions:The location of the lesion of overactive bladder is mainly about the kidney, related to the spleen, liver and lung. And the pathogenesis is based on the kidney deficiency, which also due to the adverse qi transformation in triple energizer. Clinical medication is mainly about the herbs for tonifying deficiency and the herbs for inducing diuresis and draining dampness; at the same time those herbs for regulating qi and relieving exterior syndrome should be paid attention to, which are able to smooth and regulate the qi of the whole body.

Objective:To summarize the clinical manifestations and gene mutation features of patients with nucleotide excision repair (NER) disorders.Methods:A retrospective analysis was made on clinical data of patients with NER disorders who were admitted to the Chinese People′s Liberation Army General Hospital from October 2008 to February 2022 and diagnosed in the Outpatient Department of Beijing Children′s Hospital, Capital Medical University from October 2015 to February 2022.Literature on previously reported Chinese patients with NER disorders was reviewed.Results:(1)A total of 16 patients with NER disorders were enrolled, including 6 males and 10 females.The onset age was 7.5 (4.0, 12.0) months and the age at diagnosis was 42.0 (21.5, 77.0) months.There were 3 types of NER disorders: Cockayne syndrome (CS) in 13 cases, Xeroderma Pigmentosum (XP) in 2 cases and Cerebro-Oculo-Facio-Skeletal syndrome (COFS) in 1 case.Four disease-causing genes were detected: CSA gene in 11 cases, CSB gene in 3 cases, XPG gene in 1 case, and XPD gene in 1 case.The first symptoms of the 16 patients were photosensitivity and developmental delay, and neurological symptoms were observed in all the 3 NER disorder types.XP and CS patients had skin symptoms.CS patients presented typical facial features, visual and auditory impairment, microcephaly and changes in neuroimaging features.COFS patients showed intrauterine growth retardation.(2)Results of literature review: a total of 96 Chinese patients reported were retrieved, involving 6 disease types, including CS in 45 cases, XP in 44 cases, trichothiodystrophy in 4 cases, COFS in 1 case, XP-CS in 1 case, and ultraviolet sensitive syndrome in 1 case.Nine mutated genes were identified: CSA in 33 cases, XPA in 15 cases, CSB in 13 cases, XPV in 10 cases, XPC in 9 cases, XPG in 7 cases, XPD in 7 cases, XPF in 1 case, and MPLKIP in 1 case.The common symptoms were growth failure (62 cases), skin photosensitivity (61 cases), typical facial features (52 cases), mental retardation (49 cases) and microcephaly (48 cases). Among 36 cases had imaging data 33 cases(91.7%)had calcification of basal nucleus or globus pallidus.Three cases had intrauterine growth retardation and microcephaly during pregnancy. Conclusions:Patients with such prenatal manifestations as intrauterine growth retardation and microcephaly or with typical symptoms like skin photosensitivity, typical facial features, growth failure, mental retardation, hypertonia, and calcifications of basal ganglia should be suspected of NER disorders.Early genetic testing is recommended to confirm the diagnosis.

Objective:To develop an program for training diabetes educators amid normalization stage of novel coronavirus pandemic prevention and control, and provide reference for clinical teaching under special circumstances.Methods:From January 2020 to June 2021, The head member of Diabetes Education and Management Committee of Hunan Health Management Association Xiangya Hospital of Central South University, developed and implemented a program based on core competencies of diabetes educators. It included 26 online courses, one to one education demonstration video with 7 themes, one diabetes conversation map and simulation, and three-week clinical practice. From April 2021 to June 2021, 55 health workers participated in the program. Theoretical tests, video feedback and questionnaires were used to evaluate the trainees′ diabetes knowledge, educational skills and satisfaction with the training program.Results:A total of 55 health workers participated in the program. All the participants completed the online courses and passed the quizzes, the theoretical examination score was (92.93 ± 5.28). Fifty-four participants finished the tasks of clinical practice and obtained the certificate of diabetes educator. Their communication skills and strategies of behavior change were significantly improved ( χ2 values were 4.17 -26.34, all P<0.05), and all of them were satisfied with the program. Conclusions:The training mode based on online training is flexible, convenient and effective,which is suitable for stage of novel coronavirus pandemic prevention and control.

Birth cohort is an important platform to study the effect of early-life exposure on health outcome, but large cohorts to investigate the effect of preconception exposure, especially paternal exposure, on reproductive health and birth outcome are limited. The Preconception Reproductive Health and Birth Outcome Cohort (PREBIC) is a prospective birth cohort study which pays equal attention to the contribution of environmental, psychological, behavioral as well as other factors to reproductive health and adverse birth outcomes in both men and women in Chongqing, China. PREBIC started in 2019 and plans to recruit 20 800 reproductive-age couples with child-bearing willingness. Followed up was conducted to understand the conception status of the women within two years. Women in pregnancy would be visited at first, second, third trimesters and after delivery. The offspring would be monitored until 2 years old to understand the incidences of preterm birth, low birth weight, birth defects, neurodevelopmental disorders and other outcomes. Related information and biospecimen collections (including semen, peripheral blood, urine, placenta, umbilical cord, cord blood and oral swab) were scheduled in each period. By January 2022, PREBIC had recruited 8 698 participants from all 38 districts in Chongqing. The goal of PREBIC is to establish one of the largest prospective preconception birth cohorts covering both men and women, which might provide a unique insight to understand the effects of the full reproductive cycle on reproductive health and adverse outcomes, with especial emphasis on preconception exposures.