To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

ObjectiveTo investigate the significance of different non-treatment thresholds or upper limits of normal （ULN） of alanine aminotransferase （ALT） in evaluating significant liver pathological injury in patients with chronic hepatitis B virus （HBV） infection， and to provide guidance for clinical diagnosis and treatment. MethodsThis study was conducted among 733 patients with chronic HBV infection who were hospitalized in Ningbo No. 2 Hospital from January 2015 to December 2023 and underwent liver biopsy and histopathological examination， and all patients had a persistent ALT level of ≤40 U/L and positive HBV DNA （>30 IU/mL）. According to the treatment threshold or ULN of ALT， the patients were divided into group 1 with 575 patients （≤35 U/L for male patients， ≤25 U/L for female patients）， group 2 with 430 patients （≤30 U/L for male patients， ≤19 U/L for female patients）， group 3 with 443 patients （≤27 U/L for male patients， ≤24 U/L for female patients）， group 4 with 446 patients （≤25 U/L）， group 5 with 158 patients （>35 U/L for male patients， >25 U/L for female patients）， and group 6 with 145 patients （>30 — ≤35 U/L for male patients， >19 — ≤25 U/L for female patients）. Groups 2， 5， and 6 were compared to analyze the severity of liver pathological injury in patients with different ALT levels and the constituent ratio of patients with significant liver pathological injury， and groups 1， 2， 3， and 4 were compared to investigate the value of different ULN or non-treatment thresholds of ALT in determining liver inflammation grade （G）， liver fibrosis stage （S）， and the treatment indication based on liver pathology. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Tambane’s test was used for further comparison between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Ridit analysis was used for comparison of ranked data. A multivariate Logistic regression analysis （forward stepwise） was performed with whether liver pathology met the treatment indication （≥G2 and/or ≥S2） as the dependent variable and related factors with a significant impact on the dependent variable （P <0.05） as the independent variable. The receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC）， as well as sensitivity， specificity， positive predictive value， negative predictive value， positive likelihood ratio， and negative likelihood ratio， was used to assess the diagnostic value of different non-treatment thresholds of ALT. ResultsAmong the 733 patients， 259 （35.33%） had ≥G2 liver inflammation， 211 （28.79%） had ≥S2 liver fibrosis， and 306 （41.75%） had treatment indication （≥G2 and/or ≥S2）. There was a significant difference in liver inflammation grade （G0 — G4） between groups 2， 5， and 6 （χ²=22.869， P <0.001）， and there were also significant differences in the constituent ratios of patients with ≥G2 or ≥G3 liver inflammation between the three groups （χ²=21.742 and 14.921， P<0.001 and P=0.001）. There was a significant difference in liver fibrosis stage （S0 — S4） between groups 2， 5， and 6 （χ²=16.565， P<0.001）， and there were also significant differences in the constituent ratios of patients with ≥S2， ≥S3 or S4 liver fibrosis between the three groups （χ²=13.264， 13.050， and 6.260， P=0.001， 0.001， and 0.044）. There were significant differences between groups 2， 5， and 6 in the constituent ratios of patients with or without treatment indication based on liver pathology （χ²=20.728， P<0.001）. There were significant differences between groups 2， 5， and 6 in the constituent ratio of male patients （χ²=24.836， P<0.05）， age （F=5.710， P<0.05）， ALT （F=473.193， P<0.05）， aspartate aminotransferase （AST） （F=107.774， P<0.05）， ALT/AST ratio （F=40.167， P<0.05）， γ-glutamyl transpeptidase （GGT） （H=15.463， P<0.05）， aspartate aminotransferase-to-platelet ratio index （APRI） （H=63.024， P<0.05）， and LIF-5 （5 indicators for liver inflammation and fibrosis） （H=46.397， P<0.05）. In groups 1 — 4， compared with the patients without treatment indication， the patients with treatment indication had a significantly lower constituent ratio of patients with positive HBeAg， significantly lower levels of platelet count （PLT） and HBV DNA， and significantly higher age， ALT， AST， GGT， APRI， FIB-4， and LIF-5 （all P<0.05）. The Logistic regression analysis showed that age （odds ratio ［OR］=1.044， 95% confidence interval ［CI］： 1.025 — 1.063， P<0.001）， GGT （OR=1.022， 95%CI： 1.007 — 1.038， P=0.003）， and HBV DNA （OR=0.839， 95%CI： 0.765 — 0.919， P<0.001） were influencing factors for treatment indication based on liver pathology in group 1； HBeAg （OR=1.978， 95%CI： 1.269 — 3.082， P=0.003）， age （OR=1.048， 95%CI： 1.025 — 1.071， P<0.001）， GGT （OR=1.016， 95%CI： 1.001 — 1.031， P=0.041）， and PLT （OR=0.995， 95%CI： 0.991 — 1.000， P=0.049） were influencing factors in group 2； age （OR=1.040， 95%CI： 1.014 — 1.066， P=0.002）， ALT （OR=1.047， 95%CI： 1.005 — 1.092， P=0.029）， HBV DNA （OR=0.817， 95%CI： 0.736 — 0.907， P<0.001）， and LIF-5 （OR=7.382， 95%CI： 1.151 — 47.330， P=0.035） were influencing factors in group 3； age （OR=1.054， 95%CI： 1.031 — 1.077， P<0.001）， ALT （OR=1.061， 95%CI： 1.016 — 1.107， P=0.008）， and HBV DNA （OR=0.825， 95%CI： 0.743 — 0.917， P<0.001） were influencing factors in group 4. The diagnostic performance for identifying ≥G2 liver inflammation， ≥S2 liver fibrosis， and treatment indication in groups 1 — 4 had an AUC of >0.7； group 1 showed the lowest sensitivity （28.76%） and the highest specificity， positive predictive value， positive likelihood ratio， and negative likelihood ratio in judging treatment indication； group 2 had the highest sensitivity and negative predictive value and the lowest negative likelihood ratio； groups 3 and 4 had similar diagnostic indicators. ConclusionIn patients with chronic HBV infection and a persistently low ALT level， the severity of liver histopathological injury and the constituent ratio of significant liver histopathological injury decrease with the reduction in ALT level. A higher non-treatment threshold or ULN of ALT can help to identify the patients requiring treatment （with a higher specificity）， while a lower non-treatment threshold or ULN of ALT can help to identify the patients who do not require treatment （with a higher sensitivity）.

OBJECTIVE: To investigate the molecular mechanism for a family with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: The proband, a 63-year-old female, was admitted to the First Affiliated Hospital of Wenzhou Medical University in August 2024 for lumbar disc herniation. Coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), and FⅫ activity (FⅫ:C), were carried out for the proband and her family members (9 individuals from three generations) using a one-stage clotting assay. The level of FⅫ antigen (FⅫ:Ag) was determined with an Enzyme-linked immunosorbent assay (ELISA). Sanger sequencing was conducted to identify potential variants in the F12 gene. Multiple in silico tools were used to predict the conservation, hydrophobicity, and structural impact of the identified variants. Recombinant expression plasmids were constructed and transiently transfected into HEK293T cells. The recombinant FⅫ protein was analyzed using Western blotting (WB) and ELISA. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband showed a markedly prolonged APTT (160.3 s) and significantly decreased FⅫ:C (2%) and FⅫ:Ag (5%) levels. Analysis of the F12 gene sequence revealed a 46C/T genotype in the promoter region, a heterozygous c.1457G>A (p.Cys467Tyr) missense variant in exon 12, and a heterozygous c.1561G>A (p.Glu502Lys) missense variant in exon 13. Bioinformatic analysis showed that the p.Cys467 is highly conserved across various species, and the p.Cys467Tyr variant may affect local structural stability of the FⅫ protein. The p.Cys467Tyr variant had no effect on the transcription of the F12 gene. However, the variant has significantly decreased the FⅫ:Ag levels and FⅫ protein expression in the cell culture supernatant compared to the wild-type expression vector, while in the cell lysate, it is higher than the wild-type expression vector. In other words, the p.Cys467Tyr variant has probably caused a secretion defect of FⅫ protein. CONCLUSION The 46C/T genotype, the heterozygous p.Cys467Tyr missense variant, and the heterozygous p.Glu502Lys missense variant are associated with reduced plasma FⅫ levels in this pedigree. The p.Cys467Tyr variant, which was unreported previously, did not affect the synthesis of FⅫ but may have resulted in a secretion defect.
Humans ; Female ; Middle Aged ; Mutation, Missense ; Pedigree ; HEK293 Cells ; Male ; Factor XII/genetics* ; Adult ; Factor XII Deficiency/genetics*

The construction of "Curriculum Civics" in medical schools needs to go in the same direction as "Civics Curriculum" and "Liberal Studies Education" , and explore the realization path of shaping noble souls through positive ideological and political leadership and mutual collision of hearts and minds.The integration of Wuliande’s spirit into medical education is an all-round exploration from the perspectives of value connotation, contemporary meaning and path exploration, which has important contemporary significance and application value, and is also a practical requirement for inheriting and innovating Wuliande’s spirit and constructing a "Great Thought and Politics" work system under the pattern of "Great Health" in the new era. Based on the above background, this paper explored and interpreted how to fully follow the law of talent growth and the law of education to cultivate new-age medical and health talents who are red and professional, benevolent, health guardian and public health fighter from the perspective of collaborative education of medical ethics education and ideological and political education.