Objective To investigate the effect of berberine and its mechanism in delaying silica-induced lung injury via network pharmacology and molecular docking, followed by verification with animal experiments. Methods i) Targets of berberine and silicosis were obtained from multiple databases, and the common targets were identified. A protein-protein interaction network was constructed using the STRING database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the common targets via the DAVID database. Molecular docking was conducted using AutoDock software for validation. ii) Specific pathogen-free Wistar rats were randomly divided into five groups, with six rats in each group. Rats in the model group, pirfenidone group, and low- and high-dose berberine groups received a single non-exposure intratracheal instillation of 1.00 mL silica suspension at a mass concentration of 100 g/L, whereas rats in the control group received an equal volume of 0.9% sodium chloride solution. Rats in the pirfenidone group were administered with pirfenidone solution at a dose of 100 mg/kg body weight, and rats in the low- and high-dose berberine groups were administered with berberine solutions at doses of 100 and 200 mg/kg body weight, respectively. The remaining two groups received equal volumes of 0.9% sodium chloride solution. All treatments were administered by gavage once daily for 28 consecutive days from 24 hours after silica exposure. After intervention, rats in each group were sacrificed. Histopathological changes in lung tissues were observed, and the lung organ coefficient was detected. Serum malondialdehyde (MDA) was detected by colorimetry. Serum inflammatory cytokine were detected by enzyme-linked immunosorbent assay. The expression of fibrosis markers in lung tissues was detected by immunohistochemistry. The protein expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and phosphorylated AKT (p-AKT) in lung tissues was determined by Western blot. Results i) Network pharmacology analysis identified 46 potential targets. The core targets included AKT1, tumor protein p53, caspase-3, matrix metalloproteinase-9, and albumin. GO enrichment analysis revealed that the targets related to the anti-fibrotic effect of berberine against silicosis were mainly enriched in biological processes including signal transduction, negative regulation of apoptosis, extracellular matrix degradation, and response to reactive oxygen species. KEGG enrichment analysis showed that berberine exerted anti-silicosis effects through multiple signaling pathways, such as the PI3K/AKT pathway, hypoxia-inducible factor-1 pathway, and advanced glycation end product (AGE)-receptor for AGE pathway. ii) Histopathological examination revealed that rats in the model group presented typical pulmonary fibrotic lesions. Pathological lung injury of rats was alleviated in all three intervention groups (pirfenidone group, low- and high-dose berberine group) compared with the model group. The improvement in the high-dose berberine group was superior to that in the low-dose berberine group and was comparable with that in the pirfenidone group. rats in the model group showed increased lung organ coefficient, serum MDA, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) (all P<0.05), as well as increased expression of typeⅠcollagen (COLⅠ), α-smooth muscle actin (α-SMA) and PI3K, and p-AKT/AKT ratio in lung tissues (all P<0.05) when compared with the control group. The above indicators were lower in rats in both the low- and high-dose berberine groups than those in the model group (all P<0.05). Serum MDA, IL-1β, and TNF-α, as well as relative expression of COLⅠ and α-SMA in lung tissues, were lower in the high-dose berberine group than in the low-dose berberine group (all P<0.05). Conclusion Berberine may alleviate pulmonary inflammation and fibrosis in rats through regulation of the PI3K/AKT signaling pathway, thereby delaying the progression of silicosis.

ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

In recent years, the reform of the registration, evaluation, and approval system for traditional Chinese medicine(TCM) has been promoted at the national level, with establishment of an evaluation evidence system for TCM registration that combines TCM theory, human use experience, and clinical trials(known as the "three-combined" evaluation evidence system). This system, which aligns with the characteristics of TCM clinical practice and the laws of TCM research and development, recognizes the unique value of human use experience in medicine and returns to the essence of medicine as an applied science, thus receiving widespread recognition from both academia and industry. However, it meanwhile poses new and higher challenges. This article delves into the value and challenges faced by the "three-combined" evaluation evidence system from three perspectives: registration management, medical institutions, and the TCM industry. Furthermore, it discusses how the China Association of Chinese Medicine, leveraging its academic platform advantages and leading roles, has made exploratory and practical efforts to facilitate the research and development of new TCM drugs and the implementation of the "three-combined" evaluation evidence system.
Drugs, Chinese Herbal/standards* ; Humans ; Medicine, Chinese Traditional/standards* ; China ; Drug Development

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

OBJECTIVE: To examine the mechanistic of organochlorine-associated changes in lung function. METHODS: This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function. RESULTS: Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC. CONCLUSION Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure ; Hydrocarbons, Chlorinated/metabolism* ; China ; Ethyl Ethers/metabolism* ; Environmental Monitoring ; Thyroid Hormones/blood* ; Lung/physiology* ; Inhalation Exposure/statistics & numerical data* ; Air Pollution/statistics & numerical data* ; Air Pollutants/metabolism* ; Humans ; Male ; Female ; Middle Aged ; Aged

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and congenital chronic pseudo intestinal obstruction (CIIPX). METHODS: A pedigree presented at the First Hospital of Lanzhou University for CVDPX combined with CIIX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15). RESULTS: Both the proband and his affected younger brother were found to harbor a hemizygous c.443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded in the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+PS4+PP2+PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. CONCLUSION This study confirmed the diagnosis of CVDPX/CIIX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.
Adult ; Female ; Humans ; Male ; Exome Sequencing ; Filamins/genetics* ; Genetic Diseases, X-Linked/genetics* ; Heart Defects, Congenital/genetics* ; Heart Valve Diseases/genetics* ; Pedigree ; East Asian People/genetics*

OBJECTIVE: To explore the mechanism and clinical manifestations of a case with complex structural variations involving chromosomes 5, 7, and 14, and assess the value of Chromosome conformation-based karyotyping (C-MoKa) for its diagnosis. METHODS: Two half-sibs by the same father presented at the First Hospital of Lanzhou University in December 2024 for severe multi-system abnormalities were selected as study subjects. Peripheral blood samples from the their parents were subjected to conventional chromosomal karyotyping analysis. The father was further analyzed using C-MoKa, while both siblings underwent copy number variation sequencing (CNV-seq). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-05). RESULTS: Conventional karyotype analysis indicated that the father has a karyotype of 46,XY,add(5)(p15.3). CNV-seq identified multiple chromosomal abnormalities in both siblings, including duplications and deletions of chromosomes 14 and 5. C-MoKa analysis further revealed a complex chromosomal structural variation involving chromosomes 5, 7, and 14 in the father. These variations were closely associated with the severe phenotypes noted in both children. CONCLUSION Complex chromosomal structural variations can lead to multi-system abnormalities and significantly impact reproductive health. Compared to conventional karyotyping, the C-MoKa technique has shown significant advantage in identifying such complex rearrangements. The combined application of multiple techniques can improve the accuracy of diagnosis, enabling genetic counseling for carriers to reduce their risk for producing further affected offspring.
Female ; Humans ; Male ; China ; Chromosome Aberrations ; DNA Copy Number Variations/genetics* ; Karyotyping ; Pedigree ; East Asian People/genetics*

The success of"New Medical Sciences"in higher education requires effective tools in evalua-ting students'performance in courses.Previously,we reported a teamwork(T),critique(C)and ap-preciation(A)(TCA)ideological and political model,a teaching model widely applied in Basic Medical courses.TCA is an abbreviation derived from Tricarboxylic Acid Cycle in Biochemistry as an analogy for nurturing the abilities of thinking and teamwork(T),critique(C)and appreciation(A),which hope-fully could provide students with moral norms for cognition,science and life.This paper further explores the tools to assess the educational outcomes of the TCA model,by which teachers can collect feedback and reflect on teaching quality and effectiveness.Addressing the challenges of individual differences in large classes,fragmented learning feedback,and the difficulty of measuring meta-cognition in educational evaluation,this study employs strategies of value-added assessment,matrix assessment and norm-transfer-able assessment to evaluate the TCA abilities from the aspects of thinking quality,thinking creativity,co-operation ability,iterative thinking,dialectical thinking and job responsibility.By modifying/using 18 e-valuation tools in Education and Psychology,we have established a rubric system composed of 30 primary indicators(with 11 newly designed,10 partly modified and 9 directly adopted),along with 49 secondary indicators and 98 tertiary indicators to enhance the feasibility of the evaluation process.This rubric sys-tem was applied to Biochemistry teaching among the five-year-program undergraduates at Air Force Medi-cal University.Specifically,thinking and teamwork are evaluated by creative works from"the magic bio-chemical-circle",while critiques are assessed in large classes under the guidance of basic and clinical teachers,coupled with appreciation measured by job responsibility in a task-driven virtual reality(VR)project.The results indicate that Biochemistry teaching not only accumulates knowledge in students,but also achieves the goals in nurturing values and cognition.The inclusion of creative performance evalua-tion,cooperative learning and clinical case studies,can enhance students'interpersonal skills,coopera-tion,quality of thinking,creative thinking,iterative thinking and dialectical thinking to varying degrees.TCA-based Biochemistry teaching has a long-lasting impact on character education,and is capable of in-ducing positive long-term changes in students'cognition and lifestyle.Taken together,with the help of this rubric system,teachers can promptly acknowledge the effectiveness of their teaching,thereby facilita-ting their teaching strategies.

Objective:To explore the construction of an evaluation model for aortic root anatomy and calcium burden in patients with bicuspid aortic valve (BAV) stenosis before transcatheter aortic valve replacement (TAVR) based on deep learning (DL) algorithms.Methods:A retrospective collection of 362 BAV stenosis patients who underwent TAVR from September 2023 to May 2024 was performed. All patients underwent cardiac CT angiography. The patients were divided into training group ( n=104), internal validation group ( n=206), and external validation group ( n=52). A DL model was trained on the training dataset to assess aortic root anatomy and calcification burden. The evaluation included the segmentation accuracy of the algorithm, the measurement performance of key anatomical structures (i.e., valve leaflets and type-1 and type-2 fusion raphe), and calcification burden, as well as the measurement efficiency. Overall segmentation performance was assessed using the average Dice coefficient (ADC). The fine-scale segmentation quality was validated by the 95th-percentile Hausdorff distance (HD-95) and the average symmetric surface distance (ASSD). The consistency of the measurement results was assessed using the Pearson correlation coefficient and the intraclass correlation coefficient ( ICC) with a two-way mixed model for absolute agreement. In addition, the total time and total mouse movement distance required for manual assessment versus the DL model on the validation datasets were recorded and compared. Results:The algorithm demonstrated excellent segmentation performance on aortic root anatomical targets, achieving outstanding consistency within both internal and external validation datasets (0.955