Chronic atrophic gastritis （CAG） is a digestive system disease characterized by the reduction and atrophy of the intrinsic glands of the gastric mucosa. This disease is closely related to risk factors such as Helicobacter pylori （Hp） infection，long-term unhealthy eating habits and lifestyle. As CAG is a key link in the development of gastric cancer，effectively preventing its deterioration is of great significance for the prevention of gastric cancer. At present，Western medicine mainly uses symptomatic treatments such as eradicating Hp，protecting gastric mucosa， and promoting gastrointestinal motility. However， long-term use is prone to drug resistance and cannot reverse limitations such as gland atrophy， making it urgent to explore new intervention strategies. In recent years，with the deepening of CAG mechanism research，the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway，as one of the classic signaling pathways，plays a significant role in the occurrence and development of CAG，while its systematic summary is still blank. Based on the regulatory advantages of "multi-target，multi-pathway，and low toxicity"，traditional Chinese medicine can improve the pathological process of CAG by intervening in key nodes of the PI3K/Akt pathway. In this paper，the research progress of traditional Chinese medicine regulating PI3K/Akt pathway to improve CAG was systematically reviewed for the first time. The expression of PI3K/Akt signaling pathway in CAG was discussed，including the regulation of inflammation and oxidative stress，cell proliferation and apoptosis，and autophagy. The traditional Chinese medicine flavonoids，alkaloids，terpenoids and other compounds that regulate this pathway were summarized. The traditional Chinese medicine compounds mainly include classic famous prescriptions such as Xiaochaihu Tang，Banxia Xiexin Tang，Morodan concentrated pills，Elian granules and other traditional Chinese patent medicines，as well as empirical prescriptions such as modified Leweiyin formula，and Qiling prescription. This study aims to give full play to the advantages of traditional Chinese medicine and lay a solid foundation for the wide application and further development of CAG treatment，and provide new ideas for clinical research and drug research on CAG.

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

ObjectiveTo reveal the changing pattern of fungal communities and isoflavone content during the fermentation of Sojae Semen Praeparatum. MethodsInternal transcribed spacer （ITS） amplicon sequencing was used to analyze the changes in fungal communities during the fermentation. High-performance liquid chromatography （HPLC） was employed to determine the composition and content of isoflavones. Spearman correlation analysis was conducted to identify fungal communities positively correlated with isoflavone content. ResultsDuring the fermentation of Sojae Semen Praeparatum， the abundance of Penicillium continued to increase and became the dominant genus from the "yellow cladding" to the early "secondary fermentation" stage （9 days）. However， in the mid-to-late "secondary fermentation" stage （12-21 days）， the abundance of Penicillium decreased， while the abundance of Barnettozyma increased rapidly， becoming the dominant genus during the later stages （18-21 days）. Alpha diversity analyses showed that fungal diversity was higher in the "secondary fermentation" stage than in the "yellow cladding" stage. Beta diversity analyses showed greater variability in fungal communities during the "yellow cladding" stage， with relatively stable fungal communities during the "secondary fermentation" stage. The aglycone isoflavone content exhibited a gradual increase， rising from 5.56% at the start of fermentation to 96.84% by the end. In contrast， the glucoside isoflavone content experienced a corresponding decline， decreasing from 94.44% to 3.16%. Spearman analysis showed that Penicillium， Barnettozyma， and Ilyonectria were positively correlated with the contents of daidzein， glycitein， and genistein， and promoted the conversion of isoflavones from glucoside to aglycone forms. ConclusionThe fungal communities of Penicillium， Barnettozyma， and Ilyonectria promote the conversion of isoflavones from glucoside to aglycone forms during the fermentation of Sojae Semen Praeparatum. The findings provide an important reference for improving the scalability and quality of Sojae Semen Praeparatu fermentation.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Bacillus velezensis DJ1 exhibits broad-spectrum antagonistic activity against diverse phytopathogenic fungi, while its biocontrol mechanisms against Fusarium graminearum, the causal agent of maize stalk rot, remain poorly characterized. In this study, we integrated genomics and transcriptomics to elucidate the antifungal mechanisms of strain DJ1. The results demonstrated that DJ1 inhibited F. graminearum with the efficacy of 64.4%, while its polyketide crude extract achieved the control efficacy of 55% in pot experiments against this disease. Whole-genome sequencing revealed a single circular chromosome (3 929 792 bp, GC content of 47%) harboring 12 biosynthetic gene clusters for secondary metabolites, six of which encoded known antimicrobial compounds (macrolactin H, bacillaene, difficidin, surfactin, fengycin, and bacilysin). Transcriptomic analysis identified 243 differentially expressed genes (152 upregulated and 91 downregulated, P < 0.05), which were potentially associated with the antagonistic activity against F. graminearum. KEGG enrichment analysis highlighted activation (P < 0.05) of cysteine/methionine metabolism, pentose phosphate pathway, and polyketide biosynthesis pathways, indicating that DJ1 employed synergistic strategies involving antimicrobial compound synthesis, energy metabolism enhancement, and nutrient competition to suppress pathogens. This study provides a theoretical foundation for developing novel microbial resources and application technologies to combat phytopathogenic fungi.
Fusarium/drug effects* ; Bacillus/metabolism* ; Plant Diseases/prevention & control* ; Antifungal Agents/pharmacology* ; Genomics ; Zea mays/microbiology* ; Transcriptome ; Gene Expression Profiling ; Antibiosis ; Multigene Family ; Multiomics

With the core of "molecules and cells", the integrated curriculum group of School of Basic Medical Sciences, Lanzhou University, focuses on the transfer of life molecules, reorganizes teaching content, and integrates Medical Cell Biology, Biochemistry and Molecular Biology, and Medical Genetics to construct a new integrated course of Molecular Medicine. The curriculum group actively explores and practices the mode of medical integration through reconstruction of the curriculum system and optimization of the course content. On the basis of establishing the online course system, the group explores the diversified teaching methods and evaluation systems suitable for Molecular Medicine and discusses the problems in curriculum construction.

Objective:To develop a genotyping method for the Junior blood type and report on a rare blood type with Jr(a-).Methods:Healthy O-type RhD+ volunteer donors of the Shenzhen Blood Center from January to May 2021 ( n=1 568) and a pedigree with difficult cross-matching ( n=3) were selected as the study subjects. Serological methods were used for proband′s blood type identification, unexpected antibody identification, and antibody titer determination. Polymerase chain reaction-sequence specific primer (PCR-SSP) method was used for typing the proband′s RHD gene. ABCG2 gene coding region sequencing and a PCR-SSP genotyping method were established for determining the genotypes of the proband and his family members and screening of Jra antigen-negative rare blood type among the 1 568 blood donors. Results:The proband′s ABO and RhD blood types were respectively determined as B and partial D (RHDDVI.3/RHD01N.01), Junior blood type Jra antigen was negative, and plasma had contained anti-D and anti-Jra. Sequencing of the ABCG2 gene revealed that the proband′s genotype was ABGG201N.01/ABGG201N.01 [homozygous c. 376C>T (p.Gln126X) variants], which is the most common Jr(a-) blood type allele in the Asian population. Screening of the voluntary blood donors has detected no Jr(a-) rare blood type. Statistical analysis of the heterozygotes suggested that the allelic frequency for ABCG2*01N.01 (c.376T) was 0.45%, and the frequency of Jr(a-) rare blood type with this molecular background was about 0.2‰. Conclusion:A very rare case of partial DVI.3 type and Jr(a-) rare blood type has been identified. And a method for identifying the Junior blood type through sequencing the coding regions of the ABCG2 gene and PCR-SSP has been established.

Objective To explore the impact of clinical treatment decisions on the long-term survival of different molecular subtypes of locally advanced breast cancer(LABC),and to promote the development of more effective and individualized treatment regimens for LABC.Methods The cases of LABC diagnosed by pathology from 2010 to 2015 were searched in the database.Breast cancer-specific survival(BCSS)and overall survival(OS)were estimated by plotting Kaplan-Meier curves.The log rank test(Mantel-Cox)was used to analyze the difference between the groups,and the benefit population of LABC was determined after for age,TNM stage,grade,treatment methods.Results The 5-year OS and BCSS were 77.43％and 84.34％in breast-conserving,and 68.03％and 76.90％in mastectomy,respectively.The 5-year OS and BCSS of Luminal A LABC were 79.91％and 87.23％in breast-conserving,and 71.78％and 81.16％in mastectomy,respectively.The 5-year OS and BCSS of Luminal B LABC were 79.30％and 83.14％in breast-conserving,and were 70.37％and 76.92％in mastectomy,respectively.The 5-year OS and BCSS of triple-negative LABC were 60.77％and 68.13％in breast-conserving,and those of mastectomy were 47.13％and 55.94％,respectively.The 5-year OS and BCSS of HER2 positive were 75.42％,82.05％in breast-conserving,and were 67.05％and 75.01％in mastectomy,respectively;The 5-year OS and BCSS of triple-positive LABC were 86.12％and 91.63％in breast-conserving,and 74.54％and 82.56％in mastectomy,respectively.The 5-year OS and BCSS of well differentiated and N0 triple-positive LABC patients with chemotherapy were 88.24％and 76.91％,and those of patients without chmotherapy were 88.24％and 90.91％,respectively(BCSS:P=0.812;OS:P=0.311).Conclusion In the selective population,OS and BCSS of patients with LABC undergoing breast conserving surgery were significantly better than those of mastectomy.When OS and BCSS were compared for different molecular types and stages of LABC,breast-conserving surgery was still superior to total mastectomy.LABC could be considered for highly differentiated,N0 stage Triple positive without chemotherapy.

Objective:To construct a risk prediction and column chart model for venous thromboembolism (VTE) in patients with nephrotic syndrome and provide reference for VTE prevention.Methods:To use the retrospective cohort study design, the nephrotic syndrome patients who were hospitalized in Peking University Third Hospital from January 2018 to December 2022 were selected as the study subjects by convenient sampling method. Using univariate and multivariate Logistic regression analysis to analyze the risk factors for VTE in patients with nephrotic syndrome, establish a risk prediction model, and draw a column chart. The receiver operating characteristic (ROC) working curve and Hosmer Lemeshow test were used to verify the predictive performance of the model.Results:Among the 279 collected patients,187 males and 92 females, aged (54.25 ± 16.29) years, 43 cases developed thrombosis, with an incidence rate of 15.4%. The results of univariate analysis showed that different genders, ages, activity ability, alcohol consumption history, use of diuretics, albumin, hematocrit, fibrinolytic products, activated partial thromboplastin, D-dimer quantification and glomerular filtration rate showed differences in the occurrence of VTE in patients with nephrotic syndrome ( χ2=4.22, 4.62, 12.30, Z values were -5.73 to 6.07, t=-2.07,all P<0.05). The results of multivariate Logistic regression analysis showed that age, whether diuretics were used, activated partial thromboplastin, D-dimer and glomerular filtration rate were independent influencing factors for VTE ( OR values were 0.913- 3.285, all P<0.05). The above factors were five independent variables to construct a column chart. The area under the ROC curve of the model was 0.810, and the maximum value of the Jordan index was 0.518, the sensitivity was 66.67% and the specificity was 85.15%. The Hosmer-Lemeshow goodness-of-fit test showed that the model fit well ( χ2=12.00, P=0.151). Conclusions:The constructed column chart can personalized predict the risk of thrombosis in patients with nephrotic syndrome and help nursing staff in quickly identifying high-risk patients for thrombosis and taking corresponding intervention measures in a timely manner.