Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

With the advancement of rigid endoscopic nasal surgery techniques, the indications for surgery have continued to expand, encompassing an increasing number of anatomical regions. As a surgical adjunct, imaging-guided system assists surgeons in identifying vital structures and mitigating surgical risks, and they are extensively employed in operations involving the nasal cavity, sinuses, and skull base. Nevertheless, existing imaging-guided system faces several unresolved challenges. With ongoing technological advancements and the integration of novel technologies, these systems are demonstrating renewed vigor.
Humans ; Skull Base/surgery* ; Endoscopy/methods* ; Surgery, Computer-Assisted/methods*

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

This article introduced the basic theory of quantile regression and its application in medical and public health research for methodological reference.We fit the quantile regression model to cross-sectional data from the National Health and Nutrition Examination Survey to estimate the association between sleep duration and depression levels at different quantiles of depression levels.The method showed that among people with low levels of depression,sleep duration was not significantly associated with depression level.While among people with higher levels of depression,the association of sleep duration with depression level became much more pronounced.The real data analysis shows that quantile regression can provide a comprehensive analysis of association between exposure and continuous outcome,and identify subgroups that are more sensitive to exposure,providing recommendations for targeted interventions.The method showed promising application value in medical and public health research.

Objective To study microbial characteristics of pulmonary in children with community-acquired pneumonia(CAP)of different severity,in order to provide a basis for accurate diagnosis and antibiotic treatment of pneumonia children,and provide new strategies and perspectives for the diagnosis and treatment of pulmonary microbiota in pneumonia children.Methods Bronchoalveolar lavage fluid(BALF)from 64 children with CAP of different severity hospitalized in Department of Pediatrics,Jingmen People's Hospital were collected from January to December 2023,the children were divided into severe pneumonia group(n=34)and common pneumonia group(n=30).Microbiome information of the lungs of children with CAP of different severity were obtained through metagenomic sequencing of BALF,microbial structure diversity analysis,species classification analysis,and differential analysis on the microbial bioinformatics data of two groups of samples obtained were performed.Results Alpha diversity analysis showed that there were statistically significant differences(P<0.05)in the Chao1 index,ACE index,Shannon index,and Simpson index between two groups.The principal coordinate analysis(PCoA)of Beta diversity showed a statistically significant difference in the composition of microbial communities between two groups(F=4.221,P=0.005).Through species classification analysis,it was found that at the genus level,mycoplasma was the main genus in the BALF samples of severe pneumonia group,followed by Streptococcus and Haemophilus,Streptococcus was the main genus in the BALF samples of common pneumonia group,followed by Mycoplasma and Haemophilus.Children of two groups showed statistically significant differences in microbial abundance among the top 20 species at the genus level(P<0.05),including Mycoplasma,Streptococcus,Rhodococcus,Neisseria,Prevotella,Corynebacterium,and Pseudomonas.Species diversity analysis showed that at the genus level,there were 47 species with differences(P<0.05).Conclusion There are differences in the abundance,diversity,structure,and composition of pulmonary microbiota in children with CAP of different severity.The dominant microbiota varies among children with CAP of different severity.This study enriches the pulmonary microbiome data of children with CAP.

AIM To study the chemical constituents from the branches and leaves of Toona ciliata Roem.var.pubescens(Franch.)Hand-Mazz.and their antitumor activities.METHODS The compounds were isolated and purified by silica gel,RP-18 reverse phase silica gel and semi-preparative HPLC,the structures of compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Fifteen compounds were isolated and identified as toonaolide D(1),toonaciliatin E(2),bourjotinolone A(3),(21R,23R)-epoxy-21α-ethoxy-24S,25-dihydroxyapotirucalla-7-en-3-one(4),(Z)-toonasterone C(5),(E)-toonasterone(6),3-epi-dyscusin C(7),(Z)-aglawone(8),(E)-volkendousin(9),8(14),15-isopimaradiene-2α,3α,19-triol(10),(-)-loliolide(11),cyclohexenone(12),pubinernoid A(13),quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl(14),5-hydroxymethyl-2-furancarboxaldehyde(15).The IC50 values of compounds 3 and 4 on K562 cells were 54.2 and 47.3 μmol/L,respectively,and the IC50 values on HEL cells were 47.3 and 61.1 μmol/L,respectively.CONCLUTION Compounds 4,7,10 and 11 are isolated from Toona genus for the first time,and compounds 2,15 are first isolated from this plant.Compounds 3 and 4 show weak antitumor activities.

Objective To study microbial characteristics of pulmonary in children with community-acquired pneumonia(CAP)of different severity,in order to provide a basis for accurate diagnosis and antibiotic treatment of pneumonia children,and provide new strategies and perspectives for the diagnosis and treatment of pulmonary microbiota in pneumonia children.Methods Bronchoalveolar lavage fluid(BALF)from 64 children with CAP of different severity hospitalized in Department of Pediatrics,Jingmen People's Hospital were collected from January to December 2023,the children were divided into severe pneumonia group(n=34)and common pneumonia group(n=30).Microbiome information of the lungs of children with CAP of different severity were obtained through metagenomic sequencing of BALF,microbial structure diversity analysis,species classification analysis,and differential analysis on the microbial bioinformatics data of two groups of samples obtained were performed.Results Alpha diversity analysis showed that there were statistically significant differences(P<0.05)in the Chao1 index,ACE index,Shannon index,and Simpson index between two groups.The principal coordinate analysis(PCoA)of Beta diversity showed a statistically significant difference in the composition of microbial communities between two groups(F=4.221,P=0.005).Through species classification analysis,it was found that at the genus level,mycoplasma was the main genus in the BALF samples of severe pneumonia group,followed by Streptococcus and Haemophilus,Streptococcus was the main genus in the BALF samples of common pneumonia group,followed by Mycoplasma and Haemophilus.Children of two groups showed statistically significant differences in microbial abundance among the top 20 species at the genus level(P<0.05),including Mycoplasma,Streptococcus,Rhodococcus,Neisseria,Prevotella,Corynebacterium,and Pseudomonas.Species diversity analysis showed that at the genus level,there were 47 species with differences(P<0.05).Conclusion There are differences in the abundance,diversity,structure,and composition of pulmonary microbiota in children with CAP of different severity.The dominant microbiota varies among children with CAP of different severity.This study enriches the pulmonary microbiome data of children with CAP.