ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid （4-PBA） on bile acid metabolism disorders induced by bacterial lipopolysaccharide （LPS） in late-pregnant mice， and to clarify the regulatory mechanism of endoplasmic reticulum stress （ERS） in intrahepatic cholestasis of pregnancy （ICP）. MethodsTwenty-four pregnant mice were divided into control group， LPS group， 4-PBA group， and LPS+4-PBA group. On the 16th day of pregnancy， the LPS group received intraperitoneal injection of LPS （200 μg/kg） and the 4-PBA group received injection of 4-PBA （150 mg/kg）. In the LPS+4-PBA group， 4-PBA was intraperitoneally injected first， followed by LPS administration 1 h later. Serum total bile acid （TBA）， liver injury markers， bile acid profiles， and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice（P<0.05）， activated ERS markers and inflammatory factors， and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1（all P<0.05）. 4-PBA intervention effectively inhibited ERS， reduced TBA levels（P<0.05）， and upregulated Ntcp， Bsep， Mdr3， and Mrp3 gene expression（all P<0.05）. ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters， providing a theoretical basis for targeted therapy of ICP.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

AIM:To investigate the protective effects of Klotho protein against hypoxia/reoxygenation(H/R)-in-duced damage in rat cardiomyocytes,and to elucidate its underlying mechanisms.METHODS:Rat cardiomyocyte H9c2 cells were divided into 4 groups:control,H/R,low-concentration(1 μmol/L)Klotho+H/R,and high-concentration(10 μmol/L)Klotho+H/R groups.Cells were pretreated with Klotho at specified concentrations before induction of H/R injury.Flow cytometry was used to determine cardiomyocyte apoptosis rates,while reactive oxygen species(ROS)levels were measured using the DCFH-DA probe.Additionally,superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were assessed using biochemical assay kits.Mitochondrial membrane potential was evaluated using the JC-1 as-say,and activity of caspase-3 and caspase-9 was quantified.Western blot analysis was conducted to measure the protein expression of cytochrome C(Cyt-C),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in cardio-myocytes from each group.RESULTS:Compared with the control group,the H/R group exhibited significantly increased apoptosis rates(P<0.05),elevated ROS levels and MDA content,decreased SOD activity(P<0.05),reduced mitochon-drial membrane potential(P<0.05),increased caspase-3 and caspase-9 activity(P<0.05),decreased mitochondrial Cyt-C and Bcl-2 protein expression(P<0.05),and increased cytoplasmic Cyt-C and Bax protein expression(P<0.05).In comparison with the H/R group,both low-and high-concentration Klotho treatments significantly reduced cardiomyocyte apoptosis(P<0.05),lowered ROS levels and MDA content(P<0.05),increased SOD activity(P<0.05),restored mito-chondrial membrane potential(P<0.05),decreased caspase-3 and caspase-9 activity(P<0.05),increased mitochondrial Cyt-C and Bcl-2 expression(P<0.05),and decreased cytoplasmic Cyt-C and Bax expression(P<0.05).Notably,the high-concentration Klotho group demonstrated more pronounced protective effects(P<0.05).CONCLUSION:Klotho protein exerts protective effects against H/R-induced cardiomyocyte injury,possibly by inhibiting mitochondria-mediated apoptosis.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

AIM:To investigate the protective effects of Klotho protein against hypoxia/reoxygenation(H/R)-in-duced damage in rat cardiomyocytes,and to elucidate its underlying mechanisms.METHODS:Rat cardiomyocyte H9c2 cells were divided into 4 groups:control,H/R,low-concentration(1 μmol/L)Klotho+H/R,and high-concentration(10 μmol/L)Klotho+H/R groups.Cells were pretreated with Klotho at specified concentrations before induction of H/R injury.Flow cytometry was used to determine cardiomyocyte apoptosis rates,while reactive oxygen species(ROS)levels were measured using the DCFH-DA probe.Additionally,superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were assessed using biochemical assay kits.Mitochondrial membrane potential was evaluated using the JC-1 as-say,and activity of caspase-3 and caspase-9 was quantified.Western blot analysis was conducted to measure the protein expression of cytochrome C(Cyt-C),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in cardio-myocytes from each group.RESULTS:Compared with the control group,the H/R group exhibited significantly increased apoptosis rates(P<0.05),elevated ROS levels and MDA content,decreased SOD activity(P<0.05),reduced mitochon-drial membrane potential(P<0.05),increased caspase-3 and caspase-9 activity(P<0.05),decreased mitochondrial Cyt-C and Bcl-2 protein expression(P<0.05),and increased cytoplasmic Cyt-C and Bax protein expression(P<0.05).In comparison with the H/R group,both low-and high-concentration Klotho treatments significantly reduced cardiomyocyte apoptosis(P<0.05),lowered ROS levels and MDA content(P<0.05),increased SOD activity(P<0.05),restored mito-chondrial membrane potential(P<0.05),decreased caspase-3 and caspase-9 activity(P<0.05),increased mitochondrial Cyt-C and Bcl-2 expression(P<0.05),and decreased cytoplasmic Cyt-C and Bax expression(P<0.05).Notably,the high-concentration Klotho group demonstrated more pronounced protective effects(P<0.05).CONCLUSION:Klotho protein exerts protective effects against H/R-induced cardiomyocyte injury,possibly by inhibiting mitochondria-mediated apoptosis.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

Objective To summarize the experience of integrative palliative care at Peking Union Medi-cal College Hospital and provide a reference for promoting the integrative palliative care model.Methods Twenty cases receiving integrative palliative care at Peking Union Medical College Hospital were collected.The clinical characteristics,reasons for initiating integrative palliative care,the process of integrative palliative care,and feedback from these cases were summarized.Results Insomnia(11 cases,55％)and pain(9 cases,45％)were the most common symptoms requiring control in the 20 cases.The integrative palliative care team assisted in medical decision-making for 17 cases(85％),prepared end-of-life for 9 cases(45％),assisted in the transfer for 3 cases(15％),and provided comfort care for all the 20 cases(100％).Conclusions The integrative palliative care model can help alleviate suffering in end-of-life patients and provide support to patients'families and the original medical teams.This model is worth further promotion within class A tertiary hospitals.

Objective Aiming at the problems of many items and long time to fill in the Constitution in Chinese Medicine Questionnaire(CCMQ)when evaluating individual constitution,the research uses artificial intelligence technology to select attributes,and to help construct a short version of the CCMQ.Methods Analyzing the constitution data provided by the Physical Examination Department of Jiangsu Province Hospital of Traditional Chinese Medicine,there are specific target variables as the classification of constitution types.Feature selection of genetic algorithm,cross-validation and KNN classification algorithm are used as filters to select problems,and the effect is evaluated by problem subset size,KNN classification accuracy and filling time.Results The method selected a short version of the CCMQ with 31 problems,and the average classification accuracy in the model was 86.16%,and the time was improved by 47.7%.Conclusion The algorithm can effectively find a better problem subset,achieve dimensionality reduction and have certain accuracy,thus helping to simplify the CCMQ.