Malignant gastrointestinal tumors （GT） mainly include laryngeal cancer， esophageal cancer， gastric cancer， pancreatic cancer， hepatocellular carcinoma， bile duct cancer， and colorectal cancer. At present， the morbidity and mortality of GT are high. Tumor immune escape is one of the key reasons for cancer development and treatment failure， and it is also the main direction of current tumor immunotherapy research. Traditional Chinese medicine （TCM） plays a role in treating GT and alleviating systemic symptoms， especially showing potential advantages in regulating the immune escape mechanism. This article elaborates on the immune escape mechanism of GT and systematically reviews that TCM active components or compound prescriptions act on key immune checkpoints such as programmed cell death protein-1 （PD-1） and programmed cell death ligand-1 （PD-L1） to reduce the proportion of marrow-derived suppressor cells （MDSCs）， promote the polarization of M1 macrophages， activate effector immune cells， enhance CD8⁺ T cell recruitment and interferon （IFN）-γ secretion， enhance the killing activity of natural killers （NKs）， and reduce foxhead box protein P3（FoxP3⁺）-positive regulatory T （Treg） cell infiltration. TCM active components or compound prescriptions can remodel the tumor microenvironment （TME）， such as improving immunosuppressive factors， promoting vascular normalization， and regulating intestinal microbiota. Through the regulation of TME， enhancement of antigen presentation， inhibition of immune checkpoint molecules， regulation of cellular network factors and metabolites， etc.， TCM active components or compound prescriptions enhance the immune function， thereby inhibiting the immune escape of GT. This paper summarizes and reflects on the research results of TCM in regulating immune escape to treat GT in recent years， aiming to help transform TCM from empirical medication to precision treatment based on immune regulation， reduce drug resistance and enhance treatment effect.

Objective To evaluate the inhibitory effects of prophylactic administration of α-zearalanol(α-ZAL)on bone microarchitecture and bone resorption activity in ovariectomized osteoporotic rats,and to investigate its regulatory effects on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods A total of 606-month-old unmated female Sprague-Dawley(SD)rats weighing(300±20)g were randomly divided into the sham surgery group(Sham group),ovariectomy group(OVX group),solvent group(Oil group),estradiol benzoate treatment group(Post-E2 group),α-ZAL prevention group(Pre-ZAL group),and α-ZAL treatment group(Post-ZAL group),with 10 rats in each group.An osteoporosis rat model was established using the ovariectomy method.Rats in the Sham group underwent the same surgical procedures except for ovarian removal.Seventy-two hours after ovarian removal,the Oil group received intramuscular injections of 0.5 mL of oil solvent,and the Pre-ZAL group received intramuscular injections of α-ZAL(1.5 mg·kg-1),administered every 3 days for 120 consecutive days.The Post-E2 group and Post-ZAL group began intramuscular injections of estradiol benzoate(1.5 mg·kg-1)and α-ZAL(1.5 mg·kg-1),respectively,90 days after ovariectomy,administered every 3 days for 120 consecutive days.After drug administration,bone density and bone tissue microstructure morphology were analyzed using a micro-CT small animal in vivo imaging system and staining methods.Osteoclasts were isolated and their activity was detected.Femoral BMSCs were obtained to assess their osteoblast and adipocyte differentiation capabilities,and uterine tissue morphological changes were observed via histological sections.Results Compared with the OVX group,BMD in the Sham group,Post-E2 group,Pre-ZAL group,and Post-ZAL group increased by 133.12%,75.97%,69.64%,and 24.69%,respectively(all P<0.01).BMD in the Pre-ZAL group was 36.09%higher than in the Post-ZAL group(P<0.01),and there was no significant difference in BMD between the Post-E2 and Pre-ZAL groups(P>0.05).Tb.N in the Sham group,Post-E2 group,Pre-ZAL group,and Post-ZAL group increased by 160.08%,118.14%,94.76%,and 46.76%,respectively,compared with the OVX group(all P<0.01).Tb.Ar increased by 324.21%,203.83%,177.99%,and 82.71%,respectively(all P<0.01).Tb.N in the Pre-ZAL group increased by 32.71%compared to the Post-ZAL group(P<0.05),while Tb.Ar increased by 52.15%(P<0.01).Tb.Sp in the Sham,Post-E2,and Pre-ZAL groups decreased by 58.53%,42.18%,and 35.61%,respectively,compared with the OVX group(all P<0.01).The MAR of the upper tibial cancellous bone in the Sham,Post-E2,and Pre-ZAL groups increased by 257.81%,156.72%,and 142.63%,respectively,compared with the OVX group(all P<0.01),BFR increased by 192.19%,137.23%,and 88.13%,respectively(all P<0.01).MAR and BFR in the Pre-ZAL group increased by 58.10%and 43.63%,respectively,compared with the Post-ZAL group(both P<0.01).There were no significant differences in MAR and BFR between the Post-E2 group and the Pre-ZAL group(P>0.05).MMP-9,TRAP,and CK mRNA expression was significantly downregulated in both the Post-E2 group and the Pre-ZAL group(P<0.01).The osteoblast differentiation capacity of BMSCs in the Post-E2 group and all Post-ZAL groups was enhanced,with a significant increase in the number of mineralized nodules,and the expression levels of OCN,COL1,and OPN mRNA were significantly increased(P<0.01),while the ability to differentiate into adipocytes was weakened.The number of intracellular lipid droplets in BMSCs was significantly reduced,the lipid droplet volume was smaller,and the expression levels of PPAR-γ2 and aP2 mRNA were decreased(P<0.05).There were no significant differences between the Post-E2 group and the Pre-ZAL group(P>0.05).There was no significant increase in body weight in the Post-E2,Pre-ZAL,and Post-ZAL groups,but uterine weight significantly increased in the Post-E2 group(P<0.05),with marked uterine epithelial hyperplasia.Uterine weight in the Pre-ZAL and Post-ZAL groups showed no significant difference compared to the OVX group(P>0.05),and no significant changes were observed in uterine epithelium.Conclusion α-ZAL can effectively protect bone mass,improve bone microstructure,and reduce estrogen-related uterine adverse reactions by regulating the osteogenic/adipogenic differentiation balance of BMSCs,providing a potential new therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis.

Objective In this study,clinical data of Alzheimer's disease(AD)patients,structural magnetic resonance imaging(sMRI)data,and positron emission tomography(PET)data were used to construct an auxiliary diagnostic model with good classification effects,so as to formulate a personalized treatment plan at the early stage of the patients,which is of great significance for the prevention and treatment of AD.Methods In this study,a total of 401 study subjects containing complete sMRI images and PET images were selected from the ADNI-1(Alzheimer's disease neuroimaging initiative-1,ADNI-1)database.We used statistical parameters mapping(SPM)and voxel-based morphometric(VBM)analysis of MATLAB to perform pre-processing operations such as spatial normalization and skull stripping on sMRI images and PET images of the study subjects.With the help of the brain atlas was used to segment the brain tissue structure.After that,the segmented gray matter was extracted from the corresponding brain regions based on anatomical automatic labeling,and the feature values of all brain regions were obtained.Then the extracted brain region feature values are then subjected to fisher score,support vector machine-recursive feature elimination(SVM-RFE)and least absolute shrinkage and selection operator(LASSO),a hybrid filtered-wrapped-embedded feature selection method with three different principles,to realize the dimensionality reduction of high-dimensional image data.Finally,the PAC-Bayesian strategy boosting based multi-view learning(PB-MVBoost)model is constructed based on multi-view decision fusion for clinical,sMRI and PET data.And it is compared with the traditional machine learning models support vector machine(SVM),decision tree(DT),K-nearest neighbor(KNN),random forests(RF),adaptive boosting(AdaBoost),and extreme gradient boosting(XGBoost)which are constructed after concatenating views.It is compared with multi-view multi-kernel learning models(AverageMKL,EasyMKL)and multi-view confusion matrix boosting,which is also the same multi-view decision fusion.Results Among all the multi-view fusion models of AD-MCI,the PB-MVBoost model based on decision fusion has the best performance(accuracy=0.98,F1-score=0.97,precision=0.98,recall=0.96,MSE=0.07).Among all the multi-view fusion models of MCI-NC,the model performance of PB-MVBoost based on decision fusion was the best(accuracy=0.99,F1-score=0.98,precision=0.99,recall=0.98,MSE=0.05).Conclusion In the classification of AD-MCI and MCI-NC,the distinction and calibration degree of PB-MVBoost model were optimized,indicating that the auxiliary diagnosis model of Alzheimer's disease constructed by PB-MVBoost classifier based on decision fusion performed the best,which could improve the recognition of patients with mild cognitive impairment and then assist clinical diagnosis.

Objective In this study,clinical data of Alzheimer's disease(AD)patients,structural magnetic resonance imaging(sMRI)data,and positron emission tomography(PET)data were used to construct an auxiliary diagnostic model with good classification effects,so as to formulate a personalized treatment plan at the early stage of the patients,which is of great significance for the prevention and treatment of AD.Methods In this study,a total of 401 study subjects containing complete sMRI images and PET images were selected from the ADNI-1(Alzheimer's disease neuroimaging initiative-1,ADNI-1)database.We used statistical parameters mapping(SPM)and voxel-based morphometric(VBM)analysis of MATLAB to perform pre-processing operations such as spatial normalization and skull stripping on sMRI images and PET images of the study subjects.With the help of the brain atlas was used to segment the brain tissue structure.After that,the segmented gray matter was extracted from the corresponding brain regions based on anatomical automatic labeling,and the feature values of all brain regions were obtained.Then the extracted brain region feature values are then subjected to fisher score,support vector machine-recursive feature elimination(SVM-RFE)and least absolute shrinkage and selection operator(LASSO),a hybrid filtered-wrapped-embedded feature selection method with three different principles,to realize the dimensionality reduction of high-dimensional image data.Finally,the PAC-Bayesian strategy boosting based multi-view learning(PB-MVBoost)model is constructed based on multi-view decision fusion for clinical,sMRI and PET data.And it is compared with the traditional machine learning models support vector machine(SVM),decision tree(DT),K-nearest neighbor(KNN),random forests(RF),adaptive boosting(AdaBoost),and extreme gradient boosting(XGBoost)which are constructed after concatenating views.It is compared with multi-view multi-kernel learning models(AverageMKL,EasyMKL)and multi-view confusion matrix boosting,which is also the same multi-view decision fusion.Results Among all the multi-view fusion models of AD-MCI,the PB-MVBoost model based on decision fusion has the best performance(accuracy=0.98,F1-score=0.97,precision=0.98,recall=0.96,MSE=0.07).Among all the multi-view fusion models of MCI-NC,the model performance of PB-MVBoost based on decision fusion was the best(accuracy=0.99,F1-score=0.98,precision=0.99,recall=0.98,MSE=0.05).Conclusion In the classification of AD-MCI and MCI-NC,the distinction and calibration degree of PB-MVBoost model were optimized,indicating that the auxiliary diagnosis model of Alzheimer's disease constructed by PB-MVBoost classifier based on decision fusion performed the best,which could improve the recognition of patients with mild cognitive impairment and then assist clinical diagnosis.

Depression is a common chronic mental illness.Animal models of depression are widely used to study the pathogenesis of depression as well as in the development of new antidepressant drugs.The consistency and reliability of animal models of depression to simulate human depressive symptoms directly affect the study result.However,at present,no animal models have been found that are completely consistent with the onset of human depression,which hinders the in-depth study of depression.By using scientific and reasonable modeling and evaluation method,the pathological state of depression can still be simulated to a large extent,providing a basis for further in-depth research of the pathogenesis of depression and the development of effective antidepressant drugs.This paper aims to provide a reference for researchers by reviewing several commonly used animal models and behavioral tests of depression.

Objective:To build an internet hospital cost-benefit evaluation index system based on a large public tertiary hospital, for references for improving the operation and management of internet hospitals.Methods:From May to October 2024, this study identified the elements of cost-benefit through on-site investigation, literature analysis and expert discussion, and built an initial evaluation index system of cost-benefit of internet hospitals; Delphi method and Pareto chart method were used to determine indicators and their weights; This evaluation index system was used to quantitatively evaluate an internet hospital since its operation for two years (from May 2022 to April 2024).Results:Five profit entities and 26 cost-benefit components had been identified; The expert authority coefficient of the two rounds of Delphi method was 0.73, and the Kendall coefficient was 0.80 ( P<0.001). The costs and benefits of an internet hospital since its operation for two years were 14.06 million yuan and 134.95 million yuan, respectively, with a benefit cost ratio of 9.60. Conclusions:The cost-benefit evaluation index system of internet hospitals built in this study was suitable for these relying on physical hospitals. This system was scientific and practical, and could provide references for cost-benefit evaluation of other Internet hospitals.

Objective:To explore the incidence of delirium in patients of advanced age hospitalized in internal medicine departments and analyze its influencing factors.Methods:A retrospective analysis was conducted on the medical records of 586 patients of advanced age hospitalized in internal medicine departments at the Beijing University of Chinese Medicine Third Affiliated Hospital from May 2023 to May 2024. Patients were divided into a delirium group and a non-delirium group based on whether delirium occurred. Univariate analysis and binary Logistic regression analysis were used to explore the factors influencing delirium in patients of advanced age hospitalized in internal medicine departments.Results:Among 586 patients of advanced age hospitalized in internal medicine departments, the incidence of delirium was 21.2% (124/586). Binary Logistic regression analysis showed that age, activities of daily living (Barthel Index), folate deficiency, sleep disorders, and indwelling catheters were factors influencing delirium in patients of advanced age hospitalized in internal medicine departments ( P<0.05) . Conclusions:The incidence of delirium is high among patients of advanced age hospitalized in internal medicine departments. Healthcare professionals should pay particular attention to elderly patients with advanced age, limited activities of daily living, folate deficiency, sleep disorders, and indwelling catheters, and should implement targeted preventive strategies as early as possible.

Objective:To investigate the awareness levels of doctors from various departments regarding fertility preservation to provide reference and suggestions for further improving awareness and promoting multidisciplinary development in fertility preservation.Methods:From November to December 2023, the China Alliance of Fertility Preservation initiated this survey covering 88 hospitals in 23 cities across 20 provinces in China. The survey focused on the degree of understanding of basic concepts, technological perceptions, treatment concepts, and related challenges regarding fertility preservation. Descriptive statistics and Fisher's exact test were used to analyze the difference in awareness levels across various departments.Results:There was a significant difference in the awareness of fertility preservation guidelines among physicians from different departments ( P<0.001). Reproductive center physicians had the highest level of understanding [68.3% (41/60)]. Doctors in the reproductive centers had a higher awareness rate of the five fertility preservation techniques (ovarian tissue cryopreservation, oocyte cryopreservation, sperm cryopreservation, testicular tissue cryopreservation, and embryo cryopreservation) than that in other departments (all P<0.05). Regarding treatment concepts, more reproductive center physicians believed that psychological counselling about fertility preservation before oncological treatment was necessary ( P=0.016). Hematologists had more worries and concerns about fertility preservation treatment. Additionally, 96.7% (58/60) of reproductive center physicians expressed the need to establish effective referral mechanisms within the same city, province, or across provinces. However, 55.6% (35/63) of oncologists, 64.6% (31/48) of hematologists, and 77.8% (7/9) of pediatricians considered treating primary tumors far more important than fertility preservation. Conclusion:Doctors from different departments have varying levels of understanding regarding fertility preservation. It is necessary to strengthen the dissemination and training of fertility preservation knowledge among physicians from various departments, as well as to promote a multidisciplinary treatment model to improve efficiency, to establish a comprehensive referral mechanism to improve patients' opportunities for fertility preservation.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To investigate the effects of open reading frame 1 protein(ORF1p),encoded by long interspersed nuclear element-1(LINE-1),on the proliferation,migration,and invasion of esophageal squamous cell carcinoma(ESCC)cells,and explore the underlying molecular mechanism.Methods① Western blotting was performed to compare the expression of ORF1p between normal esophageal squamous epithelial cells and ESCC cells.② Immunohistochemistry(IHC)assay was used to examine ORF1p expression in ESCC tissues and paired normal tissues adjacent to tumor.③ The effects of ORF1p knockdown and overexpression on malignant behaviors in ESCC cells were determined through functional assays.④ Xenograft tumor model in nude mice was established to evaluate the impact of ORF1p on tumor growth in vivo.⑤ Transcriptome sequencing combined with cell functional rescue experiments were conducted to identify downstream targets regulated by ORF1p.Results ① Western blot analysis demonstrated the expression of ORF1p was significantly higher in the ESCC cell lines than the normal esophageal squamous epithelial cells(P<0.05).② IHC confirmed remarkable up-regulation of ORF1p in ESCC tissues than paired adjacent normal tissues(P<0.000 1).③ Functional assays and experiments on xenograft tumor models revealed that ORF1p substantially enhanced the proliferation,migration,and invasion of ESCC cells,as well as tumorigenic potential in vivo(P<0.05).④ Functional rescue experiments showed that ORF1p facilitated the proliferation,migration,and invasion of ESCC cells by modulating AJUBA expression(P<0.05).Conclusion ORF1p is significantly up-regulated in ESCC and promotes the proliferation,migration,and invasion of ESCC cells by regulating AJUBA expression.