BACKGROUND:The self-renewal and multi-directional differentiation of pluripotent stem cells possess the potential to revolutionize people's understanding of biology,medicine,development,and disease.Stem cells play an important role in the early stage of embryonic development,and the study of them could be beneficial to understanding of the basic principles of biological development and tissue or organ formation,exploring the potential mechanisms of various diseases,studying the repair and regeneration of damaged tissues or organs,and promoting drug discovery and personalized treatment. OBJECTIVE:To review the research progress of pluripotent stem cells,summarize and categorize the fundamental types of pluripotent stem cells,and elucidate the lineage situations of various types of pluripotent stem cells in common mammals. METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched systematically,with the keywords"pluripotent stem cells;embryonic stem cells;induced pluripotent stem cells;expanded potential stem cells;livestock pluripotent stem cells"in English and Chinese.The 99 articles related to mammalian pluripotent stem cells were systematically screened according to inclusion and exclusion criteria,and then reviewed. RESULTS AND CONCLUSION:(1)According to classical theory in mouse embryonic stem cell research,the pluripotent state of stem cells is divided into two forms:na?ve and primed.Na?ve state corresponds to the inner cell mass of pre-implantation embryos before attachment to the uterine wall,while primed state corresponds to the epiblast after implantation.These two states exhibit significant differences in epigenetic features,transcriptional activity,external signal dependency,and metabolic phenotype.It is later discovered that there is an intermediate state between na?ve and primed called formative pluripotency.Therefore,the pluripotency of pluripotent stem cells is a continuous developmental process rather than a unique cell state.(2)In addition to obtaining pluripotent stem cells from the inner cell mass,there are various methods and lineages for acquiring pluripotent stem cells,including embryonic germ cells established using primitive germ cells from mouse embryos,induced pluripotent stem cells created by the dedifferentiation of adult mouse and human fibroblasts with four factors—Oct3/4,Sox2,c-Myc,and Klf4;embryonic stem cell-like cell lines cultured from somatic cell nuclear transfer,parthenogenesis,neonatal or adult testicular or ovarian tissue,very small embryonic-like stem cells derived from various adult tissues and expanded pluripotent stem cells derived from pre-implantation stages.These pluripotent stem cells all share the common characteristics of continuous self-renewal,expressing core pluripotency factors and possessing the ability to differentiate into the three primary germ layers.(3)Currently,pluripotent stem cells are being used for disease modeling to study the mechanisms of various diseases and develop new drugs.Simultaneously,scientists are attempting to use pluripotent stem cells to cultivate various tissues and organs,offering new possibilities for regenerative medicine and transplantation.However,the clinical application of pluripotent stem cells faces safety challenges,including issues of cell mutations and immune rejection.Continual improvement in the methods of generating pluripotent stem cells will make them safer and more efficient for clinical applications.(4)Based on the methods of obtaining and lineage establishment of pluripotent stem cells in mice and humans,various types of pluripotent stem cells have been established in livestock,including embryonic stem cells,induced pluripotent stem cells,germ lineages of pluripotent stem cells,and expanded potential stem cells.Research on livestock pluripotent stem cells opens up new avenues for animal reproduction,breeding,genetic engineering,disease modeling,drug screening,and the conservation of endangered wildlife.

In 1929, George Soulié de Morant and Paul Ferreyrolles co-authored their first acupuncture-moxibustion paper titled "L' Acuponcture en Chine vingt siècles avant J.-C. et la réflexothérapie moderne", greatly advancing the development of acupuncture-moxibustion in Europe. Their paper systematically explains the holistic view and the concept of yin-yang balance in traditional Chinese medicine, describes the techniques of acupuncture and moxibustion, innovatively classifies acupuncture-moxibustion as "reflexotherapy", organizes the effects of certain acupuncture points illustrated on human acupoint atlas; and for the first time, it summarizes the correspondence between acupuncture points and Weihe trigger points. In the historical background of the neo-Hippocratic movement, they used the existing theories at that time to explain acupuncture, and adopted the analogical medicine to explore the mechanisms of acupuncture-moxibustion, which gradually initiated the modern era of acupuncture-moxibustion in France. Such research method is conducive to reducing the unfamiliarity of acupuncture-moxibustion among westerners, deepening their understanding of its theories and therapeutic effect, and also integrating it with other medical research. It breaks through the limitations of traditional theories and obtains the self-improvement and progress.
Humans ; Moxibustion/history* ; Acupuncture Therapy/history* ; China ; History, Ancient ; History, 20th Century ; Acupuncture/history* ; Reflexotherapy/history* ; Acupuncture Points ; History, 19th Century ; Medicine, Chinese Traditional/history*

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.

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 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.

Objective To investigate the effects of early pulmonary rehabilitation training on lung function recovery,complication rates,and quality of life in patients who undergo thoracoscopic surgery.Methods A ran-domized controlled trial was conducted involving 132 patients who underwent thoracoscopic surgery between June 2020 and June 2023.Participants were randomly allocated to either an early pulmonary rehabilitation program(n=72)or a conventional rehabilitation program(n=60).The early intervention group commenced a staged rehabilitation protocol—including respiratory training and physical exercise—within 24 to 72 hours following surgery,whereas the conventional group received standard postoperative nursing care only.Outcomes measured included postoperative pulmonary function(FEV1,FVC),incidence of postoperative complications,length of hospi-tal stay,and quality of life scores(maximum score:40).These outcomes were compared between the two groups.Results On postoperative days 3 and 7,the early group showed significantly higher FEV1 values compared to the conventional group[(1.6±0.17)L vs.(1.3±0.21)L;(1.9±0.20)L vs.(1.6±0.11)L,respectively],as well as improved FVC measurements[(2.5±0.20)L vs.(2.1±0.14)L;(2.9±0.25)L vs.(2.3±0.23)L(all P＜0.05)].The early intervention group also demonstrated a significantly lower overall complication rate(14.3％vs.33.3％,x2=6.79,P=0.009),including reduced incidences of atelectasis(6.9％vs.20.0％,P=0.031)and pulmonary infection(4.2％vs.13.3％,P=0.044).Additionally,patients in the early group had a shorter average hospital stay[(8.4±1.2)days vs.(10.9±2.3)days,P=0.018]and reported higher quality of life scores[(35.6±3.7)vs.(30.8±4.5),P=0.032].No significant difference was observed between the two groups in terms of the overall incidence of adverse events(23.6％vs.31.7％,x2=1.07,P=0.301).Conclusions Early pulmonary rehabilitation significantly facilitates the recovery of lung function,reduces the incidence of postoperative complica-tions,enhances quality of life,and demonstrates a favorable safety profile among patients undergoing thoracoscopic surgery.Therefore,this intervention should be more broadly implemented in clinical practice to optimize postop-erative recovery outcomes.

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.

This study was aimed at investigating differentially expressed genes(DEGs)in Clonorchis sinensis(C.sinensis)meta-cercariae and newly excysted juveniles(NEJs)cultured in vitro for 1 hour or 3 hours,through transcriptomic analysis.Our objective was to explore the mechanisms underlying host invasion.Metacercariae were digested and isolated from Pseudorasbora parva infected with C.sinensis.The metacercariae excysted and developed into NEJs in vitro.Subsequently,the mRNA of metacercariae and NEJs cultured in vitro for 1 hour or 3 hours was extracted for transcriptomic sequencing analysis to screen for DEGs,and to conduct GO and KEGG analyses.A protein-protein interaction network(PPI)was constructed to identify hub genes.A total of 1 218 DEGs were de-tected.The main enriched GO terms of DEGs included transcription regulator activity and gated channel activity(primarily K+).The KEGG pathways significantly enriched in DEGs included cholesterol metabolism,lysosome,synthesis,secretion,and action of para-thyroid hormone.ZFAND4-2,BIRC6,and other genes were screened and identified as hub genes through PPI network analysis.Addi-tionally,abundant differential expression of cathepsin-related genes,including Cathepsin L and Cathepsin F,were observed before and after excystment in C.sinensis.Therefore,significant transcriptional level changes occurred in the metacercariae of C.sinensis be-fore and after excystation,and enrichment was observed primarily in signaling pathways,such as activation of growth and material me-tabolism,that regulate parasite growth and development.Meanwhile,biological events conducive to parasite invasion,migration,and adhesion were triggered.

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.