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.

Objective:To construct pancreatic cancer cell lines expressing luciferase and mesothelin (MSLN), and evaluate the feasibility of using them as target cells in analyzing the cytotoxicity activity of immune cells.Methods:Lentiviral vectors expressing luciferase and MSLN genes were constructed, and pancreatic cancer cell lines were infected after lentivirus packaging. Single-cell clones were obtained by limited dilution following antibiotic screening, and the stable expression of the target genes were verified. These cells were used as target cells to detect the cytotoxicity of immune cells by real-time cell analysis (RTCA) and luciferase activity. Besides, these luciferase-expressing cells were transplanted into B-NDG mice to establish the animal models of pancreatic cancer, and in vivo optical imaging technology was used to detect the expression of luciferase and monitor the tumor growth in mice. The cytotoxicity of chimeric antigen receptor T (CAR-T) cells was verified in these animal models. Results:Three pancreatic cancer cell lines, panc-1-luc, panc-1-luc-MSLN and capan-2-luc, that could stably express luciferase and MSLN genes were successfully constructed. The expression of the reporter gene in these cells were high, and positively correlated with the number of cells. There were 95.6% of panc-1-luc-MSLN cells expressing MSLN. MSLN-CAR-T cells had specific killing effect on MSLN-positive panc-1-luc-MSLN cells and capan-2-luc cells, with the minimum killing rates of (70.00±18.19)% and (57.00±5.29)%, respectively. But they had no cytotoxicity to MSLN-negative panc-1-luc cells. RTCA results showed that MSLN-CAR-T cells were able to lyse all three pancreatic cancer cell lines, and the minimum killing rates were (56.33±7.64)%, (93.00±2.65)% and (26.33±28.15)%, respectively. The killing of target cells by NK-92MI cells was not depended on MSLN expression. The cytotoxicity in the mice models of pancreatic cancer was consistent with the results in vitro. The in vivo and in vitro test results suggested that the expression of luciferase by target cells could reflect the cytotoxicity of immune cells. Conclusions:This study establishes three pancreatic cancer cell lines stably expressing luciferase, which can be used to evaluate the cytotoxicity of immunotherapy products targeting tumor cells in vitro and in vivo.

Objective:To investigate the satisfaction levels of the rural elderly in Dafeng district of Yancheng, Jiangsu province with the contracted family doctor services, and to identify the factors that influence their satisfaction.The findings of this study will provide valuable insights for improving the quality of the contracted family doctor services offered to the rural elderly population.Methods:The study utilized the stratified cluster sampling method to select elderly individuals aged 60 years and above from Dafeng district, Yancheng city for a questionnaire survey.Specifically, the study focused on elderly individuals who had participated in contracted family doctor services for more than six months.The survey aimed to gather information on the elderly population's general situation, as well as their understanding, utilization, and satisfaction with contracted family doctor services.The satisfaction of contracted family doctor services was analyzed using the chi square test and multivariate Logistic regression to identify the influencing factors.Results:The study surveyed 385 elderly individuals from rural areas who had contracted family doctor services.The results showed that 88.3%(340/385)of respondents were satisfied with the services they received.Additionally, 99.2%(382/385)of those surveyed were aware of the contracted family doctor services, and 81.8%(315/385)had received basic medical services from their signed-up doctors.The results of a multifactor analysis that examined the factors influencing the overall satisfaction of elderly patients with their contracted family doctor services revealed several significant factors.Specifically, being female( OR=2.557, 95% CI: 1.122-5.830, P=0.026)and unmarried( OR=7.355, 95% CI: 1.850-29.237, P=0.005), supporting the contracted family doctor services system( OR=18.442, 95% CI: 1.732-195.973, P=0.016), believing that the contracted medical institutions had excellent hardware facilities( OR=9.918, 95% CI: 2.313-42.526, P=0.002)and providing high-quality health services for the elderly( OR=8.723, 95% CI: 1.556-48.908, P=0.014), as well as experiencing improved health status after signing the contract( OR=5.006, 95% CI: 1.764-14.201, P=0.002)were all significant factors influencing their satisfaction.These findings suggest that these factors are important considerations for improving the satisfaction of elderly patients with their contracted family doctor services. Conclusions:The contracted family doctor services provided in Dafeng district, Yancheng city have been well received by the rural elderly population.Factors such as gender, marital status, attitude towards the contracted family doctor services system, improvements in health status after contracting the service, quality of the hardware facilities at the contracted medical institution, and availability of health services specifically tailored for the elderly all play a role in determining the level of satisfaction among the contracted elderly population.To better serve the elderly population, it is crucial that we prioritize their needs.This can be achieved by improving the level of "suitable aging" in the contracted services and enhancing the satisfaction of family doctors who provide these services.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

We applied literature review and the Delphi method to develop technical operation of manual lactation technique. The databases and websites were systematically searched, such as UpToDate, the Cochrane Library, CNKI, VIP, Wanfang, and SinoMed. The evidence related to the technique was evaluated by Appraisal of Guidelines for Research and Evaluation (AGREE Ⅱ), and A Measure Tool to Assess Systematic Reviews 2 (AMSTAR 2). the included evidence was classified and summarized to form the preliminary draft of the technical operation specification. A total of 26 experts were selected to evaluate the draft, and some recommendations were deleted and modified according to the screening criteria and expert opinions, resulting in the final technical specifications for manual lactation technique applicable to health care professionals. The study included 4 guidelines, 5 expert consensus articles, 2 clinical decisions, and 3 systematic reviews, and the overall quality of the evidence was fair. A total of 26 questionnaires were collected in each of 2 rounds of expert consultation, with a 100% return rate and an overall authority coefficient of 0.91. The technical practice specification was formed in 11 aspects, including assessment content, indications, contraindications, operation methods, adverse events, and treatment methods, with a total of 50 recommendations. The technical operation specification is comprehensive, and the recommendations are clearly expressed, which is in line with the real clinical situation and can provide effective reference for the clinical practice of this technique.

Objective:To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice.Methods:A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode.Results:Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD ( P<0.05). Logistic regression analysis showed that visualization of pancreatic duct ( OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation ( OR=0.14), pancreatic atrophy ( OR=0.12) and external drainage ( OR=0.11) were protective factors for pancreatitis. Conclusion:In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.

As precious Chinese medicinal materials， Moschus and Bovis Calculus are often used in the treatment of acute and severe patients. However， due to their scarce sources and high prices， wild animal resources are in urgent need of protection， natural Moschus and Bovis Calculus can no longer meet the needs of preparation production. The use of substitutes such as Moschus Artifactus， Bovis Calculus Artifactus and Bovis Calculus Sativus has alleviated the shortage of original medicinal materials to some extent， and has been widely used in the production and use of traditional Chinese medicine （TCM） preparations. According to statistics， the 2020 edition of Chinese Pharmacopoeia contains 75 TCM preparations containing Moschus and 95 preparations containing Bovis Calculus， but in the quality standards of these 134 TCM preparations， the difference between natural medicinal materials and their substitutes is not very obvious， and some quality control projects are relatively simple. Based on this， the author intends to sort out the quality standards of TCM preparations containing Moschus or Bovis Calculus in the 2020 edition of Chinese Pharmacopoeia （volume Ⅰ）， including the type， drug form， prescription dosage， maximum daily （time） dosage and the quality control items of Moschus and Bovis Calculus in the preparation， in order to explore the rationality of the quality standard of TCM preparations containing Moschus or Bovis Calculus， and to give some suggestions on standardizing the use types of Moschus and Bovis Calculus， improving the quality control items of Moschus and Bovis Calculus in TCM preparations combining modern research achievements and advanced technology.

Objective:To investigate the clinicopathological features and prognosis of IgA nephropathy (IgAN) patients with gross hematuria.Methods:The clinical and pathological data of 490 primary IgAN patients admitted in the Affiliated Hospital of Qingdao University from January 2010 to June 2019 were analyzed. Patients were divided into gross hematuria group and non-gross hematuria group. The clinical and pathological features and prognosis were compared between the two groups. All patients were diagnosed by kidney biopsy, and followed up until June 30, 2020. Kaplan-Meier survival curve was used to examine the renal survival,and Cox regression model was used to analyze the risk factors affecting renal survival in two groups.Results:Among 490 patients there were 111 patients (22.7%) in the gross hematuria group and 379 patients (77.3%) in the non-gross hematuria group. Age, hypertension, 24-h urine protein, serum creatinine, blood uric acid, blood triglycerides, total blood cholesterol level, mesangial cell hyperplasia (M1), the proportion of renal tubular atrophy or renal interstitial fibrosis (T1/2) in gross hematuria group were lower than those in non-gross hematuria group ( P<0.05), while the estimated glomerular filtration rate (eGFR) in gross hematuria group was higher than those in non-gross hematuria group ( P<0.05). Four hundred and twenty six patients (86.9%) were followed up for at least 6 months, including 93 patients in gross hematuria group and 333 patients in non-gross hematuria group. There was no statistically significant difference in treatment method between the two groups ( P>0.05). The incidence of end-point events in non-gross hematuria group was higher than that in gross hematuria group [18.6%(62/333) vs. 6.5%(6/93), χ2=8.023, P<0.05]. Kaplan-Meier survival analysis showed that the cumulative renal survival rate of the gross hematuria group was higher than that of the non gross hematuria group (χ2=11.44, P<0.001). Multivariate Cox regression analysis showed that urine protein>1 g/24 h, eGFR<60 ml·min -1·(1.73 m 2) -1, hypertension, hyperuricemia and the elevated serum IgA/C3 were risk factors for renal survival [ HR(95% CI)=3.457(1.137-10.514),2.736(1.073-6.977),2.720(1.144-6.465),2.789(1.102-7.060),1.070(1.009-1.135), all P<0.05]. Conclusions:IgAN patients with gross hematuria has less severe kidney damage and higher cumulative renal survival rate than non-gross hematuria patients. Urinary protein>1.0 g/d, hypertension, hyperuricemia and the elevated serum IgA/C3 are risk factors for adverse end-point events, to which timely attention and corresponding treatment should be given.

OBJECTIVE：To explore th e applicatio n of team situatio nal simulation education and teaching mode in clinical pharmacy teaching. METHODS ：A total of 60 clinical pharmacy interns were selected as the research objects ，and course disease was type 2 diabetes mellitus. Thirty interns were randomly selected as control group ，using traditional teaching mode ；other 30 interns were selected as trial group ，which carried out team situational simulation education and teaching mode. The teaching effects were evaluated by using the satisfaction of interns to the two modes ，the comprehensive score of graduation examination and the self-evaluation of learning effect. RESULTS ：Compared with traditional teaching mode ，team situational simulation education and teaching mode was conducive to stimulate the learning interest of interns ，improve their interpersonal communication ability ， cultivate teamwork spirit ，improve the awareness of humanistic care ，and cultivate the professional attitude of clinical pharmacists （P＜0.05）. Compared with control group ，the comprehensive score of trial group was dominantly increased （P＜0.001），and the scores of professional quality ，humanistic care and communication skills in the trial group were significantly higher than control group（P＜0.01）. In terms of self-evaluation of learning effect ，except for the pathogenesis of type 2 diabetes and the commonly used treatment regimens ，the self-evaluation scores of the other items in trial group were significantly higher than control group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Team situational simulation education and teaching mode is superior to traditional teaching mode for clinical pharmacy teaching.

Objective:To explore the effect of nursing intervention based on the integration theory of health behavior change in pelvic floor muscle exercise of patients with pelvic floor dysfunction (PFD) after early cervical cancer surgery.Methods:A total of 134 patients with pelvic floor dysfunction after early cervical cancer surgery were selected and divided into test group ( n=67) and control group ( n=67) by random digits table method. The test group received three months of pelvic floor muscle exercise based on the theory of healthy behavior change. The control group received conventional pelvic floor rehabilitation care. The Pelvic Floor Distress Inventory-Short Form 20(PFDI-20), Pelvic Floor Impact Questionnaire-7(PFIQ-7), General Self-Efficacy Scale (GSES) and Social Support Rating Scale (SSRS) were evaluated before the intervention (T0), After one month of intervention (T1) and at the end of the intervention (T2). Results:The results of repeated measurement analysis of variance showed significant group/time interaction between PFDI-20 and PFIQ-7 scores ( Finteraction=29.196,13.213, both P<0.05); significant group/time interaction between GSES and SSRS scores ( Finteraction value was 25.664,70.240, both P<0.05). At the end of the intervention, the scores of PFDI-20 and PFIQ-7 in the test group were 66.54±14.04 and 73.20±7.41, which were lower than 77.47±15.91 and 78.39±8.51 in the control group over the same period. The difference was statistically significant ( t value was -4.216, -3.765, both P<0.01); the GSES and SSRS scores of the test group were 2.86±0.30 and 50.37±2.45, which were higher than the control group (2.51±0.34 and 46.42±2.82), the differences between the groups were statistically significant ( t value was 6.447, 8.662, both P<0.01). Conclusion:The nursing intervention plan based on the integration theory of health behavior change can significantly improve the self-efficacy, social support level and quality of life of patients with PFD after early cervical cancer surgery, and enhance the short-term and long-term pelvic floor rehabilitation effect of patients.