BACKGROUND:Stem cells can promote nerve regeneration,repair damaged nerves,inhibit inflammation and apoptosis of nerve cells,and provide a new way for the treatment of Alzheimer's disease. OBJECTIVE:To make a bibliometrical analysis of the articles on stem cell therapy for Alzheimer's disease published internationally from 2004 to 2023,in order to reveal the research hotspot and trend of stem cell therapy for Alzheimer's disease. METHODS:From the Web of Science Core Collection database,by using Excel,VOSviewer,and Citespace software,the annual number of publications,countries,institutions,journals/co-cited journals,authors,and keywords of articles related to stem cells and Alzheimer's disease published from January 1,2004 to October 31,2023 were visually analyzed. RESULTS AND CONCLUSION:A total of 3 521 core papers were included,and the number of published papers increased year by year.The United States is the country with the most papers.Harvard Medical School is the most prolific institution.Maiese kenneth is the author with the most papers.International Journal of Molecular Sciences has the most papers in this field.The journal PLoS One published the most citations.At present,the field of stem cell therapy for Alzheimer's disease focuses on pathophysiological mechanism and animal experimental research,and"neurogenesis","oxidative stress","extracellular vesicles",and"mesenchymal stem cells"are the research trends in this field.Stem cell therapy for Alzheimer's disease has broad prospects.In the future,exchanges and cooperation between institutions and authors should be strengthened to further explore the main mechanism of stem cell therapy for Alzheimer's disease,solve possible clinical problems such as immune rejection,effectiveness,and safety,and further tap the potential of stem cells in the treatment of Alzheimer's disease.

As a new clinical trial mode,decentralized & digitalized clinical trial(DCT)is based on digital health equipment and uses internet and artificial intelligence technologies to complete the screening,registration,randomization,intervention,evaluation and follow-up of subjects,which is helpful to improve efficiency and reduce trial costs.The DCT mode has been applied to evaluate the treatment and management effects of cardiovascular diseases such as atrial fibrilla-tion,heart failure,coronary heart disease,and hypertension,showing broad development prospects and application space.This article will provide a brief introduction to representative DCT in the global cardiovascular disease field,and look for-ward to the application prospects of this model,providing reference and guidance for accelerating the development of cardio-vascular DCT in China.

Objective:To study the relationship between circulating inflammatory proteins and liver cancer by Mendelian randomization.Methods:Data from the genome-wide association study (GWAS) of 91 circulating inflammatory proteins were sourced from the GWAS Catalog, involving 14 824 participants of European ancestry from 11 cohorts. Summary statistics for liver cancer were obtained from the GWAS database, encompassing a total sample of 197 611 cases, a two-sample Mendelian randomization analysis was conducted to evaluate the relationship between 91 circulating inflammatory proteins and liver cancer. Among them, inverse variance weighting, weighted median method, MR-Egger, simple mode, and weighted mode were the main analysis methods. Using odds ratio (OR) values to evaluate the causal relationship between them. Cochran Q-test, MR-PRESSO, MR-Egger intercept, and "leave-one-out" analyses were used for sensitivity analysis. Reverse MR, MR-Steiger tests were employed to rule out the influence of reverse causality.Results:Among the circulating 91 inflammatory proteins, C-C motif chemokine 20 ( OR=1.28, 95% CI: 1.01-1.62), CD40 receptor ( OR=1.31, 95% CI: 1.00-1.28), fibroblast growth factor 21 ( OR=1.47, 95% CI: 1.18-1.83), glial cell line-derived neurotrophic factor ( OR=1.29, 95% CI: 1.08-1.54), interleukin-13 (IL-13) ( OR=1.24, 95% CI: 1.02-1.50), IL-20 levels ( OR=1.78, 95% CI: 1.30-2.44), IL-20 receptor subunit alpha ( OR=1.43, 95% CI: 1.06-1.93), and matrix metalloproteinase-10 ( OR=1.21, 95% CI: 1.04-1.39) have positive causal relationship with the occurrence of liver cancer. And IL-1 alpha ( OR=0.83, 95% CI: 0.71-0.96), IL-24 ( OR=0.68, 95% CI: 0.47-0.99), leukemia inhibitory factor ( OR=0.77, 95% CI: 0.60-0.98) and stem cell factor ( OR=0.87, 95% CI: 0.78-0.97) showed negative causal relationship with the occurrence of liver cancer. Heterogeneity tests for all 12 circulating inflammatory proteins revealed no outliers. Sensitivity analyses consistently demonstrated robustness, with no evidence of pleiotropy observed. Neither reverse MR nor MR-Steiger tests supported the existence of a reverse causal relationship between inflammatory proteins and liver cancer. Conclusion:The C-C motif chemokine 20, CD40L receptor, fibroblast growth factor 21, glial cell line-derived neurotrophic factor, IL-13, IL-20, IL-20 receptor subunit alpha, MMP-10, IL-1 alpha, IL-24, leukemia inhibitory factor, and stem cell factor may be causally related to the development of liver cancer.

Objective Based on the theory of Information-Knowledge-Attitude-Practice(IKAP),the reliability and validity of the discharge preparation scale for patients with diabetic foot(DF)was developed and tested,which is in accordance with the national conditions and disease characteristics of our country.Methods Based on the IKAP theoretical framework,articles were identified through literature analysis,qualitative interviews and Delphi method.After pre-investigation,a total of 483 patients with DF were selected from 3 general hospitals in Jiangxi province from June 2023 to February 2024.The items were screened by item analysis,and the reliability and validity were tested.Results The discharge preparation scale for patients with DF included 4 dimensions and 29 items.The Cronbach's α coefficient was 0.934;the scores of each dimension Cronbach's α coefficient ranged from 0.889 to 0.947;the overall split-half reliability was 0.966,and the split-half reliability of each dimension ranged from 0.901 to 0.952.A total of 4 common factors were extracted by exploratory factor analysis,and the cumulative contribution rate of variance was 68.074％.The x2/df value of confirmatory factor analysis was 1.906.The fitting fit of the model is suitable.The content validity was 0.973 at scale level and 0.875～1.000 at item level.Conclusion The reliability and validity of the discharge preparation scale for patients with DF are good,and it can be used as a tool to evaluate the discharge preparation for patients with DF.

This article reviews the construction methods, basic contents, advantages and disadvantages of the self-management assessment tools for patients with diabetic foot at home and abroad, which provides a reference for selecting the most appropriate assessment scale according to age groups and research purposes in clinical application, as well as developing and translating the rigorous, scientific, accurate and comprehensive patient self-management scale into Chinese according to different age groups and disease grades, which is consistent with China's national conditions. In order to improve the prognosis of patients with diabetic foot through personalized intervention based on the assessment results.

Objective:To investigate the current situation of satisfaction with graduate education among recent medical graduates in China, and analyze the differences between different populations, and to propose countermeasures and suggestions.Methods:From June to July 2023, a self-made questionnaire was used to survey 16 903 medical graduates who had recently earned a post-graduate degree from 78 institutions about their satisfaction with curriculum sessions, practical sessions, research training, tutoring, and institutional management. The degrees of satisfaction with education among different populations were compared through the t test and analysis of variance with the use of SPSS 26.0. Results:The scores of satisfaction of the graduates with tutoring, curriculum sessions, practical sessions, institutional management, and research training were 4.44, 4.03, 4.02, 3.90, and 3.82, respectively. Satisfaction scores for individual dimensions were significantly higher for males, doctors, non-transfers, comprehensive universities, non-agricultural household registration, moderate-to-high annual household income per capita, parents with high educational levels, and parents with mid- or senior-level occupations ( P<0.05). Conclusions:There is room for improvement in students' satisfaction with medical graduate education. To improve the quality of medical graduate education, attention should be paid to key populations, education policies, school management, and tutoring to provide appropriate education for different students.

Objective:To quantitatively evaluate the guidelines for hypertensive disorders of pregnancy (HDP) at home and abroad, and to provide a reference for the development of related guidelines in the future.Methods:Guidelines related to HDP published at home and abroad from 1 January 2018 to 31 December 2022 were retrieved from several databases, including CNKI, Wanfang Database, Yiigle, VIP Database, PubMed, Embase, and Web of Science with the terms of "hypertension in pregnancy", "hypertensive disorders of pregnancy", "pre-eclampsia", "eclampsia", and "guidelines". The retrieved guidelines were evaluated with the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) and Scientific, Transparent and Applicable Rankings (STAR) tool. According to the manual of AGREE Ⅱ two researchers graded the retrieved guidelines from six domains: scope and purpose, participants, rigor, clarity, applicability, and independence. Mean standardized score of each domain and the overall score were obtained. STAR tool was used to grade the guidelines by two researchers and one methodologist from 11 domains: registration, protocol, funding, working groups, conflicts of interest, clinical issues, evidence, consensus methods, recommendations, accessibility, and others.Results:A total of 19 related guidelines were included, covering six countries on three continents. The mean standardized scores of the 19 guidelines in the six domains of scope and purpose, participants, rigor, clarity, applicability, and independence using the AGREE II instrument were 73.98%, 63.16%, 59.98%, 66.37%, 56.36%, and 71.93%, respectively. Scores in the 11 domains of registration, protocol, funding, working groups, conflicts of interest, clinical issues, evidence, consensus methods, recommendations, accessibility, and others using the STAR tool were 0.00%, 0.00%, 76.15%, 39.87%, 58.92%, 65.19%, 60.80%, 49.78%, 78.95%, 30.89%, and 42.11%, respectively. According to the overall evaluation results, 12 guidelines were recommended and seven needed further modifications. It was found that most guidelines were unanimous in their recommendations on the prevention of preeclampsia with aspirin, medications for patients with severe hypertension, and the timing of pregnancy termination in preeclampsia patients, with the consensus rates of 10/13, 9/13, and 9/13, respectively. Besides, these recommendations were supported by substantial evidence.Conclusions:The overall quality of guidelines related to HDP at home and abroad is high, but there is still room for improvement. When developing relevant guidelines in the future, statisticians and methodologists should be included in the working groups to improve the evidence-based quality, and much attention should be paid to the disclosure of conflicts of interest guidelines. Registration and protocol are needed before publishing a guideline. The development of multiple versions for different users will conduce to improving the management of HDP.

Objective:To investigate the clinical efficacy of modified biliary-intestinal anasto-mosis by pancreaticoduodenectomy and influencing factors of postoperative biliary leakage.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopatholo-gical data of 165 patients with benign and malignant diseases around the ampullary who underwent pancreaticoduodenectomy in the Affiliated Hospital of Inner Mongolia Medical University from June 2014 to October 2020 were collected. There were 92 males and 73 females, aged (59±10)years. Of the 165 patients, 44 patients undergoing modified biliary-intestinal anastomosis within pancreatico-duodenectomy were divided into the modified group, and 121 patients undergoing traditional biliary-intestinal anastomosis within pancreaticoduodenectomy were divided into the traditional group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and postoperative situations; (3) analysis of influencing factors of biliary leakage after pancreaticoduodenectomy. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.05. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Univariate analysis was conducted using the corresponding statistical methods based on data type. All indicators in univariate analysis were included in multivariate analysis. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 165 patients, 72 cases were successfully matched, including 36 cases in the modified group and 36 cases in the traditional group, respectively. The elimination of jaundice, preoperative reduction of jaundice and hypertension confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. All patients in the two groups underwent surgery successfully. The operation time, postoperative pathological type (lower bile duct cancer, pancreatic head cancer, pancreatic cystic tumor, chronic pancreatitis, duodenal cancer), time of no drainage fluid in the drainage tube around biliary-intestinal anastomosis were 371(270,545)minutes, 6, 12, 1, 2, 15, (12±7)days in patients of the modified group, versus 314(182,483) minutes, 13, 14, 1, 4, 4, (16±8)days in patients of the traditional group, showing significant differences in the above indicators between the two groups ( Z=-3.54, χ2=10.01, t=-2.34, P<0.05). Cases with postoperative grade A biliary leakage was 0 in patients of the modified group, versus 6 in patients of the traditional group, showing a significant difference between the two groups ( P<0.05). Cases with postoperative grade B biliary leakage, cases with postoperative grade B pancreatic fistula, cases with postoperative bleeding, cases with abdominal infection, cases with incision infection, cases with delayed gastric emptying, cases undergoing unplanned readmission were 1, 0, 1, 4, 1, 5, 1 in patients of the modified group, versus 0, 1, 2, 5, 2, 5, 2 in patients of the traditional group, showing no significant difference in the above indicators between the two groups ( P>0.05). Cases with postoperative grade A pancreatic fistula, cases with overall complications, cases with Clavien-Dindo grade Ⅰ-Ⅱ complications, cases with Clavien-Dindo grade Ⅲ-Ⅳ complications were 6, 12, 6, 6 in patients of the modified group, versus 7, 14, 8, 6 in patients of the traditional group, showing no significant difference in the above indicators between the two groups ( χ2=0.09, 0.24, 0.36, 0.00, P>0.05). None of patient in the two groups had postoperative grade C biliary leakage and postoperative grade C pancreatic fistula. (3) Analysis of influencing factors of biliary leakage after pancreaticoduodenectomy. Results of multivariate analysis showed that preoperative reduction of jaundice and traditional biliary-intestinal anastomosis were independent risk factors for biliary leakage after pancreaticoduodenectomy ( odds ratio=11.37, 12.27, 95% confidence interval as 1.76-73.35, 1.14-131.23, P<0.05). Conclusions:Compared with traditional biliary-intestinal anastomosis, modified biliary-intestinal anastomosis within pancreaticoduodenectomy is safe and feasible. Preoperative reduction of jaundice and traditional biliary-intestinal anastomosis are independent risk factors for biliary leakage after pancreaticoduodenectomy.

Objective:To evaluate the role of long non-coding RNA (lncRNA) NORAD in ketamine-induced neurotoxicity in mouse hippocampal neurons and the relationship with endoplasmic reticulum stress.Methods:Primary mouse hippocampal neurons were isolated and cultured and then divided into 5 groups ( n=36 each) using a random number table method: control group (group C), ketamine group (group K), ketamine+ pcDNA3.1-NORAD plasmid group (group K+ NORAD), ketamine+ control plasmid group (group K+ NC), and ketamine+ NORAD+ tunicamycin group (group K+ NORAD+ TM). Group C was cultured with normal medium for 24 h. Group K was cultured with 40 μmol/L ketamine for 24 h. Group K+ NORAD was transfected with pcDNA3.1-NORAD overexpressing plasmid for 48 h, followed by treatment with 40 μmol/L ketamine for 24 h. Group K+ NC was transfected with pcDNA3.1 (+ ) plasmid for 48 h, followed by treatment with 40 μmol/L ketamine for 24 h. Group K+ NORAD+ TM was transfected with pcDNA3.1-NORAD overexpressing plasmid, 24 h later endoplasmic reticulum stress activator tunicamycin 1 μg/ml was added and the neurons were cultured for 24 h, and then ketamine 40 μmol/L was added and the neurons were cultured for another 24 h. Cell viability was detected by CCK-8 assay. The amount of lactate dehydrogenase (LDH) released was analyzed. Cell apoptosis was determined by TUNEL and flow cytometry methods. The NORAD expression was detected by real-time polymerase chain reaction. The expression of endoplasmic reticulum stress-related proteins protein kinase R-like ER kinase (PERK), phosphorylated PERK (p-PERK) and C/EBP homologous protein (CHOP) was detected by Western blot. Results:Compared with group C, the cell viability was significantly decreased, the amount of LDH released, percentage of apoptotic neurons and apoptosis rate were increased, NORAD expression was down-regulated, CHOP expression was up-regulated, and p-PERK/PERK was increased in group K ( P<0.05). Compared with group K, the cell viability was significantly increased, the amount of LDH released, percentage of apoptotic neurons and apoptosis rate were decreased, NORAD expression was up-regulated, CHOP expression was down-regulated, and p-PERK/PERK was decreased in group K+ NORAD ( P<0.05), and no significant change was found in the parameters mentioned above in group K+ NC ( P>0.05). Compared with group K+ NORAD, the cell viability was significantly decreased, the amount of LDH released, percentage of apoptotic neurons and apoptosis rate were increased, CHOP expression was up-regulated, and p-PERK/PERK was increased ( P<0.05), and no significant change was found in the NORAD expression in group K+ NORAD+ TM ( P>0.05). Conclusions:Over-expressed NORAD can alleviate ketamine-induced neurotoxicity in mouse hippocampal neurons via inhibition of the endoplasmic reticulum stress.

Objective:To grasp the distribution of fine antigenic epitope profiles of nucleoprotein (NP) and glycoprotein (GP) fragments of Crimean-Congo hemorrhagic fever virus (CCHFV) and to clarify the value of dominant antigenic epitopes in laboratory testing of Crimean-Congo hemorrhagic fever (CCHF).Methods:In a minimal synthetic short peptide consisting of 8 amino acids was segmentally expressed by CCHFV YL04057 strain using a modified bio-peptide synthesis method from 2014 to 2021 in the laboratory of Xinjiang University, College of Life Sciences. Using CCHFV polyclonal antibody or monoclonal antibody 14B7 (IgM) or CCHFV-positive sheep serum as antibodies, the minimal antigenic epitopes (BCEs) with antigenic activity on NP and GP fragments were identified by immunoblotting, and the obtained BCEs with sequence polymorphism were spatially clustered with CCHFV from different regions using the neighbor-joining method to determine the combination mode of BCEs with geographical correlation of regional distribution, to explore its application in establishing serological diagnosis. A prokaryotic expression plasmid (pET-32a), an E. coli expression plasmid (pGEX-KG) and a prokaryotic expression plasmid with an incomplete glutathione (GST188) tag (pXXGST-ST-1) were used to construct and express six dominant antigenic epitopes of different peptide lengths on NP fragments, and an indirect Enzyme-linked immunosorbent assay (ELISA) was established. CCHF sheep serum identified by immunofluorescence assay (IFA) was used as a control, and the specificity, sensitivity and overall compliance of the recombinant proteins with different peptide lengths of antigenic epitopes with IFA assay results were statistically analyzed. Results:CCHFV, NP and GP fragments had a total of 30 antigenically active BCEs, among which the core intermediate fragment NP2 (aa 170 th-305 th), which had a concentration of antigenic epitopes in the NP fragment, has 6 BCEs, and the NP1 (aa 1 st-200 th) and NP3 (aa 286 th-482 nd) at both ends have 9 BCEs; the Gc (aa 1 st-558 th) and Gn (aa 533 th-708 th) fragments of the GP fragment have 14 BCEs and a long antigenic peptide (AP) containing 15 amino acids, and the amino acid sequence homology of the NP fragment BCEs was 97.1% and that of the GP fragment BCEs was 89.1%. There was a significant difference ( P=0.0281, P<0.05). Among the 9 BCEs with sequence polymorphism in the GP fragment, 6 combined BCEs from GnEc1, GnE2, GnE4, GcE3, GcE6 and GcAP-4 (Ap) could cluster 15 CCHFV strains from different regions of the world into 5 geographical taxa, AsiaⅠ, AsiaⅡ, AficaⅠ, AficaⅡ and Europe. The constructs expressing PET-32a-NP (full length), PGEX-KG-NP2 (aa 170 th-305 th), pGEX-KG-NP2-1 (aa 235 th-275 th), PGEX-KG-NP2-1-1 (aa 237 th-256 th), pXXGST-1-NP2-1-2 (aa 250 th-265 th) and PGEX KG-NP2-1-3 (aa 260 th-276 th), six recombinant proteins CCHFV NP rabbit polyclonal antiserum (pAb) Western Blotting reaction positive, 33 sheep sera tested by IFA XHF as a reference, the sensitivity of the assay established by indirect ELISA using the recombinant proteins constructed from two fragments of NP2 and NP2-1 as antigens. The sensitivity, specificity and overall compliance were the best, with 73.4% (11/15) and 66.7% (10/15) for sensitivity, 100% (18/18) and 94.4% (17/18) for specificity, and 87.9% (29/33) and 81.8% (27/33) for overall compliance. Conclusion:CCHFV NP and GP are distributed with a high number of BCEs with antigenic immunoreactivity, among which the dominant antigenic epitopes are of high value in the laboratory serological diagnosis of CCHF.