Constipation is a common functional gastrointestinal disorder with a global prevalence of approximately 10％to 20％.Its causes include functional disorders,organic diseases,and drug factors,with the majority being functional constipation.In recent years,driven by advancements in biomedicine,artificial intelligence(AI),and microbiome research,significant progress has been made in the diagnosis and treatment of constipation.This review systematically explores the latest developments in constipation treatment,including the role of the gut microbiota in constipation,the metabolic regulatory effects of short-chain fatty acids(SCFAs),the impact of mental factors on intestinal motility.Additionally,it discusses future development directions such as AI-assisted diagnosis,AI-based consultation systems,personalized microbiota transplantation,and minimally invasive neuromodulation,providing new insights for precision medicine in constipation.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Objective:To carry out a scoping review on eHealth literacy in patients with cardiovascular disease to sort out eHealth literacy from four aspects of concepts, assessment tools, influencing factors and interventions, with a view to informing future research and practice.Methods:Based on Arksey and O'Malley's framework for reporting scoping reviews, the literature on eHealth literacy in patients with cardiovascular disease was systematically searched in PubMed, Web of Science, Embase, Cochrane Library, CINAHL, China National Knowledge Infrastructure, VIP, Wanfang Data, and China Biomedical Database. The search period was from database establishment to May 3, 2024. Literature was screened, summarized and analyzed.Results:A total of 23 papers were included. The concepts and theoretical frameworks on eHealth literacy had their own focus, but no consensus was reached. The most commonly used tool to assess eHealth literacy in patients with cardiovascular disease was the eHealth Literacy Scale. The influencing factors included four aspects of demographic sociological and disease-related factors, psycho-cognitive factors, eHealth literacy knowledge and skills, and other factors. Interventions to improve eHealth literacy among patients with cardiovascular disease primarily included eHealth literacy training and use of portal-related digital toolkit.Conclusions:Currently there is no specific assessment tool for eHealth literacy for cardiovascular disease patients. In the future, eHealth literacy assessment tools need to be revised and improved according to the population characteristics and cultural background of cardiovascular disease patients. E-health literacy among patients with cardiovascular disease is at a moderately low level and is influenced by multiple factors. The influencing factors can be analyzed in depth through large-sample cross-sectional studies or longitudinal studies, and then a variety of intervention programs can be constructed at home or in the community with the help of multimedia and apps, with a view to improving the e-health literacy of patients with cardiovascular diseases.

Objective:To systematically analyze the prevalence and influencing factors of psychiatric comorbidities in refractory epilepsy (RE) .Methods:The literature on the prevalence and/or influencing factors of psychiatric comorbidities in adults with RE was electronically searched in China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database, PubMed, Web of Science, Embase, CINAHL, OVID, UpToDate, and Cochrane Library. The search period was from the establishment of the database to July 31, 2024. Two researchers independently conducted literature screening, quality assessment and data extraction, and used RevMan 5.4 for Meta-analysis.Results:A total of 11 papers were included, with a total sample size of 1 953 cases, with a prevalence of 52.00% (cross sectional studies) and 53.00% (cohort studies) . Gender [ OR=4.76, 95% CI (3.69, 6.15) ] , epilepsy disease perception [ OR=1.10, 95% CI (1.01, 1.19) ] , seizure type [ OR=1.63, 95% CI (1.23, 2.15) ] , seizure frequency [ OR=1.54, 95% CI (1.04, 2.29) ] , epileptogenic foci location [ OR=2.72, 95% CI (1.69, 4.37) ] , disease duration [ OR=1.76, 95% CI (1.39, 2.24) ] , and medication [ OR=3.26, 95% CI (2.09, 5.08) ] were the influencing factors of psychiatric comorbidity in RE. Conclusions:The prevalence of psychiatric comorbidities in patients with RE is high, and studies of influencing factors lack specificity. Clinical monitoring of this population should be strengthened, and relevant influencing factors should be comprehensively analyzed to provide intervention targets for early preventive management and to safeguard the long-term management of patients with epilepsy.

Objective:To analyze the risk factors for muscle cramps in maintenance hemodialysis patients and construct a nomogram prediction model.Methods:It was a retrospective cohort study. Patients undergoing regular hemodialysis at the Blood Purification Center of the Fourth Hospital of Hebei Medical University (West and East Campuses) from June 2023 to December 2023 were enrolled in this study. Patients were divided into a muscle cramps group and a non-muscle cramps group based on whether cramps occurred during or after dialysis. Patients from the West Campus were allocated to the training set, while those from the East Campus were assigned to the validation set, with an approximately 5∶1 ratio. Multivariate logistic regression analysis was used to identify risk factors for muscle cramps in the training set. A nomogram prediction model was constructed using R software. Model performance was evaluated using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis in both the training and validation sets.Results:A total of 498 maintenance hemodialysis patients were enrolled, including 409 in the training set (22.98% incidence of muscle cramps) and 89 in the validation set. Multivariate logistic regression analysis revealed that heart failure history ( OR=8.566, 95% CI 2.448-29.979, P=0.001), pre-dialysis corrected narrowed inferior vena cava width ( OR=0.531, 95% CI 0.433-0.650, P<0.001), increased ultrafiltration rate ( OR=1.002, 95% CI 1.001-1.003, P=0.002), decreased hemoglobin level ( OR=0.971, 95% CI 0.948-0.994, P=0.014), and decreased serum albumin ( OR=0.886, 95% CI 0.799-0.982, P=0.021) were independent associated factors for muscle cramps in the training set. The nomogram model based on these factors demonstrated an area under the ROC curve ( AUC) of 0.813 (95% CI 0.760-0.866, P<0.001) in the training set, with a Brier score of 0.129, indicating stable predictive performance. In the validation set, the area under of the ROC curve was 0.821 (95% CI 0.731-0.911, P<0.001) with a Brier score of 0.142. The decision curve showed that the model provided high clinical net benefit when the risk threshold probability for muscle cramps ranged from 0.22 to 0.77. Conclusion:Combined heart failure, narrowed inferior vena cava width, increased ultrafiltration rate, and decreased hemoglobin and serum albumin levels were the independent correlated factors for muscle spasm in maintenance hemodialysis patients. The nomogram model constructed based on these risk factors holds significant clinical value for predicting muscle cramps in maintenance hemodialysis patients.

Objective:To analyze the risk factors for muscle cramps in maintenance hemodialysis patients and construct a nomogram prediction model.Methods:It was a retrospective cohort study. Patients undergoing regular hemodialysis at the Blood Purification Center of the Fourth Hospital of Hebei Medical University (West and East Campuses) from June 2023 to December 2023 were enrolled in this study. Patients were divided into a muscle cramps group and a non-muscle cramps group based on whether cramps occurred during or after dialysis. Patients from the West Campus were allocated to the training set, while those from the East Campus were assigned to the validation set, with an approximately 5∶1 ratio. Multivariate logistic regression analysis was used to identify risk factors for muscle cramps in the training set. A nomogram prediction model was constructed using R software. Model performance was evaluated using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis in both the training and validation sets.Results:A total of 498 maintenance hemodialysis patients were enrolled, including 409 in the training set (22.98% incidence of muscle cramps) and 89 in the validation set. Multivariate logistic regression analysis revealed that heart failure history ( OR=8.566, 95% CI 2.448-29.979, P=0.001), pre-dialysis corrected narrowed inferior vena cava width ( OR=0.531, 95% CI 0.433-0.650, P<0.001), increased ultrafiltration rate ( OR=1.002, 95% CI 1.001-1.003, P=0.002), decreased hemoglobin level ( OR=0.971, 95% CI 0.948-0.994, P=0.014), and decreased serum albumin ( OR=0.886, 95% CI 0.799-0.982, P=0.021) were independent associated factors for muscle cramps in the training set. The nomogram model based on these factors demonstrated an area under the ROC curve ( AUC) of 0.813 (95% CI 0.760-0.866, P<0.001) in the training set, with a Brier score of 0.129, indicating stable predictive performance. In the validation set, the area under of the ROC curve was 0.821 (95% CI 0.731-0.911, P<0.001) with a Brier score of 0.142. The decision curve showed that the model provided high clinical net benefit when the risk threshold probability for muscle cramps ranged from 0.22 to 0.77. Conclusion:Combined heart failure, narrowed inferior vena cava width, increased ultrafiltration rate, and decreased hemoglobin and serum albumin levels were the independent correlated factors for muscle spasm in maintenance hemodialysis patients. The nomogram model constructed based on these risk factors holds significant clinical value for predicting muscle cramps in maintenance hemodialysis patients.

Objective:To provide reference for improving the ability of Investigator-Initiated Trials (IIT) research ethics review in the new era by analyzing the situation of clinical research projects and ethical review in hospitals under the increasingly standardized management requirements of clinical research.Methods:Taking the IIT projects reviewed by the Ethics Committee of our Institute from 2012 to 2023 as examples, the development trend, types, characteristics and the situation of ethical review were comprehensively compared and analyzed.Results:From 2012 to 2023, the number of IIT projects in our hospital increased rapidly, especially the multi-center and high-risk projects. IIT researches in the field of oncology and neurology are hot topics at present. After the addition of scientific review, the passing rate of ethical review increased. After the promulgation of the new regulations, the application rate of follow-up examination increased to a certain extent.Conclusions:In view of the current types and distribution characteristics of IIT, as well as key weaknesses in ethical review, the ethics Committee should strengthen the qualification management of main researchers and research teams, standardize the annual follow-up review of IIT research through multiple channels such as research ethics education and information platform, promote the establishment of the responsibility system of research liaison officers, and improve the review process of off-label drug use research. High-risk IIT projects should strengthen ethical supervision, case-by-case reporting and tracking system, and vulnerable groups projects should strengthen ethical review and supervision of informed consent process, and explore the establishment of a high-quality ethical management system from the above aspects.

BACKGROUND:In recent years,human pluripotent stem cell derived kidney organoids and rodent models of diabetic kidney disease have also made some progress.However,because the pathogenesis of diabetic kidney disease is affected by environmental factors and genetic factors,the pathogenesis is complex,and the clinical treatment for diabetic kidney disease patients needs to vary from person to person.Therefore,more flexible and integrated approaches need to be developed,leading to the discovery of strong preclinical evidence to support more targeted interventions in patients with diabetic kidney disease.OBJECTIVE:To reviewthe research progress of diabetic kidney disease model from the aspects of diabetic kidney disease animal model,two-dimensional cell culture simulation diabetic kidney disease model,and three-dimensional organoid diabetic kidney disease model,to provide clues and ideas for further research.METHODS:China National Knowledge Network and PubMed databases were searched with"diabetes,diabetic nephropathy,diabetic kidney diseases,diabetic nephropathy models,diabetic nephropathy animal models,organoids,diabetic and organoids,diabetic and kidney organoids,kidney organoids,diabetic nephropathy cell models,diabetic nephropathy syndrome combined animal models"as Chinese and English search terms.Totally 101 articles were finally included for review and analysis.RESULTS AND CONCLUSION:Both in vivo and in vitro models of diabetic kidney disease are powerful tools to further study the pathogenesis of diabetic kidney disease.The interactions between multiple systems can be observed in animal models.Two-dimensional cell culture is easy to operate and low cost.The emerging kidney organoids fill the gap between two-dimensional and global levels,without species differences,and simulate the complexity of human kidney to a certain extent.With the continuous development of organoid technology,kidney organoids are expected to provide a new perspective for exploring the pathogenesis,pathophysiology,and drug screening of diabetic kidney disease.

Objective:To explore the experiences of post-traumatic growth in patients with failed assisted reproductive technology (ART), providing a basis for individualized nursing interventions.Methods:This study was a qualitative study. From November to December 2023, purposive sampling was used to select ART failed patients at Reproductive Medicine Center of Affiliated Hospital of Nantong University as participants. Data was collected through semi-structured in-depth interviews, and Colaizzi 7-step analysis method was used to summarize and analyze the data and extract themes.Results:A total of 15 ART failed patients were included, their age was (31.8±3.6) years, years of infertility was (4.7±1.7) years. After analysis, a total of four themes and nine sub-themes were extracted, namely negative emotional experiences in the early stages of trauma (anxiety and depression, psychological stress) ; diversified support systems (family support, social support) ; positive coping styles (positive binary coping between spouses, individual coping) ; post-traumatic growth experiences (mobilizing one's own positive strength, strengthening altruistic awareness, and re-planning the future) .Conclusions:Infertility patients exhibit negative emotions after experiencing ART failure, but also experience post-traumatic growth. Medical and nursing staff should provide targeted guidance based on the psychological state of ART failed patients at different stages to improve their mental health.