BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

Background and Aims:Acute pancreatitis(AP)is an acute inflammatory disease of the pancreas caused by abnormal activation of pancreatic enzymes.Although gallstones,hyperlipidemia,and alcohol use are the most common causes,a subset of patients develop AP secondary to rare etiologies that are often misdiagnosed or diagnosed late,leading to recurrence or inappropriate management.This study aims to summarize the clinical characteristics,diagnostic strategies,and treatment outcomes of four cases of AP caused by uncommon etiologies,supported by a literature review.Methods:Clinical data of 4 patients admitted to the Department of Hepatobiliary and Pancreatic Surgery,the Third Xiangya Hospital of Central South University,between November 2021 and September 2024,were retrospectively analyzed.Their etiological characteristics,diagnostic approaches,and treatment strategies were reviewed in combination with relevant literature.Results:The underlying causes of AP were intraductal papillary mucinous neoplasm,pancreatic neuroendocrine tumor,pancreatic ductal adenocarcinoma,and duodenojejunal intussusception.All cases initially presented as idiopathic AP.Three patients underwent definitive surgical treatment and recovered well,while one patient with pancreatic cancer received only palliative care due to delayed diagnosis and died three months later.Conclusion:AP secondary to rare etiologies often mimics common forms in clinical presentation but poses diagnostic challenges.For patients with recurrent or idiopathic AP,clinicians should emphasize etiological tracing and utilize advanced imaging and endoscopic modalities for early identification.Timely etiological intervention,particularly surgical management when appropriate,is essential for preventing recurrence and improving prognosis.

Background and Aims:Acute pancreatitis(AP)is an acute inflammatory disease of the pancreas caused by abnormal activation of pancreatic enzymes.Although gallstones,hyperlipidemia,and alcohol use are the most common causes,a subset of patients develop AP secondary to rare etiologies that are often misdiagnosed or diagnosed late,leading to recurrence or inappropriate management.This study aims to summarize the clinical characteristics,diagnostic strategies,and treatment outcomes of four cases of AP caused by uncommon etiologies,supported by a literature review.Methods:Clinical data of 4 patients admitted to the Department of Hepatobiliary and Pancreatic Surgery,the Third Xiangya Hospital of Central South University,between November 2021 and September 2024,were retrospectively analyzed.Their etiological characteristics,diagnostic approaches,and treatment strategies were reviewed in combination with relevant literature.Results:The underlying causes of AP were intraductal papillary mucinous neoplasm,pancreatic neuroendocrine tumor,pancreatic ductal adenocarcinoma,and duodenojejunal intussusception.All cases initially presented as idiopathic AP.Three patients underwent definitive surgical treatment and recovered well,while one patient with pancreatic cancer received only palliative care due to delayed diagnosis and died three months later.Conclusion:AP secondary to rare etiologies often mimics common forms in clinical presentation but poses diagnostic challenges.For patients with recurrent or idiopathic AP,clinicians should emphasize etiological tracing and utilize advanced imaging and endoscopic modalities for early identification.Timely etiological intervention,particularly surgical management when appropriate,is essential for preventing recurrence and improving prognosis.

Objective:To investigate the current situation and correlation between mental health and stressors of new professional master's degree graduates in clinical medicine, and to provide empirical support for improving student mental health.Methods:An online questionnaire survey was conducted among 3 587 fresh graduate students with master's degree in clinical medicine from 65 training institutions in China. SPSS 26.0 was used to compare and analyze the measurement data. Descriptive statistics were used to analyze the mental health using Symptom Checklist-90 (SCL-90) and the current status of stressors. The influence factors and correlation between mental health and stressors were analyzed by means of differentiation analysis and correlation analysis.Results:The SCL-90 overall mean score as well as the scores of obsessive-compulsive symptoms, interpersonal sensitivity, depression, terror, anxious, psychoticism, and hostility of new professional master's degree graduates in clinical medicine were all higher than the national norm ( P<0.05). Among the participants, 58.21% (2 088/3 587) exhibited varying degrees of symptoms listed in the SCL-90. Students from families with low per capita income and low parental education level have more prominent psychological problems. The top three stressors perceived were job seeking, research tasks, and self-ability. Students with positive SCL-90 symptoms reported significantly higher perceived stress in all three stressor dimensions compared to their symptom-negative counterparts ( P<0.001), indicating a significant correlation between mental health status and stressors. Conclusions:The mental health status of new professional master's degree graduates in clinical medicine is concerning and warrants focused attention from educational authorities, academic institutions, and families.

Objective:To understand the graduation destination of newly graduated medical master's students in China and analyze their employment status.Methods:A questionnaire survey was conducted on 15 942 medical master's students who graduated in 2023. Descriptive analysis, χ2 test, and Kruskal-Wallis rank-sum test were used to understand the current situation and differences in the graduation destinations, employment units, job positions, and starting salaries of different types of medical master's graduates. Results:The employment rate of medical master's graduates was 58.21% (9 280/15 942). In terms of graduation destinations, male graduates, professional degree holders, graduates from non-"Double First-Class" universities, and nursing majors had a high proportion of confirmed employment units. Male graduates, academic degree holders, graduates from "Double First-Class" universities, and basic medical science majors had a high proportion pursuing further studies domestically. In terms of employment, the highest proportion of medical master's graduates worked in hospitals (84.92%, 6 495/7 648) and the lowest proportion worked in primary-level medical and healthcare institutions (1.02%, 78/7 648). The majority (78.07%, 5 971/7 648) held professional technical positions. Starting salaries were relatively low and ranged between 3 001 and 5 000 yuan/month, accounting for 30.99% (2 370/7 648).Conclusions:The employment rate of medical master's graduates is low, with concentrated employment units and job positions, and there is a lack of talents in primary medical institutions. Colleges and universities and education management departments should adopt policy-driven approaches to support key demographic groups and encourage employment in primary healthcare. Training programs should be timely adjusted in response to market demands and focus on cultivating the comprehensive quality and job competence of medical master's graduates. Additionally, student-centered approaches should be used to strengthen the employment guidance and career planning services.

Objective:To prepare a novel ginseng polypeptide thermosensitive hydrogel,and to investigate its repair effect on heat-induced skin injury in the rats and explore the underlying mechanisms.Methods:Thermosensitive hydrogels were formulated using Pluronic F127 and β-sodium glycerophosphate(β-GP),and their phase transition temperatures,spatial structures,elemental compositions,and water retention capacities were evaluated.The rat models of heat-induced skin injury were established and the model rats were divided into PBS group,Gel group,and ginseng polypeptide gel(GP-Gel)group.After 11 d of treatment,the morphological changes of wound and collagen deposition in the wound of the rats in various groups were observed by HE and Masson staining.Immunohistochemistry was used to detect the expression levels of α-smooth muscle actin(α-SMA),connective tissue growth factor(CTGF),basic fibroblast growth factor(bFGF),proliferating cell nuclear antigen(PCNA),cell proliferation marker Ki67,epidermal growth factor(EGF),CD31,vascular endothelial growth factor(VEGF),P50 and P65 proteins in the skin wound tissue of the rats in various groups.Western blotting method was used to detect the expression levels of Toll-like receptor 4(TLR4)in the skin wound tissue of the rats in various groups.ELISA method was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-15(IL-15),and interleukin-10(IL-10)in the serum of the rats in various groups.Results:Compared with PBS and Gel groups,the wound area of the rats in GP-Gel group was reduced(P＜0.01),the expression levels of PCNA,Ki67,EGF,CD31,VEGF,α-SMA,and CTGF proteins in the skin wound tissue were increased(P＜0.05 or P＜0.01),and the expression levels of P65 and TLR4 proteins were decreased(P＜0.01);the level of anti-inflammatory factor IL-10 in serum was increased(P＜0.01),while the levels of pro-inflammatory factors TNF-α,IL-1β,IL-6 and IL-15 were decreased(P＜0.05 or P＜0.01).Conclusion:The ginseng polypeptide thermosensitive hydrogel promotes the repair of heat-induced skin injury by enhancing cell proliferation,collagen synthesis,angiogenesis,and reducing inflammatory responses.

OBJECTIVE: To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification. METHODS: A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband's father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c.728C>T variant of the TUBB8 gene, oocyte donation may be considered.
Humans ; Female ; Adult ; Mutation, Missense ; Oocytes/metabolism* ; Heterozygote ; Tubulin/genetics* ; Infertility, Female/genetics* ; High-Throughput Nucleotide Sequencing ; Pedigree

Objective:To investigate the impact of different etiologies on the spatial distribution pattern of infarcts and the mapping pattern of focal symptoms in acute ischemic stroke (AIS) using a population-based standardized spatial analysis of MRI.Methods:This was a cross-sectional study. Clinical [age, sex distribution, admission National Institutes of Health Stroke Scale (NIHSS) score and 90-day modified Rankin Scale (mRS) score at discharge, etc.] and imaging data of 2 610 patients with AIS attending 9 Medical Centers from January 2015 to December 2021 were retrospectively analyzed. All patients were categorized into 1 718 cases of large artery atherosclerosis (LAA) type, 335 cases of cardioembolism (CE) type, and 557 cases of small artery occlusion (SAO) type according to TOAST typing. All patients underwent diffusion-weighted imaging, and the detected infarct lesions were segmented and aligned to the standardized space using artificial intelligence-assisted methods, and the spatial distribution frequency heatmaps of lesion locations in patients with different TOAST subtypes were plotted and compared with each other by χ2 test. Lesion-symptom image brain maps with different clinical symptoms were further plotted, and differences of lesion-symptom image relationships among different TOAST subtypes were observed and compared with each other by interaction effect. Results:In all patients, the favored sites of infarct lesions were the bilateral middle cerebral artery region in the anterior circulation and the occipital and brainstem regions in the posterior circulation. Compared with the LAA type, the CE type lesions were more likely to occur in the anterior cerebral artery region, the occipital lobe, and the cerebellum posterior, while the SAO type lesions were more likely to occur in the perforator artery supply area. The lesion-symptom mapping results showed that AIS patients with infarct lesions in the frontoparieto-temporal region in the presence of a left middle cerebral artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the LAA type than for the CE type( P<0.05); AIS patients with infarcted lesions in the brainstem region and some cerebellar regions in the presence of vertebrobasilar artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the CE type than for the LAA type( P<0.05). Conclusion:At the population level, brain mapping reveals specific infarct distribution patterns and differences in lesion-symptom mapping patterns of different etiologies AIS patients, providing imaging evidence for the understanding of AIS pathogenetic mechanisms and clinical management.

Objective:This study aims to explore the predictive value of the ratio of caliceal pelvic height to infundibular length（CPH/IL）for the stone-free rate（SFR）in the treatment of lower calyx stones using flexible ureteroscopic lithotripsy（FURL）combined with a distally bendable negative pressure suction sheath.Methods:A retrospective analysis was conducted on the clinical data and anatomical parameters of 312 patients with lower calyx stones or combined lower calyx stones admitted to the Third Xiangya Hospital of Central South University from September 2022 to December 2023，all of whom were treated with FURL combined with a distally bendable negative pressure suction sheath. Stone clearance was defined as no residual stones or residual stones with a diameter of ≤3 mm without any symptoms. Patients were divided into the clearance group（265 cases，84.90%）and the non-clearance group（47 cases，15.10%）. There were no significant differences in gender（male/female：173/92 cases vs. 29/18 cases），age［（44.69 ± 13.14）years vs.（42.60 ± 10.93）years］，degree of hydronephrosis（no hydronephrosis/mild hydronephrosis/moderate to severe hydronephrosis：122/85/58 cases vs. 21/12/14 cases），side of lower calyx stones（left/right：157/108 cases vs. 31/16 cases），maximum diameter of stones（MDS）［（19.23 ± 6.41）mm vs.（17.77 ± 6.18）mm］，and CT value of stones［（993.46 ± 249.12）Hu vs.（1013.43 ± 300.90）Hu］between the two groups（ P > 0.05），indicating comparability between groups. There was no significant difference in the distance from the midpoint of the lower lip of the renal pelvis to the ureter at the lowest plane of the lower calyx（K-A line）between the clearance and non-clearance groups［（26.16 ± 5.18）mm vs.（25.70 ± 8.66）mm， P > 0.05］. However，significant differences were observed in the infundibulopelvic angle（IPA）［（53.97 ± 15.72）° vs.（37.43 ± 15.39）°］，infundibular length（IL）［（27.26 ± 5.11）mm vs.（33.04 ± 7.38）mm］，infundibular width（IW）［（8.27 ± 2.82）mm vs.（7.09 ± 3.20）mm］，caliceal pelvic height（CPH）［（19.96 ± 4.63）mm vs.（30.32 ± 7.56）mm］，ureter-lower calyx distance（ULD）［（23.00 ± 5.59）mm vs.（18.78 ± 6.31）mm］，CPH/IL ratio［（0.73 ± 0.11）vs.（0.92 ± 0.09）］，and curvature of the lower calyx of the renal pelvis［（0.06 ± 0.01）mm -1 vs.（0.08 ± 0.03）mm -1］between the two groups（ P <0.05）. Univariate and logistic multivariate regression analyses were used to identify the independent risk factors affecting the postoperative SFR of FURL-treated lower calyx stones and to assess the value of CPH/IL for SFR in the treatment of lower calyx stones using FURL combined with a distally bendable negative pressure suction sheath. A logistic multivariate regression model and a corresponding nomogram were constructed，and the predictive ability of the model for SFR was evaluated using the receiver operating characteristic（ROC）curve. The calibration curve and the Hosmer -Lemeshow test were used to assess the consistency and accuracy of the model. The clinical utility of the model was evaluated using decision curve analysis（DCA）. Results:Univariate analysis revealed that seven anatomical parameters differed significantly between the clearance and non-clearance groups（all P < 0.05）：infundibulopelvic angle（IPA， OR = 0.27，95% CI 0.17-0.42， P < 0.01），infundibular length（IL， OR = 2.52，95% CI 1.83-3.47， P < 0.01），infundibular width（IW， OR = 0.64，95% CI 0.45-0.90， P = 0.011），caliceal pelvic height（CPH， OR = 5.78，95% CI 3.67-9.10， P < 0.01），ureter-lower calyx distance（ULD， OR = 0.43，95% CI 0.30-0.63， P < 0.01），CPH/IL ratio（ OR = 13.62，95% CI 6.86-27.03， P < 0.01），and curvature of the lower calyx of the renal pelvis（ O = 3.15，95% CI 2.08-4.78， P < 0.01）. Multivariate logistic regression further identified CPH/IL（ OR = 9.87，95% CI 4.92-19.79， P < 0.01），IPA（ OR = 0.41，95% CI 0.23-0.71， P = 0.001），and ULD（ OR = 0.50，95% CI 0.29-0.87， P = 0.014）as independent risk factors influencing the stone-free rate after flexible ureteroscopic lithotripsy combined with a distally bendable negative-pressure suction sheath. The area under the ROC curve（AUC）of the univariate regression model showed that for IPA，the AUC was 0.788（95% CI 0.711-0.864）；for IL，it was 0.731（95% CI 0.643-0.819）；for ULD，it was 0.677（95% CI 0.586-0.767）；for CPH，it was 0.867（95% CI 0.804-0.929）；for IW，it was 0.628（95% CI 0.535-0.721）；for CPH/IL，it was 0.906（95% CI 0.850-0.961）with an optimal cutoff value of 0.882，corresponding to a sensitivity of 83.02% and a specificity of 92.08%；and for curvature of the lower calyx of the renal pelvis，it was 0.744（95% CI 0.662-0.827）. The AUC of the multivariate regression model was 0.929（95% CI 0.884-0.974）with an optimal cutoff value of 0.364，corresponding to a sensitivity of 82.98% and a specificity of 95.09%. Calibration curves demonstrated close agreement between the predicted and actual stone-free rates after FURL（C-index = 0.921）. The Hosmer-Lemeshow goodness-of-fit test indicated no significant discrepancy between predicted and observed probabilities（ P = 0.135，>0.05）. Decision-curve analysis further revealed that basing clinical decisions on the model ，s predicted probability yields a higher net clinical benefit than either withholding FURL for all patients or treating all patients regardless of risk，and it also outperforms strategies guided by any single independent predictor alone. Conclusions:IPA，IL，IW，CPH，ULD，CPH/IL ratio，and curvature of the lower calyx of the renal pelvis can all predict the postoperative SFR of FURL combined with a distally bendable negative pressure suction sheath for the treatment of lower calyx stones to varying degrees. Among them，CPH/IL has the highest predictive value. When CPH/IL >0.88，it may be difficult to use FURL to treat lower calyx stones.