Objective: To explore the role and mechanism of epiregulin (EREG) in clear cell renal cell carcinoma (ccRCC)，and to find biomarkers and therapeutic targets for ccRCC. Methods: Based on the data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases，the correlation between the expression level of EREG in ccRCC tissues and the clinical staging and survival of ccRCC patients was analyzed. The samples of 6 ccRCC cases treated in the Second Affiliated Hospital of the Air Force Medical University were collected. The expression of EREG was confirmed with immunohistochemistry and quantitative real-time polymerase chain reaction (q-PCR). The effects of EREG overexpression on the proliferation，cell cycle and apoptosis of ACHN cells were verified with CCK-8 and flow cytometry. Finally，the expressions of EREG，epidermal growth factor receptor (EGFR) and the downstream pathway proteins were detected with Western blotting. Results: Based on the databases，it was found that the expression of EREG in ccRCC samples was higher than that in adjacent tissues，and there was a positive correlation with the clinical stage. Survival analysis showed that high expression of EREG was a risk factor affecting the prognosis. The results of immunohistochemical staining and qPCR revealed that EREG was highly expressed in ccRCC. Flow cytometry showed that EREG overexpression promoted the proliferation of ACHN cells，enhanced cell cycle，and inhibited apoptosis. In addition，Western blotting suggested that EREG promoted the expressions of EREG，EGFR and the downstream proteins. Conclusion: The expression of EREG is associated with the prognosis of ccRCC patients. In vitro cell experiments have shown that it can promote the proliferation of ccRCC cells and inhibit their apoptosis，thereby leading to the progression of ccRCC. It can serve as a potential biomarker for prognosis prediction and a drug development target for ccRCC patients.

Objective:To explore the relationship between medical students' sense of meaning in life and professional commitment, to analyze the mediating role of psychological resilience and the moderating role of social connectedness, and to provide suggestions for medical students' education.Methods:Questionnaires were administered to 899 medical students from four medical colleges and universities in Beijing, China using the Meaning in Life, Professional Commitment, Psychological Resilience, and Social Connectedness scales. Pearson correlation analysis was performed using SPSS 25.0 software, and the mediating role of psychological resilience and the moderating role of social connectedness were tested based on the Process plug-in.Results:The scores of medical students' sense of meaning in life, professional commitment, psychological resilience, and social connectedness were (44.87±8.64), (95.35±18.08), (89.25±15.16), and (28.31±11.25) points, respectively; there was a significant positive correlation between the four variables ( r=0.19-0.71, all P<0.01); the sense of meaning in life significantly and positively predicted medical students' professional commitment ( β=1.48, P<0.05); psychological resilience partially mediated the relationship between the sense of meaning in life and professional commitment, with the mediating effect accounting for 20.41% of the total effect; social connectedness played a moderating role in the "Psychological Resilience-Professional Commitment" pathway. Conclusions:The level of professional commitment of medical students is positively influenced by the factors of sense of meaning in life, psychological resilience, and social connectedness. Colleges and universities should pay attention to the influence of these factors and carry out targeted educational work.

Objective:To explore the relationship between medical students' sense of meaning in life and professional commitment, to analyze the mediating role of psychological resilience and the moderating role of social connectedness, and to provide suggestions for medical students' education.Methods:Questionnaires were administered to 899 medical students from four medical colleges and universities in Beijing, China using the Meaning in Life, Professional Commitment, Psychological Resilience, and Social Connectedness scales. Pearson correlation analysis was performed using SPSS 25.0 software, and the mediating role of psychological resilience and the moderating role of social connectedness were tested based on the Process plug-in.Results:The scores of medical students' sense of meaning in life, professional commitment, psychological resilience, and social connectedness were (44.87±8.64), (95.35±18.08), (89.25±15.16), and (28.31±11.25) points, respectively; there was a significant positive correlation between the four variables ( r=0.19-0.71, all P<0.01); the sense of meaning in life significantly and positively predicted medical students' professional commitment ( β=1.48, P<0.05); psychological resilience partially mediated the relationship between the sense of meaning in life and professional commitment, with the mediating effect accounting for 20.41% of the total effect; social connectedness played a moderating role in the "Psychological Resilience-Professional Commitment" pathway. Conclusions:The level of professional commitment of medical students is positively influenced by the factors of sense of meaning in life, psychological resilience, and social connectedness. Colleges and universities should pay attention to the influence of these factors and carry out targeted educational work.

BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.

Objective:To analyze the clinical phenotype, sperm morphological characteristics and assisted reproductive therapy efficiency in patients with total globozoospermia.Methods:Four male patients with total globozoospermia were collected during November 2019 to May 2022 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region. Peripheral blood samples were collected for genetic detection and the whole exome sequencing to explore the pathogenic genes. Semen characteristics, sperm morphology and ultrastructure were analyzed. Four patients were treated with intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation (AOA). Conventional ICSI cycles ( n=9) were selected as control group, and the development dynamic parameters were monitored by Time-lapse. The fertilization and embryo development parameters, developmental dynamic parameters and clinical outcomes were analyzed between the two groups. Results:Four patients were complicated with low sperm motility and increased sperm DNA fragmentation. Sperm morphology analysis and acrosome fluorescence staining represented that all the spermatozoas were with a small round head lacked of acrosome. By the transmission electron microscope, it was observed that round-headed spermatozoas were lacked of acrosome completely, loose chromatin structure, vacuolation and other abnormal changes in the head, mitochondrial sheath in neck were reduced arranged in disorder, and the structure of "9+2" of the flagellar axial filament was incomplete. Of the 4 patients, 1 was homozygous deletion of DPY19L2 gene and 1 was homozygous frameshift mutation of DPY19L2 gene. There were no significance differences in fertilization rate, two pronuclei fertilization rate, day 3 high-quality embryo rate, day 6 blastocyst formation rate and day 6 high-quality blastocyst formation rate between total globozoospermia group and control group (all P>0.05). The developmental dynamic parameters as the time at which the second polar body is extruded, the time when both (or the last) PN disappear, two to six discrete cells in the total globozoospermia group were significantly earlier than those in control group, and the difference was statistically significant (all P<0.05). There was no significant difference in the embryo cleavage patterns between the two groups ( P>0.05). Among the 4 patients with total globozoospermia, 2 live births with signal healthy male baby were achieved by fresh embryo transfer, and 2 live births with one signal healthy male baby and one healthy female baby were achieved by frozen-thawed embryo transfer respectively. Conclusion:Abnormal morphology characteristics of spermatozoas from patients with total globozoospermia are obvious, patients with total globozoospermia could have favorable clinical outcomes following ICSI combined with AOA.

Objective:To analyze the clinical phenotype, sperm morphological characteristics and assisted reproductive therapy efficiency in patients with total globozoospermia.Methods:Four male patients with total globozoospermia were collected during November 2019 to May 2022 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region. Peripheral blood samples were collected for genetic detection and the whole exome sequencing to explore the pathogenic genes. Semen characteristics, sperm morphology and ultrastructure were analyzed. Four patients were treated with intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation (AOA). Conventional ICSI cycles ( n=9) were selected as control group, and the development dynamic parameters were monitored by Time-lapse. The fertilization and embryo development parameters, developmental dynamic parameters and clinical outcomes were analyzed between the two groups. Results:Four patients were complicated with low sperm motility and increased sperm DNA fragmentation. Sperm morphology analysis and acrosome fluorescence staining represented that all the spermatozoas were with a small round head lacked of acrosome. By the transmission electron microscope, it was observed that round-headed spermatozoas were lacked of acrosome completely, loose chromatin structure, vacuolation and other abnormal changes in the head, mitochondrial sheath in neck were reduced arranged in disorder, and the structure of "9+2" of the flagellar axial filament was incomplete. Of the 4 patients, 1 was homozygous deletion of DPY19L2 gene and 1 was homozygous frameshift mutation of DPY19L2 gene. There were no significance differences in fertilization rate, two pronuclei fertilization rate, day 3 high-quality embryo rate, day 6 blastocyst formation rate and day 6 high-quality blastocyst formation rate between total globozoospermia group and control group (all P>0.05). The developmental dynamic parameters as the time at which the second polar body is extruded, the time when both (or the last) PN disappear, two to six discrete cells in the total globozoospermia group were significantly earlier than those in control group, and the difference was statistically significant (all P<0.05). There was no significant difference in the embryo cleavage patterns between the two groups ( P>0.05). Among the 4 patients with total globozoospermia, 2 live births with signal healthy male baby were achieved by fresh embryo transfer, and 2 live births with one signal healthy male baby and one healthy female baby were achieved by frozen-thawed embryo transfer respectively. Conclusion:Abnormal morphology characteristics of spermatozoas from patients with total globozoospermia are obvious, patients with total globozoospermia could have favorable clinical outcomes following ICSI combined with AOA.

Objective To study the pathogenesis,diagnosis and treatment of pancreatic portal hypertension (PPH).Methods The clinical data of 37 patients with PPH treated in Henan Province People's Hospital from January 2008 to January 2016 were retrospectively analyzed.Result Nine patients underwent conservative treatment and 28 patients underwent surgical treatment.No deaths were observed in the perioperative and follow-up periods.One patient underwent a second operation becausc of gastrointestinal bleeding.The clinical symptoms of the remaining patients were significantly relieved after surgery.Conclusions Treatment should be individualized and directed at the underlying cause.The anatomy of the coronary vein and the location of obstruction of the splenic vein determined the degree of the variceal veins and the surgical methods.Splenectomy was the basic treatment for PPH.Subcapsular splenectomy was effective in some challenging cases.

Objective To investigate dynamic changes and clinical significance of the high-sensitive Creactive protein(hs-CRP) level in acute cerebral infarction patients with different etiological types.Methods 136 patients with acute cerebral infarction were recruited.These patients were classified into five subtypes based on Trial of Org 10172 in Acute Stroke Treatment(TOAST) criteria.Serum hs-CRP levels on the 1st,3rd,5th,7th,14th day after onset from patients and 42 healthy controls were measured with immunoturbidimetry.The neurologic impairmentscore was determined with NIHSS.Results Serum hs-CRP levels is higher on the 1th,3rd,5th,7th,14th day than that of the control group ( (4.26 ± 1.31 ),( 12.57 ± 6.29 ),( 10.23 ± 4.49 ),(7.54 ± 2.33 ),(4.25 ± 1.77) mg/Land (2.56 ± 0.86) mg/L,t = 7.89,10.26,10.99,13.55,5.97,P ＜ 0.05 ).Among 5 subtypes,serum hs-CRP was the highest in large-artery atherosclerosis group after acute ischemic stroke,and cardioembolism group was the next.Serum hs-CRP reached the highest on three or five days after disease onset and decreased slowly.High levels of hs-CRP in large-artery atherosclerosis group indicated severe neurologic functional impairment and worsen prognosis.Conclusions ACI is closely related to serum hs-CRP level,which can be used as an subjective index for severity and prognosis with the lasting,high levels of hs-CRP levels predict poor prognosis.