Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective To investigate the mechanism of microRNA-214-3p(miR-214-3p)targe-ting CHUK to regulate the nuclear factor(NF)-κB pathway in modulating the chemosensitivity of lym-phoma cells to ibrutinib.Methods The half-maximal inhibitory concentration(IC50)was used to verify the ibrutinib-resistant cell model.The expression levels of miR-214-3p and CHUK mRNA in tissues and cells were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Western blotting(WB)was employed to assess CHUK protein levels.A dual-luciferase reporter assay was performed to confirm the direct targeting relationship between miR-214-3p and CHUK.Cell viability was measured using CCK-8 assay.Flow cytometry was used to evaluate cell apoptosis.The expression of the NF-κB p65 signaling pathway was detected by WB.Results The CHUK mRNA and CHUK protein expression levels were higher in ibrutinib-resistant cells than in control cells(P＜0.05).The qRT-PCR results showed that miR-214-3p was downregulated in ibrutinib-resistant cells.The dual-luciferase reporter assay confirmed that miR-214-3p directly targeted CHUK.Transfection of miR-214-3p mimics and knockdown of CHUK(si-CHUK)reduced the number of colony-forming cells,whereas transfection of miR-214-3p inhibitor increased the number of colony-forming cells(P＜0.05).Transfection of miR-214-3p mimics and knockdown of CHUK(si-CHUK)can promote apoptosis,while transfection of miR-214-3p inhibitor can inhibit apoptosis(P＜0.05).Inhibition of the NF-κB p65 pathway was observed in cells transfected with miR-214-3p mimics(P＜0.05).Conclusion MiR-214-3p may regulate the NF-κB p65 pathway by targeting the expression of CHUK,thereby enhancing the chemosensitivity of ibrutinib to lymphoma.

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To investigate the teaching effect of the single-circulation organ system integration course Nervous System and Disease for pediatrics 5+3 program, to guide the teaching practice of the integration course, and to promote the education and teaching reform of pediatrics.Methods:A total of 56 students of the class of 2019 in the pediatrics 5+3 program of Shanghai Jiao Tong University School of Medicine were selected as subjects, and the single-circulation organ system integration course was used for teaching. With the course of Nervous System and Disease as an example, evaluation results and questionnaires were used to assess the teaching effect of the single-circulation organ system course for pediatrics from the aspects of general information, course scores, student satisfaction, and expert supervision. SPSS 22.0 was used to perform descriptive statistics and analyses.Results:The course of Neurological System and Diseases integrated the contents of 11 related disciplines, with a mean score of (74.60±7.52) points. The scores of the students for course content, teaching mode, teaching resources, teaching effect, and the degree of overall satisfaction with the course were (4.71±0.54), (4.35±0.81), (4.50±0.69), (4.50±0.72), and (4.30±0.66), respectively. The score of expert supervision was (26.38±2.06) for teaching content and (26.52±2.03) for teaching methods, which still needed to be improved.Conclusions:The construction of the single-circulation organ system integration course provides new ideas for the curriculum reform of pediatrics; however, it is necessary to improve the construction of system and mechanism, explore the coordinated development of teachers, and strengthen deep integration and student guidance, thereby improving the teaching effect of the integrated course of pediatrics and promoting the training of medical talents in pediatrics.

Objective:To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice.Methods:This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3 rd and 4 th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification ( n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results:The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group ( P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550 ±23, 235 ±9, and 856 ±35, respectively, which were significantly higher than 188 ±14, 97 ±6, and 370 ±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively , P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups ( P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group ( P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group ( P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions:hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.

AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ

Medical homogenization in multi-campus hospital plays an essential role in leveraging the advantages of public hospitals, promoting the expansion of high-quality medical resources and balancing regional layout. The Second Affiliated Hospital Zhejiang University School of Medicine deeply used digital intelligence technology to build a new integrated mobile health service system consisting of internet hospital and 5G intelligent applications, which empowered medical efficiency in multi-campus hospital. This system broke the limitations of inconsistent medical resources, unbalanced discipline layout, and insufficient information connectivity in the construction of multi-campus hospitals, and achieved remarkable results in practice. It could provide reference for the multi-campus construction of other large public hospitals.