Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Purpose/Significance Taking Jiashan county's chronic disease management mode based on blockchain as an example,new strategies for chronic disease management under the integrated county medical community mode are discussed.Method/Process U-sing the PEST-SWOT analysis method,the paper analyzes the strengths,weaknesses,opportunities and threats of the chronic disease management mode based on blockchain in Jiashan county from 4 aspects:politics,economy,society,and technology.Result/Conclu-sion The chronic disease management mode based on blockchain technology can ensure seamless connection and sharing of data,guaran-tee the security and traceability of patients'personal information and health records,and promote the common development of blockchain technology and chronic disease management in Jiashan county.

Objective:To prevent postoperative myocardial oedema or other causes of acute heart failure in congenital cardiac disease,anticipating delay sternal closure may reduce the number of children requiring cardiopulmonary resuscitation after surgery.The aim of this study was to describe the rate of delay sternal closure after surgery for congenital cardiac disease and to analyse the risk factors that may be associated with it.Methods:We retrospectively reviewed all surgeries with extracorporeal circulation in the cardiothoracic surgery intensive care unit of Shanghai Children's Medical Center in the past five years,from September 2014 to December 2018.The study cohort was divided into the delay sternal closure group (n=418) and the control group (routine chest closure,n=12 188) according to whether a delay sternal closure was applicated.Risk factors associated with delay sternal closure were identified by multivariate Logistic regression analysis.Results:A total of 12 606 cases were eligible,of which 418 (3.32%) were in the delayed sternal closure group.The most common cardiac diagnosis in the delayed sternal group was transposition of the great arteries (26.8%,112/418),whereas the most common cardiac diagnosis in the control group was ventricular septal defect (45.9%,5 599/12 188).All-cause mortality in children in the delayed sternal closure group was 3.3% (14/418) compared with 0.4% (46/12 188) in the control group,with a statistically significant difference ( P<0.05).Multivariate Logistic regression analysis showed that the need for delayed sternal closure were associated with age ( OR 0.164,95% CI 0.079-0.338, P<0.001),positive intropic support before surgery ( OR 0.42,95% CI 0.252-0.699, P=0.001),sex（ OR 0.742，95% CI 0.648-1.098， P<0.05），mean body weight（ OR 1.192，95% CI 1.078-1.318， P<0.001），positive intropic support before surgery（ OR 0.370，95% CI 0.252-0.699， P<0.001），complicated surgery ( OR 0.241,95% CI 0.159-0.367, P<0.001) and extracorporeal circulation diversion time ( OR 6.412,95% CI 4.339-9.475, P<0.001). Conclusion:Delayed sternal closure is an important management strategy for congenital cardiac surgery in infants and children.Delayed sternal closure is associated with age，sex,mean body weight at the time of surgery,positive intropic support before surgery，complicated surgery and extracorporeal circulation diversion time.

Objective:To evaluate the consistency between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) in the measurement of body composition in children aged 6-17 years in China.Methods:Fat-free mass, fat mass and fat mass percentage were measured by both BIA and DXA in 1 161 children. t-test or Wilcoxon paired test was used to evaluate the different outcome of the two methods. The correlation and consistency between the methods were evaluated by Spearman correlation coefficients ( r) and Bland-Altman analysis. Results:Body compositions measured by BIA was positively correlated with those measured by DXA (fat mass r=0.95, fat-free mass r=0.98, fat mass percentage r=0.86, all P<0.05). Comparing with DXA, BIA underestimate children's fat mass [the mean difference is -3.15 kg, and the SD is 2.35 kg, 95% limits of agreement (LoA): -7.74-1.45 kg] and fat mass percentage (the mean difference is -8.45%, and the SD is 4.63%, 95% LoA: -17.53%-0.64%). Conclusions:Body compositions measured by BIA was highly positively correlated with those measured by DXA. BIA has certain application value in the measurement of body fat mass and fat-free mass of children aged 6-17 years.

【Objective】 To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. 【Methods】 The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. 【Results】 From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. 【Conclusion】 The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.

Objective:To evaluate the clinical feasibility, safety, and advantages of small lateral cervical incision for parathyroid exploration and resection.Methods:A total of 31 consecutive patients who underwent parathyroidectomy with a small lateral cervical incision, in the Department of Endocrinology and Breast Surgery of the First Affiliated Hospital of Chongqing Medical University from Apr. to Nov. 2021, including 11 males and 20 females, aged (49.32±13.79) years, ranging from 28 to 86 years, were selected to make retrospective statistical analysis of the surgical time, hospital stay, intraoperative blood loss, postoperative drainage and postoperative complications of the patients. All patients were injected with carbon nanoparticles suspension injection guided by color ultrasound to locate the enlarged parathyroid gland before surgery. EXCEL 2019 software was used for statistical analysis.Results:Thirty-one patients underwent parathyroidectomy through a small lateral cervical incision. Primary hyperparathyroidism was performed in 19 cases (including 2 cases with bilateral small lateral cervical incision, 2 cases with unilateral excision of thyroid mass combined with parathyroidectomy, 1 case with resection of huge parathyroid adenoma, and 1 case with local anesthesia) . Twelve patients with secondary hyperparathyroidism underwent total parathyroidectomy through bilateral small lateral cervical incision and forearm autogenous parathyroid transplantation (including bilateral thyroid mass resection combined with bilateral total parathyroidectomy and forearm autogenous parathyroid transplantation in 2 cases, local anesthesia and cervical plexus nerve block in 2 cases, and ectopic parathyroid gland in thyroid in 1 case) . Among them, the average operative time of patients with primary hyperparathyroidism was (54.74±27.71 & 74.14±31.73) min, the average intraoperative blood loss was (8.11±5.05 & 14.43±10.94) ml, the average postoperative drainage was (14.37±24.64 & 26.36±32.87) ml, the average postoperative parathyroid hormone was (11.59±16.46 & 26.65±56.38) pg/ml, the average hospital stay was (10.00±5.09 & 10.96±4.55) d, and the postoperative complication rate was (3.2% & 0%) .Conclusions:Parathyroid gland exploration and resection through small lateral cervical incision is a safe and effective surgical method and can also complete thyroid exploration and parathyroidectomy at the same time. Appropriate anesthesia should be selected after a full assessment of the patient’s basic condition.

Objective: To investigate the prevalence and associated factors of congenital heart defects (CHD) among nursery, primary, and middle school students in Zhaotong, and to provide basis for CHD prevention strategies for children and adolescents. Methods: Using stratified random cluster sampling, a total of 11 343 nursery, primary and middle school students in 4 towns of Zhaotong were investigated with CHD screening and questionnaire during September to November in 2020. Results: The prevalence of CHD among nursery, primary and middle school students in Zhaotong was 11.99‰(95% CI =9.99‰-13.99‰), Yongshan County (14.90‰) > Yanjin County (10.22‰), rural (13.30‰) > urban (8.21‰)( χ 2=4.95, 4.77, P <0.05). Among 136 cases of CHD, the Ventricular Septal Defect (VSD) accounted the highest proportion (41.2%), followed by Atrial Septal Defect (ASD, 32.4% ), Patent Ductus Arteriosus (PDA, 14.0%), and Complex Congenital Heart Disease (CCHD, 5.9%) and the other CHD (others, 6.6%). The proportion of late diagnosed CHD was 50.74%, which was associated with living in rural areas of Yongshan County, low annual household income (10 000-<20 000 yuan), as well as isolated and uncomplicated CHD( OR =0.30, 0.13, 3.67 , 0.17, P <0.05). Conclusion Nursery, primary and middle schools students have the characteristics of high prevalence rate of CHD, large proportion of complex congenital heart disease, large number of late diagnosis and complex influencing factors in Zhaotong. It s in urgent need of strengthening learning prevention of CHD.

Objective:To analyze the risk factors of performing diaphragm plication(DPL) after congenital heart disease(CHD) surgery as well as the timing and clinical efficacy.Methods:Data regarding children underwent open heart surgery at Shanghai Children′s Medical Center from January 2017 to December 2019 were reviewed.According to whether DPL was performed after CHD operation or not, the children were divided into DPL group and non-diaphragm plication(NDPL)group.Clinical data including age, surgery, cardiopulmonary bypass(CPB)temperature and time of two groups were compared, meanwhile the risk factors of DPL surgery were analyzed.Based on the median of 8 days between open heart surgery and DPL, children in DPL group were divided into early surgery group(less than 8 days), and delayed operation group(no less than 8 days). The parameters of comparison included ventilator using time, hospital stay time, hospitalization expenditure, postoperative infection to evaluate the timing of DPL and effect.Results:There were 10 309 children after CHD, including 95 in DPL group and 10 214 in NDPL group.In DPL group, there were 52 males(54.7%) and 43 females(45.3%), with age 147(52, 318) d, weight(5.5±4.1) kg, height(56.8±25.6) cm, CPB time(136.8±93.4) min and aortic occlusion time(62.5±50.2) min.Compared with NDPL group, DPL group had younger age, shorter height, lighter weight, higher incidence of preoperative special treatment, higher proportion of reoperation, lower CPB temperature, longer CPB time and longer aortic occlusion time.There were significant differences between two groups( P<0.05). Multivariate Logistic regression analysis showed that younger operative age( OR=0.998, 95% CI 0.998~0.999, P<0.001), staging operation( OR=72.977, 95% CI 39.096~136.211, P<0.001), long CPB time( OR=1.006, 95% CI 1.002~1.011, P=0.008), and pulmonary venoplasty( OR=4.219, 95% CI 2.132~8.350, P<0.001) were independent risk factors for DPL after CHD.Early surgery group had lower postoperative infection rate(43.59% vs. 88.38%, P=0.007), shorter ventilator duration[168.0(99.5, 280.5) h vs.309.9(166.2, 644.5) h, P=0.029], shorter hospital stay duration[27.00(20.75, 35.00)d vs.37.00(28.00, 53.00)d, P<0.001], and lower hospitalization cost[158.36(128.99, 203.11) thousand yuan vs.232.95(174.54, 316.47) thousand yuan, P<0.001] than delayed operation group. Conclusion:Younger age, staging operation, long CPB time, and pulmonary venoplasty are independent risk factors for DPL due to diaphragmatic paralysis after pediatric CHD surgery.Early surgical intervention is beneficial for the recovery of children.