Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective To explore the difference of transfer RNA-derived small RNA(tsRNA)expression profile before and after acute myocardial infarction(AMI)and the diagnostic value of tsRNA for AMI.Methods Age-and weight-matched male C57 mice(8-10 weeks)were randomly divided into MI group and Sham group,with 4 in each group.AMI model was surgically induced in mice in MI group.After 24 h of modeling,RNA was extracted from left ventricular myocardial tissue.After removing modifications,total RNA of each sample was sequentially ligated to 3'and 5'small RNA adapters.Subsequently,reverse transcription PCR was performed.cDNA was then synthesized and amplified.The amplified products corresponding to the size of 15-40 nt RNA were screened to construct a library for sequencing.The sequencing results were compared with the mature tRNA and tRNA precursor sequences in GtRNAdb database.Differentially expressed tsRNA profiles before and after AMI were obtained.The alterations of the cleaved patterns of tRNA corresponding to the same codon before and after AMI were analyzed.According to the profile of differentially expressed tsRNA before and after AMI,tsRNA only abundantly expressed in MI group were selected and verified in myocardial tissue and plasma of mice to explore the potential of these tsRNAs as diagnostic markers of AMI.Results tsRNA profile showed good repeatability within the same group and great distinctiveness between the different groups.After AMI occurred,the cleaved patterns of a variety of tRNAs changed,including tRNA Asn-GTT,Glu-TTC,Gly-ACC,Gly-GCC,His-GTG,Ile-AAT,Ile-GAT,Pro-TGG,Ser-AGA,and Trp-CCA.Compared with the Sham group,268 tsRNAs significantly up-regulated and 1 228 tsRNAs down-regulated in MI group,and 64 tsRNAs were uniquely expressed in MI group.tRF-Gly-CCC-2-31,tiRNA-Val-CAC-1-32,tiRNA-Val-AAC-2-32,tiRNA-Glu-TTC-2-32,and tiRNA-Lys-TTT-1-34 were specifically expressed in cardiac tissue on the 1st day post AMI.Among them,tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 showed specifically abundant levels in plasma from MI group and dynamically changed with AMI duration.Conclusions The expression profile of tsRNA is significantly different before and after AMI.tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 are uniquely highly expressed in myocardial tissue and plasma from AMI mice,and might have the potential as diagnostic markers of AMI.

Objective:To explore and analyze the predictive value of EuroSCORE Ⅱ and SYNTAX Ⅱ scores for clinical outcomes in patients undergoing coronary artery bypass grafting (CABG) surgery.Methods:A total of 500 coronary artery disease (CAD) patients who underwent CABG in Shanxi Cardiovascular Hospital from April 2014 to July 2023 were selected as the study subjects, all patients were given EuroSCORE Ⅱand SYNTAX Ⅱ scores to evaluate the predictive value of EuroSCOREⅡfor perioperative mortality and SYNTAX Ⅱ for 4-year mortality. Univariate and multivariate Logistic analysis were employed to analyze the independent risk factors for perioperative and 4-year mortality.Results:There were 3 deaths during the perioperative period, with a mortality rate of 0.60%, the predicted mortality rate of EuroSCOREⅡwas 1.71%; there were 21 deaths at 4 years after surgery, with a mortality rate of 4.23% and the predicted mortality rate of SYNTAX Ⅱwas 9.02%. Logistic regression analysis showed that left ventricular ejection fraction (LVEF) was the only independent protective factor for perioperative mortality, and advanced age was the only independent risk factor for 4-year postoperative mortality in patients ( P<0.05). The analysis of the working characteristic curve of the subjects found that the area under the receiver operating characteristic curve ( ROC) of EuroSCORE Ⅱ for perioperative mortality was 0.782, and the area under ROC curve of SYNTAX Ⅱfor postoperative 4-year mortality was 0.743. Conclusion:Both EuroSCORE Ⅱand SYNTAX Ⅱhave certain predictive value for perioperative mortality and postoperative 4-year mortality in patients undergoing CABG, respectively, but the predicted mortality rate is relatively higher.

Objective:To investigate the risk factors of pleural effusion after spinal separation surgery for patients with spinal metastatic tumors.Methods:A total of 427 patients with spinal metastatic tumors from January 2014 to January 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. There were 252 males and 175 females, with an average age of 59±12 years (range, 15-87 years). All patients underwent separation surgery. Based on the chest CT within 1 month after surgery, the volume of pleural effusion was measured individually by reconstruction software. Pleural effusion was defined as small volume (0-500 ml), moderate volume (500-1 000 ml), and large volume (above 1 000 ml). Baseline data and perioperative clinical outcomes were compared between the groups, and indicators with statistically significant differences were included in a binary logistic regression analysis to determine the independent risk factors for the development of pleural effusion after isolation of spinal metastatic cancer. Receiver operating characteristic (ROC) curves were conducted to calculate the area under the curve (AUC) for each independent risk factor.Results:All patients successfully completed the operation. Among the 427 patients, there were 35 cases of large pleural effusion, 42 cases of moderate pleural effusion, and 350 cases of small pleural effusion. There were significant differences in tumor size (χ 2=9.485, P=0.013), intraoperative blood loss ( Z=-2.503, P=0.011), blood transfusion ( Z=-2.983, P=0.003), preoperative total protein ( Z=2.681, P=0.007), preoperative albumin ( Z=1.720, P= 0.085), postoperative hemoglobin ( t=2.950, P=0.008), postoperative total protein ( Z=4.192, P<0.001), and postoperative albumin ( t=2.268, P=0.032) in the large pleural effusion group versus the small and moderate pleural effusion group. Logistic regression analysis showed that decreased preoperative albumin ( OR=0.89, P=0.045) and metastases located in the thoracic spine ( OR=4.01, P=0.039) were independent risk factors for the occurrence of large pleural effusion after separation surgery. The ROC curve showed that the AUC and 95% CI for preoperative albumin, lesion location, and the combined model were 0.637 (0.54, 0.74), 0.421 (0.36, 0.48), and 0.883 (0.81, 0.92). The combined predictive model showed good predictive value. Conclusion:The volume of pleural effusion can be measured individually and quantitatively based on chest CT. Decreased preoperative albumin and metastases located in the thoracic spine are independent risk factors for the occurrence of large pleural effusion after separation surgery. The combined prediction of the two factors has better predictive efficacy.

Objective    To study the clinical characteristics of patients with partial and transitional atrioventricular septal defects (P/TAVSDs) in our hospital, and to evaluate the early follow-up outcomes from a real-world research perspective. Methods    The clinical data of all patients diagnosed with P/TAVSDs from January 1, 2018 to July 12, 2020, in our hospital were collected, and all patients' examination results were used as the real-world follow-up data, univariable Cox risk proportional model was used to analyze the outcomes. A total of 93 patients were finally included in the analysis, 72 with partial and 21 with transitional AVSD. There were 38 males and 55 females at age of 182.0 months (20.0 d to 779.5 months). Results    Univariable Cox proportional risk model suggested that at least one cardiac malformation (HR=15.00, 95%CI 3.00 to 75.00, P=0.001), preoperative moderate or greater mitral regurgitation (HR=6.60, 95%CI 1.70 to 26.00, P=0.007), and preoperative moderate or greater tricuspid regurgitation (HR=13.00, 95%CI 3.10 to 51.00, P<0.000 1) were  risk factors for moderate or greater postoperative atrioventricular valve regurgitation. Conclusion    Children with coarctation of the aorta or partial pulmonary vein connection, moderate or greater preoperative mitral regurgitation, and moderate or greater preoperative tricuspid regurgitation need to be alerted to the risk of moderate or greater postoperative atrioventricular valve regurgitation. Real-world data, with relaxed statistical P values and combined expertise, can suggest clinical conclusions that are close to those of high-quality retrospective studies.

Objective    To review the characteristics of patients who underwent atrioventricular septal defects (AVSD) repair with prosthetic valve ring implantation in our hospital, and to analyze the safety and effectiveness of this intervention. Methods    The clinical data of all patients diagnosed with AVSD who received surgery repair and prosthetic valve ring implantation from January 1, 2018 to July 12, 2020 in Guangdong Provincial People's Hospital were collected and analyzed. There were 22 patients with 9 males and 13 females at a median age of 35.00 (14.10, 53.00) years. There were 9 (40.9%) patients with prosthetic half or full rings placed on the left atrioventricular valve and 18 (81.8%) patients with prosthetic half or full rings placed on the right atrioventricular valve. Results    The median postoperative hospital stay was 7.00 (6.00, 8.80) d, and the postoperative mechanically assisted ventilation time was 11.00 (6.25, 19.00) h. There were 2 (9.1%) patients of moderate or higher postoperative atrioventricular valve regurgitation, 1 on the left and 1 on the right. There was one patient (4.5%) of the postoperative residual septal defect. There was no left ventricular inflow or outflow tract obstruction and no postoperative residual atrial septal defect during the follow-up of 152.00 (124.00, 1 030.00) d. Conclusion    Implantation of a prosthetic ring is safe and effective in patients with AVSD, and the structural strength of  the ring may be improved after the implantation. The physiological development of the AVSD annulus after prosthetic ring implantation and the results of long-term follow-up needs further attention.

Objective    To quest the risk factors of poor prognoses in children with tetralogy of Fallot (TOF) during perioperative period and evaluate its clinical application values. Methods    A retrospective analysis of the clinical data of 119 children who underwent one-stage correction of TOF in Guangdong Provincial People's Hospital from September 2016 to January 2019. The cohort includes 75 males and 44 females, with ages ranging from 3.2-137.1 (13.2±1.4) months and weights ranging from 4.6-21.0 (8.3±0.2) kg. Perioperative poor prognosis was defined as duration of mechanically assisted ventilation >48 h or secondary intubation, vasoactive-inotropic score (VIS) within 48 h >40, postoperative length of stay >14 d, and the occurrence of the major adverse events. Major adverse events were defined as early death, malignant arrhythmia, low cardiac output syndrome, non-fatal cardiac arrest, postoperative reintervention, diaphragm paralysis, and other clinical complications. Univariate and multivariate logistic analyses were used to analyze the correlation between risk factors and poor prognoses. Results    There was 1 perioperative death, and 9 with major adverse events. Variables selected by Least Absolute Shrinkage and Selection Operator (LASSO) included 2 preoperative variables (McGoon index, aortic root diameter index) and 4 intra-operative variables [left-right direction of bicuspid pulmonary valve, total length of right ventricular outflow tract (RVOT) incision index, pulmonary valve with commissurotomy, and minimum temperature in cardiopulmonary bypass (CPB)]. Univariate and multivariate logistic analyses were used to the above factors, respectively. The variables with statistical significance (P≤0.05) were McGoon index, aortic root diameter index, left-right direction of bicuspid pulmonary valve, and minimum temperature in CPB. A nomogram was established based on the above factors, and the results showed that the left-right direction of bicuspid pulmonary valve was more risky than the tricuspid pulmonary valve and the anterior-posterior direction of bicuspid pulmonary valve. The lower the McGoon index, the higher aortic root diameter, and the lower temperature in CPB, the higher risk of poor prognostic events in children with TOF. Conclusion    The left-right direction of the pulmonary bicuspid valve has a higher risk of poor prognosis than the tricuspid pulmonary valve and the anterior-posterior direction of bicuspid pulmonary valve. With the smaller McGoon index and the larger aortic root diameter, the risk of poor prognoses in children with TOF is higher. The temperature in CPB being lower than medium-low temperature obviously relates to the high incidence of poor prognostic events, which can be used as an auxiliary reference standard for decision-making in pediatric TOF surgery in the future.

Objective: To evaluate the role of tuberculin skin test prified protein derivative (PPD) in defining the screening scope of close contacts of tuberculosis cases in disposal of tuberculosis outbreak in schools. Methods: In a senior middle school in August 2019, 1 553 students of the grade two were tested by PPD because of a school tuberculosis outbreak. PPD results were compared to grade one students without any association with this tuberculosis epidemic, who were also tested by PPD when beginning school. Potential association between PPD distribution characteristics and tuberculosis case distribution were analyzed. Results: Twenty nine grade two students were diagnozed as tuberculosis infection, seven of which were PPD positive, and with the same MIRU-VNTR genotype. In grade one, 0.1 % (1/796) student showed strong PPD positive, 34.3% (273/796) student showed positive. For grade two students, significant higher rate of strong PPD positive [5.9% (45/757)], and PPD positive [52.0% (394/757)] were observed ( χ 2=45.71, 49.90, P <0.01). Proportion of strong PPD positive in the first floor of the teaching building ( 19.4 %), where tuberculosis cases clustered, was significantly higher than that in other floors ( χ 2=89.81, P <0.01); Number of strong PPD positive students increased with TB cases in each floor of the teaching building ( r =0.99, P <0.01). Proportion of strong PPD positive and PPD positive in floors of the dormitory, where TB cases lived, was significantly higher than in other floors ( χ 2=49.4, 64.9 , P <0.01). Number of strong PPD positive and PPD positive students increased with TB cases in each floor of the teaching building ( r =0.84, 0.56, P <0.01). Conclusion Strong PPD positive rate well reflects tuberculosis infection of close contacts, and is recommended for defining the scope of screening.

Objective:To investigate the epidemiological characteristics of human coronavirus (HCoV) in hospitalized children with respiratory tract infection in Hebei region, providing evidence for the diagnosis and prevention of children with respiratory tract infection.Methods:A retrospective study was conducted on 1 062 HCoV positive children hospitalized for respiratory tract infection in Children′s Hospital of Hebei Province from January 2015 to December 2020, aged from 33 days to 14 years, with a median age of 2 years. 27 932 (60.9%) were males and 17 944(39.1%) were females. And the gender, ages, seasonal distribution, HCoV-positive rates, co-detection distribution and clinical diagnosis of HCoV positive cases were analyzed by SPSS 25.0. Enumeration data were expressed by frequency and percentage; categorical variable were compared by the Pearson χ 2test. Results:The overall HCoV-positive rate was 2.31% (1 062/45 876), which was 2.37% (662/27 932) in male children and 2.23% (400/17 944) in female children. There was no statistically significant difference between genders (χ2=0.916, P=0.339). Children at age groups<1 years (2.44%) and 1-<3 years (2.63%) had higher HCoV-positive rates than those at age groups 3-<5 years (1.97%) and ≥5 years (1.38%) (χ2=27.332, P<0.01). The HCoV-positive rates from 2015 to 2018 were 2.13%, 2.45%, 2.28% and 2.23%. The HCoV-positive rate of 2019 (1.71%) was significantly lower than in 2016 (χ2=12.05, P<0.01), 2017 (χ2=7.34, P=0.01) and 2018 (χ2=6.78, P=0.01), but there was no significant difference compared with 2015 (χ2=2.84, P=0.09). The HCoV-positive rate of 2020 (3.37%) was significantly higher than in 2015 (χ2=13.636, P<0.01), 2016 (χ2=11.099, P<0.01), 2017 (χ2=15.482, P<0.01), 2018(χ2=18.601, P<0.01) and 2019(χ2=45.580, P<0.01). The positive rate was highest in spring (March to May) in 2015 and 2017 to 2018. February to April and July to September of 2016 were the peak periods of positive detection. No obvious seasonal change was observed in 2019 and the HCoV-positive rate of 2020 was extremely low from January to July, following significantly increased from August to December. 26.37% (280/1 062) of HCoV were co-detected with other respiratory pathogens and the most frequently identified mixed detection was RSV. Three or more pathogens were detected in 7.34% (78/1 062) of the HCoV-positive samples. Bronchopneumonia and bronchiolitis were more frequently observed in the single HCoV positive (61.89% and 16.75%) children compared to co-detected children(34.29% and 9.64%)(χ2=63.394 and 8.228, P<0.01). However, compared to those with HCoV mono-detection, co-detected children were more likely to have severe pneumonia (4.6% and 47.14%) (χ2=280.171, P<0.01). Conclusions:HCoV is one of the respiratory pathogens in children in Hebei region and more prevalent in spring. The susceptible population of HCoV is mainly children under the age of 3 years old. HCoV often co-detects with other respiratory pathogens, and the co-infection is one of the risk factors of severe pneumonia in children with respiratory infection.