ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A （IDH3A） on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers （n=10） and patients with heart failure （HF） （n=10）， and in the myocardium of mice subjected to transverse aortic constriction （TAC） surgery and sham operation， as well as in phenylephrine （PE）-induced neonatal rat ventricular cardiomyocytes （NRVCs）， was assessed by real-time quantitative polymerase chain reaction （RT-qPCR） and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity， IDH3A_D208A， was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype， ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid （AKG） on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay， respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients， in the myocardium of TAC-operated mice， and in PE-induced NRVCs （P = 0.005 2，P = 0.026 6，P = 0.041 3 and P = 0.006 6， respectively）. Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs （P < 0.000 1， P = 0.000 1 and P = 0.000 2， respectively）. The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs （P = 0.001 2 and P<0.000 1， respectively）， whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could， but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level， providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

Objective:To analyze the influencing factors of achieving textbook outcome (TO) after pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma, and to construct a nomograph model to explore its predictive value in TO.Methods:The clinical data of 205 patients with pancreatic ductal adenocarcinoma treated by PD in Henan University People's Hospital from January 2019 to December 2022 were analyzed retrospectively, including 88 males and 117 females with the age of (61.3±9.8) years old. Patients were divided into two groups based on whether they achieved TO after surgery: TO group ( n=113) and non-TO group ( n=92). Clinical data such as age, gender, intraoperative blood loss, operation time, blood transfusion volume, pancreatic CT value, and tumor differentiation degree were collected. Logistic regression analysis screened the influencing factors of PD postoperative TO and built a nomogram model. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. Results:Multivariate logistic regression analysis showed that the higher the degree of tumor differentiation was in patients with pancreatic ductal adenocarcinoma (high differentiation to medium differentiation: OR=7.20, 95% CI: 1.20-43.28; high differentiation to low differentiation: OR=16.55, 95% CI: 2.01-136.11), CT value>38.45 Hu ( OR=0.29, 95% CI: 0.13-0.65), blood transfusion volume ≤350 ml ( OR=8.05, 95% CI: 2.94-22.01) and operative time ≤407.5 min ( OR=10.88, 95% CI: 3.90-30.41), the easier it was to achieve TO after PD (all P<0.05). Based on the above influencing factors, a nomogram model of the postoperative effect of PD on TO was established, and the consistency index of this column graph model was 0.863 (95% CI: 0.816-0.911). The sensitivity and specificity of ROC curve were 0.804 and 0.752, respectively. The calibration diagram showed that the calibration curve fits well with the ideal curve, and the decision curve showed that the model had obvious positive net benefit. Conclusion:The degree of tumor differentiation, CT value, blood transfusion volume, and operation time are independent influencing factors for the achievement of TO after PD in patients with pancreatic ductal adenocarcinoma, and the nomogram model constructed based on which has good predictive performance for TO.

Objective:To analyze the effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) after laparoscopic radical resection.Methods:Clinical data of 165 patients with HCC undergoing laparoscopic radical resection in Henan University People's Hospital from January 2018 to December 2021 were retrospectively analyzed, including 122 males and 43 females, aged (55.5±11.4) years. Patients were divided into sarcopenia group ( n=79) and control group (non-sarcopenia, n=86) according to the skeletal muscle index. The survivals were analyzed using the Kaplan-Meier method, and were compared by the log-rank test. Univariate and multivariate Cox regression were utilized to analyze the effect of sarcopenia on the prognosis of HCC after laparoscopic radical surgery. Results:The 1- and 3-year cumulative survival rates of control group were 96.4% and 81.2%, which were higher than those of the sarcopenia group (83.2% and 48.9%, respectively, χ2=19.67, P<0.001). The 1- and 3-year recurrence-free survival (RFS) rates of control group were 88.4% and 66.1%, which were higher than those of sarcopenia group (70.9% and 37.7%, respectively, χ2=18.80, P<0.001). Multivariate Cox regression analysis showed that the risk of recurrence ( HR=1.35, 95% CI: 1.20-1.59, P<0.001) and the risk of death ( HR=2.21, 95% CI: 1.23-3.41, P=0.001) after laparoscopic radical resection for HCC in patients with sarcopenia rises compared to non-sarcopenic patients. Conclusion:Sarcopenia is a risk factor for the survival and recurrence of HCC after laparoscopic radical surgery.

Objective:To evaluate the preliminary effectiveness and safety of surgical peripheral iridectomy (SPI) combined with goniosynechilysis (GSL) and goniotomy (GT) in the treatment of advanced primary angle-closure glaucoma (PACG).Methods:A multicenter observational case series study was performed.Thirty-five eyes of 27 patients with advanced PACG, who underwent SPI+ GSL+ GT with a follow-up of at least 6 months, were included from August 2021 to January 2022 at Zhongshan Ophthalmic Center, Handan City Eye Hospital, Shijiazhuang People's Hospital, West China Hospital of Sichuan University, and the Third Affiliated Hospital of Chongqing Medical University.The mean follow-up time was 9(7, 10) months.Pre- and post-operative best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured with an ETDRS chart and a Goldmann applanation tonometer, respectively.The number of anti-glaucoma medications applied before and after surgery was recorded, and the complications after surgery were analyzed.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) and 20% reduction from baseline without anti-glaucoma medication or reoperation.Qualified success was defined as achieving criterion of complete success under anti-glaucoma medications.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2021KYPJ177). Written informed consent was obtained from each subject.Results:The mean preoperative IOP was (30.83±8.87)mmHg, which was significantly decreased to (15.69±3.70)mmHg at 6 months after the surgery ( t=8.588, P<0.001), with a 44.00% (34.78%, 60.00%) decline of 13.00(8.00, 21.00)mmHg.The median number of anti-glaucoma medications was significantly reduced from 2(0, 3) preoperatively to 0 (0, 1) postoperatively ( Z=-3.659, P<0.001). The mean preoperative and postoperative 6-month BCVA were 0.80(0.63, 1.00) and 0.80(0.60, 1.00), respectively, showing no significant difference ( Z=-0.283, P=0.777). Complete surgical success rate was 62.86%(22/35), and the qualified success rate was 91.43%(32/35). Surgical complications mainly included hyphema (6/35), IOP spike (3/35), and shallow anterior chamber (4/35). There was no vision-threatening complication. Conclusions:SPI+ GSL+ GT is preliminarily effective and safe in the treatment of advanced PACG, which provides a new option for PACG.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Objective:To study the feasibility of preserving the subvalvular structure during mitral valve replacement and whether it is more conducive to the recovery of cardiac function.Methods:The clinical data of 205 patients who underwent mitral valve replacement due to mitral insufficiency in Enshi Central Hospital from January 2017 to December 2020 were analyzed retrospectively. According to whether the subvalvular structure of mitral valve was preserved during operation, they were divided into three groups: group A was to preserve all the subvalvular structures of anterior and posterior mitral valve, group B retained all or part of the subvalvular structure of the posterior valve, in group C, all anterior and posterior subvalvular structures were removed. The operation time, cardiopulmonary bypass time and aortic occlusion time of patients in each group were counted. Postoperative ventilator use time, ICU stay time and incidence of complications; mitral flow velocities (MVE), left ventricular end diastolic dimension (LVED), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were rechecked by echocardiography at 1 week, 3 months and 6 months after operation.Results:There were no significant differences in operation time, cardiopulmonary bypass time, aortic occlusion time, ventilator use time and ICU stay time among the three groups before surgery ( P>0.05). There were no death cases in perioperative period, and all patients were cured and discharged from hospital. The results of cardiac color ultrasound showed that MVE, LVED, LVEF and LVFS were improved compared with those before operation. Postoperative ultrasound results showed no significant difference in MVE at 1 week, 3 months and 6 months ( P>0.05). At 1 week after surgery, LVED in group A was lower than that in group B and C: (44.90 ± 5.59) mm vs. (46.13 ± 6.15) mm, (48.33 ± 5.59) mm. The difference was statistically significant ( P<0.05). Three months after operation, LVED and LVFS in group A were higher than those in group B and group C: (43.37 ± 5.61) mm vs. (44.69 ± 5.45) mm and (53.42 ± 5.35) mm, (33.92 ± 3.34)% vs. (31.67 ± 3.20)% and (30.37 ± 6.96)%, respectively. The differences were statistically significant ( P<0.05). At 6 months after operation, LVED in group A was lower than that in group B and group C: (41.86 ± 3.27) mm vs. (47.85 ± 6.93) mm and (53.42 ± 8.17) mm. LVFS was higher than that in group B and group C: (33.42 ± 2.64) % vs. (32.18 ± 5.98) % and (32.28 ± 2.58) %, and the differences were statistically significant ( P<0.05). Conclusions:Preserving the whole subvalvular structure of mitral valve will not lead to prosthetic valve dysfunction and increase surgical complications. After operation, it showed better reduction of left ventricular end diastolic diameter and better left ventricular shortening rate, which was more conducive to the recovery of cardiac function.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.

Objective To analyze the association of postnatal weight gain proportion of very low birth weight (BW) preterm babies and the onset of severe retinopathy of prematurity,and investigate the optimal cut-off points and predictive ability of postnatal weight gain (WG) proportion for the onset of retinopathy of prematurity (ROP).Methods A retrospective cohort study.257 preterm infants underwent screening whose weight was less than 1500 g were enrolled in this study.Risk factors include BW,gestational age (GA),history of oxygen inhalation,need for blood transfusions,Apgar score in 1 to 10 minutes,embryo number,delivery mode,in vitro fertilization infants,and WG proportion within 6 weeks after birth and other systemic diseases were recorded.Their correlation with severe ROP is analyzed.Clinical outcomes were divided into severe ROP group (patients who suffered from ROP and required treatment) and mild and no ROP group (patients who suffered from ROP but do not require treatment and-patient without ROP).The severe ROP group included 18 patients and mild and no ROP group included 239 patients.Multiple logistic regression and receiver operating characteristic (ROC) curve were used to determine if the WG proportion was independently related to severe ROP development and if it was capable of predicting severe ROP.This study determines the predict value by comparing the area under the ROC curve (AUC) of independent risk factors.Results GA (t=-4.835,P＜0.001),BW(t=-5.192,P＜0.001),history of oxygen inhalation (x2=6.001,P=0.009),proportion of infants who had oxygen inhalation for more than 10 days(x2 =10.019,P=0.002),postnatal WG proportion at 1 week(t =-3.663,P＜ 0.001),postnatal WG proportion at 2 weeks(t=-3.425,P=0.001) had significant difference between two groups.Multiple logistic regression analysis revealed that GA (β =-0.858,P =0.008),BW (β =-0.005,P =0.010),postnatal WG proportion at 2 weeks (β=-8.745,P =0.035) were correlated to severe ROP significantly.And their area under the ROC were 0.836[95％ confidence interval (CI):0.752-0.920],0.826 (95％CI:0.947-0.903),0.744 (95％CI:0.598-0.891) respectively.The optimal cut-off points of GA,BW,and postnatal WG proportion at 2 weeks were 28.41 weeks,1241.96 g,12.80％ respectively.Conclusion Low WG proportion at 2 weeks of very low BW preterm babies is an important and independent risk factor for severe ROP and has certain predictive value of the onset of severe ROP.

Drug Resistance, Bacterial ; Gram-Positive Bacteria ; isolation & purification ; Humans ; Infant, Newborn ; Microbial Sensitivity Tests ; Sepsis ; diagnosis ; drug therapy ; microbiology