AIM:To investigate the effects of γ-synuclein on autophagy and apoptosis of colon cancer cells in-duced by endoplasmic reticulum stress,as well as the protective effect on the cells.METHODS:Gene expression profile chip analysis was performed to compare the cDNA expression profiles between human colon cancer HCT116 cells with γ-synu-clein knockdown and HCT116 cells with control siRNA,and to identify potential molecules related to autophagy and apop-tosis.In colon cancer cell lines,the functional effects of γ-synuclein on autophagy and apoptosis induced by thapsigargin(TG),an endoplasmic reticulum stress-inducing agent,were systematically explored by conducting immunofluorescence staining,Western blot,CCK-8 assay,flow cytometry,and transmission electron microscopy.Western blot was used to de-tect the expression of γ-synuclein protein,autophagy-related proteins[microtubule-associated protein 1 light chain 3(LC3),beclin-1,autophagy-related protein 5(ATG5)and ATG7],and apoptosis-related proteins[poly(ADP-ribose)polymerase(PARP),pro-caspase-3,and pro-caspase-9].To further analyze the mechanism of γ-synuclein in regulating autophagy and apoptosis,extracellular signal-regulated kinase(ERK)inhibitor PD98059,ERK inhibitor SP600125 and c-Jun N-terminal kinase(JNK)activator anisomycin were applied separately to test HCT116 cells transfected with γ-synu-clein siRNA.Subsequently,autophagy proteins,apoptosis proteins,and ERK and JNK pathway-related proteins were de-tected by Western blot.RESULTS:The TG-induced autophagy of colon cancer cells mainly occurred at the early stage(0～24 h),and apoptosis mainly occurred at the late stage(36～48 h).Endoplasmic reticulum stress up-regulated the ex-pression of γ-synuclein in colon cancer cells,which was associated with enhanced autophagy.γ-Synuclein promoted au-tophagy by activating ERK and JNK pathways at the early stage(0～24 h),and inhibited apoptosis by blocking JNK path-ways at the late stage(24～48 h)to protect HCT116 cells.In our model,γ-synuclein was observed to play a critical role in the transition from endoplasmic reticulum stress-induced autophagy to apoptosis.CONCLUSION:In the context of endo-plasmic reticulum stress,γ-synuclein promotes autophagy and inhibits apoptosis by regulating ERK and JNK signaling pathways,thus protecting colon cancer cells.This provides a potential idea for anti-tumor therapy.

Objective:To analyze the accuracy of lung ultrasound and chest X-ray in the diagnosis of neonatal pulmonary disease.Methods:We prospectively collected newborns that needed chest X-ray examination to diagnose pulmonary disease from twelve neonatal intensive care units across the country between June 2019 and April 2020.Each newborn was examined by lung ultrasound within two hours after chest X-ray examination.All chest X-ray and lung ultrasound images were independently read by a radiologist and a sonographer.When there was a disagreement, a panel of two experienced physicians made a final diagnosis based on the clinical history, chest X-ray and lung ultrasound images.Results:A total of 1 100 newborns were enrolled in our study.The diagnostic agreement between chest X-ray and lung ultrasound(Cohen′s kappa coefficient=0.347) was fair.Lung ultrasound(area under the curve=0.778; 95% CI 0.753-0.803) performed significantly better than chest X-ray(area under the curve=0.513; 95% CI 0.483-0.543) in the diagnosis of transient tachypnea of the newborn( P<0.001). The accuracy of lung ultrasound in diagnosing neonatal respiratory distress syndrome, meconium aspiration syndrome, pneumonia and neonatal pulmonary atelectasis was similar to that of chest X-ray. Conclusion:Lung ultrasound, as a low-cost, simple and radiation-free auxiliary examination method, has a diagnostic accuracy close to or even better than that of chest X-ray, which may replace chest X-ray in the diagnosis of some neonatal lung diseases.It should be noted that both chest X-ray and lung ultrasound can only be used as auxiliary means for the diagnosis of lung diseases, and it is necessary to combine imaging with the clinical history and presentation.

Mice ; Animals ; Myocytes, Cardiac ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Cardiomegaly/genetics* ; Signal Transduction ; Cells, Cultured

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

Objective: To investigate the prevalence of scoliosis among primary and middle school students in Jiaxing City, Zhejiang Province, so as to provide insights into scoliosis control among children and adolescents. Methods: Grade 4 to 6 primary school students and grade 1 to 3 junior high school students were recruited using a stratified cluster sampling method in Jiaxing City in 2019. Participants' demographic characteristics, dietary habits and nutritional status, physical activity, learning environments, reading and writing habits were collected using questionnaires. Scoliosis was screened through general examinations, forward bend test and scoliometer, and scoliosis was diagnosed with whole-spine X-ray scans in an erect position. The prevalence of scoliosis was descriptively analyzed among primary and middle school students. Results: A total of 8 026 primary and middle school students were included, 7 304 valid questionnaires were recovered, with an effective recovery rate of 91.00%. The respondents included 3 667 primary school students (50.21%) and 3 637 junior high school students (49.79%), and included 3 776 boys (51.70%) and 3 528 girls (48.30%). There were 659 participants with initial screening positive for scoliosis (9.02%), and the percentages of positive initial screening of thoracic, thoracolumbar and lumbar scoliosis were 2.93%, 4.56% and 4.56%, respectively. A higher percentage of positive initial screening of scoliosis was diagnosed among participants living in Pinghu City (10.45%), junior high school students (11.74%), girls (11.96%), students with a medical history of anemia (22.44%), students with less than 3 days of moderate-intensity physical activity in the past week (9.46%), students with less than 3 days of walking duration of over 10 minutes in the past week (10.18%), students with daily sitting duration of 5 hours and more in the past week (10.74%), students with their class seats exchanged every semester or month (10.28%), students with daily reading and writing duration of 3 hours and more after school (10.93%) and students with less than 10 cm distance from the chest at reading or writing to the edge of the table (9.67%) (all P<0.05). A total of 218 students received whole-spine X-ray scans in an erect position, 132 participants were definitively diagnosed as scoliosis (60.55%), and the estimated prevalence of scoliosis was 5.46%. Conclusion The percentage of positive initial screening of scoliosis was 9.02% among primary and middle school students in Jiaxing City. Gender, stage of learning, nutritional status, exercise frequency and habits of reading and writing may be factors affecting the development of scoliosis.

Objective:To explore the clinical utility of bronchoscopy and transbronchial cryotherapy in children with tracheobronchial tuberculosis (TBTB).Methods:Retrospective study was conducted to collect the clinical data of 10 hospitalized children who underwent bronchoscopy and were diagnosed as TBTB and in the Department of Pediatrics of Peking University First Hospital and the Department of Pediatric Respiratory Medicine of the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University from January 2011 to October 2019. The clinical characteristics of TBTB in children, and the efficacy and safety of bronchoscopy and transbronchial cryotherapy were summarized through descriptive analysis.Results:The onset age of 10 children (6 males and 4 females) ranged from 1-14 years. The clinical manifestations included fever (8/10), cough (7/10) and hemoptysis (2/10). Purified protein derivative test and interferon-γ release assay were performed in 9 and 10 patients respectively, the results were all positive. Chest CT examination was performed in all patients, and 8 patients had hilar and mediastinal lymphadenopathy. All patients underwent pediatric bronchoscopy in time, in 9 patients bronchus was found to be blocked in varying degrees by granulation tissue and caseous necrosis and in the remaining patient, obvious congestion and edema in bronchial mucosa. The bronchoscopic manifestations included 8 cases of lymph node fistula type, 1 case of granulation proliferative type and 1 case of inflammatory infiltration type. Pathological biopsies were performed in 7 cases, the findings were consistent with the pathological characteristics of tuberculosis. Nine patients were treated by pediatric bronchoscopic intervention, with 8 transbronchial cryotherapy by flexible bronchoscopy, and among them, 2 patients were treated by simultaneous rigid bronchoscopy. After 1-3 times of transbronchial cryotherapy, the blocked bronchial lumina in 8 cases were all recanalized, and the curative effect was significant without any serious complications.Conclusions:Bronchoscopy plays an important role in the diagnosis of TBTB in children and is helpful for its classification. Also, transbronchial cryotherapy has good efficacy and safety for TBTB in children, especially for the granuloproliferative type or lymph node fistula type.

Liver transplantation is the most effective method for hepatitis B-related liver failure, liver cirrhosis and hepatocellular carcinoma. However, the reactivation of hepatitis B virus (HBV) after liver transplantation is not conducive to the recovery of liver function and leads to poor clinical prognosis. The prevention and treatment of HBV reactivation is currently the focus of research by physicians and surgeons. The current viral suppression strategies can not completely eradicate HBV nor completely prevent the recurrence of HBV infection in the future. This article aims to explore the molecular mechanism of HBV reactivation after liver transplantation, in order to more effectively prevent the recurrence of hepatitis B after liver transplantation.

Objective: To observe the long-term efficacy and safety of autologous hematopoietic stem cell transplantation (AHSCT) for systemic sclerosis (SSc) patients. Methods: Between May 2007 and June 2009,4 patients with SSc were enrolled in the study. Peripheral blood stem cells were mobilized with cyclopho-sphamide (CTX) followed by granulocyte colony stimulating factor (G-CSF). Conditioning was performed with i.v. cyclophosphamide 50 mg·kg^-1·d^-1 for 4 days. The results of the modified Rodnan skin score (mRSS), thoracic high-resolution computer tomography and pulmonary function were collected after transplantation. Results: There was an improvement in mRSS, lung function and HRCT in the six months after AHSCT. Within six month to one year after transplantation, one patient had sustained and two patients recurred. After active treatments two patients were improved again. During the follow-up of 8.7 (4.1-9.8) years, three patients were stable and one patient died. Infection and hepatic function injury were the major complications. There was not transplant-related mortality. Conclusion AHSCT with CTX as a pre-conditioning regimen is safe and effective for SSc. The efficacy for patients with short course, rapid progress and edema is significant. However, long-term efficacy is poor, and long-term maintenance treatment is needed.

Objective To analyze the risk factors for anastomotic leak after total gastrectomy in gastric cancer patients and its impact on patients survival.Methods A total of 1 547 gastric cancer patients who underwent curative resection between 1999 to 2016 were enrolled.Results The anastomotic leak occurred in 106 of 1 547 patients;and it was happened at a median of (6.0 ± 2.1) day after surgery.The median postoperative hospital stay was (9 ± 3) days for non-anastomotic leak,lower than patients for anastomotic leak with (15 ± 5) days.The anastomotic leak was significantly correlated with age,lung function,BMI,serum albumin,intraoperative blood loss,operative time,smoking and diabetes (P ＜0.05).Multivariable analysis showed that the anastomotic leak was significantly correlated with diabetes,lung function,smoking (P ＜ 0.05).The 30-day mortality with anastomotic leak was lower than patients without leak.The 3'-and 5-year survival rate of patients with anastomotic leak were 53.9％ and 47.7％,significantly lower than those of 69.4％ and 58.5％ without anastomotic leak (P ＜ 0.05).By univariate analysis that BMI,pathological stage,tumor size,serum albumin,anastomotic leak were factors affecting prognosis (P ＜ 0.05).While multivariate analysis showed that anastomotic leakage was independently associated with worse overall survival.Conclusion Anastomotic leakage in patients who underwent total gastrectomy increases the 30-day mortality and associated with poorer 5-year survival.

Objective To establish a quality control method for bomeol and artificial musk in Xinfufang-Zhenzhusan and Xinfufang-Zhenzhugao.Methods We used petroleum ether-toluene-ethyl acetate (9:3:2)as developer for TLC to identify isoborneol and borneol and petroleum ether-dichloromethane (2:3) as developer for TLC to identificate musk ketone.Agilent 7890 B gas chromatograph,FDI detector;Column:Thermo-TG-WaxMS GC (0.25 mm × 30 m,0.25 mm) was employed;the carrier gas was high purity nitrogen and flow rate for 1 mg/ml,the injection port temperature is 200 C and detector temperature is 250 ℃;the split ratio is 10:1 and injection volume was 1 μl,using temperature programmed.Results The isoborneol,borneol and musk ketone in the range of 0.001-10 mg/ml showed good linearity.The recovery of the method is in the range of 95 ％ to 105 ％.The TLC for isobomeol,bomeol,musk ketone can be identified easily.Conclusions The method was simple and reasonable,which can be used for the quality control of borneol and artificial musk in the Xinfufang-Zhenzhusan and Xinfufang-Zhenzhugao.