1.Overexpression of mitoNEET inhibits ferroptosis-induced mitochondrial metabolic dysfunction in brown adipocytes
Hongyu ZHENG ; Zhen TIAN ; Yanxia WANG ; Kun ZHOU ; Zhong REN ; Zhixiang ZHOU ; Wenhao XIONG ; He ZHENG ; Zhisheng JIANG
Chinese Journal of Pathophysiology 2024;40(5):852-861
AIM:To investigate the potential impact of mitoNEET[mitochondrial protein containing Asn-Glu-Glu-Thr(NEET)sequence]on mitochondrial metabolism in brown adipocytes,and to elucidate its underlying mecha-nism.METHODS:An in vitro model of primary mouse brown adipocytes was established.Western blot were utilized to detect relevant proteins,and iron ion and ATP content was measured using kits.Mitochondrial membrane potential and re-active oxygen species(ROS)were assessed by fluorescence microscopy and flow cytometry.RESULTS:The expression of the ferroptosis-related protein ACSL4 increased by 1.13 times in ferroptosis inducer erastin treatment group,whereas the expression of SLC7A11 and GPX4 decreased by 27.33%and 25.33%,respectively,compared with control group(P<0.05).The expression of Nrf1,PGC-1α,MFN2 and UCP1 proteins,related to mitochondrial energy metabolism,de-creased by 20.98%,15.17%,15.03%and 34.22%,respectively(P<0.05).Additionally,the mitoNEET protein con-tent was significantly reduced by 42.14%(P<0.05).The iron ion content in erastin group was substantially increased by 1.80 times compared with control group.However,a notable decrease in ATP content of 14.95%was seen(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated a significant decrease in the mitochon-drial membrane potential of brown adipocytes in erastin group,with reductions of 52.18%and 61.31%(P<0.05),re-spectively.A substantial increase in mitochondrial ROS content of 80.97%was seen(P<0.05).Western blot analysis of overexpressed stable strains revealed a significant elevation in mitoNEET levels in brown adipocytes following lentivirus transfection,exhibiting an increase of 11.19 times(P<0.05),thus confirming successful transfection.The LV-mitoNEET group exhibited a significant decrease of 37.95%in the expression of ferroptosis-related protein ACSL4 in brown adipose cells compared with control group.Additionally,there was a notable increase of 77.82%and 66.3%in the expression of SLC7A11 and GPX4,respectively(P<0.05).Up-regulation was observed in the expression of MFN2(79.06%),PGC-1α(72.89%),Nrf1(40.14%),and UCP1(31.68%)(P<0.05).The test results demonstrated that the LV-mitoNEET group experienced a reduction of 43.5%in iron ion content compared with control group while exhibiting an increase of 33.5%in ATP content(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated that mitoNEET overexpression led to a significant increase in the mitochondrial membrane potential of erastin-induced brown adipocytes,with increments of 17.61%and 96.05%,respectively.Additionally,mitoNEET overexpression effec-tively reduced the production of mitochondrial ROS by 24.48%(P<0.05).CONCLUSION:Our findings suggest that mitoNEET overexpression can effectively inhibit the disruption of mitochondrial energy metabolism caused by ferroptosis-induced death of brown adipocytes.
2.Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fifth Edition)updated for the Omicron variant
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Yunxiao SHANG ; Baoping XU ; Zhisheng LIU ; Gen LU ; Jikui DENG ; Guanghua LIU ; Xiaochuan WANG ; Jianshe WANG ; Luzhao FENG ; Wei LIU ; Yi ZHENG ; Sainan SHU ; Min LU ; Wanjun LUO ; Miao LIU ; Yuxia CUI ; Leping YE ; Adong SHEN ; Gang LIU ; Liwei GAO ; Lijuan XIONG ; Yan BAI ; Likai LIN ; Zhuang WEI ; Fengxia XUE ; Tianyou WANG ; Dongchi ZHAO ; Zhengyan ZHAO ; Jianbo SHAO ; Wong Wing-kin GARY ; Yanxia HE ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(1):20-30
China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.
3.Prognostic analysis of steatosis donor liver transplantation: a multicenter clinical trial
Fengqiang GAO ; Kai WANG ; Libin DONG ; Zhisheng ZHOU ; Xuyong WEI ; Li ZHUANG ; Wan LI ; Guoyue LYU ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2023;44(1):23-30
Objective:To explore the early and medium-long term outcomes of steatosis donor liver transplantation(LT)for an optimal clinical application.Methods:From January 2015 to December 2020, this retrospective cohort study was conducted jointly at Shulan (Hangzhou) Hospital, First Affiliated Hospital of Zhejiang University and First Hospital of Jilin University. The relevant clinicopathological and follow-up data were collected from 1535 LT recipients. For comparison, propensity score was utilized for case-control matching of steatosis and non-steatosis donor livers. According to presence or absence of liver steatosis, the recipients were divided into two groups of steatosis donor liver (n=243) and non-steatosis donor liver (n=1292). And 1∶1 propensity score matching was made for two groups. Then early and medium-long term outcomes of two groups were examined. Counts were described as absolute numbers. Kaplan-Meier method was employed for calculating survival time and plotting survival curve and Log-rank test for survival analysis. COX regression model was utilized for univariate and multivariate analyses. Based on basic metabolic disease pre-LT, steatosis donor liver recipients were divided into three subgroups: BMI ≥25 kg/m 2 with hypertension or diabetes (n=21), BMI<25 kg/m 2 and no hypertension or diabetes (n=130) and other recipients (n=92). A comparative study was performed for determining the prognosis of subgroups according to the different characteristics of recipient and donor liver. Results:No significant inter-group difference existed in 2-year survival post-LT ( P=0.174). However, significant inter-group difference in survival existed after 2 years post-LT ( P=0.004). And 3/5-year survival rate of steatosis donor liver was 66.4% and 44.2% respectively. Both were significantly lower than those of non-steatosis donor liver. Multivariate Cox regression analysis indicated that steatosis donor liver and male recipients were independent risk factors for prognosis >2 years survival post-LT( P=0.008, P=0.004). Subgroup analysis of steatosis liver donors showed that the prognosis of patients with BMI ≥25 kg/m 2 with hypertension or diabetes was significantly worse than other subgroups (BMI <25 kg/m 2 with no hypertension or diabetes and other recipients) <2 years survival post-LT ( P=0.029, P=0.043). Conclusions:Steatosis donor liver does not affect early survival of recipients, yet reduces medium-long term survival rate of recipients notably. In steatosis donor liver recipients, early survival rate declines markedly in recipients with preoperative BMI ≥25 kg/m 2 with hypertension or diabetes as compared with BMI <25 kg/m 2 with no hypertension or diabetes group.
4.Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors.
Lijuan MA ; Boyi LI ; Jinchen MA ; Chunyuan WU ; Nan LI ; Kailin ZHOU ; Yun YAN ; Mingshuang LI ; Xiaoyan HU ; Hao YAN ; Qi WANG ; Yanfei ZHENG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2023;13(6):2765-2777
Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.
5.Expert consensus on the diagnosis, treatment and prevention of monkeypox in children
Rongmeng JIANG ; Yuejie ZHENG ; Lei ZHOU ; Luzhao FENG ; Lin MA ; Baoping XU ; Hongmei XU ; Wei LIU ; Zhengde XIE ; Jikui DENG ; Lijuan XIONG ; Wanjun LUO ; Zhisheng LIU ; Sainan SHU ; Jianshe WANG ; Yi JIANG ; Yunxiao SHANG ; Miao LIU ; Liwei GAO ; Zhuang WEI ; Guanghua LIU ; Gang LIU ; Wei XIANG ; Yuxia CUI ; Gen LU ; Min LU ; Xiaoxia LU ; Runming JIN ; Yan BAI ; Leping YE ; Dongchi ZHAO ; Adong SHEN ; Xiang MA ; Qinghua LU ; Fengxia XUE ; Jianbo SHAO ; Tianyou WANG ; Zhengyan ZHAO ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(13):964-973
Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.
6.Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fourth Edition)
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Yunxiao SHANG ; Baoping XU ; Zhisheng LIU ; Gen LU ; Jikui DENG ; Guanghua LIU ; Xiaochuan WANG ; Jianshe WANG ; Luzhao FENG ; Wei LIU ; Yi ZHENG ; Sainan SHU ; Min LU ; Wanjun LUO ; Miao LIU ; Yuxia CUI ; Leping YE ; Adong SHEN ; Gang LIU ; Liwei GAO ; Lijuan XIONG ; Yan BAI ; Likai LIN ; Zhuang WEI ; Fengxia XUE ; Tianyou WANG ; Dongchi ZHAO ; Zhengyan ZHAO ; Jianbo SHAO ; Kwok-keung Daniel NG ; Wing-kin Gary WONG ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(14):1053-1065
Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.
7.Meta-analysis of the efficacy and safety of oral atenolol versus oral propranolol in the treatment of infantile hemangioma
Jianmin ZHENG ; Zhisheng ZHU ; Chaoyang WANG ; Shize ZHU
Chinese Journal of Plastic Surgery 2022;38(3):275-283
Objective:To explore the difference of the efficacy, safety and recurrence rate of oral atenolol compared with oral propranolol in the treatment of infantile hemangioma, so as to provide evidence-based medicine basis and reference for clinic.Methods:A comprehensive search was conducted on the English databases Web of Science, PubMed, Cochrane Library, Embase, U. S. National Library of Medicine Clinical Trials Registry Platform (https: //clinicaltrials.gov) and on the Chinese databases CNKI, CBM, VIP, Wanfang Data from January 2008 to June 2021, according to our defined inclusion and exclusion criteria, randomized controlled trials of oral atenolol versus oral propranolol in the treatment of infantile hemangioma were selected for performing meta-analysis, and the outcome indicators were treatment efficiency, incidence of adverse reactions, and recurrence rate. Meta-analysis was performed by using RevMan 5.3 software, and sensitivity analysis of the result was performed, and the main outcome indicators were tested for publication bias (Egger’s test) by using Stata 16 software.Results:Finally, 5 randomized controlled trials references were included. Our meta-analysis showed that there was no significant difference in the effective rate between oral atenolol and oral propranolol in the treatment of infantile hemangioma ( RR=0.93, 95% CI 0.84-1.02, P=0.110). There was a statistically significant difference in the overall incidence of adverse reactions ( RR=0.78, 95% CI 0.61-0.99, P =0.040), bronch-related and central nervous system related to β 2-blockade( RR=0.55, 95% CI 0.40-0.76, P<0.001) adverse reactions, which were lower in the atenolol group than in the propranolol group; there was a statistically significant difference in the recurrence rate ( RR=0.57, 95% CI 0.39-0.84, P=0.005), which was lower in the atenolol group than in the propranolol group. The sensitivity analysis showed that the result after the exclusion of any 1 study were less variable compared with the result of the previous analysis, and the conclusion obtained were unchanged, suggesting that the result of the meta-analysis were stable and reliable. The Egger’s test showed that P=0.502, which suggested that there was no obvious publication bias. Conclusions:In the treatment of infantile hemangioma, oral atenolol has equivalent efficacy compared with oral propranolol, with less overall incidence of adverse reactions (which can reduce the incidence of bronch-related and central nervous system adverse reactions) and lower recurrence rate.
8.Meta-analysis of the efficacy and safety of oral atenolol versus oral propranolol in the treatment of infantile hemangioma
Jianmin ZHENG ; Zhisheng ZHU ; Chaoyang WANG ; Shize ZHU
Chinese Journal of Plastic Surgery 2022;38(3):275-283
Objective:To explore the difference of the efficacy, safety and recurrence rate of oral atenolol compared with oral propranolol in the treatment of infantile hemangioma, so as to provide evidence-based medicine basis and reference for clinic.Methods:A comprehensive search was conducted on the English databases Web of Science, PubMed, Cochrane Library, Embase, U. S. National Library of Medicine Clinical Trials Registry Platform (https: //clinicaltrials.gov) and on the Chinese databases CNKI, CBM, VIP, Wanfang Data from January 2008 to June 2021, according to our defined inclusion and exclusion criteria, randomized controlled trials of oral atenolol versus oral propranolol in the treatment of infantile hemangioma were selected for performing meta-analysis, and the outcome indicators were treatment efficiency, incidence of adverse reactions, and recurrence rate. Meta-analysis was performed by using RevMan 5.3 software, and sensitivity analysis of the result was performed, and the main outcome indicators were tested for publication bias (Egger’s test) by using Stata 16 software.Results:Finally, 5 randomized controlled trials references were included. Our meta-analysis showed that there was no significant difference in the effective rate between oral atenolol and oral propranolol in the treatment of infantile hemangioma ( RR=0.93, 95% CI 0.84-1.02, P=0.110). There was a statistically significant difference in the overall incidence of adverse reactions ( RR=0.78, 95% CI 0.61-0.99, P =0.040), bronch-related and central nervous system related to β 2-blockade( RR=0.55, 95% CI 0.40-0.76, P<0.001) adverse reactions, which were lower in the atenolol group than in the propranolol group; there was a statistically significant difference in the recurrence rate ( RR=0.57, 95% CI 0.39-0.84, P=0.005), which was lower in the atenolol group than in the propranolol group. The sensitivity analysis showed that the result after the exclusion of any 1 study were less variable compared with the result of the previous analysis, and the conclusion obtained were unchanged, suggesting that the result of the meta-analysis were stable and reliable. The Egger’s test showed that P=0.502, which suggested that there was no obvious publication bias. Conclusions:In the treatment of infantile hemangioma, oral atenolol has equivalent efficacy compared with oral propranolol, with less overall incidence of adverse reactions (which can reduce the incidence of bronch-related and central nervous system adverse reactions) and lower recurrence rate.
9.Predictive effect of liver fibrosis score and other factors on the prognosis of liver transplantation for liver cancer
Binhua PAN ; Xuyong WEI ; Zhikun LIU ; Li ZHUANG ; Jianhui LI ; Mengfan YANG ; Zhisheng ZHOU ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2021;42(3):131-135
Objective:To explore the value of aspartate aminotransferase(AST)and platelet (PLT)ratio index(APRI)in the prognosis of liver transplantation(LT)for hepatocellular carcinoma and establish a nomogram model for evaluating its clinical application potential.Methods:From January 2015 to December 2019, retrospective review was conducted for clinical data of LT for hepatocellular carcinoma(HCC)at First Affiliated Hospital of Zhejiang University School of Medicine and Shulan(Hangzhou)Hospital(601 cases). They were randomized into two groups of modeling (399 cases)and validation(202 cases)and then divided into low and high APRI groups according to the APRI value at Month 1 post-transplantation. The independent risk factors of recurrence and prognosis post-LT were screened in modeling group using univariate and multivariate Cox regression analyses and were further used for constructing a nomogram prediction model. The receiver operating characteristic curve(ROC)and survival curve were utilized for verifying the accuracy of nomogram prediction model.Results:Univariate and multivariate Cox regression analyses revealed that independent risk factors for the prognosis of HCC-LT included cold ischemic time(CIT) >8 h, beyond Hangzhou criteria, surgical bleeding volume >1 000 ml and APRI >1.5. The AUC of HCC-LT recurrence prediction model was 0.734(95%CI: 0.681~0.787)and 0.749(95%CI: 0.671~0.817)in modeling and validation groups; the AUC of HCC-LT mortality prediction model was 0.735(95%CI: 0.679~0.790)and 0.758(95%CI: 0.682~0.834)in modeling and validation groups.Conclusions:APRI>1.5 is an independent risk factor for postoperative recurrence and mortality after HCC-LT. The nomogram prediction model based upon CIT, Hangzhou criteria, intraoperative bleeding volume and APRI can effectively predict the recurrence and overall survival of LT for HCC.
10.Diagnosis, treatment and prevention of 2019 novel coronavirus infection in children: experts′ consensus statement (Third Edition)
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Baoping XU ; Zhisheng LIU ; Likai LIN ; Yunxiao SHANG ; Sainan SHU ; Yan BAI ; Min LU ; Gen LU ; Jikui DENG ; Wanjun LUO ; Lijuan XIONG ; Miao LIU ; Yuxia CUI ; Leping YE ; Liwei GAO ; Yongyan WANG ; Xuefeng WANG ; Jiafu LI ; Tianyou WANG ; Dongchi ZHAO ; Jianbo SHAO ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2021;36(10):721-732
2019 novel coronavirus(2019-nCoV) outbreak is one of the public health emergency of international concern.Since the 2019-nCoV outbreak, China has been adopting strict prevention and control measures, and has achieved remarkable results in the initial stage of prevention and control.However, some imported cases and sporadic regional cases have been found, and even short-term regional epidemics have occurred, indicating that the preventing and control against the epidemic remains grim.With the change of the incidence proportion and the number of cases in children under 18 years old, some new special symptoms and complications have appeared in children patients.In addition, with the occurrence of virus mutation, it has not only attracted attention from all parties, but also proposed a new topic for the prevention and treatment of 2019-nCoV infection in children of China.Based on the second edition, the present consensus further summarizes the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of treatment of 2019-nCoV infection in children.

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