1.Autophagy in skeletal muscle dysfunction of chronic obstructive pulmonary disease: implications, mechanisms, and perspectives.
Xiaoyu HAN ; Peijun LI ; Meiling JIANG ; Yuanyuan CAO ; Yingqi WANG ; Linhong JIANG ; Xiaodan LIU ; Weibing WU
Journal of Zhejiang University. Science. B 2025;26(3):227-239
Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy- and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
Pulmonary Disease, Chronic Obstructive/physiopathology*
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Autophagy/physiology*
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Humans
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Muscle, Skeletal/pathology*
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Mitophagy
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Animals
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Mitochondria/metabolism*
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Lysosomes
2.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
3.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
4.A national multi-center prospective study on the perioperative practice of enhanced recovery after surgery for choledochal cysts in children
Ming YUE ; Jiexiong FENG ; Yan′an LI ; Yuanmei LIU ; Zhigang GAO ; Qi CHEN ; Hongwei XI ; Qiang YIN ; Chengji ZHAO ; Yuzuo BAI ; Wanfu LI ; Libin ZHU ; Weibing TANG ; Hongqiang BIAN ; Huizhong NIU ; Zhiheng GUO ; Heying YANG
Chinese Journal of General Surgery 2024;39(11):827-832
Objective:To evaluate the safety and efficacy of enhanced recovery after surgery(ERAS) in the perioperative period of congenital choledochal cysts in children.Methods:This is a multicenter prospective randomized controlled study. The clinical data of 273 pediatric congenital choledochal cysts(CCC) patients who underwent surgery at 14 medical centers with complete follow-up data were collected through the medical data analysis platform. Among them, 123 cases in ERAS group were managed perioperatively in strict accordance with ERAS mode, and 150 cases in conventional group were managed according to traditional mode. The length of hospital stay,time to first farting, time to complete feeding, the incidence of complications, cost and readmission rate within 30 days,stress indexes and liver function were compared between the two groups.Results:Compared with the conventional group, median time to start farting (2.0 d vs. 3.0 d, P<0.001), median time to complete feeding (5.0 d vs. 7.0 d, P<0.001), median postoperative hospitalization time (6.0 d vs. 9.0 d, P<0.001),the median total length of stay(13.0 d vs. 15.0 d, P<0.001) were shorter,the median hospitalization cost (37,000 yuan vs.43,000 yuan P<0.001) was lower, and stress indexes recovered quickly. The incidence of postoperative hospital stay and readimission rate within 30 d were not statistically different between the two groups. Conclusion:It is safe and feasible to implement ERAS for children with CCC in the perioperative period, which can reduce stress response, speed up recovery,and save medical costs.
6.Epidemiological characteristics of scarlet fever in Minhang District, Shanghai from 2005 to 2020
Nian LIU ; Wei ZHONG ; Zhaowen ZHANG ; Weibing WANG
Shanghai Journal of Preventive Medicine 2022;34(8):770-773
ObjectiveTo analyze the epidemiological characteristics of scarlet fever in Minhang District, Shanghai from 2005 to 2020, and to provide scientific basis for the investigation and prevention of scarlet fever. MethodsWe collected the scarlet fever incidence data through the China Information System for Disease Control and Prevention; used SPSS 17.0 to conduct descriptive epidemiological analysis; and used EpiInfo to analyze and compare the differences in incidence rates between different regions. ResultsA total of 12 012 scarlet fever cases were reported in Minhang District, Shanghai from 2005 to 2020. There were more cases in 2011, 2015 and 2017, and the difference in annual incidence was statistically significant (χ2=6 023.977, P<0.001). Scarlet fever could occur throughout the year, but the peak incidence was from April to June and November to January of the following year. The gender ratio between men and women is 1.57:1, and the patients were concentrated in 4-6 years old. The incidence rate difference in 13 neighborhoods was statistically significant (χ2=2 455.516, P<0.001). The four communities with the highest average annual incidence rate were Xinzhuang Town, Zhuanqiao Town, Maqiao Town, and Gumei Street. ConclusionFrom 2005 to 2020, the incidence of scarlet fever in Minhang District, Shanghai presents a double peak, which matches well the student semesters, and scarlet fever patients are mainly students. Attention should be paid to infection source management and epidemic surveillance in schools and other collective units, implementation of morning inspections and daily disinfection, and other prevention and control measures.
7.The relationship between scarlet fever and meteorological factors in Minhang District, Shanghai, 2009‒2020
Nian LIU ; Zhaowen ZHANG ; Jinhua PAN ; Weibing WANG ; Xiaohua LIU
Shanghai Journal of Preventive Medicine 2022;34(9):870-873
ObjectiveTo study the relationship between scarlet fever and meteorological factors in Minhang District, Shanghai, and provide scientific basis for prevention and control of scarlet fever and establishment of a scarlet fever early warning system. MethodsData of thea scarlet fever epidemic were obtained from China Disease Control and Prevention Information System, and the meteorological data were obtained from Shanghai Minhang Meteorological Bureau. A generalized additive model was used to explore the relationship between scarlet fever incidence and meteorological factors in the R3.6.1 software. ResultsBetween 2009 and 2020, there was a rapid increase in the incidence of scarlet fever starting from 2011. There was a negative correlation between scarlet fever and wind velocity: the higher the wind velocity, the fewer cases. The correlation of number of cases with air temperature and atmospheric pressure was non-linear. The number of scarlet fever cases was positively correlated with air temperature below 17 degrees Celsius, and negatively correlated with air temperature above 17 degrees Celsius. The number of cases decreased with the increase of atmospheric pressure when atmospheric pressure was less than 1 017 MPa, and increased with the increase of atmospheric pressure when atmospheric pressure was more than 1 017 MPa. ConclusionThe incidence of scarlet fever is negatively correlated with wind speed, which can be reduced by opening windows for ventilation. The incidence of scarlet fever has a nonlinear relationship with air temperature and air pressure. The findings of this study provide scientific information for better understanding the epidemic trend of scarlet fever in Minhang District, contribute to the establishment of an early warning system, improve the active prevention and intervention of risk factors of the disease, and reduce its social burden.
8.Analysis of cerebrovascular disease between 1996 and 2021 in Minhang District of Shanghai
Linli CHEN ; Lijing CHEN ; Jingyi NI ; Shuili XUAN ; Wei LIU ; Xiuhong TIAN ; Yiqin GU ; Ruonan HUANG ; Weibing WANG
Shanghai Journal of Preventive Medicine 2022;34(12):1214-1218
ObjectiveTo analyze the changing trend of cerebrovascular disease burden in Minhang District of Shanghai from 1996 to 2021, and to provide scientific evidence for government to formulate targeted cerebrovascular disease prevention and control strategies. MethodsMortality, years of life lost(YLL), years of lived with disability(YLD) and disability⁃adjusted life years(DALY) were used to evaluate the burden of cerebrovascular diseases in Minhang District. Joinpoint linear regression was used to analyze the trend of disease burden. ResultsFrom 1996 to 2021, the YLL rate of cerebrovascular diseases in Minhang District showed a downward trend (whole population: APC=-1.69%, t=-6.9, P<0.05), The YLD rate of cerebrovascular diseases showed a slow upward trend (whole population: APC=1.17%, t=3.5, P<0.05), The DALY rate of cerebrovascular diseases showed a downward trend, and fluctuated since 2003 (whole population: APC= -1.43%, t=-5.6, P<0.05). The YLL rate of cerebrovascular diseases in men was higher than that in women, and the YLD rate of cerebrovascular diseases in women was higher than that in men. After 2014, the DALY of cerebrovascular diseases in men was higher than that in women. With the increase of age, the burden of cerebrovascular diseases increased, and the burden of disease increased significantly in the age group above 70. ConclusionThe burden of cerebrovascular diseases in Minhang District is at a high level, and there are differences in age, gender and other aspects. Measures such as screening, intervention and rehabilitation need to be improved to reduce disability and premature death caused by cerebrovascular diseases and to reduce the burden of cerebrovascular diseases on individuals, families and society.
9.Assessment of COVID-19 Omicron epidemic trend in Shanghai based on time-varying reproduction number
Zhixi LIU ; Wenlong ZHU ; Weibing WANG
Shanghai Journal of Preventive Medicine 2022;34(6):541-544
ObjectiveTo assess the epidemic trend of COVID-19 Omicron and the effectiveness of containment measures in Shanghai by estimating the time-varying reproduction number (Rt). MethodsBased on the daily reported confirmed cases and asymptomatic infections in Shanghai from February 20 to April 26, 2022, the R package "Epiestim", which was built by Bayesian framework method, was used to estimate the variation curve of Rt during the epidemic period and to analyze the trend of the epidemic. ResultsIn the early stage of the epidemic, after the implementation of school closure and nuclear acid screening in some communities, Rt continued to fluctuate between 2.000 and 3.000, reaching a peak of 2.740 (95%CI: 2.640‒2.830) on March 21, but began to decline around one week after the city lock-down on April 1. As of April 18, the Rt value in Shanghai was below the threshold of 1.000 for the first time, reaching 0.955 (95%CI: 0.951‒0.961). ConclusionAfter the implementation of public health measures with increasing strength of containment in Shanghai, the transmission rate gradually decreased, reflecting the effectiveness of the interventions. In the actual prevention and control process, the containment work should not be relaxed in order to keep the Rt below 1.000.
10.Graeb score predicts the outcome of high-grade aneurysmal subarachnoid hemorrhage patients with intraventricular hemorrhage
Guofeng ZHANG ; Rui LIANG ; Hui LIU ; Xinyong ZHANG ; Zhi CAO ; Weibing LIU ; Youjia TANG
International Journal of Cerebrovascular Diseases 2021;29(7):507-513
Objective:To investigate the predictive value of Graeb score for the outcome of high-grade aneurysmal subarachnoid hemorrhage (aSAH) patients with intraventricular hemorrhage (IVH).Methods:Consecutive high-grade aSAH patients with IVH admitted to the No. 1 People's Hospital of Jiujiang from January 2012 to March 2020 were enrolled retrospectively. High-grade aSAH was defined as grade Ⅳ to Ⅴ according to the World Federation of Neurological Surgeons (WFNS) scale. The outcome of patients was evaluated by the modified Rankin Scale (mRS) at 3 months after discharge. A score of ≤2 was defined as a good outcome and a score of >2 were defined as a poor outcome. Multivariate logistic regression model was used to evaluate the correlation between Graeb score and clinical outcome, and the receiver operating characteristic (ROC) curve was used to determine the predictive value of Graeb score for clinical outcome. Results:A total of 86 high-grade aSAH patients with IVH were enrolled. Aneurysm treatment: craniotomy clipping in 42 patients (48.8%), intravascular embolization in 21 (24.4%), and conservative treatment in 23 (26.7%). Twenty-nine patients (33.7%) had a good outcome and 57 (66.3%) had a poor outcome. Multivariate logistic regression analysis showed that the Graeb score >6 (odds ratio [ OR] 26.360, 95% confidence interval [ CI] 4.106-169.235; P<0.001), the modified Fisher grade 3-4 ( OR 11.674, 95% CI 1.540-88.512; P=0.017) and complicated with chronic hydrocephalus ( OR 21.236, 95% CI 2.883-156.431; P=0.003) were the independent risk factors for the poor outcome. ROC curve analysis showed that the area under the curve of the Graeb score predicting for poor outcome was 0.843 (95% CI 0.760-0.926; P<0.001), the best cut-off value was 6.5, and the corresponding sensitivity and specificity were 71.9% and 86.2%, respectively. Conclusion:The Graeb score is an independent influencing factor affecting the clinical outcome of high-grade aSAH patients with IVH. Graeb score >6.5 had higher predictive value for the poor outcome in such patients.

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