[摘 要] 目的：探讨绿茶单体表没食子儿茶素没食子酸酯（EGCG）对大鼠肝癌发生过程中肠道菌群结构变化的影响。方法：建立二乙基亚硝胺（DEN）诱导的肝癌大鼠模型。将26只SD大鼠随机分成3组，分别为正常对照组、肝癌组和EGCG干预组。从实验开始第1天起，EGCG干预组每日给予EGCG（40 mg/kg）灌胃，正常对照组和肝癌组给予等量生理盐水灌胃，1次/日，持续至第20周。灌胃结束后，采集大鼠粪便样本，提取DNA，进行高通量16S rRNA V3-V4区测序；处死大鼠，取肝，观察肿瘤形成情况，并计算肝癌发生率。对测序数据进行生物信息学分析：经质控、聚类获得操作分类单元（OTU）表，据此计算α多样性指数（包括Observed species、Chao1、Shannon和Simpson指数），并进行β多样性分析。同时，对物种进行分类学注释，比较各组间菌群组成与丰度差异。结果： EGCG干预组大鼠（8只）肝脏肿瘤形成率明显低于肝癌组（10只）（50% vs 100%， P = 0.023），正常对照组（8只）大鼠无肿瘤发生。在肠道菌群方面，肝癌组操作分类单元（OTU）数量远低于正常对照组（P <0.001），而EGCG干预组OTU数量总体上高于肝癌组（P = 0.021）。α多样性分析显示，肝癌组Shannon指数低于正常对照组（P < 0.05）；此外，与肝癌组相比，EGCG干预组的Observed species指数、Chao1指数、Shannon指数和Simpson指数均显著提高（P < 0.05）。β多样性分析及主坐标分析（PCoA）表明，三组肠道菌群结构存在显著分离（PERMANOVA， R² = 0.3918， P = 0.001），其中EGCG干预组群落结构介于肝癌组与正常对照组之间，并更接近于正常对照组。肝癌组大鼠较正常大鼠肠道菌群中链球菌等潜在致病菌富集，丁酸产生相关菌（如丁酸球菌属、瘤胃球菌属等）丰度显著降低（P < 0.05）。相比之下，在EGCG干预肝癌发生过程中，大鼠肠道菌群结构相对稳定。厚壁菌门/拟杆菌门比值较肝癌组显著提高（P < 0.05），益生菌（如双歧杆菌属、乳杆菌属等）和丁酸产生相关菌（如丁酸球菌属）富集。结论：EGCG干预可降低DEN诱导的大鼠肝癌发生率，并有助于稳定肠道菌群结构，其作用可能与增加菌群多样性、促进益生菌及丁酸产生菌富集、恢复菌群平衡有关。

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Diamond-Blackfan anemia(DBA),also known as congenital pure red cell aplasia,is a rare genetic disorder characterized by bone marrow failure,congenital anomalies,and severe red blood cell abnormalities.The rarity of the condition,and consequently limited patient pool and scarcity of research models,means that the pathogenic mechanisms associated with genetic mutations in DBA remain uncertain,and the clinical treatment options are limited.This review synthesizes the findings from zebrafish,mouse,and human cellular models of DBA mutations.We clarify the pathogenic mechanisms and monitor the progression of drugs into clinical trials,thereby aiding further in-depth explorations into the etiology and therapeutic advancements for DBA.

Diamond-Blackfan anemia(DBA),also known as congenital pure red cell aplasia,is a rare genetic disorder characterized by bone marrow failure,congenital anomalies,and severe red blood cell abnormalities.The rarity of the condition,and consequently limited patient pool and scarcity of research models,means that the pathogenic mechanisms associated with genetic mutations in DBA remain uncertain,and the clinical treatment options are limited.This review synthesizes the findings from zebrafish,mouse,and human cellular models of DBA mutations.We clarify the pathogenic mechanisms and monitor the progression of drugs into clinical trials,thereby aiding further in-depth explorations into the etiology and therapeutic advancements for DBA.

Objective The aim of this study was to screen and verify the proteins interacting with Vimentin,investigate the regulatory relationship between FABP5 and candidate proteins,and further explore the mechanism of FABP5 in hepatocellular carcinoma.Methods Immunoprecipitation combined with tandem mass spectrometry(IP-MS)was used to screen the proteins that bind to FABP5.The binding relationship between FABP5 and candi-date interacting proteins was verified from the exogenous and endogenous levels by Co-immune precipitation assay(Co-IP).RT-qPCR,Western blot and immunofluorescence were used to observe the effect of knockdown FABP5 on the transcription and translation of Vimentin in HCC cells.The effect of overexpressing FABP5 on the cytoskeleton of HCC cell was observed by phalloidin staining.Results 336 potential target proteins that bind to FABP5 were identi-fied through IP-MS.Based on literature,five candidate proteins related to tumors were selected,namely PRDX1,PRSS3,PKM,HSP90AA1,and Vimentin.The binding relationship between FABP5 and Vimentin protein was con-firmed through both exogenous and endogenous Co-IP.Knockdown FABP5 has no significant effect on the expression of Vimentin mRNA,but it can inhibit the expression of Vimentin protein,and overexpression of FABP5 can affect the cytoskeleton of HCC cell.Conclusions FABP5 promotes the migration and invasion of HCC cells by the regula-tion of Vimentin and the influence of cytoskeletal remodeling,and thus it is expected to be a potential target for anti-HCC and provide new ideas for the treatment of HCC.

Objective:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), this study aims to investigate the current development status of the construction and governance of the achievement transformation system in China′s new research and development institutions, explore the tools and means to improve the efficiency of scientific and technological achievement transformation in the biopharmaceutical field, and explore effective ways for medical institutions to promote scientific and technological achievement transformation in the biopharmaceutical achievement transformation chain.Methods:By reviewing the policies and regulations issued by national and local departments in recent years, and reviewing literature and real cases related to the transformation of scientific and technological achievements in medical institutions in the past five years, an analysis was conducted.Results:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), strategies and suggestions were proposed to promote the transformation of scientific and technological achievements in new research and development institutions.Conclusions:A scientific research and development and verification platform mainly based on large scientific facilities, through the establishment of a professional transfer office team, is more conducive to the construction and governance of a hospital park close transformation model of scientific and technological achievements, promoting the two-way integration and development of the biopharmaceutical industry and medical institutions, and promoting the rapid marketization of medical scientific and technological achievements.

Objective To explore application value of transaxillary single-port gasless endoscopic-assisted fibroadenomas excision in adolescents.Methods A retrospective analysis was conducted on clinical data of 60 cases of fibroadenoma from June 2019 to June 2023.The patients were 17.3(range,13-19)years old.There were 54 cases of unilateral tumors and 6 cases of bilateral tumors.The average number of tumors was 2.5(range,1-13),and the mean tumor diameter was 4.0(range,3-10)cm.The fibroadenoma excision was performed by using transaxillary single-port gasless endoscopy.Results Of the 60 patients,the average operation time was 64.9(range,35-130)min and the intraoperative blood loss was less than 20 ml.Postoperative complications occurred in 5 cases(8.3％).At 3 months after surgery,the psychosocial well-being scores of BREAST-Q Scale were increased from(79.2±8.9)to(83.4±9.9)(P＜0.001).Conclusion Transaxillary single-port gasless endoscopic-assisted fibroadenomas excision is safe and effective for multiple or large fibroadenomas in adolescents,offering minimal invasion and concealed incision.

Objective:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), this study aims to investigate the current development status of the construction and governance of the achievement transformation system in China′s new research and development institutions, explore the tools and means to improve the efficiency of scientific and technological achievement transformation in the biopharmaceutical field, and explore effective ways for medical institutions to promote scientific and technological achievement transformation in the biopharmaceutical achievement transformation chain.Methods:By reviewing the policies and regulations issued by national and local departments in recent years, and reviewing literature and real cases related to the transformation of scientific and technological achievements in medical institutions in the past five years, an analysis was conducted.Results:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), strategies and suggestions were proposed to promote the transformation of scientific and technological achievements in new research and development institutions.Conclusions:A scientific research and development and verification platform mainly based on large scientific facilities, through the establishment of a professional transfer office team, is more conducive to the construction and governance of a hospital park close transformation model of scientific and technological achievements, promoting the two-way integration and development of the biopharmaceutical industry and medical institutions, and promoting the rapid marketization of medical scientific and technological achievements.

ObjectiveTo analyze the dynamic response relationship between urban development and mortality rate in Shanghai， and to predict the trend of mortality rate changes. MethodsBy analyzing the total mortality rate （TMR）， gross domestic product （GDP） and socio-demographic index （SDI） in Shanghai from 1978 to 2017， a vector autoregressive （VAR） model was constructed to evaluate the impact of urban development on the mortality rate. ResultsThe fitted R2 of the VAR model was 0.92. The short-term effect of GDP on the improvement of death level was negative， while the long-term effect was positive， and the SDI was negative regardless of the short-term and long-term effects. By the tenth year， GDP and SDI contributed 10.61% and 27.25% to TMR changes， respectively. The model predicted that the mortality rate in Shanghai would be 9.17 per thousand by 2030. ConclusionLong-term economic growth can effectively promote a decline in population mortality. However， as the economy develops vigorously， the adverse effects of declining birth rates and population aging on population health during the era of high-level population development should not be ignored.

ObjectiveTo determine the influence of COVID-19 prevention and control on the epidemic characteristics and dynamics of notifiable infectious diseases in the first quarters， Zhejiang Province， and to explore more effective countermeasures against infectious diseases. MethodsDescriptive epidemiology was conducted to determine the change in notifiable infectious diseases during the prevention and control of COVID-19 in Zhejiang Province by retrieving the data of notifiable infectious diseases from 2017 to 2022 in the Chinese information system for disease control and prevention. Cumulative reported new cases of notifiable infectious diseases in the first quarters of 2017‒2019 were compared with that of 2020‒2022. ResultsA total of 546 753 cases of notifiable infectious diseases were newly reported in the first quarters of 2017‒2019， with an average incidence of 321.92/10⁵. In contrast， a total of 509 908 cases of notifiable infectious diseases were newly reported in the first quarters of 2020‒2022， during which the COVID-19 epidemic occurred， with an average incidence of 270.39/10⁵. The incidence in 2020‒2022 significantly declined by 51.53/10⁵， compared with that in 2017‒2019 （χ²=8 072.06， P<0.001）. In the first quarters of 2020‒2022， the average incidence of zoonotic diseases and vector-borne diseases decreased by more than 50%. In addition， the incidence of respiratory， enteric， blood-borne， and sexually transmitted diseases declined to certain degree. ConclusionThe decline in the newly reported cases of non-COVID-19 notifiable infectious diseases in the first quarters of 2020‒2022 indicates that the countermeasures against COVID-19 epidemic， such as multi-disease co-prevention， multi-sectoral collaboration， societal mobilization and personal hygiene and protection， may also decrease the incidence of multiple infectious diseases. It suggests the countermeasures are effective， which would provide evidence for routine prevention and control of infectious diseases in future.