[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

OBJECTIVE To investigate the suspected outbreak of one incident of carbapenem-resistant Acinetobacter baumannii(CRAB)infection in an intensive care unit(ICU)so as to provide experience and reference for preven-tion and control of multidrug-resistant organisms(MDROs)infections in a grass-root hospital.METHODS The epidemiological survey and environmental hygiene surveillance were performed for 8 patients with CRAB infection who were detected in ICU of Qingbaijiang District People's Hospital from Jul.21,2022 to Aug.6,2022 so as to find out the infection sources and transmission routes and take targeted intervention measures.RESULTS Totally 8 patients had CRAB infection in the ICU in a short time period,the drug resistance spectrum was basically the same;the CRAB infection/colonization rate was 12.50％(8/64),the incidence rate of CRAB infection was 7.81％(5/64),which was higher during this period than that during the same period in 2020 and 2021(P＜0.05).The environmental hygiene surveillance showed that the isolation rate of CRAB was 6.00％(3/50).The strains isolated from the hand washing sink between bed 2 and bed 3,the hanging tower of bed 13 and the countertops of treat-ment rooms showed the basically same result of drug susceptibility testing with CRAB strains isolated from the patients.This incident had been effectively under control through targeted prevention and control strategies such as the control and separation of the patients,subgrouping treatment and nursing,repeated deep cleaning and disinfec-tion as well as strict implementation of hand hygiene.CONCLUSION The overloaded enrollment of patients,insuf-ficient between-bed interval,poor and delayed cleaning and disinfection of environmental object surfaces,extensive contamination of instrument and facilities,spare supplies and hand washing sink are probably the leading causes of outbreak and prevalence of CRAB.

Objective:To analyze the characteristics of highly cited articles on spine and spinal cord injuries published in Chinese Journal of Trauma (hereinafter referred to as the "Journal") from 1985 to 2024. Methods:All the articles related to spine and spinal cord injuries published in the Journal from 1985 to 2024 were retrieved from the Wanfang Database and the articles with citation frequency ≥15 times were defined as highly cited, with the retrieval cut-off date of April 15, 2025. For articles related to spine and spinal cord injuries, the total publication count, number of cited articles, total citation frequency, average citation frequency per article, number of fund-supported articles were recorded and analyzed. For the highly cited articles among them, the total number of articles, types of literature, distribution periods, number of fund-supported articles, core authors, institution distribution, region distribution, frequency of and key words were also statistically analyzed.Results:From 1985 to 2024, the Journal published 1 182 articles on spinal and spinal cord injuries, of which 993 (84.01%) were cited, with a total citation frequency of 10 739 and an average of 10.81 citations per article. A total of 388 articles (32.83%) were supported by research funds. There were 184 highly cited articles on spinal and spinal cord injuries, with the following characteristics: (1) The most common type of highly cited literature was original articles (150 articles, 81.52%), while consensus and guideline articles achieved the highest average citation rate (44.75 citations per article). (2) The period 2015-2019 had the highest number of highly cited articles, accounting for 33.70%. (3) Fifty-four highly cited articles (29.35%) were supported by research funds, including 19 by national-level funds and 35 by funds of other levels. (4) Among the highly cited articles, 8 (4.35%) were authored by one person, and 176 (95.65%) were co-authored by two or more persons. Sixty-two authors who published ≥3 highly cited articles were identified as core authors. (5) A total of 123 highly cited articles (66.85%) were authored by researchers affiliated with a single institution, whereas 61 articles (33.15%) were the result of inter-institutional collaboration. Fifteen first-author institutions published≥3 highly cited articles. (6) Regions with ≥15 highly cited articles were Zhejiang Province (28 articles), Chongqing Municipality (23 articles), Guangdong Province (18 articles), Shaanxi Province (18 articles), Jiangsu Province (16 articles), and Shanghai Municipality (15 articles). (7) The top five key words in the highly cited articles were "spinal fractures" (71 times), "thoracic vertebrae" (45 times), "lumbar vertebrae" (44 times), "spinal cord injuries" (27 times), and "vertebroplasty" (27 times).Conclusions:Over the 40-year period, original articles constitute the majority of highly cited articles on spine and spinal cord injuries in the Journal, while consensus and guideline articles demonstrate the highest average citation frequency. Nearly 30% of the highly cited articles receive research funding support. Core authors and institutions show a relatively concentrated distribution, with spinal fractures, spinal cord injuries, and vertebroplasty emerging as research hotspots in the field.

Objective:To analyze the current policy design of outpatient benefit policies for patients with hypertension and diabetes(H&D)in urban and rural residents in China,and to provide references for optimizing the outpatient benefit mechanism for patients with H&D.Methods:A questionnaire survey was conducted to collect data on the basic features of General Outpatient Benefit(GOB),Outpatient Medication Guarantee Mechanisms for Hypertension and Diabetes(OMGM-H&D)and Outpatient Benefit for Patient with Chronic and Special Diseases(OB-C&S),focusing on deductibles,policy reimbursement ratios,and maximum payment limits.Descriptive statistical analysis was performed on the data.Results:A total of 334 regions were surveyed,of which 253 regions(75.34％)had implemented all three policies.Regional analysis revealed significant differences(P<0.001)in reimbursement ratios for GOB and the OMGM-H&D between the eastern,central,and western regions,with the western region having notably higher ratios than the eastern and central regions.However,no significant difference (P>0.05) was observed in the reimbursement ratios for OB-C&S across regions. Regarding deductibles,no significant regional difference (P>0.05) was found for GOB,but significant differences (P<0.05) existed for the OMGM-H&D and OB-C&S. Additionally,the annual maximum payment limits for all three policies showed significant regional variations (P<0.001). Conclusions:The outpatient benefits policy for patients with H&D have achieved full coverage nationwide among urban and rural residents in China,but regional equity in benefit levels requires improvement. It is recommended to strengthen data feedback mechanisms and promote provincial-level pooling of medical insurance.

AIM To compare total sugar,total protein,total phenol,total flavonoid,calycosin-7-O-β-D-glucoside,liquiritin,lobetyolin,quercetin,isoferulic acid,hesperidin,glycyrrhizic acid contents and their antioxidant activities,hypoglycemic activities of big honey pill,small honey pill,water pill,concentrated pill,granule,mixture and decoction of Buzhong Yiqi Recipe.METHODS Anthraquinone-sulfuric acid method,Coomassie brilliant blue method,Folin-phenol colorimetry method,sodium nitrite-aluminum nitrate method and HPLC were adopted in the content determination of total sugar,total protein,total phenol,total flavonoid and seven constituents,respectively,after which the scavenging capacities,reducing powers on DPPH·free radical,ABTS+free radical,hydroxyl free radical,and inhibition capacity on α-glucosidase activity were detected.Subsequently,correlation analysis was performed.RESULTS Total sugar,total protein,total phenol and total flavonoid contents demonstrated significant differences among different dosage forms(P＜0.05,P＜0.01).Calycosin-7-O-β-D-glucoside,glycyrrhizin,codonoside and quercetin displayed the highest contents in the decoction,while those of isoferulic acid,hesperidin and glycyrrhizin were observable in the mixture.The water pill exhibited the strongest antioxidant activity,while those of the concentrated pill and mixture were weak;the big honey pill exhibited the strongest hypoglycemic activity,while that of the decoction was the weakest.Total protein,total phenol,total flavonoid and liquiritin contents displayed significant positive correlations between antioxidant activity(P＜0.05,P＜0.01),while hesperidin content displayed significant negative correlation between the latter(P＜0.05);total protein,calycosin-7-O-β-D-glucoside,codonoside and quercetin contents displayed significant negative correlations between hypoglycemic activity(P＜0.05,P＜0.01).CONCLUSION Active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms exist differences,total sugar,total protein,total flavonoids,calycosin-7-O-β-D-glucoside,licorice glycoside,hesperidin,codonoside and quercetin can be taken as quality control indices for this prescription.

OBJECTIVE To investigate the suspected outbreak of one incident of carbapenem-resistant Acinetobacter baumannii(CRAB)infection in an intensive care unit(ICU)so as to provide experience and reference for preven-tion and control of multidrug-resistant organisms(MDROs)infections in a grass-root hospital.METHODS The epidemiological survey and environmental hygiene surveillance were performed for 8 patients with CRAB infection who were detected in ICU of Qingbaijiang District People's Hospital from Jul.21,2022 to Aug.6,2022 so as to find out the infection sources and transmission routes and take targeted intervention measures.RESULTS Totally 8 patients had CRAB infection in the ICU in a short time period,the drug resistance spectrum was basically the same;the CRAB infection/colonization rate was 12.50％(8/64),the incidence rate of CRAB infection was 7.81％(5/64),which was higher during this period than that during the same period in 2020 and 2021(P＜0.05).The environmental hygiene surveillance showed that the isolation rate of CRAB was 6.00％(3/50).The strains isolated from the hand washing sink between bed 2 and bed 3,the hanging tower of bed 13 and the countertops of treat-ment rooms showed the basically same result of drug susceptibility testing with CRAB strains isolated from the patients.This incident had been effectively under control through targeted prevention and control strategies such as the control and separation of the patients,subgrouping treatment and nursing,repeated deep cleaning and disinfec-tion as well as strict implementation of hand hygiene.CONCLUSION The overloaded enrollment of patients,insuf-ficient between-bed interval,poor and delayed cleaning and disinfection of environmental object surfaces,extensive contamination of instrument and facilities,spare supplies and hand washing sink are probably the leading causes of outbreak and prevalence of CRAB.

Objective:To analyze the current policy design of outpatient benefit policies for patients with hypertension and diabetes(H&D)in urban and rural residents in China,and to provide references for optimizing the outpatient benefit mechanism for patients with H&D.Methods:A questionnaire survey was conducted to collect data on the basic features of General Outpatient Benefit(GOB),Outpatient Medication Guarantee Mechanisms for Hypertension and Diabetes(OMGM-H&D)and Outpatient Benefit for Patient with Chronic and Special Diseases(OB-C&S),focusing on deductibles,policy reimbursement ratios,and maximum payment limits.Descriptive statistical analysis was performed on the data.Results:A total of 334 regions were surveyed,of which 253 regions(75.34％)had implemented all three policies.Regional analysis revealed significant differences(P<0.001)in reimbursement ratios for GOB and the OMGM-H&D between the eastern,central,and western regions,with the western region having notably higher ratios than the eastern and central regions.However,no significant difference (P>0.05) was observed in the reimbursement ratios for OB-C&S across regions. Regarding deductibles,no significant regional difference (P>0.05) was found for GOB,but significant differences (P<0.05) existed for the OMGM-H&D and OB-C&S. Additionally,the annual maximum payment limits for all three policies showed significant regional variations (P<0.001). Conclusions:The outpatient benefits policy for patients with H&D have achieved full coverage nationwide among urban and rural residents in China,but regional equity in benefit levels requires improvement. It is recommended to strengthen data feedback mechanisms and promote provincial-level pooling of medical insurance.

Objective:To analyze the characteristics of highly cited articles on spine and spinal cord injuries published in Chinese Journal of Trauma (hereinafter referred to as the "Journal") from 1985 to 2024. Methods:All the articles related to spine and spinal cord injuries published in the Journal from 1985 to 2024 were retrieved from the Wanfang Database and the articles with citation frequency ≥15 times were defined as highly cited, with the retrieval cut-off date of April 15, 2025. For articles related to spine and spinal cord injuries, the total publication count, number of cited articles, total citation frequency, average citation frequency per article, number of fund-supported articles were recorded and analyzed. For the highly cited articles among them, the total number of articles, types of literature, distribution periods, number of fund-supported articles, core authors, institution distribution, region distribution, frequency of and key words were also statistically analyzed.Results:From 1985 to 2024, the Journal published 1 182 articles on spinal and spinal cord injuries, of which 993 (84.01%) were cited, with a total citation frequency of 10 739 and an average of 10.81 citations per article. A total of 388 articles (32.83%) were supported by research funds. There were 184 highly cited articles on spinal and spinal cord injuries, with the following characteristics: (1) The most common type of highly cited literature was original articles (150 articles, 81.52%), while consensus and guideline articles achieved the highest average citation rate (44.75 citations per article). (2) The period 2015-2019 had the highest number of highly cited articles, accounting for 33.70%. (3) Fifty-four highly cited articles (29.35%) were supported by research funds, including 19 by national-level funds and 35 by funds of other levels. (4) Among the highly cited articles, 8 (4.35%) were authored by one person, and 176 (95.65%) were co-authored by two or more persons. Sixty-two authors who published ≥3 highly cited articles were identified as core authors. (5) A total of 123 highly cited articles (66.85%) were authored by researchers affiliated with a single institution, whereas 61 articles (33.15%) were the result of inter-institutional collaboration. Fifteen first-author institutions published≥3 highly cited articles. (6) Regions with ≥15 highly cited articles were Zhejiang Province (28 articles), Chongqing Municipality (23 articles), Guangdong Province (18 articles), Shaanxi Province (18 articles), Jiangsu Province (16 articles), and Shanghai Municipality (15 articles). (7) The top five key words in the highly cited articles were "spinal fractures" (71 times), "thoracic vertebrae" (45 times), "lumbar vertebrae" (44 times), "spinal cord injuries" (27 times), and "vertebroplasty" (27 times).Conclusions:Over the 40-year period, original articles constitute the majority of highly cited articles on spine and spinal cord injuries in the Journal, while consensus and guideline articles demonstrate the highest average citation frequency. Nearly 30% of the highly cited articles receive research funding support. Core authors and institutions show a relatively concentrated distribution, with spinal fractures, spinal cord injuries, and vertebroplasty emerging as research hotspots in the field.