Objective To investigate whether curcumin is a potential drug for the treatment of gastrointestinal stromal tumors(GIST).Methods The differential genes of imatinib-resistant cells and non-resistant cells were analyzed by cell transcriptology.The antitumor activity of curcumin was verified by cell counting kit-8(CCK-8)method,and the concentration of Curcumin ranged from 5 to 80 μg·mL-1for GIST-T1 and GIST-T1/IMR cells.20 μg·mL-1 Curcumin as the experimental group,phosphate buffered solution as the control group.The contents of interleukin-6(IL-6),reactive oxygen species(ROS)and nitric oxide(NO)were measured by enzyme linked immunosorbent assay.The cell cycle changes were analyzed by flow cytometry.Results Using non-resistant cells as a contrast,the results showed that there were 1 300 up-regulated genes and 1 609 down-regulated genes in imatinib-resistant cells.The 50％inhibiting concentration values of Curcumin on GIST-T1 and GIST-T1/IMR cells were(15.33±1.36)and(10.49±2.12)μg·mL-1,respectively.In GIST-T1 cells,the IL-6 levels in experimental group and control group were(3.45±0.01)and(5.64±0.42)pg·mL-1;the ROS levels were(2 841.42±81.83)and(4 174.32±439.12)pg·mL-1;the iNOS levels were(7.02±0.08)and(8.08±0.03)μmol·L-1,respectively.In GIST-T1/IMR cells,the IL-6 levels in experimental group and control group were(2.47±0.30)and(6.30±0.01)pg·mL-1;the ROS levels were(4 706.40±146.71)and(8 254.34±342.35)pg·mL-1;the iNOS levels were(6.42±0.09)and(7.29±0.04)μmol·L-1,respectively.Among the 2 cells,the differences of above indicators were statistically significant between the experimental group and the control group(P＜0.05,P＜0.01).Curcumin blocked the cell cycle of GIST-T1 and GIST-T1/IMR in G1 phase,further shortens S phase and G2 phase.Conclusion Curcumin can inhibit the secretion of inflammation and regulate the proliferation of GIST.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Biological evidence is relatively common evidence in criminal cases,and it has strong pro-bative power because it carries DNA information for individual identification.At the scene of fire-related cases,the complex thermal environment,the escape of trapped people,the firefighting and res-cue operations,and the deliberate destruction of criminal suspects will all affect the biological evi-dence in the fire scene.Scholars at home and abroad have explored and studied the effectiveness of biological evidence identification in fire scenes,and found that the blood stains,semen stains,bones,etc.are the main biological evidence which can be easily recovered with DNA in fire scenes.In order to analyze the research status and development trend of biological evidence in fire scenes,this paper systematically sorts out the relevant research,mainly including the soot removal technology,appearance method of typical biological evidence,and possibility of identifying other biological evidence.This pa-per also prospects the next step of research direction,in order to provide reference for the identifica-tion of biological evidence and improve the value of biological evidence in fire scenes.

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.

Foods can be contaminated with foodborne pathogens through a variety of pathways, including water, air and soil. Food safety events caused by foodborne pathogens show a serious impact on human health. However, due to the diversity of foodborne pathogens and the complexity of food matrices, the rapid detection of foodborne pathogens was difficult. The conventional microbial culture and physiological and biochemical identification can hardly meet the need of rapid detection of foodborne pathogens in the field. It is necessary to develop rapid detection technologies for foodborne pathogens. Clustered regularly interspaced short palindromic repeats (CRISPR) and associated protein (Cas) are an adaptive immune systems of prokaryotes with specific recognition and cleavage of nucleic acid sequences, which shows good potential for development of nucleic acid detection and biosensing in the field. According to different forms of application, paper-based analytical devices can be categorized into test paper, lateral flow assay and microfluidic paper-based chips, etc. As a good simplicity and low-cost analytical testing tools, they show good prospects in the field of rapid testing. Therefore, the rapid and sensitive detection of foodborne pathogens can be realized by combining the efficient recognition ability of CRISPR/Cas system and the simplicity of paper-based analytical devices. In this paper, we briefly introduce an overview of the CRISPR/Cas system for nucleic acid detection, and this section focuses on an overview of the features and principles of the class 2 system, including types II, V and VI, which uses a single effector. The application of CRISPR/Cas system based test paper analysis, lateral flow assay and microfluidic paper-based chips for the detection of foodborne pathogens are highlighted in the paper, and finally the advantages, current challenges and future prospects of CRISPR/Cas system in combination with paper-based analytical devices to establish detection methods are discussed.

Objective To investigate the screening and prevalence of tuberculosis among freshmen in different schools in Baoding City,and provide reference for tuberculosis control in schools.Methods Screening data of tu-berculosis and tuberculin test(PPD)of freshmen from 156 schools in different regions of Baoding City from Septem-ber 2021 to March 2022 were collected.PPD screening results of students from different regions and different school stages were analyzed and compared.Results A total of 68 177 freshmen from 156 schools were investigated for suspected symptoms and close contact history of pulmonary tuberculosis.PPD screening was conducted on 63 939 students.13 821 students were PPD positive,with a positive rate of 21.62％.3 083 students were strongly posi-tive,with a strong positive rate of 4.82％.15 cases of tuberculosis were found,and the reported incidence was 23.46/100 000.PPD positive rate and strong positive rate as well as incidence of tuberculosis in students in different school stages presented statistically significant differences(all P＜0.01).Positive rate and strong positive rate in students in different school stages showed upward trends(all P＜0.01).PPD positive rate and strong positive rate of students from schools in plain and mountainous areas presented statistically significant differences([22.28％vs 17.89％];[4.85％vs 3.62％],both P＜0.01).PPD positive rate and strong positive rate between students from boarding junior school and non-boarding junior school were significantly different,respectively([23.94％vs 21.60％];[5.07％vs 3.56％],both P＜0.01).Conclusion It is necessary to strengthen tuberculosis screening and health education for freshmen,especially those from boarding schools in plain areas,screening latent Mycobac-terium tuberculosis infection as early as possible,take corresponding measures to prevent and control the spread of tuberculosis,and reduce the risk of tuberculosis.

Objective:To investigate effects of mesalazine(MS)on proliferation,apoptosis and inflammatory injury of cell model of ulcerative colitis(UC)induced by lipopolysaccharide(LPS),as well as transforming growth factor-β1(TGF-β1)/Smad signaling pathway effect in this study.Methods:Human colonic epithelial cells NCM-460 cultured in vitro were induced UC model by LPS,and divided into Con group(no treatment),LPS group(1 mg/L LPS),MS group(0.1,0.2,0.4 mg/L MS+1 mg/L LPS)and inhibitor group(10 μmol/L TGF-β1/Smad signaling pathway inhibitor LY2109761+0.2 mg/L MS+1 mg/L LPS).Cell morphology,proliferation,apoptosis and levels of inflammatory factors and TGF-β1/Smad pathway-related markers were examined by inverted microscope,EdU assay,Hoechst 33258 staining,ELISA and Western blot.Results:LPS treatment highly induced cell proliferation rate and Smad7 pro-tein level compared with Con group,while apoptotic cells,inflammatory factors TNF-α and IL-6,soluble interleukin-2 receptor(sIL-2R)release,as well as TGF-β1,p-Smad2,p-Smad3 protein expressions were increased;the above effects induced by LPS was reversed by MS in a dose-dependent manner(P<0.05).Compared with 0.2 mg/L MS group,NCM-460 cells proliferation rate and Smad7 expression were increased,while apoptotic cells,TNF-α and IL-6,sIL-2R releases,and TGF-β1,p-Smad2,p-Smad3 protein expressions were decreased(P<0.05).Conclusion:MS can attenuate LPS-induced apoptosis and inflammatory injury in NCM-460 cells,and this protection was possibly through suppressing TGF-β1/Smad signaling pathway.

The author analyzed the characteristics of phase Ⅰ clinical trials of macromolecular drugs,the characteristics of evaluation indicators of phase Ⅰ clinical trials of macromolecular drugs,such as safety evaluation,pharmacokinetic and pharmacodynamic evaluation,and efficacy evaluation.And the control points of subjects management,management of experimental macromolecule drugs,and identified and potential risk factors of macromolecule drugs in the implementation of risk management for phase Ⅰ clinical trials of macromolecule drugs were discussed in depth based on previous clinical trial research experience.Through discussion and analysis,the author suggests that each research center can formulate risk control strategies according to the actual situation,improve the efficiency of risk control,and facilitate the smooth implementation of clinical trials and improve the quality of clinical trials.

Objective:To assess the impact of exposure to particulate matter with aerodynamic diameter ≤2.5 μm(PM2.5)on non-accidental mortality under different apparent temperature levels and to further explore the modification effect of apparent temperature.Methods:This study used time-series design.Tianjin and Ningbo from China,Bangkok and Chiang Mai from Thailand were selected as the re-search sites,and the apparent temperature was applied as the exposure index.Through the quantitative estimation of the threshold temperature,the corresponding pollutant concentration was divided into high and low levels,and the generalized Poisson additive model was used to evaluate the association between PM2.5 exposure and non-accidental death of residents at different temperature levels.Results:The ave-rage concentrations of PM2.5 in Tianjin,Ningbo,Bangkok,and Chiang Mai during the study period were(73.6±35.6),(48.0±32.1),(33.5±28.4)and(32.6±28.6)μg/m3,respectively;the average daily non-accidental death counts were 148,57,28,and 8.The analysis of the generalized Poisson addi-tive model showed that the daily non-accidental death counts increased by 0.43％(95％CI:0.33％-0.54％)per 10 μg/m3 increase of PM2.5 in lag 0 day in Tianjin of China;0.27％(95％CI:0.08％-0.46％)per 10 μg/m3 increase of PM2.5 in lag 2 days in Ningbo of China.The effect was magnified in high temperature levels in Tianjin and in low temperatures in Ningbo and Bangkok.The mortality effect of PM2 5 in various temperature levels stayed still in co-pollutant regression models.Conclusion:Exposure to fine particulate matter had an adverse effect on non-accidental mortality,which reminded us to give further attention to the pollution control.The findings also indicated that apparent temperature might modify mortality effects of PM2 .5 and the modification effect varied in different regions.Protective policies due to regional differences should be made and more scientific and social attention on mutual effect of air pollution and climate change needs to be appealed.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.