Objective:To investigate effect of galangin(Gal)on immune function in nephrotic syndrome(NS)rats by regula-ting stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods:A NS rat model was established by injecting doxorubicin into tail vein.After successful modeling,rats were randomly grouped into Model group,Gal low,medium and high doses groups,activator group.Twelve rats were randomly selected as control group,and each group was given corre-sponding drug by gavage and intraperitoneal injection,once a day for 6 consecutive weeks.Biochemical indicators such as 24-hour urine protein,urea nitrogen(BUN),creatinine(Scr)and total cholesterol(TC)were detected in rats;HE staining was applied to observe pathological damage in rat kidney tissue;spleen and thymus were taken and weighed,and organ index was calculated;flow cytometry was applied to detect levels of CD3+T,CD4+T,CD8+T,Th1 and Th2 cells in rat peripheral blood;ELISA was applied to detect IL-10,IL-2,TNF-α,IgG and IgM in serum;qRT-PCR and Western blot were applied to detect mRNA and protein expressions of SDF-1 and CXCR4.Results:Compared with control group,24-hour urine protein,BUN,Scr,TC,triglyceride(TG)contents,CD8+T,Th1,Th1/Th2,IL-2,TNF-α,SDF-1,CXCR4 mRNA and protein expressions of rats in Model group were obviously in-creased,albumin(ALB)content,spleen index,thymus index,CD3+T,CD4+T,Th2 cell proportions,CD4+T/CD8+T,IL-10,IgG,and IgM levels were obviously reduced(P<0.05);compared with Model group,24-hour urine protein,BUN,Scr,TC,TG contents,CD8+T,Th1,Th1/Th2,IL-2,TNF-α,SDF-1,CXCR4 mRNA and protein expressions of rats in Gal low,medium and high doses groups were gradually decreased,ALB content,spleen index,thymus index,CD3+T,CD4+T,Th2 cell proportions,CD4+T/CD8+T,IL-10,IgG and IgM levels were gradually increased(P<0.05);compared with high-dose Gal group,changes in above indicators in activator group of rats were obviously reversed(P<0.05).Conclusion:Gal may enhance T lymphocyte immune function by inhibiting SDF-1/CXCR4 pathway,thereby alleviating renal injury in NS rats.

AIM:Regulatory T cells(Tregs)are a specialized subset of CD4+T cells primarily involved in im-munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen-tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un-explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1fl/fl)mice and Treg-specific AMPKα1 knockout mice(AMPKα1fl/flFoxp3cre mice).RESULTS:Compared to AMPKα1fl/fl mice,the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significant-ly reduced.Additionally,while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure,both its size and the ra-tio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduc-tion in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4+T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice.Importantly,the proportion of Siglec-F+CD11b+eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4+T cells in peripheral blood,alongside a decrease in the proportion of mature CD8+T cells.Similar-ly,the proportion of CD4+T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice.In lymph nodes,the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1fl/fl mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3+T cell population,particularly the CD8+T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1fl/flFoxp3cre mice,the percentage of CD4+T cells was markedly in-creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/fl mice.CONCLUSION:The populations of mature Tregs,CD8+T cells and eosinophils in various im-mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.

Objective:To analyze the clinicopathological factors affecting the prognosis of patients after curative resection of lung metastases (LMs) from colorectal cancer (CRC) and to construct a clinical risk scoring (CRS) model.Methods:This study retrospectively collected clinicopathological data and follow-up information on 132 patients who underwent radical resection of LMs from CRC at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2010 and December 2020. We analyzed the clinicopathological factors influencing patient prognosis using univariate and multivariate Cox proportional hazards regression models, and we developed a risk stratification model for prognostic prediction.Results:The median follow-up duration for the cohort of 132 patients was 54.2 months. During this period, 61 patients (46.2%) experienced recurrence or distant metastasis, resulting in a 5-year DFS rate of 54.1%. Additionally, 33 patients (25.0%) died, corresponding to a 5-year overall survival (OS) rate of 76.7%. Univariate Cox proportional hazards regression model analysis indicated that ten clinicopathological factors were significantly associated with OS (all P＜0.05). These factors include the total number of lymph nodes (LNs) dissected from the primary tumor (PT) <16, the number of negative LNs from the PT <13, pN(+) of the PT, logarithmic odds of positive lymph nodes (LODDS) of the PT ≥-1.1, lymph nodes ratio (LNR) of the PT ≥0.02, preoperative carcinoembryonic antigen (CEA) level before LMs resection ≥10 ng/ml, the presence of hilar/mediastinal LN metastasis, the number of LMs ≥2, the maximum diameter of LMs ≥2.5 cm, and the necessity for hilar/mediastinal lymphadenectomy. Multivariate Cox proportional hazards regression analysis identified the number of negative LNs <13 ( HR=3.01, 95% CI: 1.28-7.03, P=0.011), pN(+) of the PT ( HR=5.04, 95% CI: 1.51-16.84, P=0.009), preoperative CEA level before LMs resection ≥10 ng/ml ( HR=5.39, 95% CI: 1.80-16.19, P=0.003), the number of LMs ≥2 ( HR=2.47, 95% CI: 1.09-5.60, P=0.030), and the necessity for hilar/mediastinal lymphadenectomy ( HR=2.74, 95% CI: 1.15-6.52, P=0.023) as independent prognostic risk factors. Patients were categorized based on independent risk factors, revealing statistically significant differences in OS across the groups with CRS scores of ≤2, 3～4, and ≥5 ( P＜0.001). Conclusions:Independent risk factors associated with LMs from CRC patients include the number of negative LNs <13, pN(+) of the PT, preoperative CEA level before LMs resection ≥10 ng/ml, the number of LMs ≥2, and the necessity for hilar/mediastinal lymphadenectomy. Patients scoring 3 or higher on the CRS model may warrant cautious assessment for the appropriateness of direct surgical treatment.

Objective:To investigate whether continued low-dose aspirin (LDA) intervention affects the incidence of pre-eclampsia (PE) and adverse pregnancy outcomes in pregnant women with high-risk PE screening in the first trimester and reassessed as low risk at 28 weeks of gestation.Methods:This study was a prospective observational cohort study. From April 2022 to April 2024, a total of 106 pregnant women who underwent prenatal examination in the Affiliated Jiangyin Hospital of Nantong University were enrolled. They were assessed as high risk of PE by multiple indicators combined screening at 11-13 +6 weeks of gestation, received LDA intervention, and were reassessed as low risk of PE at 28 weeks of gestation. The patients were divided into withdrawal group (49 cases) and continuation group (57 cases). The incidence of PE and adverse pregnancy outcomes were compared between the two groups. Results:(1) There were no statistically significant differences in general conditions and the incidence of pregnancy complications between the two groups (all P>0.05). During the PE risk screening at 11-13 +6 weeks of gestation, there were no statistically significant differences in mean arterial pressure (MAP) and ultrasound uterine artery pulsation index (UtPI) between the two groups (all P>0.05), but the placental growth factor (PlGF) level in the withdrawal group was significantly lower than that in the continuation group ( P=0.023). There was no significant difference in the proportion of pregnant women with high risk of PE before 32 weeks and 34 weeks of pregnancy between the two groups (all P>0.05). (2) There were 7 cases (14%, 7/49) of PE in the withdrawal group, including 1 case (2%, 1/49) of early-onset PE and 3 cases (6%, 3/49) of PE before 37 weeks of pregnancy. There were 11 cases (19%, 11/57) of PE in the continuation group, including 2 cases (4%, 2/57) of early-onset PE and 4 cases (7%, 4/57) of PE before 37 weeks of pregnancy. There were no significant differences in the incidence of PE (including early-onset PE and PE before 37 weeks of pregnancy), gestational hypertension, severe PE, chronic hypertension complicated with PE and chronic hypertension complicated with pregnancy between the two groups (all P>0.05). (3) There were no significant differences in cesarean section rate, preterm birth rate, placental abruption, postpartum hemorrhage, fetal growth restriction, fetal distress rate, neonatal birth weight, neonatal asphyxia, and 1-minute and 5-minute Apgar scores between the two groups (all P>0.05). No stillbirth occurred in the two groups. Conclusion:For pregnant women with high risk of PE screening in the first trimester and taking LDA intervention, there is no difference in the incidence of PE and adverse pregnancy outcomes whether to continue LDA or not after being reassessed as low risk at 28 weeks of gestation.

The “Technical Guideline for Epidemic Prevention and Control Disinfection in Large-Scale Events”(hereinafter referred to as “the Guideline”), organized and compiled by the National Disease Control and Prevention Administration, was officially released in April 2024. This guideline aims to ensure the effective implementation of large-scale group activities, mitigate the impact of infectious disease outbreaks on such events, and maintain hygiene and safety standards at event venues. During the compilation process, data were systematically collected in alignment with epidemic prevention requirements and disinfection principles, incorporating research findings from domestic and international disinfection practices. Information was gathered through field investigations, expert consultations in epidemiology and disinfection, and roundtable discussions with representatives from organizations responsible for disinfection operations at large-scale events, thereby ensuring the scientific rigor and practical applicability of the content. The Guideline provides comprehensive technical disinfection guidance for relevant authorities and event organizers, addressing critical aspects such as disinfection protocols, operational principles, emergency response strategies, and technical specifications. By standardizing hygiene assurance measures for large-scale events, including considerations of participant demographics, venue characteristics, and event scale, the guideline establishes a framework to proactively minimize the risk of infectious disease transmission.

To analyze the epidemiological characteristics of COVID-19 in Fujian Province from the 49th week of 2022 to the 5th week of 2023,after further optimization of China's COVID-19 prevention and control measures on December 7,2022(the 49th week of 2022),this study used multi-dimensional surveillance data to dynamically assess population infection levels and their changing trends.The aim of the study was to provide a scientific basis for early warning of epidemic risk,medical resource allocation,and evalu-ation of socio-economic impact.A multi-source data surveillance system was constructed,encompassing surveillance of fever clinics at medical institutions(weekly collection of visits,positive nucleic acid and antigen test results,inpatients,and severe cases in sec-ondary or above hospitals),population nucleic acid test monitoring(weekly person-times and positivity rates of single-tube tests from the provincial system),sentinel hospital monitoring(weekly proportion of influenza-like illness visits at 18 sentinel hospitals and re-lated viral testing data),and monitoring of novel coronavirus variants(weekly systematic collection of genomic sequences of local and imported cases).Line charts were plotted weekly,and time series analysis,molecular epidemiological methods,and an improved SEIAR model were used to simulate epidemic spread.During the study period,the COVID-19 epidemic in Fujian Province exhibited three distinct stages.In the infection peak stage(52nd week of 2022),the provincial fever clinic visits reached 606 893 person-times,and a 49.2%positivity rate in population single-tube nucleic acid tests and 63.8%positivity rate in sentinel hospital monitoring were observed.In the medical load peak stage(2nd week of 2023),274 460 inpatients and 28 487 severe cases were recorded.In the epidemic decline stage(4th to 5th weeks of 2023),fever clinic visits decreased by 96.3%with respect to the peak,the single-tube nucleic acid test positivity rate decreased to 6.3%,and the sentinel hospital COVID-19 nucleic acid test positivity rate was 6.4%.All 508 sequenced local cases were Omicron variants,predominantly BA.5.2 and its sub-lineages(67.4%).Among 56 imported se-quenced cases,BA.5.2 and its sub-lineages accounted for 50.0%,and 16.1%comprised nine variants of interest including XBB and BQ.The model predicted the infection peak in the 52nd week of 2022,whereas the hospitalization peak lagged by approximately 10.6 days.Multi-source data monitoring revealed a three-stage development of the COVID-19 epidemic in Fujian.The BA.5.2 strain was dominant during the epidemic.The combination of multi-source monitoring data and modeling provides important references for epi-demic prevention and control,and highlights the need to improve the monitoring system in follow-up.

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0％,10％,and 20％)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20％silicate bioactive glass fibers have a more obvious effect.

Objective: To investigation and analyze the causes and characteristics of a food poisoning incident caused by Clostridium perfringens in schools, so as to provide a reference for prevention and control of food poisoning incidents. Methods: From March 11 to 12,2024,on site epidemiological and hygienic investigations were conducted by using food poisoning case questionnaires and on site hygienic investigation forms in Shenzhen. Information related to the poisoning incident was collected through field investigations and telephone interviews. A case control study was used to analyze the suspected food responsible for the incident. Risk analysis in χ 2 analysis was used to obtain OR values. Results: The Clostridium perfringens food poisoning incident involved two schools, with a cumulative total of 52 cases. School A had an attack rate of 2.21%(45/2 040), school B had an attack rate of 1.29% (7/544). The main clinical symptoms were diarrhea (100.00%) and abdominal pain (84.62%), with a minority experiencing fever ( 3.85 %). Analysis via the case control study indicated that consuming mushroom and meat sauce during lunch on March 11, 2024, was a risk factor for the poisoning incident ( OR =124.50, 95% CI =14.53-937.51, P <0.05). On site investigation revealed that the mushroom and meat sauce provided by the schools on March 11 was prepared by the catering company the previous day, stored without refrigeration, and not reheated before serving the next day. A total of 31 patient anal swabs, 16 food samples, and 14 kitchen staff anal swabs were sent for laboratory testing. Clostridium perfringens was isolated from 22 case samples. Among these, type A Clostridium perfringens (alpha toxin) was detected in 8 case samples, 4 kitchen staff anal swabs, and 2 retained samples of the mushroom and meat sauce. Conclusions The incident is a food poisoning outbreak caused by Clostridium perfringens contamination in schools. Avoiding cross contamination and ensuring proper storage are key to preventing Clostridium perfringens food poisoning.