[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。

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Objective: To explore the association of physical activity and sugar sweetened beverage consumption with psychological sub health among middle school students in Bao an District, Shenzhen, so as to provide a reference for adolescent mental health promotion. Methods: A questionnaire survey was conducted in November 2024 by a stratified cluster random sampling method to select 6 926 junior and senior middle school students from 5 middle schools in Shenzhen. The questionnaire from Youth Risk Behavior Surveillance System was used to assess the consumption of sugar sweetened beverages, and physical activity Rating Scale was used to assess the level of physical activity, and Brief Instrument on Psychological Health of Youths was used to evaluate the psychological sub health status. The Chi -square test was used to analyze the differences in the detection rates of psychological sub health among different groups of middle school students, and a multivariate Logistic regression model was established to analyze the effects of physical activity and sugar sweetened beverage consumption and their combined effects on the psychological sub health of middle school students. Results: The detection rate of psychological sub health among middle school students in Bao an District, Shenzhen was 18.93%. Multivariate Logistic regression analysis showed that, after controlling for confounding factors such as gender, school stage, family residence, family economic status, parental literacy, academic stress and number of friends, lack of physical activity or excessive sugar sweetened beverage consumption were associated with increased risks of psychological sub health among middle school students ( OR =1.36, 1.45); and the highest risk of psychological sub health was found in middle school students who were lack of physical activity and excessive sugar sweetened beverage consumption ( OR =2.59) ( P <0.01). Further analysis by school stages showed that junior high school students with sufficient physical activity and excessive intake of sugary drinks ( ROR =2.10), lack of physical activity and excessive intake of sugary drinks ( ROR =2.31) were at higher risks of psychological sub health than senior high school students( P <0.05). Conclusions Insufficient physical activity and excessive sugar sweetened beverage consumption are closely associated with an increased risk of psychological sub health among middle school students. Effective interventions should be targeted to reduce the risk of psychological sub health problems among middle school students.

Objective To analyze the burden and epidemic trends of gastric cancer in China from 1990 to 2021, and to provide a scientific basis for the formulation of effective prevention and control strategies. Methods　Data from the 2021 Global Burden of Disease (GBD) database were used to extract the number of the incidence, prevalence, and death cases, as well as the disability-adjusted life years (DALY) for gastric cancer in China from 1990 to 2021. The corresponding crude rates and age-standardized rates were calculated. The Joinpoint regression model was employed to analyze the trends in the burden of gastric cancer, and a comprehensive examination was conducted from multiple dimensions including age, gender, and time. Results From 1990 to 2021, the age-standardized incidence rate (ASIR) of gastric cancer in China decreased from 48.03 per 100,000 to 29.05 per 100,000, the age-standardized prevalence rate (ASPR) decreased from 67.17 per 100,000 to 57.23 per 100,000, the age-standardized mortality rate (ASMR) decreased from 46.05 per 100,000 to 21.51 per 100,000, and the age-standardized DALY rate (ASDR) decreased from 1181.61 per 100,000 to 501.26 per 100,000. The AAPCs of ASIR, ASPR, ASMR, and ASDR were -1.61%, -0.50%, -2.44%, and -2.75%, respectively. The incidence, prevalence, mortality and DALY rates showed a trend of increasing first and then decreasing with age. Although females had higher incidence, prevalence, mortality, and DALY numbers in the older age groups, males exhibited higher crude rates across all age groups. Conclusion　The overall disease burden of gastric cancer in China showed a downward trend from 1990 to 2021, and men and middle-aged and elderly people are the key populations for prevention and control efforts.

Objective:To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing.Methods:From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed.Results:The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [ M ( Q1, Q3) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant ( P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups ( P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion:The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective:To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing.Methods:From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed.Results:The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [ M ( Q1, Q3) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant ( P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups ( P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion:The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

Objective: To investigate the prevalence and associated factors of sexting among college students in Jiangxi Province, so as to provide a reference for sexual education interventions in colleges. Methods: A combined method of random cluster sampling and convenience sampling was used to conduct an anonymous questionnaire survey on 13 042 students from 14 colleges in Jiangxi Province in October 2023. A self designed questionnaire was used to collect data on sexting among students, and Chi square tests and binary Logistic regression analysis were conducted to explore the factors associated with sexting among college students in Jiangxi Province. Results: The reported rate of sexting among college students in Jiangxi Province was 11.5%. Binary Logistic regression analysis showed that female students, non only children, and those who do not view pornographic novels/videos/films had a lower likelihood of engaging in sexting ( OR =0.72, 0.83, 0.23, P <0.05). Students who identified as homosexual, lacked knowledge about AIDS, did not mind premarital sex, and had indifferent attitudes towards multiple sexual partners were more likely to engage in sexting ( OR =1.66, 1.53, 1.25, 2.26, 1.78, P <0.05). Students who smoke, drink, and report a history of high risk sexual behavior were more likely to engage in sexting behavior ( OR=1.38-12.20, P <0.05); night owls showed a negative correlation with sexting behavior ( OR=0.24-0.58, P <0.05). Conclusions A significant proportion of college students in Jiangxi Province engage in sexting. It is recommended that colleges and universities strengthen their sexual education efforts and focus on cultivating internet literacy to promote the physical and mental health development of college students.

Objective:To investigate the relationship between plasma fluoride content, daily calcium intake and blood cell parameters in children and adolescents.Methods:This study was based on the National Health and Nutrition Examination Survey (NHANES) database of the United States from 2013 to 2016, with 3 684 children and adolescents aged 6 - 19 as the research subjects. Information on plasma fluoride content, daily calcium intake and blood cell parameters from the database were collected. Non-linear relationships between plasma fluoride content, daily calcium intake and blood cell parameters were analyzed using restricted cubic splines. If there was a non-linear relationship, the optimal inflection point was calculated using threshold/saturation effect analysis method. Subsequently, multiple linear regression models were used to analyze the associations among the three, and the modification effect of daily calcium intake (binary classification, stratified by median daily calcium intake) on the association between plasma fluoride content and blood cell parameters was analyzed.Results:There was no non-linear relationship between plasma fluoride content and white blood cell count, hemoglobin content and platelet count ( Pnon-linear > 0.05), but there was a non-linear relationship between plasma fluoride content and erythrocyte count and hematocrit ( Pnon-linear < 0.001). After adjusting for confounding factors, the optimal inflection points of the effects of plasma fluoride content on erythrocyte count and hematocrit were 0.54 and 0.31 μmol/L, respectively. There was no non-linear relationship between daily calcium intake and blood cell parameters ( Pnon-linear > 0.05). After adjusting for confounding factors, for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.49 × 10 9/L ( P = 0.009). There was a saturation effect in the association between plasma fluoride content, erythrocyte count and hematocrit: when plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.46 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 6.29% for every 1 μmol/L increase ( P = 0.006). The above associations were not statistically significant when plasma fluoride content was higher than the optimal inflection points ( P > 0.05). After stratification according to the median daily calcium intake, in the low-calcium group (daily calcium intake < 0.87 g), for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.77 × 10 9/L ( P = 0.001). When plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.41 × 10 12/L for every 1 μmol/L increase ( P = 0.002). When plasma fluoride content was ≥0.54 μmol/L, erythrocyte count decreased by 0.47 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When the plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 8.29% for every 1 μmol/L increase ( P = 0.011). The above associations were not statistically significant in the high-calcium group (daily calcium intake ≥0.87 g, P > 0.05). There was an interaction of daily calcium intake and plasma fluoride content on platelet count ( Pinteraction = 0.070), as demonstrated by an increase in platelet count of 12.68 × 10 9/L ( P = 0.013) in the low-calcium group and a decrease in platelet count of 9.05 × 10 9/L ( P = 0.035) in the high-calcium group for every 1 μmol/L increase in plasma fluoride content. Conclusions:The blood cell parameters of children and adolescents are closely related to plasma fluoride content, but not directly related to daily calcium intake. However, the correlation between plasma fluoride content and blood cell parameters varies among different calcium intake populations, and daily calcium intake can modify the association between plasma fluoride content and platelet count.

Objective:To analyze the cognitive changes and alterations in the topological properties of functional and structural brain networks in elderly women with mild cognitive impairment (MCI), and explore the relationship between brain network and cognitive function, and find the neuroimaging mechanism of cognitive decline in female patients with MCI.Methods:A cross-sectional study was conducted, collecting clinical data from 38 elderly women with MCI, aged 60-79, recruited between October 1, 2019 and May 31, 2021, through community visits, online advertisements, free consultations by experts at the First Hospital of China Medical University and outpatient promotions. A matched control group of 37 healthy women of similar age was also recruited. Both groups underwent comprehensive neuropsychological assessments and MRI data collection, Brain functional and structural networks were constructed, and the corresponding global and nodal topological metrics were calculated. Differences in general demographic data, cognitive function scores, and network topology attribute indexes were compared. Pearson correlation analysis was used to explore the relationship between the altered topological properties of brain networks and cognitive function differences.Results:Cognitive function assessments showed that compared to the healthy control group, elderly women with MCI scored lower on the Rey Auditory Verbal Learning Test-N5 (AVLT-N5), Digit Span Test (DST), Clock Drawing Test (CDT), and Verbal Fluency Test (VFT) (1.95±1.02 vs 6.42±1.63, t=14.85; 7.14±1.58 vs 8.08±1.29, t=2.93; 3.30±1.12 vs 3.73±0.55, t=2.20; 15.49±3.87 vs 18.53±3.80, t=3.60; all P<0.05). The results of brain functional and structural network nodal topological properties indicated that the left inferior parietal angular gyri, left supramarginal gyrus, right orbital inferior frontal gyrus, and right insula showed incomplete white matter network structure or reduced efficiency in brain network functional transmission ( P<0.05). Conversely, regions such as the left cuneus, left superior frontal gyrus orbital part, left middle occipital gyrus, left precuneus, right superior parietal gyrus, and left paracentral lobule showed enhanced structural integrity of white matter network or increased efficiency in brain network functional transmission ( P<0.05). Correlation analysis suggested that abnormal nodal topological attributes were associated with language function (VFT), short-term memory (AVLT-N5), and visuospatial ability (CDT) in patients with MCI(All P<0.05). Conclusion:Elderly women with MCI exhibit declines in short-term memory, linguistic function, attention, and visuospatial abilities. Changes in the topological properties of brain function and structural networks occur in regions such as the orbital superior frontal gyrus, middle occipital gyrus, and cuneus in the elderly women.