ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

Objective: To investigate the epidemiological characteristics and spatial-temporal clustering of severe fever with thrombocytopenia syndrome (SFTS) in Huai'an City, Jiangsu Province from 2011 to 2024, so as to provide a basis for optimizing local SFTS prevention and control strategies, and identifying high-risk areas and key populations. Methods: Data on SFTS incidence and deaths in Huai'an City from 2011 to 2024 were collected from the Infectious Disease Reporting Information System of the Chinese Disease Prevention and Control Information System. The reported incidence, mortality, and fatality rates were calculated. Descriptive analysis was performed on temporal, population, and regional distribution. The average annual percent change (AAPC) was used to analyze the trend in the reported incidence of SFTS. Global and local spatial autocorrelation analyses were employed to examine the spatial distribution patterns and spatial association patterns of SFTS incidence while spatio-temporal scanning analyses was used to assess the spatial-temporal clustering of SFTS. Results: A total of 337 SFTS cases were reported in Huai'an City from 2011 to 2024, with the reported incidence rising from 0.17/100 000 to 1.88/100 000. There were 20 deaths, with an average annual mortality of 0.03/100 000, and a fatality rate of 5.93%. The incidence showed obvious seasonality, with a peak in May and June (148 cases, accounting for 43.92%). Spring and summer accounted for 107 cases (31.75%) and 159 cases (47.18%), respectively. The reported SFTS cases were mainly male, farmers, and individuals aged ≥41 years, accounting for 56.38%, 79.23%, and 96.74%, respectively. The population distribution of death cases was basically consistent with that of incident cases. Xuyi County was a high-incidence area, with a total of 332 reported cases, accounting for 98.52%. All death cases were reported in this county. Spatial autocorrelation analyses revealed a positive spatial correlation in SFTS incidence from 2019 to 2024, with Moran's I values ranging from 0.214 to 0.336 (all P<0.05). Heqiao Town, Tianquanhu Town, and Guiwu Town in Xuyi County were identified as high-high clustering areas. Spatio-temporal scanning analyses showed that cluster 1 was consistent with the high-high clustering areas, with an aggregation time from the second quarter of 2019 to the second quarter of 2022. Conclusions From 2011 to 2024, the reported incidence of SFTS in Huai'an City showed an upward trend, with a high incidence in spring and summer. Males, farmers, and the middle-aged and elderly population were the key populations for prevention and control. Xuyi County was the key area for prevention and control.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

Malignant tumors are one of the major causes of death in the population. Owing to limited clinical treatments， susceptibility to drug resistance， and generally low cure rates of conventional therapies， new treatment strategies need to be explored. Compared with existing therapies， traditional Chinese medicine （TCM） has unique advantages， such as low side effects， in the treatment of malignant tumors. Ferroptosis is a recently characterized form of regulated cell death associated with iron metabolism imbalance， lipid peroxidation， antioxidant system malfunction and other aspects. Studies have shown that TCM regulates Fe³⁺， Fe²⁺， glutathione， glutathione peroxidase 4 and other substances related to ferroptosis， thereby affecting lipid peroxidation and antioxidant processes， and then inducing ferroptosis. Through these mechanisms， TCM plays a key role in inhibiting the growth and spread of tumor cells and is involved in multiple stages of malignant tumor progression. In this study， we systematically retrieved the literature indexed in PbuMed and China National Knowledge Infrastructure （CNKI） with the keywords TCM， ferroptosis， and malignant tumors. We outlined the mechanisms of ferroptosis and its association with malignant tumors， and summarized the research progress on the prevention and treatment of malignant tumors through the modulation of ferroptosis by TCM monomers， single herbs， and compounds. The study aims to provide new perspectives for the prevention and treatment of malignant tumors by TCM.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

Malignant tumors are one of the major causes of death in the population. Owing to limited clinical treatments， susceptibility to drug resistance， and generally low cure rates of conventional therapies， new treatment strategies need to be explored. Compared with existing therapies， traditional Chinese medicine （TCM） has unique advantages， such as low side effects， in the treatment of malignant tumors. Ferroptosis is a recently characterized form of regulated cell death associated with iron metabolism imbalance， lipid peroxidation， antioxidant system malfunction and other aspects. Studies have shown that TCM regulates Fe³⁺， Fe²⁺， glutathione， glutathione peroxidase 4 and other substances related to ferroptosis， thereby affecting lipid peroxidation and antioxidant processes， and then inducing ferroptosis. Through these mechanisms， TCM plays a key role in inhibiting the growth and spread of tumor cells and is involved in multiple stages of malignant tumor progression. In this study， we systematically retrieved the literature indexed in PbuMed and China National Knowledge Infrastructure （CNKI） with the keywords TCM， ferroptosis， and malignant tumors. We outlined the mechanisms of ferroptosis and its association with malignant tumors， and summarized the research progress on the prevention and treatment of malignant tumors through the modulation of ferroptosis by TCM monomers， single herbs， and compounds. The study aims to provide new perspectives for the prevention and treatment of malignant tumors by TCM.

[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。

OBJECTIVE: To explore the serological and molecular genetic characteristics of a family with subtype B(A)06. METHODS: A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036). RESULTS: The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family. CONCLUSION The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans ; ABO Blood-Group System/genetics* ; Female ; Pedigree ; Male ; Infant, Newborn ; Asian People/genetics* ; Genotype ; China ; Blood Grouping and Crossmatching ; Hyperbilirubinemia, Neonatal/blood* ; East Asian People

Objective To construct an index system for assessment of schistosomiasis transmission risk following natural disasters such as rainstorms, floods, earthquakes, mudslides, and landslides, so as to provide insights into rapid identification of schistosomiasis transmission risk post-disasters and formulation of targeted schistosomiasis control strategies. Methods An initial framework for the index system for assessment of schistosomiasis transmission risk following natural disasters was drafted through literature review, brainstorming, and focus group discussions. Two rounds of expert correspondence consultations were conducted using the Delphi method to refine and finalize the system, and the degrees of expert activeness, authority and endorse ment, and consensus were evaluated. In addition, the weights of each index were calculated using the analytic hierarchy process. Results A total of 18 experts participated in the consultation. The expert positive coefficients were 100.00% and 94.44% for two rounds of consultations, with authority coefficients of 0.92 and 0.94, respectively. The coefficients of coordination on the index importance, rationality and operability were 0.209, 0.185, 0.222 and 0.407, 0.214, 0.257 for two rounds of consultations, respectively, and all consistency tests were statistically significant (χ² = 246.771 to 505.278, all P values < 0.001). Following two rounds of expert consultations, an index system consisting of 6 first-level indicators, 15 second-level indicators, and 49 third-level indicators was ultimately constructed. In terms of first-level indicators, “disaster situation”, “previous epidemics”, “healthcare guarantee”, “response capacity” and “emergency recovery” had the highest weights, each at 18.18%. Regarding second-level indicators, “Schistosoma japonicum infections in animals”, “S. japonicum infections in snails” and “medical treatment” had the highest weights, each at 7.35%. In terms of third-level indicators, ten items had the highest weights, including “identification of schistosomiasis cases”, “detection of S. japonicum infections in wild feces”, “detection of S. japonicum infections in snails”, “reserves of schistosomiasis diagnostic/testing reagents and consumables”, “reserves of chemotherapy agents for human and animal schistosomiasis”, “reserves of cercariacides”, “periodical surveillance on schistosomiasis”, “identification of schistosomiasis transmission risk and timely response”, “normal provision of diagnosis and treatment services” and “post-disaster schistosomiasis surveillance”, each at 2.40%. Conclusion A scientific, systematic, and practical index system has been constructed for assessment of schistosomiasis transmission risk following natural disasters, which may provide insights into rapid post-disaster identification of schistosomiasis transmission risk, formulation of targeted schistosomiasis control strategies and optimization of resource allocation.

Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.