OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1（ STAT1）/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Neonatal rats， with an equal number of males and females， were randomly divided into control group， model group， curcumin low-dose （Cur-L）， medium-dose （Cur- M） and high-dose （Cur-H） groups， and Cur-H+STAT1 transcription enhancer [2-（1，8-naphthyridin-2-yl）phenol] group （Cur-H+2- NP group）， with 15 rats in each group. Except for the control group， rats in other groups were injected with a suspension of group B Streptococcus （1×104 cfu/mL， 10 μL） into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment， rats in Cur-L， Cur-M and Cur-H groups were intraperitoneally injected with 1.25， 2.5 and 5 mg/kg curcumin， respectively， and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP， once a day， for 3 consecutive weeks. After the last administration， modified Loeffler score was conducted， white blood cells （WBC） count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β and IL-18]， brain water content and blood-brain barrier permeability were detected； the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells， the positive expression of ionized calcium-binding adapter molecule-1 （Iba-1）， the co-localization of Iba-1 and NLRP3， as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway （phosphorylated STAT1， NLRP3， apoptosis-associated speck-like protein containing a CARD， gasdermin D， caspase-1， IL-1β and IL-18） were examined. RESULTS Compared with the control group， the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities， accompanied by neuronal edema and necrosis， as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group， while the WBC count， levels of inflammatory factors， brain water content， blood-brain barrier permeability， HE staining score， number of degenerated neurons， percentage of apoptotic cells， positive expression of Iba-1， percentage of Iba-1 and NLRP3 co-localization- positive cells， and expressions of pathway-related proteins were all significantly rose/increased/upregulated （P＜0.05）. Compared with the model group， the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees， with significant improvements in all quantitative indicators （P＜0.05）； conversely， 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators （P＜0.05）. CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage， reduce neuroinflammation， inhibit cell apoptosis and pyroptosis， and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

ObjectiveTo systematically synthesize the illness experiences and unmet needs of patients with stroke during the rehabilitation phase. MethodsQualitative studies focusing on the illness experiences and needs of stroke patients in the rehabilitation period were retrieved from the databases of Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, CBM, Wanfang data and VIP. The search timeframe was from database inception to December, 2024. Methodological quality was evaluated using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. A meta-synthesis method was adopted to categorize and integrate the findings. ResultsA total of ten studies were included. Forty-nine themes were extracted and further grouped into ten categories, which were finally integrated into three overarching themes: negative illness perceptions, multifaceted rehabilitation motivations and unmet multidimensional needs. ConclusionPatients with stroke undergo complex physical and psychological experiences during rehabilitation and present diverse and multidimensional needs.

ObjectiveTo systematically synthesize the illness experiences and unmet needs of patients with stroke during the rehabilitation phase. MethodsQualitative studies focusing on the illness experiences and needs of stroke patients in the rehabilitation period were retrieved from the databases of Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, CBM, Wanfang data and VIP. The search timeframe was from database inception to December, 2024. Methodological quality was evaluated using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. A meta-synthesis method was adopted to categorize and integrate the findings. ResultsA total of ten studies were included. Forty-nine themes were extracted and further grouped into ten categories, which were finally integrated into three overarching themes: negative illness perceptions, multifaceted rehabilitation motivations and unmet multidimensional needs. ConclusionPatients with stroke undergo complex physical and psychological experiences during rehabilitation and present diverse and multidimensional needs.

ObjectiveTo systematically synthesize the illness experiences and unmet needs of patients with stroke during the rehabilitation phase. MethodsQualitative studies focusing on the illness experiences and needs of stroke patients in the rehabilitation period were retrieved from the databases of Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, CBM, Wanfang data and VIP. The search timeframe was from database inception to December, 2024. Methodological quality was evaluated using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. A meta-synthesis method was adopted to categorize and integrate the findings. ResultsA total of ten studies were included. Forty-nine themes were extracted and further grouped into ten categories, which were finally integrated into three overarching themes: negative illness perceptions, multifaceted rehabilitation motivations and unmet multidimensional needs. ConclusionPatients with stroke undergo complex physical and psychological experiences during rehabilitation and present diverse and multidimensional needs.

[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。

In the era of deep technologization with the flourishing development of newquality productive forces， China’s medical science and technology innovation has transitioned from “following” to “leading”， and the ethical governance environment of medical science and technology has undergone profound changes. However， the traditional ethical governance system of medical science and technology faces several issues， such as outdated ethical governance concepts， inadequate ethical norms， excessive hidden ethical risks， and numerous loopholes in governance systems， which fail to effectively respond to the diverse and complex ethical risk challenges. To this end， it is essential to promote the transformation of ethical governance thinking in medical science and technology based on the reality of newquality productivity forces and deep technologization， as well as to shift unilateral， extensive， and single governance into comprehensive， precise， and early-warning governance. Additionally， it is necessary to cultivate an ethical governance concept that prioritizes ethics and prevention， establish a diverse and collaborative ethical governance model， set up a prevention mechanism focused on major ethical risks， as well as enhance the systems of ethical communication， review， and feedback in medical science and technology.

AIM: To analyze the current status and influencing factors for insufficient hyperopia reserve in preschool children from Changzhi City, Shanxi Province, and to provide reference and basis for myopia prevention and control in this district.METHODS: A stratified cluster random sampling strategy was used to select 2 854 preschool children(5 708 eyes)from 29 child-care centers in Changzhi City between January and May 2024. Hyperopia reserve was assessed through measurements and questionnaire surveys. Totally 2 820 cases(5 640 eyes)were finally included, with 34 cases excluded(32 cases of uncooperativeness and 2 cases of distractibility). The univariate analysis and multivariate Logistic regression were performed to analyze the associated influencing factors of insufficient hyperopia reserve.RESULTS: A total of 580 preschool children with insufficient hyperopia reserve were detected, with an incidence of 20.57%. Logistic regression analysis revealed that male(OR=1.723, 95% CI: 1.419-2.093), maternal myopia(OR=2.210, 95% CI: 1.681-2.906), paternal myopia(OR=1.426, 95% CI: 1.059-1.921), myopia in both parents(OR=2.761, 95% CI: 2.110-3.612), preterm infants(OR=1.740, 95% CI: 1.294-2.342), the mean daily sleep duration <10 h(OR=1.272, 95% CI: 1.024-1.579), and the mean daily outdoor activity time <2 h(OR=1.222, 95% CI: 1.005-1.485)were risk factors for insufficient hyperopia reserve(all P<0.05). Conversely, using blackout curtains during the day and turning off lights at night(OR=0.598, 95% CI: 0.405-0.883)were identified to be protective factors(P<0.05).CONCLUSION: Sex, genetics, gestational age, sleep duration and environmental conditions, and outdoor activity time are potentially associated with insufficient hyperopia reserve in preschool children. Caregivers should prioritize the management of these risk factors to prevent the occurrence of myopia.

OBJECTIVE To analyze adverse drug reactions （ADRs） in pediatric patients with Mycoplasma pneumoniae pneumonia （MPP）， and investigate the influential factors associated with the occurrence of ADRs. METHODS Clinical records of pediatric patients with MPP in Xinxiang Central Hospital （hereinafter referred to as “our hospital”） from Oct. 1st， 2023 to Sept. 30th， 2024 collected from the Hospital Information System were retrospectively reviewed using the global trigger tool （GTT）. The positive triggers were further reviewed to confirm the occurrence of ADRs， and the characteristics of those ADRs were analyzed. The children were divided into the ADR group and the non-ADR group. Univariate analysis and multivariate Logistic regression analysis were performed to investigate the potential influential factors for ADRs in MPP children. RESULTS A total of 1 325 MPP children were included. Out of 24 designed triggers， 14 were positive， with a positive trigger rate of 58.3%. There were 1 301 positive trigger cases， involving 846 pediatric patients. After assessment， 399 cases of ADRs were identified in 372 pediatric patients， yielding a positive predictive value of triggers at 30.7%. The main types of ADRs were abnormal blood cells （230 cases， 57.6%）， skin and its appendages damage （78 cases， 19.5%）， and gastrointestinal system damage （42 cases， 10.5%）， which predominantly occurred 4 days or more， within 2-3 days and within 2-3 days after medication， respectively. They were more prevalent in pediatric patients aged＞3-10 years （295 cases， 79.3%）. The major categories of drugs associated with ADRs included intravenous corticosteroids （209 cases）， cephalosporins （180 cases）， macrolides （38 cases）， tetracyclines （28 cases） and traditional Chinese medicine （TCM） injections （28 cases）. These ADR reports were classified into 3 types： 1 serious case， 394 general cases and 4 new cases. In terms of causality assessment， 1 case was assessed as certain， 19 cases as probable， and 379 cases as possible. In terms of ADR outcomes， 151 cases fully recovered， while the outcomes for 248 cases remained unknown. Univariate analysis and multivariate Logistic regression analysis revealed that a history of allergies [OR＝5.231， 95%CI （2.004， 13.656）， P＜0.05]， the number of medications used [OR＝1.064， 95%CI （1.027， 1.103）， P＜0.05]， and intravenous corticosteroid administration [OR＝3.223， 95%CI （2.341， 4.437）， P＜0.05] were independent risk factors of ADRs in pediatric patients with MPP. The use of azithromycin [OR＝0.544， 95%CI （0.376， 0.786）， P＜0.05] was identified as an independent protective factor against the occurrence of ADRs in pediatric patients with MPP. CONCLUSIONS Children with MPP in our hospital exhibit a higher incidence of ADRs， primarily involving abnormal blood cells， skin and its appendages damage， and gastrointestinal system damage. A history of allergies， the number of medications used， intravenous corticosteroid administration， and the use of azithromycin are associated with the occurrence of ADR in MPP pediatric patients.

Thymocyte selection-associated high mobility group box (TOX), a member of the high mobility group protein super-family, plays an important role in T cell development, functional maintenance, and exhaustion. It has been recently found that TOX exerts critical immunoregulatory functions during pathogen infections, and TOX expression is strongly associated with the intensity and tolerance of host immune responses. This review systematically summarizes the structural and functional features of TOX and focuses on its expression dynamics, mechanisms of action, and immunomodulatory effects during viral, bacterial, and parasitic infections, which provides a theoretical support to better understanding of the role of TOX in infectious diseases and provides new insights into development of potential immunotherapeutic strategies targeting TOX.