OBJECTIVE To investigate the effects of galangin on rheumatoid arthritis （RA） in rats by regulating the Janus kinase 3 （JAK3）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Fifty male SD rats were taken， and an emulsion composed of bovine type Ⅱ collagen and Freund’s complete adjuvant was injected subcutaneously to establish an induced arthritis model. The rats that were successfully modeled were randomly divided into model group， low， medium and high dose groups of galangin （1， 5， 15 mg/kg）， and methotrexate group （positive control， 2 mg/kg）， with 10 rats in each group. Another 10 normal rats were taken as the normal group. Starting from the 15th day of modeling， each group of rats was gavaged with the corresponding drug solution or normal saline containing 0.5% Tween 80 once a day for 28 consecutive days. The arthritis index （AI） scores and paw volume of rats were compared before and after gavage administration. Twenty-four hours after the last administration， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10 were determined， the pathological changes in ankle joint synovial tissue were observed， and the protein expressions of UNC-51 like kinase 1 （ULK1）， Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， B cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3， JAK3， phosphorylated JAK3 （p-JAK3）， STAT3 and phosphorylated STAT3 （p-STAT3） in the synovial tissue of the ankle joint were detected， as well as the fluorescence intensity of LC3-positive areas. RESULTS Compared with the model group， the pathological changes such as cellular proliferation of ankle joint synovial tissue and infiltration of inflammatory cells in rats of each administration group showed improvement. Moreover， their AI scores and paw pad volumes （on day 28 after gavage）， the levels of IL-6 and TNF-α， the protein expression of Bcl-2， and the phosphorylation levels of JAK3 and STAT3 were all significantly reduced （ P ＜0.05）. The levels of IL-4 and IL-10， the protein expressions of ULK1， Beclin-1， Bax， caspase-3 and LC3， as well as the fluorescence intensity of LC3-positive areas， were all significantly increased （ P ＜0.05）. Moreover， the effect of galangin was in a dose-dependent manner （ P ＜0.05）. CONCLUSIONS Galangin can induce sustained autophagy in synovial tissue cells of RA rats， promote cell apoptosis， inhibit synovial cell proliferation， and alleviate persistent inflammatory responses. The above anti-RA effects may be related to the inhibition of the JAK3/STAT3 pathway.

Objective To compare the clinical characteristics of pneumococcal meningitis in different age groups, and to provide a basis for early diagnosis of pneumococcal meningitis. Methods Cerebrospinal fluid and/or serum samples were collected from 1742 suspected cases of meningitis in Baoji, Shaanxi Province from August 2013 to July 2019. Streptococcus pneumoniae was detected by isolation culture and real-time fluorescence quantitative polymerase chain reaction. Retrospective analysis of clinical manifestations, biochemical indicators and other information of laboratory confirmed cases was conducted by χ² test or Fisher's exact test. Results A total of 1742 samples of encephalitis or meningitis cases were detected, and 41 cases were confirmed as laboratory-confirmed Streptococcus pneumoniae infection. Among them, there were 12 cases (29.27%) in the infant group, 14 cases (34.15%) in the child group, and 15 cases (36.59%) in the adult group. The proportion of the adults with headache was significantly higher than that of the infants (χ²=11.408，P＜0.017). The proportion of the adults with consciousness disorder, elevated white blood cells and elevated neutrophils were significantly higher than those in the infant and the child groups（Fisher's exact test, P＜0.017；χ² =6.428，P＜0.017；χ² =10.898，P＜0.017；χ² =6.421，P＜0.017；χ² =9.758，P＜0.017；χ² =7.744，P＜0.017). The proportion of the infants with cerebrospinal fluid turbidity was significantly higher than that of the children (Fisher's exact test，P＜0.017). The proportion of the infants with decreased white blood cells and reduced glucose in cerebrospinal fluid was significantly higher than that of the children group and the adult group（Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.017; Fisher's exact test, P＜0.017). Conclusion Most adult patients with pneumococcal meningitis have headache and consciousness disorders, with significantly increased proportion of white blood cells and neutrophils. Infant patients tend to have cloudy appearance of cerebrospinal fluid, leukopenia in blood, and decreased glucose in cerebrospinal fluid.

AIM:To evaluate the optimal timing of preoperative intravitreal anti vascular endothelial growth factor(VEGF)therapy in proliferative diabetic retinopathy(PDR)using intraoperative fluorescein angiography(IOFA).METHODS:A retrospective case series study was conducted on patients who underwent vitrectomy for PDR with vitreous hemorrhage(VH)at Sichuan Provincial People's Hospital from January 2023 to February 2025. Patients were divided into three groups according to the interval between intravitreal conbercept injection and surgery: Group A(3 d before surgery), Group B(7 d before surgery), and Group C(14 d before surgery). IOFA was used to assess the number and size of retinal neovascularization(NV). Additional data were collected including preoperative best corrected visual acuity(BCVA), vitreous hemorrhage grading, operative time, frequency of intraoperative endodiathermy, duration of high perfusion pressure, vitreoretinal adhesion grade, postoperative BCVA, and central macular thickness(CMT). Multidimensional analyses were performed.RESULTS:This study enrolled a total of 91 patients(94 eyes)with PDR accompanied by vitreous hemorrhage. Among them, Group A consisted of 31 patients(31 eyes; 18 males, 13 females; mean age 53.26±12.38 y), Group B consisted of 34 patients(37 eyes; 21 males, 13 females; mean age 51.61±14.16 y), and Group C consisted of 26 patients(26 eyes; 18 males, 8 females; mean age 51.00±12.02 y), with baseline characteristics comparable among the three groups(all P>0.05). Comparative analysis of NV visualized via IOFA revealed that both the number and size of NVs were significantly lower in Groups B and C than in Group A(all P<0.0167), while no statistically significant differences were observed between Groups B and C(both P>0.05). No significant differences were found among the three groups regarding other intraoperative parameters, including operation time, frequency of electrocoagulation application, duration of high perfusion pressure, or grading of vitreoretinal adhesion(all P>0.05).CONCLUSION:IOFA confirms that preoperative anti-VEGF therapy administered 7 or 14 d before surgery is more effective than a 3 d interval in suppressing retinal NV activity in PDR patients.

[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 analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

ObjectiveBased on 16S rDNA technology and molecular biology methods， the molecular mechanism of Shenling Baizhusan in the treatment of diarrhea-predominant irritable bowel syndrome （IBS-D） was investigated. MethodsThe 42 SD rats with SPF were randomly divided into no control group， SLBZS-H， medium （SLBZS-M）， low （SLBZS-L） dose group， positive control group and model group， with 7 rats in each group. The rat model of IBS-D was prepared by ice-cold senna （0.45 g∙mL^-1） gavage （10 mL∙kg^-1） combined with restraint stress for 14 consecutive days. After successful modeling， the corresponding drugs were given to each group with a gavage volume of 10 mL∙kg^-1： The positive group was administered with 2.36 ， 1.18， 0.59 g∙mL^-1 of Shenling Baizhusan in the Positive group and the Model group with the same volume of normal saline for 14 d. The general condition of the rats： Weight， feces， mental state and death were observed and recorded. The body weight， abdominal wall retraction reflex score （AWR） and loose stool rate of rats in each group were measured before （the first day）， after the model （day 14） and after treatment （day 28）. Hematoxylin-eosin staining was used to observe the morphological characteristics of colon tissues of experimental animals. Enzyme-linked immunosorbent assay was used to quantitatively analyze the concentration of inflammatory mediators in the peripheral blood of experimental animals. Western blotting was used to detect the expression levels of key proteins of Toll-like receptor 4 （TLR4）， Toll-like receptor 2 （TLR2）， myeloid differentiation factor 88 （MyD88） and nuclear factor-κB （NF-κB） signaling pathway in rat colon tissue. 16S rDNA technology was used to detect the structural changes of intestinal microbiota in rats. ResultsCompared with Control， the colon of the Model group showed partial mucosal epithelial shedding and inflammatory cell infiltration. The contents of TNF-α， IL-1β， IL-6 and 5-HT in serum increased （P<0.05）， the protein expressions of TLR2， TLR4， MyD88 and NF-κB in colon tissue increased （P<0.05）， the diversity indices of Richness， Chao1， abundance-based coverage estimator（ACE） and Shannon decreased （P<0.05）， and the phylum Firmicutes， Actinobacteria， The relative richness of Bacteroides-H， Lactobacillus and Ligilactobacillus decreased （P<0.05）， while the relative richness of Bacteroidetes， Proteobacteria and Prevotella increased （P<0.05）. Compared with the model group， the colonic structure and organization of the SLBZS-H group， SLBZS-M group， SLBZS-L group and Positive group were clearer， and only a small number of inflammatory cells were present in some areas， and the serum contents of TNF-α， IL-1β， IL-6 and 5-HT were decreased （P<0.05）， TLR2， TLR4， The protein expressions of MyD88 and NF-κB decreased （P<0.05）， and compared with the model group， the diversity indices of Richness， Chao1， ACE and Shannon in the SLBZS-H， SLBZS-M and SLBZS-L groups increased （P<0.05）， and the richness of Firmicutes and Actinobacteria increased （P<0.05）. The richness of Proteobacteria and Prevotella decreased （P<0.05）， and the abundance of Prevotella decreased （P<0.05）， Bacteroides-H， Muribaculum， Lactobacillus and salivarius in the Positive group salivarius （P<0.05）. ConclusionShenling Baizhusan can effectively treat IBS-D， and its molecular mechanism may be to play a therapeutic role by improving intestinal flora and inhibiting the TLRS/MyD88/NF-κB signaling pathway to reduce inflammatory response.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Objective: To investigate the association of the joint effect of body fat levels and dyslipidemia with cardiovascular structural abnormalities in children, so as to provide a scientific reference for the early prevention of cardiovascular damage. Methods: Based on the data from the second follow up (October 2021 to January 2022) of the Huantai Children Cardiovascular Health Follow up Cohort, 1 308 children with complete data were included. The fat mass percentage (FMP), fat mass index (FMI), subcutaneous fat mass (SFM) and visceral fat mass (VFM), left ventricular mass index (LVMI), relative wall thickness (RWT), thickening of carotid intima-media thickening (cIMT) , left ventricular hypertrophy (LVH) and left ventricular geometric remodeling (LVG), triglyceride (TG), total cholesterol (TC) ,high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were obtained. Multivariable Logistic regression model was used to analyze the associations of FMP, FMI, SFM and VFM with thickening of cIMT, LVH and LVG. The joint effects of these body fat indicators and dyslipidemia on the aforementioned cardiovascular outcomes were further explored. Restricted cubic spline model was used to examine the dose response relationships between body fat levels and cardiovascular structural abnormalities. Results: Elevated body fat levels were significantly associated with an increased risk of cardiovascular structural abnormalities, exhibiting J shaped dose response relationships (all P <0.05). Compared with the group with normal body fat and normolipidemia, the risks of thickening of cIMT, LVH, and LVG in the group with elevated FMP combined with dyslipidemia were higher[ OR (95% CI )=11.70 (6.49-21.27), 5.53 (2.97-10.17), 2.33 (1.30-4.05)]; in the group with elevated FMI combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )= 11.68 (6.43-21.38), 6.98 (3.73-12.92), 2.65 (1.50-4.61)]; in the group with elevated SFM combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )=10.55 (5.83-19.24), 5.11 (2.71-9.45), 1.99 (1.11- 3.46 )]; and in the group with elevated VFM combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )=12.44 (6.76-23.14), 6.17 ( 3.31 -11.38), 2.30 (1.30-3.99)] (all P <0.05). Sex stratified analyses showed that the risk of thickening of cIMT in the combined exposure group of all four body fat indicators and dyslipidemia was significantly higher in girls than in boys (all P <0.01). Conclusions Elevated body fat levels and dyslipidemia have a combined effect in children, collectively increasing the risk of cardiovascular structural abnormalities. Prevention of cardiovascular damage in children should focus on both adiposity management and blood lipid regulation.

Objective: To explore the association between problematic short video use (PSVU) and executive function among students in grades 3 to 6 of primary school, so as to provide references for intervening in primary school students PSVU. Methods: In September 2024 (T1), using a convenience sampling method, 520 students in grades 3 to 6 from a primary school in Xi an City of Shaanxi Province were selected as research subjects. They were followed up at three time points: T1, T2 (January 2025), and T3 (May 2025) using an adapted version of the Internet Addiction Test and Questionnaire of Executive Functioning of Chinese. Pearson correlation and cross lagged model were used to analyze the correlation between PSVU and executive function among primary school students at each time point. Results: The mean PSVU scores of primary school students at T1-T3 were (35.51±12.46, 34.86± 12.64 , 35.16±13.37) respectively, and the mean executive function scores were (68.31±12.95, 64.92±12.99, 66.58±14.13) respectively. Correlation analysis results indicated that PSVU scores and executive function scores were positively correlated in all three measurements ( r =0.26~0.62, all P <0.01). Cross lagged analysis results showed that executive function scores at T1 could positively predict PSVU scores at T2 ( β =0.21), and executive function scores at T2 could positively predict PSVU scores at T3 ( β = 0.20) (both P <0.01). Conclusion The level of executive function in students from grades 3 to 6 of primary school can unidirectionally predict the severity of their PSVU.

The Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.