Objective: To investigate the protective effects of Gouqizi (Lycii Fructus, GQZ)-Danshen (Salviae Miltiorrhizae Radix et Rhizoma, DS) against hydrogen peroxide (H2O2)-induced oxidative injury in 661W retinal photoreceptor cells and to explore whether these effects involve angiopoietin-like 4 (ANGPTL4). Methods: Liquid chromatography-mass spectrometry (LC-MS) was used to identify the major components of GQZ-DS aqueous extract. An H2O2-induced oxidative injury model was established in 661W cells. Working concentrations of H2O2 and GQZ-DS were determined using the cell counting kit-8 (CCK-8) assay. Cells were subjected to GQZ-DS, ANGPTL4 knockdown, or ANGPTL4 overexpression as indicated. Flow cytometry was used to analyze cell cycle distribution, apoptotic rate, and intracellular reactive oxygen species (ROS). Colorimetric determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity using the thiobarbituric acid (TBA) method was performed. The protein expression level of ANGPTL4 was assessed by immunofluorescence. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify the mRNA level of ANGPTL4. Western blot was used to detect the protein levels of ANGPTL4 and cleaved caspase-3. Results: LC-MS identified five major constituents in the GQZ-DS aqueous extract: 2-O-β-D-glucopyranosyl-L-ascorbic acid, rutin, D-galactose, salvianolic acid A, and tanshinone IIA. The CCK-8 method selected 300 μmol/L H2O2 as the oxidative stress condition for experiments, and 0.05 and 0.1 g/mL were selected as the low and high doses of GQZ-DS, respectively, for subsequent experiments. The intervention with H2O2 resulted in reduced cell viability, elevated ROS and MDA levels, decreased SOD activity, increased apoptotic rate, upregulated cleaved caspase-3 expression, and G0/G1 phase cell cycle arrest of 661W cells. Both low and high doses of GQZ-DS alleviated these alterations, with high dose exhibiting stronger protective effects (P < 0.05 or P < 0.01). GQZ-DS also downregulated ANGPTL4 expression at both the mRNA and protein levels. Following plasmid transfection of cells, the study further revealed that ANGPTL4 knockdown mitigated oxidative stress and apoptosis-related injury, whereas ANGPTL4 overexpression exacerbated these pathological changes. Moreover, GQZ-DS partially reversed the degree of cellular oxidative damage induced by ANGPTL4 overexpression. Conclusion GQZ-DS can alleviate the H2O2-induced oxidative injury of 661W retinal photoreceptor cells, and the effects are related to the down-regulation of ANGPTL4 expression.

Objective To establish a rat model of perimenopausal dry eye with liver and kidney yin deficiency from the perspective of"measuring evidence by prescription"in Chinese medicine.Methods Thirty SPF-grade female SD rats were divided randomly into sham-operated,model,and Qiju Dihuang soup groups(n=10).Rats in the latter two groups underwent bilateral ovariectomy and were given 0.1％benzalkonium chloride eye drops combined with provocation for 10 weeks to establish a model of perimenopausal dry eye with liver and kidney yin deficiency.After modeling,rats in the Qiju Dihuang soup group were gavaged with Qiju Dihuang soup at a dose of 8.37 g/(kg·d),rats in the sham-operated and model groups were gavaged with saline at a rate of 1 mL/100(g·d)for 21 d.The general condition,retinal screen test scores,tear secretion,time of tear film rupture,and corneal fluorescein staining were observed and recorded in each group.Serum levels of follicle-stimulating hormone(FSH),estradiol(E2),and progesterone(PROG)were measured by enzyme-linked immunosorbent assay.Pathological damage to the cornea and lacrimal glands were detected by hematoxylin/eosin staining.Expression levels of the inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-a in the cornea were detected by immunohistochemistry.Results Compared with the sham-operated group,rats in the model group showed behavioral signs of slow action and reaction,irritability,body mass loss,and increased anal temperature(P＜0.05),decreased retinal screen test scores(P＜0.05),tear secretion(P＜0.05),and time of tear film rupture(P＜0.05),and pathological damage to the cornea and lacrimal glands.FSH levels increased and E2 and PROG levels decreased(P＜0.05)and expression levels of IL-1 and TNF-α increased in the model group compared with the sham group.All the above indexes were significantly improved in the Qiju Dihuang soup group compared with the model group.Conclusions From the perspective of"measuring evidence by formula"in Chinese medicine,we successfully established a rat model of perimenopausal dry eye with liver-kidney yin deficiency syndrome,which provides a theoretical and experimental basis for future systematic and in-depth research on the mechanism of perimenopausal dry eye with formula and evidence.

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.
Humans ; Biological Products/therapeutic use* ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Gouty/drug therapy* ; Arthritis/drug therapy* ; Osteoarthritis/drug therapy*

Objective:To investigate the clinical characteristics and genetic etiology of fetal Dandy-Walker spectrum (DWS) anomalies.Methods:This retrospective cohort study analyzed 28 fetuses with ultrasonographically confirmed DWS (ten classic Dandy-Walker malformations and 18 Dandy-Walker variants) at the First Affiliated Hospital, Zhengzhou University from January 2019 to June 2024. All cases underwent systematic ultrasonographic evaluation. Genetic analyses included chromosomal karyotyping alone ( n=4) or combined with copy number variation sequencing (CNV-seq) ( n=10). Descriptive statistics and Chi-square tests (or Fisher's exact test) with Bonferroni correction were applied. Results:(1) Among 28 fetuses, seven (25.0%) had isolated DWS and 21 (75.0%) non-isolated DWS. Central nervous system anomalies were most common (53.6%, 15/28). (2) Karyotyping identified abnormalities in four cases (4/14), including two triploidies, one case of mosaicism for a derivative chromosome der(1;10), and one 17p deletion. CNV-seq detected anomalies in six cases (25.0%, 6/24), four of which were missed by karyotyping: 3q23 deletion (encompassing ZIC1/ ZIC4), 13q11 duplication, and other critical variants. (3) Combined testing yielded a higher detection rate (28.6%, 8/28) than karyotyping alone (4/14, χ2=4.62, P=0.032) or CNV-seq alone (25.0%, 6/24, χ2=4.83, P=0.028) ( P=0.048 and 0.044 after Bonferroni correction). Conclusions:DWS demonstrates significant genetic heterogeneity, primarily involving chromosomal numerical anomalies (e.g., triploidy) and copy number variations (e.g., 3q23 deletion). Combined karyotyping and CNV-seq improves detection rates of genetic abnormalities.

Objective To investigate the kinematic patterns of gate-turning techniques in sitting alpine skiing at the Winter Paralympic Games and their impacts on skiing performance.Methods Using drone footage and inertial sensor technology,kinematic data were collected from 11 alpine sit-skiers preparing for the Winter Paralympics.Key technical indicators such as turning radius,skiing speed,and trajectory length were analyzed for their relationship with skiing performance.Results The minimum turning radius during gate turns was(15.80±3.55)m,and turning radius showed a significant positive correlation with skiing time(r=0.40,P=0.02)and trajectory length(r=0.88,P＜0.01).The maximum skiing speed was(16.92±1.60)m/s,which was strongly negatively correlated with total skiing time(P＜0.01).Exit speed was also significantly positively correlated with total skiing distance(P＜0.05).Additionally,single-gate technical characteristics(such as turning radius and speed variation),were strongly reflective of overall skiing performance.Conclusions Optimizing turning radius and minimizing speed loss are critical for improving skiing efficiency.Single-gate kinematic analysis provides a scientific basis for overall technique optimization and offers valuable guidance for training and competition strategy design.

Human papillomavirus (HPV) can cause various tumors such as cervical cancer in women. Further study of HPV infection and its pathogenic mechanism, as well as the development of vaccines and anti-tumor drugs, have been hindered due to the strong host specificity and tissue affinity of HPV, along with the challenges in in vitro culture and the lack of animal infection models. To advance the study of HPV infection and its pathogenic mechanism and to development better prevention and treatment measures, it is important to establish an animal model that closely resembles the infection and pathogenesis pathways in humans. This article reviews previous research on HPV-related animal models using mice, rabbits, macaques, and Drosophila, including infectious models, tumor models, and transgenic models, aiming to provide reference for the selection of appropriate animal models for HPV-related research.

Objective:To investigate the correlations between physical, psychological and social frailty in elderly patients with multimorbidity.Methods:This study utilized a mixed method. A questionnaire survey was conducted from February to June 2024, among elderly patients with multimorbidity attending 4 primary health care centers in urban Beijing selected by the convenience sampling method. The FRAIL Frailty Assessment Scale, WHO-5 Index of Well-Being Scale, and HALFT Scale were used to assess the patients′ physical, psychological, and social frailty, respectively. Spearman correlation analysis was used to analyze the correlation between different dimensions of frailty in elderly with multimorbidity. Logistic regression model was used to analyze the factors influencing physical, psychological and social frailty. The elderly with multimorbidity who were assessed to have at least 1 or more types of frailty in the quantitative study were selected for in-depth interviews in the form of online and offline combination. The topics of in-depth interview included the real experience of the different dimensions of frailty, the possible causes and the difficulties caused. The sample size was determined according to the principle of information saturation. Thematic analysis was used to summarize, code and analyze the interview data.Results:A total of 919 participants were included in the quantitative study, with a mean age of (74.09±6.03) years, 329(35.80%) were males and 590(64.20%) were females. The prevalence of physical, psychological, and social frailty was 17.85%(164/919), 21.44%(197/919), 11.21%(103/919), respectively. A total of 21 participants were included in the qualitative study, with a mean age (76.90±5.13)years, 5(23.81%) males and 16(76.19%) females. Spearman correlation analysis showed that physical and psychological frailty were moderately correlated ( r=0.311, P<0.001), psychological and social frailty were weakly correlated ( r=0.218, P<0.001), and physical and social frailty were weakly correlated ( r=0.267, P<0.001). Logistic regression analysis showed that the age, the number of multimorbidities, the psychological frailty and social frailty were the influencing factors for physical frailty (all P<0.05). The gender, number of multimorbidity, type of medication taken, physical frailty and social frailty were influencing factors of psychological frailty (all P<0.05). And age, number of multimorbidities, physical frailty and psychological frailty were influencing factors of social frailty (all P<0.05). A total of 3 themes were extracted through in-depth interviews, namely, "physical and psychological frailty are interrelated""physical and social frailty are interrelated", and "psychological and social frailty are interrelated". Conclusions:The physical, psychological, and social frailty in elderly patients with multimorbidity interacts with each other. Whereas the number of multimorbidities is a common risk factor for all three.

Objective:To analyze the current status, research hotspots, and development trends on the integration of primary care and prevention in China.Methods:This was a bibliometric analysis. Literature related to research on the integration of primary care and prevention in China was retrieved from CNIKI, Wanfang, VIP, Chinese Medical Journal Full Text Database, PubMed, and Web of Science for the period from January 1, 2015, to April 1, 2025. CiteSpace software was used to conduct a visual analysis of publication volume, authors and their collaborations, institutions, and keywords in the included literature.Results:A total of 292 domestic publications on the integration of primary healthcare and public health were analyzed. Research on primary healthcare-public health integration in China exhibited an overall upward trend from 2015 to 2025. Based on publication volume and temporal distribution, domestic research can be categorized into an exploratory phase (2015-2020) and a rapid development phase (2021-2025). The institutions publishing relevant research were predominantly universities and research centers, with a low institutional network density (0.013), indicating relative weak inter-institutional collaboration. The co-occurrence density among authors was 0.013 9. Collaboration predominantly occurred in small clusters, with limited cross-regional cooperation. Keywords that appeared frequently and had an intermediary centrality exceeding 0.1 included chronic diseases (0.40), public health (0.23),health management (0.18), and hypertension (0.17). Keyword clustering analysis showed that the top three categories mainly focused on public health, chronic diseases, and health management. Since 2024, emerging keywords with high burst intensity have included big data, health literacy, primary care hospitals, and infectious diseases.Conclusions:Research on the integration of medical and preventive care at the primary healthcare level in China has entered a stage of rapid development. Current research hotspots focus primarily on chronic disease management, the implementation status and barriers of primary healthcare and prevention integration models. Future research is expected to emphasize the application of intelligent technologies, and the enhancement of public health emergency response capacity.

Aim To investigate the effect of hypobaric hypoxia on macrophage necroptosis and atherosclerotic plaque instability and explore the underlying mechanisms.Methods Mouse bone marrow-derived macrophages were i-solated and cultured,and divided into control group(21％oxygen concentration)and hypoxia group(3％oxygen concen-tration).After 48 hours,cell necroptosis was detected,and the expression of cell necroptosis related proteins was deter-mined by Western blot.Healthy male ApoE-/-mice were randomly divided into control group and hypobaric hypoxia group.After the intervention for 16 weeks,the plasma lipids and inflammatory cytokines were measured,the areas of ath-erosclerotic plaque and necrotic core were evaluated by HE staining.The content of plaque collagen was detected by Mas-son staining.The number of macrophages in the plaque and the expression of necrotic apoptosis related proteins were de-tected by immunohistochemical staining and Western blot.Results Hypoxia induced increased necrotic apoptosis of macrophages(P＜0.01),while necroptotic inhibitor necrostatin-1(Nec-1)reduced hypoxia induced cell death(P＜0.05);hypoxia leads to a decrease in the expression of adenosine deaminase acting on RNA 1(ADAR1)in macrophages(P＜0.01),and an increase in the expression of Z-DNA binding protein 1(ZBP1),phosphorylated receptor-interacting serine/threonine-protein kinase(p-RIPK3),and phosphorylated mixed lineage kinase domain-like protein(p-MLKL)(all P＜0.01).Compared with the control group,the plasma lipid levels of ApoE-/-mice in the hypobaric hypoxia group did not change significantly(P＞0.05),the plasma inflammatory cytokines(TNF-α,IL-1β,IL-6 and MCP-1)increased(all P＜0.05),the area of atherosclerotic plaque increased(P＜0.05),the area of plaque necrotic core increased,the content of plaque collagen decreased,the number of macrophages increased,the expression of ADAR1 decreased,and the expres-sion of ZBP1 and p-MLKL increased(all P＜0.01).Conclusion Hypobaric hypoxia causes the imbalance of A-DAR1/ZBP1 expression in macrophages,activates RIPK3/MLKL signaling pathway,promotes macrophage necroptosis,in-creases the area of plaque necrosis core,and leads to increase instability of atherosclerotic plaque.

Objective To evaluate the advantages of a real-time computer endoscopy-assisted system(EndoAngel)for colorectal lesions detection in colonoscopy.Methods 2 000 patients who underwent EndoAngel assisted colonoscopy and conventional colonoscopy were selected for the study in a single-center,self-controlled study.According to different examination methods,the patients were divided into artificial intelligence(AI)group and traditional colonoscopy group,each with 1 000 cases.The results were statistically analyzed and compared with the polyp detection rate and adenoma detection rate of the two groups using pathological diagnosis as the gold standard.Further subgroup analysis will be conducted based on the seniority of the operating physicians.Results AI group's polyp detection rate was higher(39.3％)than conventional colonoscopy group polyp detection rate(29.0％),with statistically significant difference(x2=23.59,P=0.000).Of these,the detection rates of hyperplastic polyps and adenomatous polyps were 19.1％and 25.2％,which were significantly higher than those of 12.4％and 20.8％in the conventional colonoscopy group,and the differences were statistically significant(x2=16.92,P=0.000;x2=5.46,P=0.019).Further subgroup analysis of the two groups by physician seniority,the polyp detection rate of AI low seniority group(36.6％)was higher than that of conventional colonoscopy low seniority group(20.40％),with a statistically significant difference(x2=32.20,P=0.000).Among them,the detection rates of hyperplastic polyp(17.8％)and adenomatous polyp(23.6％)in AI low seniority group were higher than those in the conventional colonoscopy low seniority group(12.8％vs 13.6％),and the differences were significant(x2=4.82,P=0.028;x2=16.51,P=0.000).There were no significant differences in adenomatous polyp detection rates between the two groups of senior physicians.Conclusion EndoAngel assisted system can improve the polyp detection rate of colonoscopy,especially for the effect of low seniority physicians is more significant.