Objective: To analyze the epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors, so as to provide a scientific basis for the targeted prevention and control of infectious diseases for children and adolescents. Methods: Using data from the "Infectious Disease Reporting Information Management System" of the "China Disease Prevention and Control Information System" covering the period from January 1, 2012 to December 31, 2024, the study analyzed clinical and confirmed cases of hand, foot, and mouth disease, other infectious diarrhea, and acute hemorrhagic conjunctivitis among individuals aged 6-19 years old to describe demographic and temporal characteristics. It used Joinpoint regression to calculate the average annual percent change (AAPC) and annual percent change (APC) to analyze incidence trends, and Spearman s correlation was combined to generalize linear models so as to assess the association between category C intestinal infectious diseases and meteorological factors. Results: From 2012 to 2024, a cumulative total of 61 019 cases of hand, foot, and mouth disease among children and adolescents, 58 498 cases of other infectious diarrhea, and 6 377 cases of acute hemorrhagic conjunctivitis were reported. The AAPC in the incidence rates of these three diseases was 19.19%, 31.03% and 31.48 %, respectively(all P <0.05). Notably, the incidence of hand, foot, and mouth disease increased significantly after 2022 (APC= 133.66 %, P <0.01). The temporal distribution showed that hand,foot,and mouth disease was most prevalent in May,June and July (seasonal index of 2.39,3.64,1.97), other infectious diarrhea was most prevalent in February,March and December (seasonal index of 1.22,1.25,1.47), and acute hemorrhagic conjunctivitis peaked in September and October (seasonal index of 4.22,2.16). Monthly average temperature could increase the risk of hand,foot,and mouth disease( β = 0.18 ,95% CI =0.11-0.25); as monthly average wind speed increased, the incidence of other infectious diarrhea ( β =-0.86, 95% CI = -1.50 to -0.22) and acute hemorrhagic conjunctivitis ( β =-1.32, 95% CI =-2.60 to -0.05) both decreased (all P < 0.05 ). Conclusions Among children and adolescents in Shenzhen, category C intestinal infectious diseases remain prevalent throughout the year；the number of reported hand, foot, and mouth disease cases has shown an upward trend in recent years.Temperature and wind speed significantly affect the number of reported cases of three types with category C intestinal infectious diseases.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

AIM: To explore the clinical effect of atomization fumigation of self-formulated Zhibai Dihuang Decoction in the treatment of dry eye syndrome after diabetic cataract(DC)surgery with Yin deficiency and dry heat pattern.METHODS: This study is a prospective controlled study. From February 2022 to June 2024, 80 patients(97 eyes)with Yin deficiency and dry heat type DC postoperative dry eye who met the inclusion and exclusion criteria in our hospital were selected. They were randomly divided into an observation group of 40 cases(49 eyes)and a control group of 40 cases(48 eyes)using a random number table method. The control group was treated with sodium hyaluronate eye drops, while the observation group was treated with a combination of atomization fumigation of self-formulated Zhibai Dihuang Decoction on the basis of the control group. The clinical efficacy, subjective symptom scores, visual indicators [tear film break-up time(BUT), Schirmer's test(SIt), corneal fluorescein staining(FL)], tear inflammatory factors [interleukin-1 β(IL-1β), macrophage chemoattractant protein-1(MCP-1), lipid peroxidation(LPO)], and safety between the two groups.RESULTS: The improvement rate of the observation group was 96%, which was higher than that of the control group(79%, P<0.05). After treatment, the 4 subjective symptom scores in both groups were lower than those before treatment, and the subjective symptom scores of ocular dryness, foreign body sensation, burning sensation, and photophobia in the observation group were lower than those in the control group(all P<0.05). After treatment, BUT and SIt in both groups were higher than those before treatment, and FL was lower than that before treatment, with the observation group having higher BUT and SIt and lower FL than the control group(all P<0.05). After treatment, IL-1β, MCP-1, and LPO in both groups were lower than those before treatment, and the observation group had lower levels of IL-1β, MCP-1, and LPO than the control group(all P<0.05). No adverse reactions were observed in either group.CONCLUSION: The atomization and fumigation of self-formulated Zhibai Dihuang Decoction is significantly effective in treating dry eye syndrome after DC surgery with Yin deficiency and dry heat pattern. It can effectively reduce subjective symptom scores, improve visual indicators and tear inflammatory factors, and has a high level of safety.

ObjectiveTo evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.MethodsThis was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control (n = 40) and intervention (n = 40) groups. The control group received conventional orthopedic treatment, whereas the intervention group received TEAS and conventional treatment. The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks. The primary outcomes were muscle thickness (MT) and cross-sectional area (CSA) of the rectus femoris and gastrocnemius muscles, whereas the secondary outcome measure was echo intensity (EI). Data were collected before the fixation operations (baseline assessment) and 4 and 8 weeks after intervention.ResultsCompared with baseline, the MT and CSA were reduced in both groups by the end of treatment, whereas EI increased in both groups. At week 4, the reduction in the rectus femoris CSA in the intervention group was significantly lower than that in the control group (P = .02); however, the between-group differences in the MT and EI (all P .05) were not significant. No serious adverse events were observed in either group.ConclusionOur study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA. Because this was only a pilot trial, subsequent studies will need longer follow-ups and larger sample sizes.

Schizophrenia(SZ)is a psychiatric disorder characterized by abnormalities in brain structures and function.Diffusion MRI,such as diffusion tensor imaging(DTI),diffusion kurtosis imaging(DKI),diffusion spectrum imaging(DSI),neurite orientation dispersion and density imaging(NODDI),as well as high angular resolution diffusion imaging(HARDI)can help reveal microstructural abnormalities of white matter in SZ patients.The research progresses of diffusion MRI for SZ were reviewed in this article.

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*