Background Prenatal exposure to fine particulate matter (PM_2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM_2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM_2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM_2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM_2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM_2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM_2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM_2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM_2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM_2.5, compared with the PM_2.5+siNC group, the PM_2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM_2.5-induced cortical damage in offspring mice during pregnancy.

ObjectiveTo observe the clinical efficacy of the Yiqi Yangyin Huoxue prescription （YYHP） in the treatment of cathartic colon （CC） and its effects on fecal short-chain fatty acids （SCFAs）， and to explore the correlations among CC severity indicators and between these indicators and patient history. MethodsAccording to the inclusion and exclusion criteria， 98 patients meeting the diagnostic criteria of both traditional Chinese and Western medicine for CC with the syndrome of Qi-Yin deficiency complicated by blood stasis were randomly assigned to an observation group and a control group. The observation group received YYHP granules， while the control group received lactulose. Both medications were administered twice daily， one sachet each time， half an hour after breakfast and dinner， with a treatment course of 8 weeks. The primary constipation symptom score， Patient Assessment of Constipation Quality of Life （PAC-QOL） score， and TCM syndrome score were assessed before and after treatment and at the 8^th week after the end of treatment. The overall clinical effective rate， as well as the efficacy attenuation index and degree， were evaluated. Fecal SCFA levels were measured using gas chromatography-mass spectrometry （GC-MS）. Spearman correlation analysis was performed to explore the correlations among CC severity indicators and between these indicators and patient history. ResultsThe overall clinical effective rate in the observation group （95.83%） was higher than that in the control group （78.72%） （P<0.05）. After treatment， the total scores for primary constipation symptoms， PAC-QOL， and TCM syndromes decreased in both groups （P<0.05）， with more significant reductions in the observation group （P<0.05）. The severity of all primary constipation symptoms was alleviated in both groups （P<0.05）. In terms of "excessive straining and difficult defecation"， "anal heaviness， incomplete evacuation， and bloating sensation"， "abdominal distension"， and "defecation frequency"， the observation group showed better efficacy than the control group （P<0.05）. Scores of the four PAC-QOL dimensions and the scores and severity of primary and secondary TCM symptoms were reduced in both groups （P<0.05）， with more significant reductions in the observation group （P<0.05）. After treatment， acetic acid， propionic acid， butyric acid， and total SCFAs in the observation group increased significantly （P<0.05）. The efficacy attenuation index and degree in the observation group were lower than those in the control group （P<0.05）. No severe adverse reactions occurred in either group， and there was no statistically significant difference in the incidence of adverse reactions between the two groups. Positive correlations of varying degrees were observed among the total scores of primary constipation symptoms， PAC-QOL， and TCM syndromes， as well as between these scores and the history of stimulant laxative use， disease duration， and age. ConclusionYYHP can effectively alleviate the primary constipation symptoms in CC patients， improve quality of life， and ameliorate TCM syndromes， with good safety. It also has the advantage of a lower rebound degree after drug withdrawal， and its mechanism may be related to increasing fecal SCFA levels. Long-term abuse of stimulant laxatives may aggravate the severity of CC and prolong the disease course.

BackgroundPersistent cognitive impairment is prevalent among patients with stable schizophrenia. While serum total bile acid （TBA） level in acute-phase patients are known to be associated with cognitive dysfunction， the relationship between serum TBA and multi-dimensional cognitive functions in stable phase patients remains unclear. ObjectiveTo investigate the correlation between serum TBA level and cognitive function in patients with stable schizophrenia， and to evaluate its predictive value for cognitive impairment， thereby providing a serological biomarker for the timely identification and objective assessment of cognitive dysfunction. MethodsA cross-sectional study was conducted on 137 inpatients with stable schizophrenia at The Fourth People's Hospital of Yancheng from March to December 2024. All participants met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Cognitive function was evaluated using the Chinese Brief Cognitive Test （C-BCT）， patients were categorized into four groups： normal cognition （n=28）， mild impairment （n=28）， moderate impairment （n=47）， and severe impairment （n=34）. Fasting venous blood samples were collected， and serum TBA level was quantified using an enzymatic cycle assay. Spearman correlation analysis was ultilized to determine the relationship between serum TBA level， overall cognitive function， and specific cognitive domains. Binary Logistic regression model was used （adjusting for covariates such as age， gender， and disease duration） to analyze the impact of serum TBA level on overall and individual cognitive functions. The predictive value of serum TBA level for overall cognitive impairment was evaluated using receiver operating characteristic （ROC） curve. ResultsSerum TBA levels differed significantly among the four groups （H=18.677， P<0.01）. Specifically， serum TBA levels in both the moderate and severe cognitive impairment groups were significantly higher than those in the normal cognitive group （adjusted P<0.01）. Serum TBA level was positively correlated with the severity grading of overall cognitive impairment （r_s=0.354， P<0.05）， and negatively correlated with T-scores on the trail making test （r_s=-0.328， P<0.05）， continuous performance test （r_s=-0.247， P<0.05）， digit span （r_s=-0.265， P<0.05）， and symbol coding （r_s=-0.221， P<0.05）. Binary Logistic regression analysis identified serum TBA level as an independent risk factor for overall cognitive impairment （OR=1.322， 95% CI： 1.021 - 1.713， P=0.034）， with a particularly robust predictive ability for impaired information processing speed （OR=1.325， 95% CI： 1.057 - 1.661， P=0.015）. The area under ROC curve （AUC） for serum TBA level in predicting overall cognitive impairment was 0.738， with a sensitivity of 60.61% and a specificity of 78.64%. ConclusionIn patients with stable schizophrenia， elevated serum TBA levels are associated with worse overall cognitive function， as well as deficits in information processing speed， attention， working memory， and executive function. Serum TBA serves as an independent risk factor and exhibits moderate predictive value for overall cognitive impairmen，particularly in the domain of information processing speed. ［Funded by Yancheng Municipal Health Commission Medical Research Project （number， YK2024141）］

Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

Objective:To investigate the pain intensity,location and relationship between pain and foot-ankle function in patients with functional ankle instability(FAI).Method:From September 2022 to July 2023,163 FAI patients were assessed at Beijing Tongren Hospital,with ankle pain location,pain intensity(visual analogue scale,VAS),and foot-ankle function(American or-thopedic foot and ankle society ankle and hindfoot score,AOFAS)scores recorded.The VAS and AOFAS of various pain locations and the number of pain locations was compared across groups.Multiple linear regression was used to examine the association between the number of pain locations,VAS,and AOFAS.Result:Out of 163 FAI patients,150 reported the pain.Among them,37.33％had pain in a single location,34％in two locations,and 28.67％in multiple locations(＞2).The most common pain locations were the sinus tarsi(32％)and the anterior talofibular ligament(31％).There were no significant differences in VAS and AO-FAS among different pain locations in FAI patients with the same number of pain locations(P＞0.05).The VAS of FAI patients with multi-location pain(＞2 regions)was higher than that of patients with single-loca-tion pain and 2-location pain(P＜0.01),whereas the AOFAS was lower(P＜0.05).The number of pain loca-tions and VAS were negatively correlated with AOFAS score(P＜0.05),which could predict 20.9％of the AO-FAS score.Conclusion:The majority of FAI patients experience pain,and the pain intensity and number of pain loca-tions impact foot and ankle function.When establishing and implementing rehabilitation strategies for FAI pa-tients,pain relief and minimizing the number of pain locations should be emphasized.Future research should investigate effective pain management measures to improve ankle function in patients with FAI at specific loca-tions with a high incidence(e.g.,tarsal sinus,anterior talofibular ligament).

Objective To explore the protective effect of resveratrol on myocardial damage caused by sepsis in rats.Methods Forty SD rats were randomly divided into control group,model group,experimental group and combined group,with 10 rats in each group.Except the control group,the other rats were intraperitoneally injected with 20 mg·kg-1 lipopolysaccharide,while the control group was injected with the same amount of normal saline.Two hours before modeling,the experimental group and combinated group were given 50 mg·kg-1 resveratrol by gavage,and the control group and model group were given the same amount of normal saline by gavage.The combined group was injected with 10 nmol of micro RNA-155(miR-155)agomir through the tail vein,and the other group was injected with equal volume of normal saline through the tail vein.Left ventricular function parameters of rats were measured by echocardiography.The level of myocardial injury markers was detected by colorimetry.Quantitative reverse transcription polymerase chain reaction was used to detect the expression of miR-155.The expression of sirtuin 1(SIRT1)and related proteins of nuclear factor κB signaling pathway were detected by Western blot.Results The left ventricular ejection fraction of control group,model group and experimental group were(80.78±12.85)％,(55.92±7.86)％and(71.55±10.71)％,respectively;left ventricular fractional shortening were(34.08±5.75)％,(22.92±2.96)％,(28.72±4.25)％,respectively;left ventricular end disatolic diameter were(3.12±0.46),(6.34±0.69),(4.95±0.57)mm,respectively;the left ventricular end systolic diameter were(5.98±0.65),(7.24±0.80),(6.16±0.78)mm,respectively;the fractional shortening were(38.91±5.38)％,(22.67±3.53)％,(30.74±3.97)％,and the expression levels of creatine kinase-MB were(661.56±85.44),(1181.41±142.14),(915.02±105.19)U·L-1,respectively;the expressions levels of cardiac troponin Ⅰ were(148.17±28.48),(448.17±60.34)and(375.44±49.01)ng·mL-1,respectively.The expression of miR-155 in control group,model group,experimental group and combined group were 1.00±0.12,3.79±0.45,1.87±0.23 and 4.03±0.49,respectively;the protein relative expression levels of nuclear factor κB(NF-κB)were 1.00±0.08,5.04±0.59,2.73±0.35,5.58±0.63,respectively;the protein relative expression levels of inhibitor of NF-κB-β were 1.00±0.11,3.03±0.37,1.35±0.15 and 2.89±0.34,respectively;the protein relative expressions of inhibitor of NF-κB-α were 1.00±0.13,0.86±0.08,1.21±0.18,0.77±0.09,respectively;the protein relative expression levels of SIRT1 were 1.00±0.16,0.66±0.07,0.93±0.14,0.54±0.06,respectively.The above indicators of the model group were compared with the control group,the experimental group were compared with the model group,and the above indicators of the combined group were compared with the experimental group,and the differences were statistically significant(all P＜0.05).Conclusion Resveratrol can alleviate myocardial injury and improve cardiac function in sepsis rats,which may be achieved by down-regulating the expression of miR-155,up-regulating the level of SIRT1,and inhibiting the nuclear factor κB signaling pathway.

Objective:To study the characteristics of thyroid-associated ophthalmopathy (TAO) clinical trials based on WHO International Clinical Trials Registry Platform (ICTRP).Methods:The WHO ICTRP database was searched from their inception to October 25, 2024.Data including the basic registration information, study type, study design, study stage, intervention measures and outcomes were extracted, and a descriptive analysis of the included trials was performed using bibliometric method.Results:A total of 288 trials were identified, the number of registrations for TAO interventional clinical trials was on the rise.Among them, 13 trials without key registration information, 93 without intervention, 2 with non-TAO subjects, 28 without control group, and 4 with duplicate study registration numbers or extension studies were excluded.Finally, 142 intervention trials were included in this study.The top three in registration numbers were China (44 trials), the United States (40 trials), and Europe (31 trials), and most of them were single-center studies (99 trials, accounting for 69.7%). For study design, 131 trials were randomized controlled trials, and 122 trials reported its masking method.Main stage of the trials was phase Ⅲ (31 trials, accounting for 21.8%). Drug treatments (121 trials, accounting for 85.2%) were the main intervention measures, and most of them were monoclonal antibody drugs (55 trials). Clinical activity score (81 trials) and exophthalmia (80 trials) were the commonly used outcome measures.Conclusions:The number of registrations for TAO interventional clinical trials is on the rise, with monoclonal antibody drugs as the main intervention measures.However, issues such as the limited registration number, uneven distribution of countries/regions, incomplete information, and low quality of study design remain to be addressed.Researchers should raise the awareness of registration and design of clinical trials, deepen international and interregional cooperation, improve the review and tracking mechanism of clinical trial registration platforms, and promote the high-quality development of TAO clinical trials.

Objective:To compare the antitumor effects of FLASH irradiation(FLASH-RT) and conventional irradiation (CONV-RT) in murine breast cancer models, alongside analyzing metabolites and metabolic pathways impacted by each treatment.Methods:Female BALB/c mice bearing breast cancer tumors were randomly assigned to three groups: FLASH-RT(625 Gy/s, 23.64 Gy), CONV-RT(0.54 Gy/s, 21.33 Gy), and Sham-RT(0 Gy/s), with single irradiation. Tumor volumes were monitored over two weeks, after which mice were euthanized, and tumor samples were collected for metabolomic analysis.Results:Statistical analysis indicated no significant difference in body weight changes between mice receiving FLASH and conventional irradiation ( P>0.05). However, compared with the sham-irradiation group, both FLASH-RT ( P<0.05) and CONV-RT ( P<0.05) resulted in statistically significant differences in tumor volume changes, demonstrating effective tumor growth suppression by both radiotherapy regimens. Metabolomic analysis revealed that FLASH-RT significantly downregulated levels of the unsaturated fatty acid oleic acid (VIP=1.867, FC=0.091) and the lipid metabolite cardiolipin (VIP=1.373, FC=0.419), while upregulating the saturated fatty acid palmitic acid(VIP=1.592, FC=3.234 3)and the lipid metabolite phosphatidylcholine(VIP=2.784, FC=4.116). Differential metabolites were predominantly enriched in lipid metabolism and amino acid metabolism pathways, suggesting energy metabolic reprogramming and membrane structural remodeling in the tumor model. Pathway enrichment analysis demonstrated significant perturbation in the glycerophospholipid metabolism pathway (KEGG pathway P<0.01), with its associated metabolite phosphatidylcholine (VIP=2.784) showing a marked increase, reaching 4.12-fold higher levels compared to the CONV-RT group..This metabolic dysregulation may reflect altered tumor cell membrane fluidity or aberrant signal transduction. Conclusions:Both FLASH-RT and CONV-RT effectively inhibit tumor growth in murine breast cancer models, with FLASH-RT exhibiting distinct immunomodulatory metabolic characteristics, and the FLASH-RT shows the clinical potential in breast cancer therapy.

Sustainability is a critical issue in China's medical and health assistance and cooperation with Africa.As China enters a new phase in this field,achieving sustainability presents both opportunities and challenges.Summarizing past successes and identifying barriers are of great practical significance for future development.This study examines the current state of China's medical and health assistance and cooperation with Uganda and finds that China has actively sought to integrate into local communities by collaborating with Ugandan medical institutions.However,several factors continue to constrain the sustainability of these efforts,including Uganda's fragmented public-private healthcare system heavily reliant on external aid,the personnel structure of Chinese medical teams,and linguistic and cultural barriers between China and Uganda.Based on official policy documents from both countries and field research findings,this study recommends supporting and assisting Uganda in establishing an independent healthcare system,with a particular focus on maternal and child health,youth health,and chronic disease management.Furthermore,strengthening cultural exchanges can contribute to the sustainable development of China-Uganda and broader China-Africa medical and health assistance and cooperation.