AIM:To investigate the role of serum high-sensitivity C-reactive protein(hsCRP)in the pathogenesis and progression of diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM).METHODS:A nested case-control study was conducted involving 187 T2DM patients(187 eyes)who attended at Eye Center, Beijing Tongren Hospital, Capital Medical University from June 2017 to October 2024. Patients were categorized into three groups: the diabetes mellitus(DM)group, non-proliferative DR(NPDR)group, and proliferative DR(PDR)group. Baseline information was collected, including age, sex, duration of DM, and duration of hypertension. All patients underwent fasting biochemical tests and comprehensive ophthalmic examinations.RESULTS: A positive correlation was observed between hsCRP and fasting blood glucose(FBG; P=0.004)and glycated hemoglobin A1c(HbA1c; P=0.048)by Spearman's rank correlation coefficient analysis. After adjusting for confounding factors, multivariable Logistic regression identified hsCRP as a significant risk factor for DR(OR=2.67, 95% CI: 1.19-5.96, P=0.017). CONCLUSION:Serum hsCRP is positively correlated with FBG and HbA1c and can serve as an important predictor of the severity of DR.

Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective To study the quality comparability of human coagulation factor Ⅷ(FⅧ)produced before and after the change of factory site.Methods A comparative study was carried out on quality quantitative indexes,related im-purities and stability data of FⅧ produced before and after the change of factory site.Results The FⅧ quantitative quality before and after the change of factory site all met the quality standard,and the related impurities including aluminum resi-due,tributyl phosphate residue,polysorbate 80 residue and PEG residue all met the quality standard.Other impurities in-cluding human fibrinogen,fibronectin,plasminogen,IgA,IgM and IgG were extremely low in content and equivalent in quality.The content of VWF(von Willebrand factor)had no obvious change before and after the change of factory site,but was significantly higher than that of other domestic manufacturers'commercial products.The results of accelerated stability and long-term stability tests showed that the titer of FⅧ fluctuated within the methodological error range,and the results all met the quality standard.Conclusion The change of factory site of FⅧ has no effect on the quality.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Objective To explore the analgesic initiation mechanism of three-manipulation and three-acupoint tuina in model rats with minor chronic constriction injury(CCI).Methods Fifty-six SD rats were divided randomly into eight groups:normal group,sham group,model 1 group,model 2 group,tuina 1 group,tuina 2 group,tuina 1+transient receptor potential vanilloid-1(TRPV1)antagonist group,and tuina 2+transient receptor potential ankyrin 1(TRPA1)antagonist group.The model,tuina,and tuina+antagonist groups were established with minor CCI models.The tuina and tuina+antagonist groups received the three-method three-point intervention(point method,dial method,kneading method,Yinmen point,Chengshan point,Yanglingquan point)7 days after modeling.The model and sham groups were subjected to grasping restraint,and the normal group received no intervention.After the respective interventions,each group was tested for changes in mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)to detect different types of pain.The nitric oxide(NO)content of the dorsal root ganglion(DRG)was determined by the nitrate reductase method,and changes in protein and gene expression levels of components of the TRPV1/TRPA1-NO-cGMP-protein kinase G(PKG)signaling pathway in the DRG of each group were determined by enzyme-linked immunosorbent assay,Western blot,and qPCR.Results Compared with the model group,MWT and TWL were prolonged in the tuina 1 and tuina 2 groups.Expression levels of TRPV1,TRPA1,NO,soluble guanylate cyclase-β,cGMP,and PKG1 in the DRG were significantly decreased in the tuina 1,tuina 2,tuina 1+TRPV1 antagonist,and tuina 2+TRPA1 antagonist groups.Conclusions Tuina can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one-time intervention.Tuina can exert immediate and continuous analgesic effects via the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway.

Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P＜0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P＜0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P＜O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P＜0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.

Objective To explore the analgesic initiation mechanism of"three-manipulations and three-acupoints"of tuina on minor chronic constriction injury(minor CCI)model rats.Methods According to the random number table method,35 SD rats were randomly divided into five groups:normal group,sham group,model group,tuina group,and tuina+MK-801 group.The model group,tuina group,and tuina+MK-801 group were subjected to ligation of the right sciatic nerve trunk to establish a minor CCI rat model.The sham group was only exposed to the right sciatic nerve without ligation,and the normal group was not subjected to any operation.The normal group was not subjected to any intervention measures.On the seventh day after modeling,the model group and the sham group underwent 9 minutes of grasping restraint,while the tuina group underwent one intervention of three-manipulations(point method,dialing method,and kneading method)and three-acupoints(right"Yinmen"(BL37),"Chengshan"(BL57),and"Yanglingquan"(GB34)acupoints)with each manipulation and acupoint intervention for 1 minute for a total of 9 minutes.The tuina+MK-801 group received intrathecal injection of MK-801 from the fifth to seventh days after modeling,with a dose of 6 μg(10 μL)per day,tuina intervention was performed 30 minutes after the last intrathecal injection,and the specific operation of tuina was the same as that of the tuina group.Before modeling,after modeling,and after intervention,each group of rats was subjected to cold sensitivity threshold(CST)and mechanical withdrawal threshold(MWT)testing.After intervention,immunohistochemistry was used to detect the positive expression of cyclic guanosine monophosphate(cGMP)in the spinal dorsal horn(SDH)at L4-6 segments;protein expressions of N-methyl-D-aspartate receptor 1(NMDAR1),neurogenic nitric oxide synthase(nNOS),soluble guanylyl cyclase β(sGCβ),and protein kinase G1(PKG1)in SDH at L4-6 segments were detected by Western blotting;mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 in SDH at L4-6 segments were detected by real-time PCR.Results Compared with the normal and sham groups,after modeling,CST increased and MWT decreased in the model group,tuina group and tuina+MK-801 group(P＜0.05);after intervention,the positive protein expression of cGMP was increased,the protein expressions of NMDAR1,nNOS,sGCβ,and PKG1 were increased,and mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 were increased in SDH at L4-6 segments in the model group(P＜0.05).Compared with the model group,after intervention,CST decreased and MWT increased in the tuina group and tuina+MK-801 group(P＜0.05);the positive protein expression of cGMP was decreased,the protein expressions of NMDAR1,nNOS,sGCβ,and PKG1 were decreased,and mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 were decreased in SDH at L4-6 segments in the tuina group and tuina+MK-801 group(P＜0.05).Conclusion One-time tuina intervention can effectively improve the symptoms of thermal and mechanical hyperalgesia induced by peripheral nerve injury,which may initiate analgesia through the NMDAR1/cGMP/protein kinase G signaling pathway,thereby exerting immediate analgesic effect.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Objective:To explore the coverage of influenza and pneumonia vaccination and factors influencing the vaccination in children.Methods:A cross-sectional questionnaire survey was conducted in children's parents in Beijing and Gansu by using two-stage cluster-sampling to investigate the influenza and pneumonia vaccination rates and influencing factors in children.Results:A total of 2 377 parents were included in the study, and the results indicated that the influenza vaccination coverage was 35.93% and the pneumonia vaccination coverage was 16.58% in children in survey areas, the vaccination rate of both vaccines was 11.65%. The top three reasons for vaccination for both vaccines were being aware of severity of the diseases (influenza vaccine: 36.02%; pneumonia vaccine: 49.61%), being required by school or organization (influenza vaccine: 28.76%; pneumonia vaccine: 25.45%) and being aware of the susceptibility of the diseases (influenza vaccine: 26.41%; pneumonia vaccine: 13.88%). The top three reasons for having no vaccinations were personal unwillingness, concern about vaccine and vaccine accessibility. Families with multi children, living in rural areas and lower family income were the negative factors for both types of vaccinations.Conclusions:The influenza and pneumonia vaccination coverage in children need further improvement, and rural families and families with multi children are the key concern groups for expanding vaccination coverage. Health education about influenza and pneumonia vaccinations, coordinating vaccine supply and decreasing vaccine prices play an important role in improving influenza and pneumonia vaccination coverage.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).