Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

AIM To investigate the effects of Xuesaitong Capsules(Panax notoginseng saponins)on ischemia/reperfusion injury in a mouse model of skin frostbite.METHODS The mice were randomly divided into the control group,the model group,the dexamethasone group(1 mg/kg),and the low-dose,medium-dose,and high-dose Xuesaitong Capsules groups(0.036,0.072,and 0.144 g/kg),with eight mice in each group.A frostbite model was established using a dry ice-cooled ceramic(ferrite)magnet.On the 2nd day after modeling,each group started its corresponding dosing by gavage for 14 consecutive days.The wound healing,histopathological changes,and serum levels of high-sensitivity C-reactive protein(hs-CRP),thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-K-PGF1α),nitric oxide(NO)and endothelin(ET)were assessed using ELISA.The superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels in skin tissues were measured biochemically.The protein expressions of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,Toll-like receptor(TLR)4 and phosphorylated nuclear factor-KB p65(p-NF-κB p65)in skin tissues were determined by Western blot.Additionally,LncRNA H19 mRNA expression in skin tissues was evaluated using RT-qPCR.RESULTS After the final administration,compared with the control group,the model group exhibited partial scab detachment,wound healing,and larger wound areas;hyperkeratosis with incomplete keratinization,detachment of the dermis and subcutaneous tissue,partial loss of appendages,subcutaneous edema,and dilated,congested,and hemorrhagic stromal vessels with extensive lymphocyte infiltration revealed by the histopathological examination;elevated serum levels of hs-CRP,TXB2,and ET(P＜0.05,P＜0.01);decreased 6-K-PGF1α and NO levels(P＜0.05,P＜0.01);reduced SOD activity in skin tissues(P＜0.01);increased MDA levels(P＜0.01);and upregulated protein expressions of TNF-α,IL-1β,IL-6,TLR4 and p-NF-κB p65,as well as LncRNA H19 mRNA expression(P＜0.05,P＜0.01).Compared with the model group,the group intervened with high-dose Xuesaitong Capsules displayed reduced wound areas(P＜0.01);decreased serum levels of hs-CRP,TXB2 and ET(P＜0.05,P＜0.01);increased 6-K-PGF1α and NO levels(P＜0.05,P＜0.01);enhanced SOD activity(P＜0.05,P＜0.01);reduced MDA level in skin tissues(P＜0.05,P＜0.01);and down-regulated TNF-α,IL-1β,IL-6,TLR4 and p-NF-κB p65 protein expressions and suppressed LncRNA H19 mRNA expression in skin tissues as well(P＜0.05,P＜0.01).CONCLUSION Xuesaitong Capsules alleviate ischemia/reperfusion injury in frostbite-injured mice by exerting anti-inflammatory and anti oxidative stress effects and restoring vascular endothelial function mediated by the downregulation of LncRNA H19 expression and inhibition of the TLR4/NF-κB signaling pathway.

BACKGROUND:In the occurrence and development of demyelinating diseases of the central nervous system,neuroinflammation caused by microglia is the main pathological feature,so inhibiting the inflammatory response is very important to alleviate demyelination.Hydroxysafflor yellow A can protect the blood-brain barrier,inhibit neuronal apoptosis,and improve neurological function.OBJECTIVE:To explore the mechanism of hydroxysafflor yellow A inhibiting bicyclohexanone oxalyl dihydrazone-induced demyelination in mice.METHODS:(1)In vivo:Thirty healthy male C57BL/6 mice were randomly divided into three groups:normal group,cuprizone group,and hydroxysafflor yellow A group.The mice in the cuprizone group and the hydroxysafflor yellow A group were fed with 0.2％cuprizone diet for 6 weeks to establish mouse models of demyelination.The mice in the normal group were fed with normal diet.At the end of the 4th week,the mice in the hydroxysafflor yellow A group were intraperitoneally injected with hydroxysafflor yellow A 20 mg/kg per day.The mice in the normal and cuprizone groups were intraperitoneally injected with normal saline for 2 weeks.The behavioral changes of mice were evaluated by open field test and elevated plus maze test.The loss of myelin sheath in corpus callosum was detected by black gold staining,myelin basic protein and degraded myelin basic protein immunofluorescence staining.The activation of microglia and the expression of inflammatory factors were detected by I ba-1 immunofluorescence staining and ELISA,respectively.The protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 in the brain of mice in each group were detected by western blot assay.(2)In vitro experiment:The inflammation model of BV2 microglia was established by lipopolysaccharide induction.BV2 cells were divided into normal group,lipopolysaccharide group(1 μg/mL),and lipopolysaccharide(1 μg/mL)+hydroxysafflor yellow A(25 μmol/L)group.The expression levels of tumor necrosis factor α and interleukin 6 in the supernatant were detected by ELISA.RESULTS AND CONCLUSION:(1)Compared with the normal group,the mice in the cuprizone group had severe anxiety,abnormal autonomic movement ability,and a large amount of myelin sheath loss in the corpus callosum.The average fluorescence intensity of myelin basic protein was significantly reduced,and the average fluorescence intensity of degraded myelin basic protein was significantly increased.The number of lba1+microglia increased,the contents of interleukin 1β,tumor necrosis factor α,and interleukin 6 in the brain increased,and the protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 increased significantly.The above symptoms and indexes of mice were reversed after hydroxysafflor yellow A treatment.(2)Hydroxysafflor yellow A significantly inhibited the expression of inflammatory factors such as tumor necrosis factor α,and interleukin 6 induced by lipopolysaccharide in BV2 microglia.(3)The above results demonstrate that hydroxysafflor yellow A can significantly improve cuprizone-induced demyelination in mice.The mechanism of action is related to the inhibition of microglial activation-mediated inflammatory response through the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor κB p65 signaling pathway.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective:To summarize the clinical symptoms of cyclic vomiting syndrome（CVS）in children and investigate its association with small intestinal bacterial overgrowth（SIBO）.Methods:A total of 89 children who were diagnosed as CVS and improved lactulose hydrogen breath test (LHBT) in the Pediatric Department of Beijing Tsinghua Changgung Hospital from June 2020 to June 2023 were selected as CVS group.Simultaneously，50 healthy children with physical examination in our hospital were selected as the control group. According to the results of LHBT,the children with CVS were divided into SIBO group (LHBT positive) and non-SIBO group (LHBT negative). The clinical data of children in each group were compared.Results:Among the 89 CVS patients，there were 42 males and 47 females，with a mean age of（7.50±3.54）years.Common accompanying symptoms included excessive sleepiness（76 cases，85.39%），anorexia(62 cases，69.66%），constipation（55 cases，61.80%），abdominal pain（34 cases,38.20%）and so on. There were no significant differences in age and gender between children in CVS group and control group ( P>0.05). The body mass index of CVS group was lower than that of control group.The positive rate of LHBT was higher than that of the control group (56.18% vs. 8.00%),the difference was statistically significant ( P<0.05),and the concentrations of hydrogen and methane in CVS group were higher than those of the control group at different time points( P<0.05).Among 89 children with CVS,there were 50 cases in SIBO group and 39 cases in non-SIBO group. There were no significant differences in gender,age and body mass index between the two groups ( P>0.05). The constipation rate and moderate/severe disease rate in SIBO group were higher than those in non-SIBO group (88.00% vs. 28.21%,94.00% vs. 43.59%),and the differences were statistically significant ( P<0.05). Conclusion:The incidence of SIBO in children with CVS is higher,and SIBO may play a key role in CVS. CVS children with SIBO have higher disease severity.

Objective:To assess the nutritional status and risk of children with cyclic vomiting syndrome（CVS）and to provide a clinical evidence for nutritional support.Methods:A total of 160 children diagnosed with CVS and 160 healthy controls were prospectively enrolled in the study，who were admitted to Beijing Tsinghua Changgung Hospital from April 2021 to February 2024.Nutritional status was assessed by anthropometric indices（height，weight，and body mass index），and it was expressed in standard deviation score（Z score）.Nutritional risk screening tool STRONGkids was applied to nutritional risk screening，and the laboratory assessment（albumin，pre-albumin，hemoglobin，urea nitrogen and creatinine）were measured.Results:Among the 160 cases，there were 73 males and 87 females，including 18 cases of mild seizures and 142 cases of moderate and severe seizures，with the average onset age of（47.54±2.96）months and an average diagnosis age of（74.89±3.68）months.The average duration from the first attack to diagnosis was（27.35±2.36）months，and the average course of the disease was（41.35±2.63）months.The malnutrition rate of children in CVS was 36.9%（59/160），of which 18.1%（29/160）was severely malnourished.There was a statistically significant difference in the weight-for-age Z-score（WAZ），height-for-age Z-score（HAZ），and body mass index-for-age Z-score（BAZ）between the CVS group and the control group（ P<0.001）.We found a statistically significant difference in laboratory indicators（albumin，pre-albumin，hemoglobin，urea nitrogen and creatinine）between the two groups（all P<0.001）and hemoglobin was positively correlated with WAZ，HAZ and BAZ（ r=0.346,0.250,0.277，all P<0.01）.Using the STRONGkids nutritional risk screening tool，there were 43 cases with moderate nutritional risk and 117 cases with high nutritional risk，and children with high nutritional risk were likely to have lower WAZ，HAZ and BAZ than the children with moderate nutritional risk，and there was a significant difference in WAZ，HAZ，BAZ，hemoglobin，and creatinine between the two groups（ P<0.05）.And there was a correlation between the degree of CVS attack and nutritional risk grouping（ r=0.543， P<0.001）. Conclusion:Children with CVS have a high incidence of malnutrition，and the serum albumin，prealbumin，hemoglobin，urea nitrogen and creatinine levels are of great value for nutritional assessment.The STRONGkids score method helps to evaluate nutritional risk in children with CVS.

Objective:To investigate the characteristics of gut microbiota distribution in children with cyclic vomiting syndrome（CVS）complicated by constipation.Methods:The children with CVS, aged from 1 to 16 years, who were admitted to Beijing Tsinghua Changgung Hospital from June 2022 to January 2024, were divided into constipation group and normal group(non-constipation group) according to whether they were complicated with constipation or not.The clinical data and stool samples of children were collect. The abundance, diversity and composition of intestinal flora in fecal samples of two groups were detected by metagenomics sequencing.Results:A total of 20 children with CVS were collected, including 10 patients in constipation group and 10 patients in normal group.There were no significant differences in general demographic data between the two groups, including age at admission, age at first onset, body mass index, gender distribution, disease severity, endoscopic findings, and abdominal pain patterns.Microbiome analysis yielded 470 operational taxonomic units (OTUs), with 414 OTUs identified in normal group and 56 OTUs in constipation group. The abundance and diversity of intestinal flora in constipation group were significantly lower than those in normal group. Principal coordinate analysis and principal component analysis indicated significant structural differences in gut microbiota composition between the two groups. LEfSe analysis revealed distinct taxonomic patterns between the two groups, with the normal group demonstrating predominant representation of Firmicutes at the phylum level, while the constipation group showed higher relative abundance of Bacteroidetes and Actinobacteria. KEGG pathway analysis revealed that the carbon metabolism pathways was significantly enriched in the constipation group.Conclusion:There are significant differences in intestinal flora between CVS children with and without comorbid constipation.Bacteroides and Actinomycetes play an important role in constipation of children with CVS. The diversity and metabolic function of intestinal flora may be one of the pathological mechanisms of CVS complicated with constipation.

Objective To explore different construction models and experiences of clinical laboratory centers under exist-ing Integrated county healthservices entity,analyze and discuss the characteristics of various construction models,and provide ref-erences for the development of county-level clinical laboratory centers.Methods Based on the five factors of"man,machine,material,method,and environment"in Total Quality Management theory,an interview outline and questionnaire were designed for county-level clinical laboratory centers.Eleven county-level clinical laboratory centers across the country were investigated to analyze their construction models,investment returns,and other aspects.Literature reviews and case studies were also conducted to summarize the construction models and characteristics of county-level clinical laboratory centers.Results The construction models of county-level clinical laboratory centers are mainly divided into five types,each with distinct features.Through an analy-sis of the investment returns of these models unde rIntegrated county healthservices entity,it was found that a profit distribution ratio of approximately 5∶5 between county-level clinical laboratory centers and township health centers for referred samples is more conducive to maintaining the stability of sample sources.The construction model of county-level clinical laboratory centers is closely related to the medical service capacity of both county and township levels.Conclusion Counties with stronger county hospital capabilities tend to establish relatively independent regional laboratory centers based on the county hospital's laboratory department.Regardless of the model,the primary goal of county-level clinical laboratory centers should be to provide high-quality testing services coverage across the entire county.The key to the success of county-level clinical laboratory centers lies in motiva-ting grassroots personnel.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.