A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P＜0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P＜0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To compare the therapeutic effects of different inhaled medications on patients with frequent cough in chronic obstructive pulmonary disease (COPD), including changes in symptoms and acute exacerbation.Methods:This study was based on the RealDTC study, and the study subjects were stable COPD patients from the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2016 to March 2023. The demographic characteristics, smoking status, history of biofuel exposure, history of acute exacerbation in the past year, lung function, COPD Assessment Test (CAT) score, modified British Medical Research Council Respiratory Difficulty Questionnaire (mMRC) score, and inhalation medication regimen of the patients were collected. Patients with frequent cough are defined as having a cough score of ≥2 in the first item of the CAT score. According to the type of inhaled medication, patients with frequent cough are divided into l long-acting muscarine anticholinergic (LAMA), long-acting β2 agonists (LABA)+ LAMA, inhaled corticosteroids (ICS)+ LABA, and ICS+ LABA+ LAMA groups. At the 6th month follow-up, CAT scores were collected and symptom control was evaluated, including minimum clinical improvement (MCID) (defined as a decrease of ≥2 points from baseline in CAT scores at the 6th month) and improvement in cough symptoms (defined as a decrease of ≥1 point from baseline in cough scores). During a one-year follow-up, the number of acute exacerbations was evaluated. The relationship between different inhaled medications and prognosis in patients with frequent cough in COPD was evaluated using multivariate logistic regression analysis.Results:A total of 653 patients with frequent cough in COPD were included, with a CAT score of (16.4±6.1) and a cough score of 3(2, 3). After 6 months of follow-up, 403 patients (61.7%) achieved MCID, and 394 patients (60.3%) had improved cough symptoms; During a one-year follow-up, 227 patients (34.8%) experienced acute exacerbation. After receiving inhalation medication treatment, the CAT scores and cough scores of four groups of patients with frequent cough, namely LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA, decreased compared to before treatment (all P<0.05). There was a statistically significant difference in the proportion of △CAT score, MCID, and acute exacerbation among the four groups of LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA (all P<0.05), while there was no statistically significant difference in the proportion of △cough score and cough score reduction ≥1 point (all P>0.05). The results of multivariate logistic regression analysis showed that compared with patients treated with LAMA or ICS+ LABA drugs, patients with frequent cough in COPD treated with LABA+ LAMA or ICS+ LABA+ LAMA drugs were more likely to achieve MCID and less likely to experience acute exacerbation (all P<0.05). Conclusions:Compared with LAMA or ICS+ LABA, patients with frequent cough in COPD who receive LABA+ LAMA or ICS+ LABA+ LAMA drug treatment are more likely to improve symptoms and have a lower risk of acute exacerbation.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Objective To investigate the application value of tear inflammatory factors in early evaluation of the occurrence of complications after trabeculectomy in glaucoma patients.Methods A total of 150 eyes of 150 patients with angle-closure glaucoma who underwent trabeculectomy in Department of Ophthalmology of Zhangjiagang Hospital of Traditional Chinese Medicine were included.The clinical data of all patients were collected,and the levels of inflammatory factors(including G-CSF,GM-CSF,IFN-γ,MCP-1,TNF-α,IL-12,IL-13,IL-15,IL-1β,IL-4,IL-7,IL-10,IL-17,IL-5)in tears were detected before surgery.According to the occurrence of postoperative complications,the patients were divided into the complication group and the control group,and the clinical data of the two groups were compared.Logistic regression was used to analyze the related factors of the occurrence of complications after trabeculectomy in glaucoma patients.The predictive model of tear inflammatory factors was established by Logistic regression,and the receiver operating characteristic(ROC)curve was drawn to analyze the value of this model in early evaluation of the occurrence of complications after trabeculectomy in glaucoma patients.Results Complications occurred in 35(23.33%)of 150 glaucoma patients after trabeculectomy,including 24 cases of shallow anterior chamber,5 cases of ciliary body or choroid detachment,3 cases of iridocyclitis,2 cases of hyphema,and 1 case of retinal detachment.IFN-γ,GM-CSF and IL-5 levels of the patients in the complication group were lower than those in the control group(P<0.05).There was no significant difference in the levels of other inflammatory factors of patients between the two groups(P>0.05).Multivariate Logistic regression analysis showed that increased levels of IFN-γ(OR=0.999),GM-CSF(OR=0.988)and IL-5(OR=0.996)were independent protective factors for complications after trabeculectomy in glaucoma patients(P<0.05).ROC curve analysis showed that the sensitivity and specificity of the model were 94.29%and 83.84%in early evaluation of the occurrence of complications after trabeculectomy in glaucoma patients,and the AUC was 0.906,which was higher than that predicted by IFN-γ(AUC=0.642),GM-CSF(AUC=0.721)and IL-5(AUC=0.666)alone.Conclusion Preoperative analysis of tear inflammatory factors in glaucoma patients can early evaluate the occurrence of postoperative complications,especially the combined detection of IFN-γ,GM-CSF and IL-5 levels is of great significance for predicting the occurrence of complications.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.