Ecto-nucleotide pyrophosphatases/phosphodiesterases(ENPPs)are involved in the hydrolysis of different purine nu-cleotides in a range of physiological processes.In recent years,it has also been found to be involved in tumor progression,with ENPP1 often overexpressed in local recurrence and tumor metas-tasis,which is associated with poor prognosis and survival in a range of solid tumors.The role of ENPP1 in tumors is mainly fo-cused on tumor proliferation,metastasis,immunity,recurrence,etc.,and it is speculated that ENPP1 can be used as a prognos-tic indicator for a variety of tumors.ENPP1 promotes the immu-nosuppressive tumor microenvironment by being obliquely in-volved in the regulation of ATP/adenosine homeostasis by com-bining with other components,which crosses with interferon gene stimulators to impair its potent immune response through the hy-drolysis of the effector 2',3'-cyclic GMP-AMP.Therefore,EN-PP1 blockade has become an effective means to induce immune remodeling and inhibit tumorigenesis and development.The ex-isting ENPP1 inhibitors mainly include natural small molecule compounds,nucleotide ENPP1 inhibitors,non-nucleotide EN-PP1 inhibitors,and novel small molecule ENPP1 inhibitors.So far,a small number of ENPP1 inhibitors have been developed and are rarely suitable for in vivo experiments,and they are still in the stage of developing effective compounds or lead com-pounds,and the research on ENPP1 inhibitors needs to be fur-ther studied.This review summarizes and discusses the role of ENPP1 in tumors,and summarizes the current research progress of various ENPP1 agents and their current research progress,in order to provide a reference for further research on the prepara-tion of drug candidates.

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

Objective To investigate the differentially expressed genes(DEGs)and their molecular interactions in unstable carotid atherosclerotic plaques.Methods Gene expression datasets related to carotid atherosclerotic plaques(GSE41571,GSE118481,and E-MTAB-2055)were downloaded from Gene Expression Omnibus(GEO)and European Bioinformatics Institute(EBI)ArrayExpress databases.The co-regulated DEGs in at least two datasets of unstable carotid plaques were merged and analyzed using Gene Ontology Biological Process(GO-BP),Kyoto Encyclopedia of Genes and Genomes(KEGG),Protein-Protein Interaction(PPI)Networks and subnetwork analysis,relationships between miRNAs/transcription factors and target genes,and drug-gene interaction database.Quantitative real-time PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to detect the expression levels of some DEGs in carotid plaques and plasma from 58 patients with carotid atherosclerosis.Results GO enrichment analysis showed that DEGs in unstable carotid atherosclerotic plaques were mainly enriched in genes related to inflammatory response and extracellular matrix structure genes.KEGG enrichment analysis indicated that upregulated DEGs in unstable carotid plaques were enriched in extracellular matrix receptor(ECM-receptor)interaction,PI3K-Akt,Hippo and transforming growth factor-β(TGF-β)signaling pathways,while downregulated DEGs were primarily enriched in lysosomes,phagosomes,and chemokines processes.PPI network analysis suggested that COL1A2,COL4A2,insulin-like growth factor binding protein 6(IGFBP6),COL4A5,C1QA,CXCL10,CXCL2,CXCR4,and CSF1R may play important roles in PPI networks.Prediction of drug-gene interactions revealed that CSF1R had the most drug interaction,CXCL2 was most antagonized by drugs,and IGFBP6 was most activated by drugs.qRT-PCR showed that the expression level of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.001).ELISA results showed that plasma concentration of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.0001).Receiver operating characteristic(ROC)suggested that the area under the curve(AUC)for plasma IGFBP6 levels to identify unstable plaques was 0.894(95%CI 0.810-0.977),with a cutoff value of 142.08 ng/ml.Conclusion IGFBP6 may become an important biomarker for predicting unstable carotid atherosclerotic plaques.

Objective:To explore the effect of laryngeal massage combined with feeding training on swallowing function and quality of life in patients with poststroke swallowing disorders.Methods:From November 2021 to October 2022, convenience sampling was used to select 148 patients with poststroke swallowing disorders in the Department of Neurosurgery and Rehabilitation at the North China University of Science and Technology Affiliated Hospital. The patients were divided into a control group, a laryngeal massage group, a feeding training group, and a combination group using the random number table method, with 37 cases in each group. The control group was given routine nursing, while the laryngeal massage group and feeding training group respectively received laryngeal massage and feeding training on the basis of routine nursing. The combination group underwent laryngeal massage combined with feeding training on the basis of routine nursing. Before and after 2, 4, and 8 weeks of intervention, the Water Swallowing Test, Standardized Swallowing Assessment (SSA), and Chinese version Swallowing Quality of Life Questionnaire (SWAL-QOL) were used to compare the swallowing function and quality of life of four groups of patients with poststroke swallowing disorders.Results:After 2, 4, and 8 weeks of intervention, the Water Swallowing Test rating and efficacy evaluation of the 4 groups of patients with poststroke swallowing disorders were better than those before intervention ( P<0.05). Moreover, the SSA scores decreased compared to before intervention ( P<0.05), and the SWAL-QOL scores increased compared to before intervention ( P<0.05). The Water Swallowing Test efficacy evaluation and SWAL-QOL scores in the combined group were higher than those of the other groups ( P<0.05), while the SSA scores were lower than those of the other groups ( P<0.05) . Conclusions:Laryngeal massage and feeding training can improve the swallowing function and quality of life of patients with poststroke swallowing disorders, and the combination of the 2 interventions has a significant effect.

Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.
Child ; Humans ; Child, Preschool ; Case-Control Studies ; Cohort Studies ; Serogroup ; Vaccines, Conjugate/therapeutic use* ; China ; Pneumococcal Infections/prevention & control*

Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I² = 0; P = 0.003), total sperm count (I² = 46.3%; P = 0.043), progressive motility (I² = 50.0%; P < 0.001), total sperm motility (I² = 76.1%; P = 0.047), and normal sperm morphology (I² = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.
Pregnancy ; Female ; Humans ; Male ; Semen Analysis ; Semen ; Infertility, Male ; Sperm Motility ; COVID-19 ; Sperm Count ; Spermatozoa ; Testosterone ; Gonadal Steroid Hormones

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.
Humans ; Rifampin/therapeutic use* ; Antibiotics, Antitubercular/therapeutic use* ; Mycobacterium tuberculosis ; Ethambutol/pharmacology* ; Isoniazid/pharmacology* ; Paraffin Embedding ; Retrospective Studies ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant/drug therapy*

ObjectiveTo observe the clinical efficacy and safety of treating mediate-risk pure ground glass pulmonary nodules （pGGNs） based on the state theory. MethodsA prospective clinical randomized controlled trial was used. Totally 141 cases of mediate-risk pGGNs were divided into treatment group （92 cases） and control group （49 cases） according to the random table method. The treatment group was given the basic Sanjie Formula （基础散结方） orally with modification according to the identification of traditional Chinese medicine （TCM） state， 1 dose per day， 3 months as a course of treatment.Three months after the treatment patients were checked by CT. Patients who were clinically judged as cure， moderate to low risk， and turned to surgical resection do not carry out a second course of treatment，and the rest of the patients continued to complete the second courses. Patients in the control group did not receive any treatment and were only followed up periodically. Patients in both groups received a CT review 3 months and 6 months after enrolled. Comprehensive curative effect was evaluated according to the reduction rate of the area of pulmonary nodules shown in chest CT， to further explore the clinical effective difference for patients at different TCM state； the risk of malignancy index （Mayo score） was calculated by Mayo model at enrollment and 3 months and 6 months after enrolled. Adverse events were monitored continuously during the study. ResultsDuring the follow-up， 8 cases in the treatment group and 7 cases in the control group were lost. A total of 126 cases completed the whole process， including 84 cases in the treatment group and 42 cases in the control group. The total effective rates at 3 months and 6 months of the treatment group were 46.15% （30/65） and 45.71% （32/70） in the treatment group， while the total effective rates at 3 months and 6 months in the control group were 12.5% （4/32） and 10.00% （4/40）. Compared with the control group， the comprehensive curative effect of 3 months and 6 months of enrollment in treatment group was significantly better than that in corresponding control group （P＜0.01）. The pulmonary nodule area and Mayo score in the treatment group decreased after 3 and 6 months of enrollment （P＜0.01）. In contrast， there was no statistically significant difference in nodule area between pre- and post-enrollment time points in the control group （P＞0.05）， and probability of Mayo risk increased in the control group after 6 months of enrollment compared to pre-enrollment （P＜0.05）. Among the 84 patients in the treatment group， there were 15 cases of qi deficiency state， 7 cases of yin deficiency state， 5 cases of yang deficiency state， 20 cases of qi depression state， 32 cases of damp-heat state， and 5 cases of harmonious state； the difference in the distribution of the total clinical effective rate of the patients with different TCM states after treatment was statistically significant （P＜0.05）， and the total effective rate of two-by-two comparison of qi depression state was higher （13/20，65.00%） than that of the total effective rate of damp-heat state （8/32，25.00%， P＜0.00833）. There were no significant changes in blood routine， urine routine， liver function and kidney function in both groups， and no adverse events occurred. ConclusionTreating mediate-risk pGGNs based on the state theory can effectively reduce the area of pulmonary nodules and inhibit the growth of malignant risk of pulmonary nodules.

Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.
Child ; Humans ; Child, Preschool ; Case-Control Studies ; Cohort Studies ; Serogroup ; Vaccines, Conjugate/therapeutic use* ; China ; Pneumococcal Infections/prevention & control*

Objective:To investigate the effect of hepatic venous pressure gradient (HVPG) on the prevention of rebleeding in cirrhotic patients of hepatitis B with gastroesophageal variceal hemorrhage receiving endoscopic therapy, and its influence on prognosis.Methods:Fifty eight patients with esophageal and gastric varices due to cirrhosis of hepatitis B admitted to Minhang Hospital Affiliated to Fudan University (from January 2019 to September 2021, n=18) and Zhongshan Hospital Affiliated to Fudan University (from January to September 2017, n=40) were retrospectively included. All of them underwent HVPG determination and endoscopic treatment. They were divided into HVPG≤18 mmHg group and HVPG>18 mmHg group. The rebleeding and survival status of these patients with endoscopic treatment was compared after a follow-up period of 2 years, and Cox regression was performed to analyze the related factors for rebleeding and survival. Results:A total of 58 individuals were included, which were divided into two groups: HVPG≤18 mmHg group (35) and HVPG>18 mmHg group (23). During the 2-year follow-up after the first endoscopic treatment, 13 patients (22.41%) developed rebleeding, including 4 patients in the HVPG≤18 mmHg group and 9 patients in the HVPG>18 mmHg group. The non-bleeding rate in HVPG≤18 mmHg group was significantly higher than that in HVPG>18 mmHg group (91.3% vs 68.7%, RR=3.54, 95% CI: 1.08-11.60, P=0.026), and the difference was statistically significant. Four patients died, including 1 patient in the HVPG≤18 mmHg group and 3 patients in the HVPG>18 mmHg group. There was no statistically significant difference in 2-year survival between the two groups (96.7% vs 86.5%, RR=4.44, 95% CI: 0.45-43.58, P=0.162). Cox regression multivariate analysis was used to analyze the above data, and the results suggested portal vein thrombosis ( HR=3.826, 95% CI: 1.263-11.585, P=0.018), HVPG>18 mmHg ( HR=4.243, 95% CI: 1.290-13.955, P=0.017) were independent risk factors for rebleeding in 2 years after endoscopic therapy. Conclusions:For patients with high HVPG, it should be fully evaluated and considered to receive other pressure lowering therapy, and treatment conversion should be carried out as soon as possible after endoscopic treatment failure.