Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To summarize and analyze the composition characteristics and problems of basic medical insurance policies for traditional Chinese medicine in various provinces of China,providing reference for optimizing and improving subsequent basic medical insurance policies for traditional Chinese medicine.Methods:Based on the perspective of policy instrument,combined with two dimensions of policy instrument types and policy development process,the content analysis method is used to quantitatively analyze the content of the basic medical insurance policies for traditional Chinese medicine released at the provincial level from 2011 to 2023.Results:The 93 included policy documents were coded and sorted,with a cumulative total of 487 codes.From the perspective of policy instrument dimensions,subcategories of policy instruments involve diverse themes,but there are differences in the level of attention paid to each policy tool.From the perspective of policy development process,each link also presents a discrete trend,indicating a dominant feature of policy planning and implementation.Conclusion:To improve the basic medical insurance policy system of traditional Chinese medicine in China,it is necessary to optimize the combination of policy instrument and construct a coordinated and balanced policy instrument framework;Overall planning of the development process of traditional Chinese medicine medical insurance policies,highlighting the unique advantages of traditional Chinese medicine;Emphasize policy synergy between dimensions and strengthen the implementation of traditional Chinese medicine medical insurance policies.

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.
Humans ; United States ; Schools, Public Health ; Schools ; Universities ; Public Health ; Centers for Disease Control and Prevention, U.S.

Objective To conduct a survey on the status of noise hazards in Tianjin in 2020, to analyze the main distribution characteristics of noise hazards, and to put forward corresponding preventive and control measures. Methods A unified questionnaire was used to investigate the city-wide enterprises with more than 5 employees, normal production and operation, and noise hazards. The χ² test was used to analyze the survey results. Results There were 8 560 enterprises with noise hazards, which were concentrated in the five outer suburban districts, the four districts around the city and the Binhai New Area, mainly small and medium-sized enterprises. Totally, 223 800 people were exposed to noise. The rates of noise hazard detection and physical examination of workers were 25.88% and 17.66%, and the rate of over standard detection and the rate of abnormal physical examination were 13.09% and 1.62%, respectively. The differences in noise detection rate, over standard detection rate and physical examination rate were significant in different administrative regions, enterprise scales and industries. The detection rate and physical examination rate of enterprises in the five outer suburban districts, micro-scale enterprises, and paper products industries were the lowest, while the rate of exceeding standards was the highest in the railway, shipping, aerospace and other transportation equipment manufacturing industries. Conclusion Noise is a common occupational hazard in enterprises in Tianjin. There are a large number of people who are exposed to noise. The detection rate and physical examination rate of noise are at a low level. Individual industries have a high rate of exceeding the standard. The current situation of noise hazard prevention and control is not optimistic. It is recommended to pay attention to it and take effective intervention measures.

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

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: 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 explore the medium-long term efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for gastrointestinal hemorrhage in patients with idiopathic non-cirrhotic portal hypertension (INCPH).Methods:From March 2013 to July 2018, clinical data of 13 INCPH patients, including 5 males, 8 females,with gastrointestinal hemorrhage were retrospectively analyzed, who were diagnosed at the First Affiliated Hospital of Zhengzhou University, Anyang Fifth People′ s Hospital and Yuncheng Central Hospital. All patients received TIPS treatment. The general information, postoperative survival rate, the incidence of rebleeding, shunt dysfunction rate, and incidence of hepatic encephalopathy were analyzed.Results:All 13 patients with INCPH completed TIPS successfully with an average age of 45±8 (33 to 59) years. The hepatic venous pressure gradient (HVPG) decreased from 20.0-26.0 (22.6±1.9) mmHg before procedure to 8.0-14.0 (9.4±3.2) mmHg after. The median follow-up time was 44±7 (31 to 53) months. One patient died of liver failure 27 months after TIPS. Hepatic encephalopathy occurred cumulatively in 1 case (1/13), 1 case (1/13) and 1 case (1/13) in 12, 24 and 36 months after TIPS. Stent restenosis occurred cumulatively in 2 cases (2/13), 3 cases (3/13) and 3 cases (3/13) in 12, 24 and 36 months after TIPS. Portal vein thrombosis occurred cumulatively in 2 cases (2/13), and no primary liver cancer developed.Conclusions:TIPS is safe and effective in the treatment of INCPH with gastrointestinal bleeding with favorable medium-long term outcome.

Objective: To describe the clinical characteristics of Mycoplasma pneumoniae infection and analyze the factors associated with co-infections with other pathogens in children, and provide evidence for improvement of community acquired pneumonia (CAP) prevention and control in children. Methods: Based on the surveillance of hospitalized acute respiratory infections cases conducted in Soochow University Affiliated Children's Hospital (SCH), the CAP cases aged <16 years hospitalized in SCH between 2018 and 2021 were screened. The pathogenic test results of the cases were obtained through the laboratory information system, and their basic information, underlying conditions, and clinical characteristics were collected using a standardized questionnaire. The differences in clinical characteristics between M. pneumoniae infection and bacterial or viral infection and the effect of the co-infection of M. pneumoniae with other pathogens on clinical severity in the cases were analyzed; logistic regression was used to analyze the factors associated with the co-infections with other pathogens. Results: A total of 8 274 hospitalized CAP cases met the inclusion criteria. Among them, 2 184 were positive for M. pneumoniae (26.4%). The M. pneumoniae positivity rate increased with age (P<0.001), and it was higher in girls (P<0.001) and in summer and autumn (P<0.001). There were statistically significant differences in the incidence of wheezing, shortness of breath, wheezing sounds and visible lamellar faint shadow on chest radiographs, as well as fever and hospitalization days among M. pneumoniae, bacterial, and viral infection cases (all P<0.05). In the cases aged <60 months years, co-infection cases had higher rates of wheezing, gurgling with sputum and stridor; and in the cases aged ≥60 months, co-infection cases had a higher rate of shortness of breath (all P<0.05). Multifactorial logistic regression analysis showed that being boys (aOR=1.38,95%CI:1.15-1.67), being aged <6 months (aOR=3.30,95%CI:2.25-4.89), 6-23 months (aOR=3.44,95%CI:2.63-4.51), 24-47 months (aOR=2.50,95%CI:1.90-3.30) and 48-71 months (aOR=1.77,95%CI:1.32-2.37), and history of respiratory infection within 3 months (aOR=1.28,95%CI:1.06-1.55) were factors associated with co-infections of M. pneumoniae with other pathogens. Conclusions: M. pneumoniae was the leading pathogen in children hospitalized due to CAP. M. pneumoniae infections could cause fever for longer days compared with bacterial or viral infections; M. pneumoniae was often co-detected with virus or bacteria. Being boys, being aged <72 months and history of respiratory infection within 3 months were associated factors for co-infections.
Bacteria ; Child ; Coinfection/epidemiology* ; Community-Acquired Infections/epidemiology* ; Dyspnea ; Female ; Humans ; Male ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma/microbiology* ; Respiratory Sounds ; Respiratory Tract Infections/epidemiology* ; Virus Diseases

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.
China ; Disaster Planning ; Humans ; Public Health ; Public Health Administration