A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Nitrofurantoin(NFT)is a nitrofuran antibiotic commonly used as a veterinary drug to treat bacterial infections in animals.However,due to the low solubility and bioaccumulation properties,NFT is prone to leave excessive residues in animal-derived foods and water systems,posing serious threats to human health and ecosystems.Therefore,there is an urgent need to develop an efficient and rapid detection method for NFT.In this work,nitrogen-doped carbon nanomaterials with unique bowl-like structures(N-CNBs)were synthesized via a hydrothermal-carbonization method.The morphology,surface structure,and specific surface area of N-CNBs were characterized using transmission electron microscopy(TEM),scanning electron microscopy(SEM),and X-ray photoelectron spectroscopy(XPS).The N-CNB modified glassy carbon electrode(N-CNB/GCE)was prepared,and the electrochemical test revealed that the N-CNB/GCE exhibited higher conductivity and larger electrochemical active surface area compared to bare GCE and nitrogen-doped hollow carbon nanosphere-modified electrode(N-HCNS/GCE).Additionally,the N-CNB/GCE demonstrated superior electrocatalytic activity toward NFT.An NFT electrochemical sensor was constructed based on N-CNB/GCE.The detection conditions of the sensor were optimized,and differential pulse voltammetry(DPV)was employed for NFT detection under optimal experimental conditions.The established NFT electrochemical sensor had a wide linear range of 0.4-500 μmol/L,a low detection limit(S/N=3)of 0.015 μmol/L and high selectivity,with excellent stability and reproducibility.The practical feasibility of this sensor was confirmed by analysis of NFT in milk and tap water samples,with spiked recoveries ranging from 94.2%to 108.9%.

Objective To evaluate the prognostic value of C-reactive protein (CRP), performance status (PS), lactate dehydrogenase (LDH), albumin (ALB) and derived neutrophil-to-lymphocyte ratio (dNLR) composite index (C-PLAN) as a prognostic indicator in advanced esophageal cancer patients treated with immune checkpoint inhibitor (ICI). Methods Hematologic indexes of 147 patients with advanced esophageal cancer treated by ICI in the Affiliated Hospital of Yangzhou University were collected before the first immunotherapy. CRP, PS, LDH, ALB and dNLR were scored and added to obtain C-PLAN index. Chi-square test was used to analyze the correlation between C-PLAN index and clinicopathological features; Kaplan-Meier survival curve was used to analyze the effects of C-PLAN index on overall survival (OS) and progression-free survival (PFS). Univariate and multifactor Cox proportional regression models were used to analyze whether C-PLAN index could be used as an independent factor affecting prognosis. Results A total of 147 patients with advanced esophageal cancer were divided into low-risk group (scored < 2, n=46) and high-risk group (scored ≥2, n=101) according to C-PLAN index. C-PLAN index was not correlated with age, sex, PS score, smoking, clinical stage, body mass index, pathological type, treatment strategy and operation (P>0.05). PFS and OS in the low-risk group were significantly better than those in the high-risk group (P < 0.001). In univariate Cox regression analysis, C-PLAN index was the influencing factor of PFS (P < 0.001) and OS (P=0.002). In multivariate Cox analysis, C-PLAN index was an independent prognostic factor of PFS (P=0.001) and OS (P=0.006). Conclusion C-PLAN index can be used as a reliable clinical index to predict the prognosis of patients with advanced esophageal cancer treated by ICI.

Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.
Male ; Humans ; Adult ; Middle Aged ; Female ; Receptors, Chimeric Antigen/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Immunotherapy, Adoptive ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Cell- and Tissue-Based Therapy

To construct a non-communicable disease system recommended by WHO, develop the key techniques and promote their applications, obtain the main health indicators and understand the prevalence of chronic diseases, and provide support for the prevention, control and research of chronic diseases. Based on factor analysis, K-means clustering and multi-cluster random sampling, 30 typical sampling areas at provincial level were designed and constructed; By referring to WHO's Non-communicable Disease Surveillance Framework and the American behavioral risk factor sampling and questionnaire and combined with China's actual needs, a comprehensive surveillance system for chronic diseases, covering morbidity and mortality, risk factor exposure and community management and control of chronic diseases, was established, a "5+12+1" quality control system for surveillance data collection, management, analysis and feedback was formed and a three-level surveillance information management platform and information technology construction standards in the province were established, resulting the integration of life registration, chronic disease case reporting and community chronic disease management. Using these key techniques, we have obtained high-quality surveillance data of the whole province, produced the main health indicators, carried out research of chronic diseases, and analyze the prevalence and changing trend of the main chronic diseases and related risk factors to boost the government's practical projects for the reform of the people's livelihood and facilitate the construction of "Healthy Zhejiang". The successful experiences and key techniques have been applied in the construction of chronic disease surveillance system in some provinces in China.
China/epidemiology* ; Chronic Disease ; Chronic Disease Indicators ; Humans ; Noncommunicable Diseases ; Prevalence

Objective To understand the impact of social environmental support on tobacco use among junior high school students before and after the implementation of Beijing Tobacco Control Regulations, and to provide scientific basis for formulating adolescent tobacco control strategies and intervention measures. Methods The two-stage sampling method was used to conduct a questionnaire survey among three junior middle schools randomly selected from Shunyi District of Beijing using the global adolescent tobacco epidemic questionnaire before and after the ban was implemented. Results After the implementation of tobacco control,the influence of exposure to second-hand smoking at home and in public places on the current smoking rate of junior high school students (χ²=13.802, P=0.003; χ²= 27.909, P<0.001), the attempting smoking rate (χ²=31.757, P<0.001); χ²=37.691, P<0.001) was statistically significant. The junior high school students' attitude and cognition of tobacco use and the smoking rate of good friends are common risk factors affecting junior high school students' tobacco use. After the implementation of smoking control, the probability of smoking among junior high school students with good friends around them decreased from 21.417 times to 5.244 times; The probability of attempting smoking decreased from 4.518 times to 3.416 times. Conclusion After the smoking ban, the overall situation of tobacco use of junior high school students is not optimistic. All the factors in environmental perception system are closely related to junior high school students' tobacco use behavior, and the peer effect is the most obvious. Improving the environmental perception system is conducive to the prevention and control of adolescent smoking.

This study aims to construct a dynamic two-dimensional characterization technique for the hygroscopicity of traditional Chinese medicine extracts and investigate the effect of material properties of powders on hygroscopicity. The dynamic hygroscopicity-time curves of the powders were measured at 25 ℃ and 75% humidity, and the semi-equilibrium hygroscopicity time (t_1/2) and equilibrium hygroscopicity (F^∞) were derived as two-dimensional evaluation indicators. Finally, the correlation between the material properties and the hygroscopic behavior was analyzed by principal component analysis (PCA) and partial least squares analysis (PLS). The results showed that the dynamic two-dimensional characterization system of hygroscopicity constructed with 1/t_1/2 = 0.1 h^-1 and F^∞ = 15% as the center can classify the hygroscopic behavior of traditional Chinese medicine extracts into four categories: fast hygroscopicity with strong hygroscopicity, slow hygroscopicity with strong hygroscopicity, fast hygroscopicity with weak hygroscopicity and slow hygroscopicity with weak hygroscopicity. The moisture absorption was negatively correlated with D₅₀, D₉₀, ρ_b and ρ_t; the moisture absorption rate was negatively correlated with D₁₀, D₅₀, D₉₀, ρ_b, ρ_t, and positively correlated with moisture content. The hygroscopicity dynamic two-dimensional characterization indicators of Chinese medicine extracts (CMEs) constructed in this study matched with the physical properties. The method of dynamic multi-dimensional characterization technology is feasible and scientific, and the idea has strong promotional value.