Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Objective To study the correlation between Periostin, interleukin-33 (IL-33), and chronic cough after thoracoscopic lobectomy in patients with coronary artery bypass grafting (CABG) combined with lung cancer. Methods A total of 102 lung cancer and coronary heart disease patients at Tianjin Chest Hospital from January 2022 to January 2024 were prospectively enrolled, and they were divided into a chronic cough group (n=42) and a non-chronic cough group (n=60) based on whether chronic cough occurred after surgery. Serum levels of Periostin and IL-33 were measured on the 1st, 7th, and 14th days post-lobectomy. The Pearson method was employed to analyze the correlation between Periostin and IL-33 levels and the severity of cough. Univariate and multivariate logistic regression analyses were conducted to identify factors influencing the occurrence of chronic cough. Additionally, receiver operating characteristic (ROC) curve analysis was utilized to assess the potential value of serum Periostin and IL-33 levels in predicting postoperative chronic cough. Results In patients with chronic cough, the peripheral blood Periostin and IL-33 levels measured on days 7 and 14 were significantly higher than those in patients with non-chronic cough, and the interactions between the two groups and at different time points were significant (P<0.001). The degree of cough was positively correlated with the levels of Periostin and IL-33 on days 7 and 14 (P<0.05), but had no significant correlation with the levels on day 1 (P>0.05). In patients with lung cancer, after thoracoscopic lobectomy, Periostin [OR=1.619, 95%CI (1.295, 2.025)] and IL-33 [OR=1.831, 95%CI (1.216, 2.758)] on day 7 and Periostin [OR=1.952, 95%CI (1.306, 2.918)] and IL-33 [OR=1.742, 95%CI (1.166, 2.603)] on day 14 were identified as risk factors for chronic cough. ROC curve analysis showed that the sensitivity of Periostin on day 7 was 69.05%, the specificity was 71.67%, and the area under the curve (AUC) was 0.756 [95%CI (0.616, 0.893)]. The sensitivity of Periostin on day 14 increased to 71.43% and the specificity was 76.67%, AUC was 0.762 [95%CI (0.633, 0.898)]. At the same time, the critical value of IL-33 on day 7 was 45.03 pg/mL, the sensitivity and specificity were both 83.33%, the AUC was 0.884 [95%CI (0.789, 0.980)], and the critical value of IL-33 on day 14 was 56.01 pg/mL, the sensitivity was 85.71%, the specificity was 80.00%, and the AUC was 0.899 [95%CI (0.799, 0.999)]. Joint logistic regression analysis of Periostin and IL-33 levels on days 7 and 14 showed showed that the sensitivity was 95.24%, the specificity was 95.00%, and the AUC reached 0.993 [95%CI (0.979, 1.000)]. Conclusion Periostin and IL-33 levels, measured at various time points, are abnormally elevated following thoracoscopic lobectomy in patients with combined CABG and lung cancer. These levels significantly correlate with cough severity. Given their predictive potential for chronic cough, these markers are deemed valuable biomarkers.

ObjectiveTo conduct an epidemiological investigation, isolate and identify the pathogenic bacteria, and perform whole-genome sequencing (WGS) analysis of a food poisoning outbreak in Suzhou High-tech Zone, so as to provide references for the prevention and management of similar incidents. MethodsAn epidemiological investigation was carried out on affected individuals and restaurant staff. Multi-pathogen screening was performed on rectal swab samples from affected cases and restaurant staff, as well as on environmental swab samples from food preparation areas and retained food samples. WGS was performed on the pathogens isolated from the samples. ResultsA total of 15 cases were identified through hospital visit record reviews and on-site inquiries. Of the 15 case samples, 14 tested positive for Staphylococcus aureus (SA). In addition, 3 out of 15 staff samples and 6 out of 34 retained food samples tested positive for SA. WGS results revealed that the 6 food-derived isolates and 13 case-derived isolates shared the same sequence type (ST), Staphylococcal Protein A (SPA) type, and enterotoxin gene profile, with whole-genome single nucleotide polymorphism (wgSNP) differences of ≤5. Two novel SA sequence types: ST9159 and ST9161, were also identified in this study. ConclusionThis food poisoning outbreak is caused by contamination food with SA harbouring the seb and sec enterotoxin genes. The primary causes of contamination and cross-contamination included improper food handling practices, the use of the same utensils for raw and cooked foods, and extended storage of certain dishes at room temperature. Strengthening sanitary supervision in food handling facilities is crucial for reducing the occurrence of similar incidents.

Objective To investigate the role and mechanism of RNA-Specific adenosine deaminase 3 (Adar3) in regulating macrophage polarization during Coxsackievirus B3(CVB3)-induced viral myocarditis (VM). Methods Bone marrow-derived macrophages (BMDM) from mice were cultured in vitro and induced into M1/M2 macrophages using interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) or interleukin 4 (IL-4), respectively. The mRNA expression levels of Adar1, Adar2, and Adar3 in each group of cells were assessed by real-time quantitative PCR (qRT-PCR). Specific siRNAs targeting the Adar3 gene were designed, synthesized, and transiently transfected into M2 macrophages. The mRNA levels of M2 polarization-related marker genes-including arginase 1 (Arg1), chitinase 3-like molecule 3 (YM1/Chi3l3), and resistin-like molecule alpha (RELMα/FIZZ1)-were detected by qRT-PCR. RNA sequencing was performed to analyze the signaling pathways affected by Adar3. The expression levels of Wnt/β-catenin signaling pathway were further validated using qRT-PCR and Western blot. The adeno-associated virus overexpressing Adar3 was designed, synthesized, and injected into mice via tail vein. Three weeks later, a myocarditis mouse model was established. After an additional week, the phenotype and function of cardiac macrophages, as well as multiple indicators of VM (including echocardiography, body weight, histopathology and serology) were examined. Additionally, the protein levels of the Wnt/β-catenin signaling pathway were assessed. Results Compared to M0-type macrophages, the expression level of Adar3 was significantly increased in M2-type macrophages. After transfection of Adar3 siRNA, the mRNA levels of Arg1, YM1 and FIZZ1 in M2 macrophages were downregulated. RNA sequencing revealed 149 upregulated genes and 349 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and subsequent validation experiments indicated that Adar3 modulated the Wnt/β-catenin signaling pathway. In vivo experiments demonstrated that Adar3 overexpression alleviated the cardiac dysfunction of VM mice. The proportion of M1 macrophages in the heart decreased, while the proportion of M2 macrophages increased. At the same time, the Adar3 overexpression activated the Wnt/β-catenin signaling pathway. Conclusion Adar3 promotes macrophage polarization toward the M2 phenotype by activating the Wnt/β-catenin signaling pathway, thereby alleviating VM.
Animals ; Adenosine Deaminase/metabolism* ; Macrophages/immunology* ; Wnt Signaling Pathway/genetics* ; Myocarditis/immunology* ; Mice ; Coxsackievirus Infections/metabolism* ; Male ; Mice, Inbred BALB C ; Enterovirus B, Human/physiology* ; beta Catenin/genetics*

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Cirrhosis is a severe disease caused by chronic inflammatory damage to the liver due to various factors,often complicated by portal hypertension.The primary causes of portal hypertension include increased intrahepatic vascular resistance and increased portal venous blood flow.Carvedilol,a third-generation non-selective beta-blocker(NSBB)with alpha-1 receptor-blocking role,is superior to traditional NSBBs in reducing portal pressure.It is believed that carvedilol significantly reduces hepatic venous pressure gradient(HVPG)through multiple mechanisms,prevents variceal bleeding,and extends patient survival.This paper reviews the mechanisms and clinical applications of carvedilol in the treatment of portal hypertension,focusing on its efficacy in the primary and secondary prevention of varices and its impact on the survival of cirrhotic patients with refractory ascites.

AIM: To analyze the distribution frequency of gene polymorphisms of β receptor blockers, angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, calcium antagonists, and diuretics in hypertensive patients from southern Anhui province, and provide a theoretical basis for gene detection of hypertension drugs and personalized medication. METHODS: Drug gene testing information from 839 hospitalized patients with hypertension at Yijishan Hospital of Wannan Medical College from July 2021 to April 2023 were collected, and the distribution frequency of each gene locus were analyzed. RESULTS: The genotype frequencies of ACE (I/D) I/I, I/D, and D/D were 42.1%, 46.0%, and 11.9%, respectively. the genotype frequencies of ADRB1 (1165G>C) G/G, G/C, and C/C were 8.3%, 40.0%, and 51.6%, respectively. The genotype frequencies of AGTR1 (1166A>C) A/A, A/C, and C/C were 90.2%, 9.8%, and 0.0%. The genotype frequencies of CYP2C9*3 (1075A>C) *1/*1, *1/*3, and *3/*3 were 91.3%, 8.7%, and 0.0%, respectively; the genotype frequencies of CYP2D6* 10 (100C > T) *1/*1, *1/*10, and *10/*10 were 25.0%, 36.6%, and 38.4%, respectively. The genotype frequencies of CYP3A5*3 (6986A>G) *1/*1, *1/*3, and *3/*3 were 7.0%, 39.0%, and 54.0%, respectively. The frequencies of NPPA (2238T>C) T/T, T / C, and C / C genotypes were 97.9%, 2.1%, and 0.0%, respectively. In addition, there was a significant difference in the genotype distribution frequency of multiple drug related gene loci in southern Anhui compared to other regions in China (P< 0.05). CONCLUSION: The genotype distribution frequency of hypertensive drug related gene loci had certain bias in southern Anhui, and were significant different from other regions in China, indicating that conducting genetic polymorphism testing of hypertensive drugs had certain guiding significance for the individualized application of hypertensive drugs in southern Anhui.

Objective:To design a new type of intelligent power-assisted hip disarticulation prosthesis and to use experiments to verify its kinematic performance.Methods:The main body of the prosthesis was designed using a double parallel four-link configuration based on a remote motion center mechanism. A series elastic actuator was used to provide external power for the prosthesis, and an antagonistic torsion spring structure was used to achieve bidirectional energy storage assistance in hip flexion and extension. A control system based on impedance control was established. By setting up an auxiliary force field to compensate for the difference between the actual angle of the prosthesis and the target angle, the prosthesis assist function was realized. Finally, the traditional hip disarticulation prosthesis was used as a comparison to test the overall performance of the new intelligent power-assisted hip disarticulation prosthesis worn by normal people.Results:For the new smart-assisted hip-disarticulation prosthesis, the goodness-of-fit of its hip joint angle curve to that of a normal person was 86%, which was 14% higher than that of the traditional hip-disarticulation prosthesis (72%). The goodness-of-fit of the healthy-side angle of the new smart-assisted hip disarticulation prosthesis to the normal human was 94%, which was the same as that of the traditional hip disarticulation prosthesis.Conclusions:A new type of intelligent power-assisted hip disarticulation prosthesis is designed to realize the function of prosthesis-assisted movement.