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.

Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective:To analyze the incidence and progression of overactive bladder(OAB)symp-toms following radical prostatectomy for prostate cancer patients and to identify related risk factors.Methods:A retrospective study was conducted on 263 local stage prostate cancer patients who underwent radical prostatectomy at Peking University Third Hospital from January 2013 to May 2017.Clinical base-line information,comprehensive imaging features,perioperative parameters,preoperative urinary control status,pathological diagnosis,and the incidence of OAB within one year postoperatively were collected and analyzed.In the imaging features,two parameters were defined:Bladder wall thickness(BWT)and bladder mucosal smoothness(BMS),which were used to predict the occurrence of OAB.Patients were evaluated based on their clinical baseline characteristics,including age,body mass index(BMI),co-morbidities,and prostate-specific antigen(PSA)levels.The imaging characteristics were assessed using preoperative MRI,focusing on BWT and BMS.Perioperative parameters included operative time,blood loss,and length of hospital stay.The OAB symptoms were assessed using the overactive bladder symptom score(OABSS)and the international prostate symptom score(IPSS).These scores were correlated with the postoperative incidence of OAB.Results:Among the 263 patients who underwent radical prostatecto-my,52(19.8％)exhibited OAB within one year postoperatively.Of the 40 patients with preoperative OAB symptoms,17(42.5％)showed remission postoperatively,while 23(57.5％)had persistent symptoms.Additionally,29 patients developed new-onset OAB,accounting for 55.77％of all postopera-tive OAB cases.Univariate analysis indicated that BWT,BMS,OABSS,and IPSS score were all associ-ated with the occurrence of postoperative OAB.Further multivariate analysis identified BMS as an inde-pendent risk factor for long-term OAB(P＜0.001).Conclusion:Long-term postoperative overactive bladder is a common complication following radical prostatectomy.The findings suggest that preoperative MRI measurements of bladder wall thickness and bladder mucosal smoothness during bladder filling phase can predict the risk of OAB occurrence postoperatively.Identifying these risk factors preoperatively can help in counseling patients about potential complications and in developing strategies to mitigate the risk of developing OAB after surgery.Early detection and management of these parameters might improve the quality of life for patients undergoing radical prostatectomy.

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 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.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.