Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

Aim To investigate the signaling pathways related to telmisartan-induced insulinotropic effect in rats.Methods(1)Islets and cells were isolated from Wistar rats.Islets were treated with different drugs,then supernatant liquid was collected for insulin secretion.The changes in intracellular Ca2+([Ca2+]i)concentrations of β-cells and the effects on ion channel were observed using calcium imaging tech-nology and patch-clamp technology respectively.(2)CHO-Kv2.1 cell line was constructed with lentivirus vector overexpressing Kv2.1 channel,then patch-clamp experiment was performed on CHO-Kv2.1 cells to observe the direct effect of telmisartan on Kv2.1 channel.Results Different from telmisartan,valsar-tan and irbesartan under high glucose condition did not exhibit insulinotropic effect,elevation of[Ca2+]i lev-els,and inhibition of Kv channels in[3 cells.GW9662,a peroxisome proliferator-activated receptorγ(PPARγ)blocker,did not influence the effects of telmisartan on insulin secretion,[Ca2+]i level and Kv channel.CHO cells had no endogenous outward potas-sium currents,while Kv2.1 channel current and its concentration dependent suppression by telmisartan were both detected on CHO-Kv2.1 cells.Conclusion Neither AT-1 receptors nor PPARγ is involved in telmisartan-induced insulinotropic effect,and the effect of telmisartan is partly due to the direct inhibition of kv2.1 channel.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

This study was aimed at analyzing the genomic characteristics of Salmonella typhimurium(1,4,[5],12:i:1,2)in Urumqi from 2018 to 2021,to provide evidence for the monitoring of this serotype and handling of public health emergen-cies.A total of 26 Salmonella typhimurium isolates were obtained from the feces of people with diarrhea in Urumqi.Whole-genome sequencing(WGS)combined with bioinformatic analysis was used to predict serovars,MLST types,plasmid repli-cons,antimicrobial resistance genes,and virulence genes;in addition phylogenomic analysis based on genome-wide single nucleotide polymorphisms(wgSNPs)was conducted to determine the epidemiological relatedness among isolates.A total of 47 resistance genes representing ten categories were de-tected with a high prevalence,including aac(6')-Iaa(100％),blaTEM-1B(30.8％),tet(A)(42.3％),qnrS1(30.8％),and sul3(23.1％),encoding resistance to aminoglycosides,β-lac-tams,tetracyclines,quinolones,and sulfa,in addition to chro-mosomic mutations affecting the gyrA gene.Moreover,12 plasmids were detected,among which IncFIB(S)and IncFII(S)(34.6％)were dominant.The differences in virulence genes a-mong strains isolated in different periods were reflected primarily in the typical virulence genes associated with Salmonella vir-ulence mechanisms.In addition,cgMLST indicated that the dominant type of Salmonella typhimurium was cgST36414,con-tainning 10 strains.Moreover,wgSNP analysis indicated that Salmonella typhimurium isolates in Urumqi were consistent with the epidemic trends in 15 provinces and cities in China and also showed local evolution.Salmonella typhimurium isolates in Urumqi frequently carried a variety of resistance genes and plasmid replicons,which are key in the dissemination and evolution of drug resistance.Close communication links may exist with various sources of flora in the food chain,thus posing severe chal-lenges in public health monitoring and prevention.Therefore,the construction of the laboratory routine monitoring network based on internet information systems should be strengthened to improve the timeliness of monitoring and limit the spread of multidrug-resistant strains.

This study was aimed at analyzing the genomic characteristics of Salmonella typhimurium(1,4,[5],12:i:1,2)in Urumqi from 2018 to 2021,to provide evidence for the monitoring of this serotype and handling of public health emergen-cies.A total of 26 Salmonella typhimurium isolates were obtained from the feces of people with diarrhea in Urumqi.Whole-genome sequencing(WGS)combined with bioinformatic analysis was used to predict serovars,MLST types,plasmid repli-cons,antimicrobial resistance genes,and virulence genes;in addition phylogenomic analysis based on genome-wide single nucleotide polymorphisms(wgSNPs)was conducted to determine the epidemiological relatedness among isolates.A total of 47 resistance genes representing ten categories were de-tected with a high prevalence,including aac(6')-Iaa(100％),blaTEM-1B(30.8％),tet(A)(42.3％),qnrS1(30.8％),and sul3(23.1％),encoding resistance to aminoglycosides,β-lac-tams,tetracyclines,quinolones,and sulfa,in addition to chro-mosomic mutations affecting the gyrA gene.Moreover,12 plasmids were detected,among which IncFIB(S)and IncFII(S)(34.6％)were dominant.The differences in virulence genes a-mong strains isolated in different periods were reflected primarily in the typical virulence genes associated with Salmonella vir-ulence mechanisms.In addition,cgMLST indicated that the dominant type of Salmonella typhimurium was cgST36414,con-tainning 10 strains.Moreover,wgSNP analysis indicated that Salmonella typhimurium isolates in Urumqi were consistent with the epidemic trends in 15 provinces and cities in China and also showed local evolution.Salmonella typhimurium isolates in Urumqi frequently carried a variety of resistance genes and plasmid replicons,which are key in the dissemination and evolution of drug resistance.Close communication links may exist with various sources of flora in the food chain,thus posing severe chal-lenges in public health monitoring and prevention.Therefore,the construction of the laboratory routine monitoring network based on internet information systems should be strengthened to improve the timeliness of monitoring and limit the spread of multidrug-resistant strains.

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.
Humans ; Female ; Adult ; Middle Aged ; Male ; Contrast Media ; Retrospective Studies ; Stroke Volume ; Gadolinium ; Ventricular Function, Left ; Magnetic Resonance Imaging ; Cardiomyopathy, Hypertrophic/diagnostic imaging* ; Death, Sudden, Cardiac ; Risk Assessment

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To investigate the diagnostic value of ultrasound contrast agent enema (UCAE) for anastomotic leakage (AL) after rectal cancer surgery.Methods:From January 2020 to December 2022, a total of 95 patients with presacral fluid collection after rectal cancer surgery in the Sixth Affiliated Hospital of Sun Yat-sen University who received perineal ultrasound (PNUS) and UCAE were retrospectively selected. Among them, 70 patients (73.3%) were diagnosed with AL.After PNUS scanning, all patients received a diluted ultrasound contrast agent administered through the rectum. Receiver operating characteristic (ROC) curve were used to compare the accuracies of PNUS, UCAE, CT, MRI and water-soluble contrast enema in the diagnosis of AL. Factors that may have impacts on the sensitivity of UCAE were thoroughly analyzed.Results:UCAE improved the consistency (Kappa value: 0.757 vs 0.292, P<0.001) and accuracy (AUC: 0.893 vs 0.693, P<0.001) of PNUS in the diagnosis of AL, and its diagnostic accuracy was comparable to that of CT (AUC 0.807), MRI (AUC 0.811) and water-soluble contrast enema (AUC 0.923) (all P>0.05). For mid-to-high AL (anastomotic stoma distance ≥70 mm) and tiny AL (≤3 mm), the sensitivity of UCAE decreased significantly (anastomotic stoma position: 25.0% vs 85.5%, P=0.001; anastomotic leak diameter: 42.9% vs 87.5%, P=0.002). Conclusions:UCAE can significantly improve the diagnostic accuracy and consistency of PNUS for AL after rectal cancer surgery, and its diagnostic sensitivity is affected by the anastomotic stoma distance and the diameter of the leak.