BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

ObjectiveTo investigate the prevalence of polycystic ovary syndrome （PCOS） among female college students at a university in Fuzhou City， Jiangxi Province， and to facilitate early detection and intervention of PCOS. MethodsUsing a stratified sampling method， a total of 450 female freshmen were randomly selected for PCOS screening. A self-designed questionnaire was used for data collection， covering menstrual status， high androgen signs， lifestyle， dietary habits， and awareness of PCOS. Sample t test and χ² test were used to compare the basic information and dietary habits between PCOS and non-PCOS cases. The correlation between various indicators and the prevalence of PCOS was analyzed by a logistic regression model. ResultsA total of 12 PCOS cases were identified， with a prevalence rate of 2.99%. PCOS cases exhibited statistically significant differences compared to non-PCOS cases in terms of waist-to-hip ratio， waist circumference， abdominal obesity， the proportion of overweight or obese individuals， and a preference for sweet food （all P<0.05）. Multivariate logistic regression analysis revealed a significant correlation between preference for sweet food and the occurrence of PCOS （OR=4.858， 95%CI=1.199‒19.675，P=0.027）， as well as a significant correlation with PCOS accompanied by abdominal obesity （OR=7.083， 95%CI=0.773‒64.937， P=0.048）. Among the female college students surveyed， 37.90% had never heard of PCOS， 51.62% were only familiar with the name of the disease， and 10.47% had attempted to search for PCOS-related information. ConclusionThe prevalence of PCOS among female college students should not be overlooked and unhealthy dietary habits may be a crucial factor contributing to the occurrence of PCOS during this period. Early screening for PCOS during puberty is crucial.

Objective:To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) .Methods:A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors.Results:All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis ( P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion:PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

Objective:To investigate whether silencing information regulator 1 (SIRT1) activation can relieve paclitaxel-induced neuropathic pain by inhibiting mitochondrial damage in dorsal root ganglion neurons.Methods:Forty-eight healthy male SD rats were randomly divided into solvent control group, paclitaxel group, paclitaxel+SIRT1 inhibitor group and paclitaxel+SIRT1 agonist group ( n=12). Neuropathic pain model in the later 3 groups was prepared by intraperitoneal injection of paclitaxel at 8 mg/kg on the 1 st, 4 th and 7 th d of experiment, respectively; rats in the paclitaxel+SIRT1 inhibitor group and paclitaxel+SIRT1 agonist group were respectively injected with SIRT1 inhibitor EX527 or agonist SRT1720 30 min before the first injection of paclitaxel. In addition, neuropathic pain model was established in 12 rats (model group) by the same method and SIRT1 expression in the dorsal root ganglion tissues was detected by Western blotting 1 d before experiment and on the 3 rd, 7 th and 14 th d of experiment, respectively. Von-Frey filament was used to detect the 50% paw withdrawal mechanical threshold (PWMT), and thermal radiation thermal pain detector was used to evaluate the paw withdraw thermal latency (PWTL) 1 d before experiment and on the 3 rd, 7 th and 14 th d of experiment. On the 7 th d of experiment, 6 rats in each group were sacrificed with excessive anesthesia after PWMT and PWTL detection; L 4-L 6 dorsal root ganglion tissues were rapidly isolated and primary neurons were cultured; Western blotting was used to detect SIRT1 expression in the dorsal root ganglion tissues, JC-1 mitochondrial membrane potential detection kit was used to detect mitochondrial membrane potential (ratio of orange-red fluorescence to green fluorescence), hydrogen peroxide (H 2O 2) detection kit was used to detect H 2O 2 concentration, and mitochondrial superoxide detection kit and mitochondrial green fluorescence probe kit were used to detect mitochondrial superoxide expression. Results:In the model group, SIRT1 expression in the dorsal root ganglion tissues one d before experiment was significantly decreased compared with that on the 3 rd, 7 th and 14 th d of the experiment ( P<0.05). On 3 rd, 7 th and 14 th d of experiment, compared with the solvent control group, the paclitaxel group had significantly decreased 50% PWMT ([6.37±2.27] g, [5.47±2.42] g and [5.34±1.74] g), and PWTL ([9.38±1.27] s, [9.70±1.97] s and [9.12±1.21] s, P<0.05); compared with the paclitaxel group, the paclitaxel+SIRT1 agonist group had significantly increased 50% PWMT ([13.86±3.72] g, [11.87±3.10] g and [12.39±2.94] g) and PWTL ([14.25±2.63] s, [13.29±2.94] s and [14.43±3.91] s), and the paclitaxel+SIRT1 inhibitor group had significantly decreased 50% PWMT [(2.20±1.43] g, [2.43±1.44] g and [2.21±1.56] g) and PWTL ([4.47±1.66] s, [3.65±1.80] s and [3.14±1.59] s, P<0.05). On the 7 th d of experiment, the paclitaxel group had significantly decreased SIRT1 protein expression (53.95±7.37) and ratio of orange-red fluorescence to green fluorescence (48.74±14.57), and significantly increased H 2O 2 concentration ([4.86±0.69] μmol/L) and mitochondrial superoxide expression (180.17±12.08) in the dorsal root ganglion tissues compared with the solvent control group ( P<0.05); compared with the paclitaxel group, the paclitaxel+SIRT1 agonist group had significantly increased SIRT1 expression (97.51±10.09) and ratio of orange-red fluorescence to green fluorescence (83.52±8.60) and decreased H 2O 2 concentration ([2.30±0.39] μmol/L) and mitochondrial superoxide expression (90.17±18.84) in the dorsal root ganglion tissues ( P<0.05); compared with the paclitaxel group, the paclitaxel+SIRT1 inhibitor group had significantly decreased SIRT1 expression (30.80±6.31) and ratio of orange-red fluorescence to green fluorescence (24.60±6.19) and increased H 2O 2 concentration ([10.67±1.85] μmol/L) and mitochondrial superoxide expression (294.52±26.94) in the dorsal root ganglion tissues ( P<0.05). Conclusion:SIRT1 activation can alleviate paclitaxel-induced neuropathic pain by inhibiting mitochondrial damage in dorsal root ganglion neurons.

OBJECTIVE: Our study aimed to conduct genomic characterization of Salmonella strains carrying the bla _NDM-1 gene in the intestinal tract of healthy individuals. The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations, and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes. METHODS: We performed antimicrobial susceptibility testing and employed second- and third-generation sequencing techniques to analyze Salmonella strains harboring the bla _NDM-1 gene, to surveil drug-resistant bacteria in the intestines of healthy subjects. Sequence comparison was conducted using both core- and pan-genome approaches. Concurrently, conjugation experiments were carried out to assess the efficiency of plasmid transfer. RESULTS: We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China. This strain harbored an IncHI2/IncHI2A plasmid carrying bla _NDM-1 along with multiple antibiotic resistance genes (ARGs). Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs. Pan-genomic analysis revealed that bla _NDM-1-positive plasmids could traverse bacterial species barriers, facilitating cross-host transmission. CONCLUSION This study marks the first detection of bla _NDM-1 in Salmonella strains isolated from healthy individuals. We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying bla _NDM-1, which have the potential to be harbored and transmitted among healthy individuals. Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.
beta-Lactamases/genetics* ; Plasmids/genetics* ; Humans ; Anti-Bacterial Agents/pharmacology* ; China ; Microbial Sensitivity Tests ; Salmonella typhimurium/isolation & purification* ; Salmonella/isolation & purification* ; Salmonella Infections/microbiology*

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

While generative artificial intelligence(AI), exemplified by ChatGPT, demonstrated impressive capabilities in understanding the semantics and context of natural language, and generating coherent and meaningful responses, its performance in the medical field, which required high-level expertise and complex reasoning, remained uncertain. This article aimed to explore the potential applications and challenges of generative AI technology, with ChatGPT as a representative example, in enhancing the capabilities of primary healthcare services. Generative AI, represented by ChatGPT, had potential applications in enhancing primary healthcare services, including clinical assistance in diagnosis, electronic medical record documentation, remote management of chronic patients, and patient education. However, limitations such as the inability to guarantee accuracy, lack of doctor-patient interaction, language barriers, and concerns related to data security, patient privacy, and ethical considerations constrained its practical implementation. Therefore, the application of ChatGPT in improving the capabilities of primary healthcare services required extensive discussion and analysis throughout society. A comprehensive evaluation of potential risks and the establishment of corresponding policies and regulations were necessary to ensure the prudent and responsible introduction and application of ChatGPT, ultimately achieving the goal of empowering primary healthcare services.

BACKGROUND: The molecular mechanisms of heart failure (HF) are still poorly understood. Circular RNA (circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF. METHODS & RESULTS: We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs (DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-miRNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10 mRNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively. CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns; while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.