BACKGROUND: The profile and clinical significance of the oral microbiome in patients with non-obstructive hypertrophic cardiomyopathy (noHCM) and obstructive hypertrophic cardiomyopathy (oHCM) remain unexplored. The objective of this study was to evaluate the difference of oral microbiome between noHCM and oHCM patients. METHODS: This cross-sectional study enrolled 18 noHCM patients and 26 oHCM patients from Fuwai Hospital, Chinese Academy of Medical Sciences between 2020 and 2021. Clinical and periodontal evaluations were conducted, and subgingival plaque samples were collected. Metagenomic sequencing and subsequent microbial composition and functional analyses were performed. RESULTS: Compared to oHCM patients, those with noHCM had higher systolic blood pressure (138.1 ± 18.8 mmHg vs . 124.2 ± 13.8 mmHg, P = 0.007), a larger body circumference (neck circumference: 39.2 ± 4.0 cm vs . 35.1 ± 3.7 cm, P = 0.001; waist circumference: 99.7 ± 10.5 cm vs . 92.2 ± 10.8 cm, P = 0.027; hip circumference: 102.5 ± 5.6 cm vs . 97.5 ± 9.1 cm, P = 0.030), a greater left ventricular end-diastolic diameter (46.6 ± 4.9 mm vs . 43.1 ± 4.9 mm, P = 0.026), and a lower left ventricular ejection fraction (64.1 ± 5.7 % vs . 68.5 ± 7.8%, P = 0.048). While overall biodiversity and general microbial composition were similar between the noHCM and oHCM groups, ten taxa displayed significant differences at the genus and species levels, with Porphyromonas gingivalis showing the highest abundance and greater enrichment in noHCM (relative abundance: 7.79535 vs . 4.87697, P = 0.043). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified ten distinct pathways, with pathways related to energy and amino acid metabolism being enriched in oHCM patients, and those associated with genetic information processing less abundant in the oHCM group. Metabolic potential analysis revealed ten significantly altered metabolites primarily associated with amino sugar and nucleotide sugar metabolism, porphyrin metabolism, pentose and glucuronate interconversion, and lysine degradation. CONCLUSIONS The higher abundance of Porphyromonas gingivalis , which is known to impact cardiovascular health, in noHCM patients may partially account for clinical differences between the groups. Pathway enrichment and metabolic potential analyses suggest microbial functional shifts between noHCM and oHCM patients, potentially reflecting inherent metabolic changes in HCM.
Humans ; Cardiomyopathy, Hypertrophic/microbiology* ; Female ; Male ; Microbiota/genetics* ; Middle Aged ; Cross-Sectional Studies ; Adult ; Mouth/microbiology* ; Aged

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Objective To explore the mechanism underlying the protective effect of Lonicerae japonicae flos(LJF)extract against doxorubicin(DOX)-induced liver injury in mice.Methods Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets,based on which the protein-protein interaction(PPI)network was constructed using STRING database for screening the core targets using Cytoscape software.DAVID database was used for bioinformatics analysis,and the core components and core targets were verified using molecular docking study.In a mouse model of DOX-induced liver injury,the effect of LJF extract on liver pathologies,serum levels of ALT and AST,and hepatic expressions of HYP,ROS,TNF-α,IL-6,COL-IV and P53 proteins were evaluated using HE and Masson staining,ELISA,and Western blotting.Results We identified 12 core targets from 43 intersection genes involving cancer pathway,IL-17 signaling pathway,and TNF signaling pathways.Molecular docking study suggested that 10 core components of LJF could bind to different core targets.The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis,increased ROS content,and enhanced expressions of TNF-α,IL-6,HYP,COL-IV and P53 proteins in the liver tissue.All these changes in the mouse models were significantly alleviated by treatment with LJF extract,suggesting obviously lowered levels of oxidative stress,inflammation and fibrosis in the liver tissues.Conclusion LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53,TNF and IL-6 to reduce liver oxidative stress,inflammation and fibrosis.

Objective:To compare the diagnostic efficacy of 68Ga-PSMA-11 PET/ CT and multi-parameter magnetic resonance imaging (mpMRI) for pelvic lymph node metastases in prostate cancer patients who received neoadjuvant endocrinology or not after initial diagnosis. Methods:Data of 52 patients with moderate and high-risk prostate cancer admitted to Xijing Hospital from February to October 2023, aged (65.8±6.6) years, preoperative prostate-specific antigen (PSA) 26.67 (13.09, 84.89) ng/ml, were retrospectively analyzed. Before operation, there were 28 cases of cT 2stage, 16 cases of cT 3 stage and 8 cases of cT 4 stage. There were 22 cases of cN 0 and 30 cases of cN 1. All patients underwent 68Ga-PSMA-11 PET/CT and mpMRI at the same time, and were diagnosed positive lymph nodes in 28 and 21 cases, respectively. Risk stratification were high risk in 45 cases, and medium risk in 7 cases. According to the preoperative endocrine treatment, they were divided into the newly diagnosed group without treatment (24 cases) and the endocrine treated group (28 cases), whose ages were (65.0±7.1) years and (66.8±6.1) years, respectively. Preoperative PSA was 26.17 (16.73, 61.18) ng/ml and 27.32 (11.94, 130.18) ng/ml, respectively. Gleason scores ≤7 were in 10 cases (41.7%) and 6 cases (21.4%), and Gleason scores >7 were in 14 cases (58.3%) and 22 cases (78.6%), respectively. There were 15 (62.5%) and 13 (46.4%) cases of cT 1-2 stage, and 9 (37.5%) and 15 (53.6%) cases of cT 3-4 stage, respectively. There were 16 (66.7%) and 6 (21.4%) cases of stage N 0, 8 (33.3%) and 22 (78.6%) cases of stage N 1, respectively. There were 22 (91.7%) and 20 (71.4%) cases of stage M 0, 2 (8.3%) and 8 (28.6%) cases of stage M 1, respectively. PET/CT diagnosis of lymph node positive was in 9 cases (37.5%) and 19 cases (67.9%), and mpMRI diagnosis of lymph node positive was in 5 cases (20.8%) and 16 cases (57.1%). The number of positive lymph nodes diagnosed by PET/CT was 13 (72.2%) and 47 (90.1%), and the number of positive lymph nodes diagnosed by mpMRI was 8 (44.4%) and 32 (61.5%). There was no significant difference ( P>0.05). All patients underwent radical prostatectomy as well as enlarged pelvic lymph node resection. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two imaging examinations in the diagnosis of lymph node metastasis were compared according to the results of postoperative pathological examination of lymph nodes. Receiver operating characteristic (ROC) curve was used to compare the accuracy of the two imaging tests in the diagnosis of pelvic lymph node metastasis in the newly diagnosed untreated group and the endocrine treated group. Results:In this study, of 52 cases, 26 (50.0%) had positive lymph nodes by pathological examination. In this study, a total of 681 lymph nodes were dissected, with 70 lymph nodes (10.28%) being pathologically positive, and the positive rate of 26 patients was 17.99% (70/389). The PET/CT and mpMRI detection rates of 26 node-positive patients were 92.3% (24/26) and 57.7% (15/26), respectively. There were 9 (37.5%) and 17 (60.7%) lymph node positive patients in the untreated group and the endocrine therapy group, respectively. There were 320 and 361 lymph nodes were clear, with 18 (5.6%) and 52 (14.4%) positive lymph nodes, respectively. The detection rates of PET/CT and mpMRI were 88.89% (8/9) and 94.12% (16/17)in the untreated group, and 44.44% (4/9) and 64.71% (11/17)in the endocrine treated group, respectively. In the newly treated group, the area under the curve (AUC) of PET/CT and mpMRI for diagnosing positive lymph nodes were 0.911 and 0.689 ( P=0.027), the sensitivity were 88.9% and 44.4%, and the specificity were 93.3% and 93.3%, respectively. PPV were 88.9% and 80.0%, and NPV were 93.3% and 73.7%, respectively. In the endocrine therapy group, the AUC of PET/CT and mpMRI for lymph node positive diagnosis were 0.834 and 0.596 ( P=0.011), the sensitivity were 94.1% and 64.7%, the specificity were 72.7% and 54.5%, and the PPV were 84.2% and 68.8%, respectively. NPV were 88.9% and 50.0%, respectively. Conclusions:For prostate cancer patients, regardless of whether they receive neoadjuvant endocrine therapy, 68Ga-PSMA-11 PET/CT can accurately detect pelvic lymph node metastasis, and the diagnostic efficacy is significantly better than that of mpMRI.

Objective:To conduct evidence-based exercise training for patients with peripheral arterial disease, develop review indicators, analyze barriers and enablers in the evidence-based practice process, and develop change strategies.Methods:Guided by the clinical evidence application model of the Joanna Briggs Institute Evidence-Based Health Care Center, the study identified clinical nursing problems, formed the evidence-based practice team, systematically searched, evaluated, and summarized evidence of exercise training in patients with peripheral arterial disease, developed review indicators, and clarified review methods. The baseline review was conducted from October 1 to 31, 2022. The integrated-promoting action on research implementation in health services (i-PARIHS) framework was used to analyze the barriers and enablers of the baseline review results, and corresponding strategies were formulated.Results:A total of 20 best evidence were included, and 11 review indicators were developed, with only one indicator having a compliance rate of 100%. This study analyzed 22 barriers and 24 enablers, and formulated 14 change strategies.Conclusions:The review indicators constructed based on the best evidence are scientific, effective, appropriate, and feasible. The analysis of barriers and enablers, as well as the formulation of change strategies, can provide guarantees for promoting clinical practice of exercise training for patients with peripheral arterial diseases.

Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Objective To explore the mechanism underlying the protective effect of Lonicerae japonicae flos(LJF)extract against doxorubicin(DOX)-induced liver injury in mice.Methods Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets,based on which the protein-protein interaction(PPI)network was constructed using STRING database for screening the core targets using Cytoscape software.DAVID database was used for bioinformatics analysis,and the core components and core targets were verified using molecular docking study.In a mouse model of DOX-induced liver injury,the effect of LJF extract on liver pathologies,serum levels of ALT and AST,and hepatic expressions of HYP,ROS,TNF-α,IL-6,COL-IV and P53 proteins were evaluated using HE and Masson staining,ELISA,and Western blotting.Results We identified 12 core targets from 43 intersection genes involving cancer pathway,IL-17 signaling pathway,and TNF signaling pathways.Molecular docking study suggested that 10 core components of LJF could bind to different core targets.The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis,increased ROS content,and enhanced expressions of TNF-α,IL-6,HYP,COL-IV and P53 proteins in the liver tissue.All these changes in the mouse models were significantly alleviated by treatment with LJF extract,suggesting obviously lowered levels of oxidative stress,inflammation and fibrosis in the liver tissues.Conclusion LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53,TNF and IL-6 to reduce liver oxidative stress,inflammation and fibrosis.

Objective:To investigate the clinical effect of the giant deep inferior epigastric artery paraumbilical perforator flap in repairing the circular high-voltage electric burn wounds on the wrist.Methods:A retrospective observational study method was used. From September 2016 to October 2021, thirteen male patients (aged 20-43 years) with annular high voltage (10-100 kV) electrical burns on the wrist were admitted to the Beijing Jishuitan Hospital. At the early stage after injury, the patient's wrist was subjected to incision, tension reduction and debridement, with the wound area after debridement being 27 cm×16 cm-32 cm×19 cm; in 12 patients with vascular injury, the radial or ulnar artery was reconstructed by great saphenous vein transplantation, with the length of 15-25 cm; the wrist wound was repaired by free transplantation of the deep inferior epigastric artery paraumbilical perforator flap (if the wound was giant, the lower abdominal flap carrying other perforators was used), with the area of 30 cm×19 cm-35 cm×20 cm. The donor site was repaired by direct suture+skin grafting or relay flap transplantation. After surgery, the survival of flap in recipient area, as well as survival of the skin or flap in donor site were observed. During follow-up, the appearances of the flap in recipient area and the recovery of hand function, as well as the healing of donor site, occurrence of abdominal wall hernia, and scar in skin graft area were observed.Results:After surgery, all the 13 patients' paraumbilical perforator flaps survived. Among them, 3 patients had subcutaneous fat necrosis at the distal end of the wrist flap, and the wound had mild infection, which healed after re-expansion and dressing change. All the skin grafts in the donor site of 10 patients survived, and the flaps in the donor site of 3 patients survived well. The patients were followed up for 6 months to 3 years. The flaps in recipient area were in good shape, 8 cases had partial recovery of hand function, and 5 cases had loss of finger flexion function; the donor site of abdominal flap healed well with no abdominal hernia occurred, and the skin graft site had no obvious scar hyperplasia and was soft in texture.Conclusions:Early vascular reconstruction after injury, together with free transplantation of the giant deep inferior epigastric artery paraumbilical perforator flap are effective in repairing circular high-voltage electrical burn wounds on the wrist.

Malignant pleural mesothelioma(MPM) is a kind of rare and aggressive malignant neoplasm. Surgery plays one of the most important roles in the treatment of MPM. However, due to the high morbidity and mortality reported, the survival benefit and indication of surgery are still controversial. This article will review the surgical indications, discuss and compare the roles of extrapleural pneumonectomy(EPP) and pleurectomy / decortication(P/D) which aim to achieve macroscopic complete resection(MCR) in the treatment of MPM. Finally, we summarized the progress of other treatment methods including targeted therapy and immunotherapy.