ABSTRACT
High salinity, an adverse environmental factor affecting about 20% of irrigated arable land worldwide, inhibits plant growth and development by causing oxidative stress, damaging cellular components, and disturbing global metabolism. However, whether and how reactive oxygen species disturb the metabolism of salt-stressed plants remain elusive. Here, we report that salt-induced hydrogen peroxide (H2O2) inhibits the activity of plastid triose phosphate isomerase (pdTPI) to promote methylglyoxal (MG) accumulation and stimulates the sulfenylation of pdTPI at cysteine 74. We also show that MG is a key factor limiting the plant growth, as a decrease in MG levels completely rescued the stunted growth and repressed salt stress tolerance of the pdtpi mutant. Furthermore, targeting CATALASE 2 into chloroplasts to prevent salt-induced overaccumulation of H2O2 conferred salt stress tolerance, revealing a role for chloroplastic H2O2 in salt-caused plant damage. In addition, we demonstrate that the H2O2-mediated accumulation of MG in turn induces H2O2 production, thus forming a regulatory loop that further inhibits the pdTPI activity in salt-stressed plants. Our findings, therefore, illustrate how salt stress induces MG production to inhibit the plant growth.
Subject(s)
Hydrogen Peroxide , Pyruvaldehyde , Hydrogen Peroxide/metabolism , Pyruvaldehyde/metabolism , Salt Stress , Oxidative Stress , Plants/metabolism , Chloroplasts/metabolism , Stress, PhysiologicalABSTRACT
Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.
Subject(s)
Colorectal Neoplasms , Salmonella Infections , cdc42 GTP-Binding Protein , Humans , Acetylation , Carcinogenesis , cdc42 GTP-Binding Protein/metabolism , Cell Transformation, Neoplastic , p21-Activated Kinases/metabolism , Signal TransductionABSTRACT
BACKGROUND: Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated. RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1ß) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed. CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.
Subject(s)
Monocytes , Mycobacterium bovis , Humans , BCG Vaccine , Trained Immunity , Proto-Oncogene Proteins c-akt/genetics , THP-1 Cells , Phosphatidylinositol 3-Kinases , CytokinesABSTRACT
BACKGROUND: Hypertension is a risk factor for cholangiocarcinoma (CCA). The effect of anti-hypertensive drugs on the prognosis of CCA is not clear. METHODS: This is a retrospective study of 102 patients (56.9% males, median age 66 years) diagnosed with CCA and hypertension concurrently and received radical surgery (R0), with a median follow-up of 36.7 months. Kaplan-Meier analysis, Cox regressions, and propensity score (PS) matching were applied for statistical analysis. RESULTS: Results of multivariable cox analysis showed that renin-angiotensin system inhibitors (RASis) usage was a protective factor for progression-free survival (PFS) (hazard ratio [HR] = 0.55, 95% confidence interval [95% CI]: 0.32-0.96) and overall survival (OS) (HR = 0.40, 95% CI: 0.20-0.79), respectively. Calcium channel blockers, diuretics, and ß-blockers didn't show significant associations. The association of RASis usage and PFS and OS was derived by PS matching, with a cohort of 28 RASis users and 56 RASis non-users. The median PFS and OS of RASis users (PFS, 17.6 months (9.2-34.4); OS, 24.8 months (16.5-42.3)) were longer than RASis non-users (PFS, 10.5 months (4.1-24.1); OS, 14.6 months (10.6-28.4)). The 1 year, 2 years, and 3 years' survival rates of RASis users (89.1%, 77.0%, and 65.5%) were higher than RASis non-users (70.9%, 54.0%, and 40.0%). CONCLUSIONS: RASis usage improves the survival of patients with CCA and hypertension concurrently.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hypertension , Male , Humans , Aged , Female , Antihypertensive Agents , Cohort Studies , Retrospective Studies , Propensity Score , Renin-Angiotensin System , Enzyme Inhibitors , Bile Ducts, IntrahepaticABSTRACT
Methylglyoxal (MG) is a byproduct of glycolysis that functions in diverse mammalian developmental processes and diseases and in plant responses to various stresses, including salt stress. However, it is unknown whether MG-regulated gene expression is associated with an epigenetic modification. Here we report that MG methylglyoxalates H3 including H3K4 and increases chromatin accessibility, consistent with the result that H3 methylglyoxalation positively correlates with gene expression. Salt stress also increases H3 methylglyoxalation at salt stress responsive genes correlated to their higher expression. Following exposure to salt stress, salt stress responsive genes were expressed at higher levels in the Arabidopsis glyI2 mutant than in wild-type plants, but at lower levels in 35S::GLYI2 35S::GLYII4 plants, consistent with the higher and lower MG accumulation and H3 methylglyoxalation of target genes in glyI2 and 35S::GLYI2 35S::GLYII4, respectively. Further, ABI3 and MYC2, regulators of salt stress responsive genes, affect the distribution of H3 methylglyoxalation at salt stress responsive genes. Thus, MG functions as a histone-modifying group associated with gene expression that links glucose metabolism and epigenetic regulation.
Subject(s)
Gene Expression Regulation, Plant , Histone Code , Pyruvaldehyde/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Epigenesis, Genetic , Salt Stress/genetics , Transcription Factors/metabolismABSTRACT
BACKGROUND: Remote ischemic perconditioning (RIPerC) has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury (IRI). This study investigated the role of exosomes in RIPerC of liver grafts in rats. METHODS: Twenty-five rats (including 10 donors) were randomly divided into five groups (n = 5 each group): five rats were used as sham-operated controls (Sham), ten rats were for orthotopic liver transplantation (OLT, 5 donors and 5 recipients) and ten rats were for OLT + RIPerC (5 donors and 5 recipients). Liver architecture and function were evaluated. RESULTS: Compared to the OLT group, the OLT + RIPerC group exhibited significantly improved liver graft histopathology and liver function (P < 0.05). Furthermore, the number of exosomes and the level of P-Akt were increased in the OLT + RIPerC group. CONCLUSIONS: RIPerC effectively improves graft architecture and function, and this protective effect may be related to the increased number of exosomes. The upregulation of P-Akt may be involved in underlying mechanisms.
Subject(s)
Exosomes , Liver Transplantation , Reperfusion Injury , Rats , Animals , Liver Transplantation/adverse effects , Proto-Oncogene Proteins c-akt , Exosomes/pathology , Reperfusion Injury/etiology , Reperfusion Injury/prevention & control , Reperfusion Injury/pathology , Ischemia , Liver/surgery , Liver/pathology , ReperfusionABSTRACT
Esophageal angiolipoma is a rare disease with unspecific clinical manifestations.This paper reported a case of esophageal angiolipoma confirmed by upper gastrointestinal endoscopy and summarized the clinical manifestations,endoscopic and pathological features,treatment and prognosis of the patients by reviewing the relevant literature,aiming to provide references for clinical diagnosis and treatment of this disease in the future.
Subject(s)
Angiolipoma , Humans , Angiolipoma/surgery , Angiolipoma/diagnosis , Angiolipoma/pathology , PrognosisABSTRACT
Objectiveï¼ To observe the clinical effect of Manlyman Spray combined with biofeedback therapy in the treatment of premature ejaculation (PE)ï¼Methodsï¼ A total of 60 primary premature ejaculation patients with stable sexual partners and regular sexual activity (≥ï¼ times per week) from April 2021 to October 2022 were involved in the clinical observation, The patients' age is (34.3 ± 4.9) years old, and the course of the disease is (112.5 ± 65.5) months, and Manlyman Spray combined with biofeedback therapy was used to treat patients for 8 weeks. Manlyman Spray was sprayed 3 times on the surface of the penisqd for 4 weeks, and Biofeedback therapy is treated twice a week according to the AI setting module, for a total of 8 weeks. Before and 8 weeks after medication and at 4 weeks after drug withdrawal, the Intravaginal Ejaculation Latency Time (IELT), Premature Ejaculation Diagnostic Tool (PEDT) scores and Clinical Global Impression of Change (CGIC) scores were Obtained and compared. Resultsï¼ After 8 weeks of treatment, the IELT of the patients was significantly prolonged (ï¼»351.4 ± 76.7ï¼½ vs ï¼»87 ± 16.8ï¼½,P<0.05) and at 4 weeks after drug withdrawal, the therapeutic effect still existed (ï¼»345.9 ± 80.3ï¼½ vs ï¼»87 ± 16.8ï¼½,P<0.05), the PEDT scores were significantly improved after treatment (ï¼»18.2 ± 1.1ï¼½ vs ï¼»9.0 ± 1.4ï¼½,P<0.05)and at 4 weeks after drug withdrawal(ï¼»18.0 ± 1.2ï¼½ vs ï¼»9.0 ± 1.4ï¼½,P<0.05), and so were the CGIC scores (ï¼»13.4 ± 1.3ï¼½ vs ï¼»3.3 ± 1.4ï¼½,P<0.05, and ï¼»12.6 ± 1.6ï¼½ vs ï¼»3.3 ± 1.4ï¼½,P<0.05). Conclusionï¼ The combination of Manlyman Spray and biofeedback therapy can effectively treat primary premature ejaculation, with a long duration of treatment and good safety, and the specific mechanism needs further study.
Subject(s)
Premature Ejaculation , Male , Humans , Adult , Premature Ejaculation/therapy , Biofeedback, Psychology , Treatment Outcome , Ejaculation , Sexual BehaviorABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with extremely poor prognosis. Gemcitabine resistance is a major challenge in the treatment of PDAC. Here, we showed that LINC00460 was associated with the response to gemcitabine both in PDAC patients and PDAC-PDX. After knocking down LINC00460 in PDAC tumor cells, results of RNA sequencing followed by gene ontology analysis indicated that LINC00460 influenced the activity of growth factors and modified the extracellular matrix. FISH showed that LINC00460 is mostly located in the cytoplasm. Results of RNA pull-down, LC-MS/MS, RIP, and immunoblotting confirmed that LINC00460 could directly bind to PDAP1. Furthermore, we demonstrated that LINC00460 mediated the cellular communication of PDAC tumor cells and CAFs by PDAP1/PDGFA/PDGFR signaling pathway and regulated the gemcitabine-resistance function of CAFs, which could be reversed by treatment with a PDGFR inhibitor (crenolanib). PDAC-PDX tumors with lower expression of LINC00460 showed a better response to gemcitabine plus crenolanib treatment. Our finding supported the application of LINC00460 in precision medicine that uses gemcitabine plus crenolanib to treat PDAC with low expression of LINC00460.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , RNA, Long Noncoding , Humans , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Cell Line, Tumor , Chromatography, Liquid , Drug Resistance, Neoplasm/genetics , Intercellular Signaling Peptides and Proteins , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Tandem Mass Spectrometry , RNA, Long Noncoding/genetics , Gemcitabine , Pancreatic NeoplasmsABSTRACT
BACKGROUND: Routine lymphadenectomy in pancreatic neuroendocrine tumors (pNETs) is debated. There lacks accurate model to predict lymph node metastasis (LNM) preoperatively in pNETs. Therefore, this study aimed at developing a nomogram in predicting LNM in pNETs preoperatively. METHODS: Patients undergoing surgery from Surveillance, Epidemiology, and End Results (SEER) database (design cohort, n = 2742) and First Affiliated Hospital of Sun Yat-sen University (validation cohort, n = 136) were enrolled. Nomogram was developed based on risk factors determined by logistic regression analyses. The performance of nomogram was evaluated by area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis. RESULTS: In design cohort, 915 of 2742 patients had LNM. Tumor in the pancreatic head, T stage, and tumor size were significantly associated with LNM (all p < 0.05). Prediction of nomogram was accurate with AUC of 0.776 in design cohort and 0.622 in validation cohort. The nomogram showed good agreement between prediction and observation in the design and validation cohort. Based on nomogram-predicted risk, patients with higher risk of LNM had worse overall survival over patients with lower risk of LNM (log-rank p < 0.001). CONCLUSIONS: The novel nomogram could accurately predict LNM in pNET preoperatively. For patients with high risk of LNM, lymphadenectomy was recommended.
Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Lymphatic Metastasis , Neuroendocrine Tumors/surgery , Nomograms , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Lymph Node ExcisionABSTRACT
The clinical application of most materials used to fill severe bone defects is limited owing to the insufficient ability of such materials to induce bone regeneration over a long repair period. The purpose of this study was to establish a model for the alveolar process cleft in rabbits to evaluate the effect of active bone material in bone defect repair. The active bone material used in this study is a new bone repair material composed of a heterogeneous collagen membrane implanted with modified recombinant human bone morphogenetic protein 2. This proposed active bone material can specifically bind to collagen. Twenty-four young Japanese white rabbits (JWRs) were selected and randomly divided into four groups (normal, control, material, and bone morphogenetic protein groups). The alveolar process cleft model was established by removing an equal volume bone at the left maxillary position. Blood samples were collected from the JWRs 3 and 6 months after the surgery to evaluate the biocompatibility of the active bone materials. Subsequently, the skull model was established, and the appearance was observed. Imaging methods (including X-ray examination and micro-computerized tomography scanning), tissue staining, and immunohistochemistry were employed for the evaluation. The bone collagen material and active bone material exhibited high biocompatibility. In addition, the ability of the active bone material to induce bone repair and regeneration was higher than that of the bone collagen material. The active bone material exhibited satisfactory bone regeneration performance in rabbits, indicating its potential as an active material for repairing congenital alveolar process clefts in humans.
Subject(s)
Alveolar Process/surgery , Bone Morphogenetic Protein 2/pharmacology , Bone Regeneration , Transforming Growth Factor beta/pharmacology , Alveolar Process/abnormalities , Alveolar Process/diagnostic imaging , Animals , Bone Transplantation , Collagen/administration & dosage , Disease Models, Animal , Osteogenesis , Rabbits , Radiography , Random Allocation , Recombinant Proteins/pharmacologyABSTRACT
BACKGROUND: Identifying practical and distinguished indicators and influencing factors of male aging may be useful in predicting subsequent aging trends, designing personalized prevention, and improving lifestyle and health. METHODS: A cross-sectional, population-based study was performed in Jiashan County, China in 2016. A total of 690 local male residents, aged 40 to 80 years, were eligible for recruitment. Demographic and lifestyle information was collected through structured interviews. A self-designed head scale, the Medical Outcomes Study 36-item Short Form (SF-36), International Index of Erectile Function (IIEF5), Aging Males' Symptoms (AMS), and International Prostate Symptom Score (IPSS) were used. Analysis of variance, local polynomial regression smoothing curves, multiple linear regression, and partial correlation analyses were performed. RESULTS: All the scales deteriorated with increasing age (P < 0.01), especially from the age of 60. The most significant changes between adjacent age groups were found in IIEF5 scores (16.7, 43.5 and 39.4%). Income, nutrition, personality and neighborhood relationship had an effect on SF-36 and AMS after adjusting for age (P < 0.01). Furthermore, neighborhood relationship modified the age effect on the head scale score and IIEF5 (P = 0.03); nutrition modified the relationship between age and SF-36 (P < 0.01). CONCLUSIONS: Recession of reproductive health may be a distinct predictor of male aging. The associations of social inequalities or personality and health offer potential interventions for men's health in aging. Self-reported scales may limit the precision and more physical fitness tests could be combined for a more precise assessment.
Subject(s)
Aging , Health Status , Aged , China , Cross-Sectional Studies , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
BACKGROUND: The study aimed at establishing a nodal staging score (NSS) to quantify the likelihood that pathologic node-negative gallbladder cancer (GBC) patients are indeed free of lymph node (LN) metastasis. METHODS: Clinicopathological data of 1374 GBC patients with T1b-T2 stages were collected from the Surveillance, Epidemiology and End Result database (design cohort [DC], n = 1289) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 85). NSS was derived from the count of examined LNs (ELNs) and T stage by using a beta-binomial model, and represented the probability that a node-negative patient is correctly staged. The prognostic value of NSS in node-negative GBC was evaluated by survival analysis. RESULTS: The probability of missing a nodal disease in node-negative GBC patients with T1b-T2 stages (pT1bN0 and pT2N0) decreased as the number of ELNs increased. NSS increased as the number of ELNs increased. For pT1bN0 and pT2N0 patients, examination of 5 and 27 lymph nodes could ensure an NSS of 90.0%, respectively. Multivariate analysis revealed that NSS was an independent predictor for overall survival in pT1bN0 and pT2N0 GBC patients (DC, HR:0.53, 95%CI: 0.42-0.66, p < 0.001; VC, HR: 0.33, 95%CI: 0.14-0.76, p = 0.009). CONCLUSION: NSS could evaluate the adequacy of nodal staging and predict the prognosis in pT1bN0 and pT2N0 GBC patients, and hence was helpful to guide their treatment strategies.
Subject(s)
Gallbladder Neoplasms , Gallbladder Neoplasms/surgery , Humans , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Models, Statistical , Neoplasm Staging , PrognosisABSTRACT
BACKGROUND: Alveolar cleft is a type of cleft lip and palate that seriously affects the physical and mental health of patients. In this study, a model of the alveolar cleft phenotype was established in rabbits to evaluate the effect of bone collagen particles combined with human umbilical cord mesenchymal stem cells (HUC-MSCs) on the repair of alveolar cleft bone defects. METHODS: A model of alveolar clefts in rabbits was established by removing the incisors on the left side of the upper jaw bone collagen particles combined with HUC-MSCs that were then implanted in the defect area. Blood biochemical analysis was performed 3 months after surgery. Skull tissues were harvested for gross observation, and micro-focus computerised tomography (micro-CT) analysis. Tissues were harvested for histological and immunohistochemical staining. The experiments were repeated 6 months after surgery. RESULTS: Bone collagen particles and HUC-MSCs showed good biocompatibility. Bone collagen particles combined with HUC-MSCs were markedly better at inducing bone repair and regeneration than bone collagen particles alone. CONCLUSIONS: Combining HUC-MSCs with bone collagen particles provides a simple, rapid and suitable method to fill a bone defect site and treat of alveolar cleft bone defects.
Subject(s)
Cleft Lip/therapy , Collagen/pharmacology , Mesenchymal Stem Cell Transplantation , Umbilical Cord/cytology , Animals , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cleft Lip/diagnostic imaging , Cleft Lip/drug therapy , Cleft Lip/pathology , Collagen/therapeutic use , Humans , Male , Rabbits , X-Ray MicrotomographyABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignancies and the fourth leading cause of cancer-related death worldwide. Our previous study showed that EYA4 functioned by suppressing growth of HCC tumor cells, but its molecular mechanism is still not elucidated. Based on the results of gene microassay, EYA4 was inversely correlated with MYCBP and was verified in human HCC tissues by immunohistochemistry and western blot. Overexpressed and KO EYA4 in human HCC cell lines confirmed the negative correlation between EYA4 and MYCBP by qRT-PCR and western blot. Transfected siRNA of MYCBP in EYA4 overexpressed cells and overexpressed MYCBP in EYA4 KO cells could efficiently rescue the proliferation and G2/M arrest effects of EYA4 on HCC cells. Mechanistically, armed with serine/threonine-specific protein phosphatase activity, EYA4 reduced nuclear translocation of ß-catenin by dephosphorylating ß-catenin at Ser552, thereby suppressing the transcription of MYCBP which was induced by ß-catenin/LEF1 binding to the promoter of MYCBP. Clinically, HCC patients with highly expressed EYA4 and poorly expressed MYCBP had significantly longer disease-free survival and overall survival than HCC patients with poorly expressed EYA4 and highly expressed MYCBP. In conclusion, EYA4 suppressed HCC tumor cell growth by repressing MYCBP by dephosphorylating ß-catenin S552. EYA4 combined with MYCBP could be potential prognostic biomarkers in HCC.
Subject(s)
Carcinoma, Hepatocellular/metabolism , DNA-Binding Proteins/genetics , Liver Neoplasms/metabolism , Trans-Activators/genetics , Trans-Activators/metabolism , Transcription Factors/genetics , beta Catenin/metabolism , Adult , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Nucleus/metabolism , Cell Proliferation , DNA-Binding Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Male , Middle Aged , Phosphorylation , Prognosis , Serine/metabolism , Survival Analysis , Transcription Factors/metabolism , Transcription, Genetic , beta Catenin/chemistryABSTRACT
INTRODUCTION: Most of conclusions on the relationship between age and reproductive health in aging men relied on cross-sectional data. AIM: To better characterize the natural degradation trajectory of reproductive health of aging men based on longitudinal data. METHODS: A community cohort study was performed in randomly selected men 40 to 80 years old, initiated in 2012 and followed up in 2014 and 2016. Participants were investigated by face-to-face structured interview, including demographic information and International Index of Erectile Function (IIEF-5) and Aging Males' Symptoms (AMS) scales. MAIN OUTCOME MEASURES: The differences among the 3 assessments of IIEF-5 and AMS were analyzed, and progression trajectories were traced. RESULTS: The high degree of variability on AMS and IIEF-5 was evident across individual subjects, as was the variability within individuals. The average IIEF-5 score of 248 subjects decreased from 16.9 to 14.1 during the 4 years, and the total AMS score increased from 22.6-27.0 (P < .001). Longitudinal data, both of individuals and of groups, showed the more rapid increase or decrease on AMS or IIEF-5 scores over 4 years in the 61-70 age group than in other age groups. CLINICAL IMPLICATION: The evidence of the greatest changes on AMS and IIEF-5 scores in the 61-70 age group prompts the importance of early intervention to postpone the degradation of reproductive health. STRENGTH & LIMITATIONS: Compared with cross-sectional data, longitudinal data can provide a more natural progression trajectory of reproductive health of aging male individuals. The low follow-up rate might affect the parameter estimation to some extent. CONCLUSION: Cohort data over 4 years' follow-up showed more abrupt changes on AMS and IIEF-5 scores in the 61-70 age group than in other age groups. Zheng J-B, Liang Q-F, Li J-H, et al. Longitudinal Trends of AMS and IIEF-5 Scores in Randomly-Selected Community Men 40 to 80 Years Old: Preliminary Results. J Sex Med 2019;16:1567-1573.
Subject(s)
Aging/physiology , Penile Erection/physiology , Reproductive Health , Adult , Aged , Aged, 80 and over , Cohort Studies , Cross-Sectional Studies , Erectile Dysfunction/physiopathology , Humans , Longitudinal Studies , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
AIMS: This study aimed to develop a valuable nomogram by integrating molecular markers and tumor-node-metastasis (TNM) staging system for predicting the long-term outcome of patients with hepatocellular carcinoma (HCC). METHODS: The gene expression profiles of HCC patients undergoing liver resection were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. One hundred and ninety-nine patients from TCGA and 94 patients from GEO were selected to be part of the training cohort and validation cohort respectively. Univariate and multivariate cox analyses were performed to identify genes with independent prognostic values for overall survival (OS) of HCC patients in training cohort. Risk score was calculated based on the coefficients and Z-score of 3 genes for each patient. The nomogram was developed based on the risk score and TNM staging system. Discrimination and predictive accuracy of the nomogram were measured by using the concordance index (C-index) and calibration curve. The efficacy of the nomogram was tested in the external validation cohort. RESULTS: Univariate and multivariate cox analyses revealed that EXT2 (p = 0.035, hazard ratio 13.412), ETV5 (p = 0.010, hazard ratio 4.325), and CHODL (p < 0.001, hazard ratio 6.286) were independent prognostic factors and chosen for further nomogram establishment. The C-index of the nomogram for predicting the OS in the training cohort was superior to that of the TNM staging system (0.77 vs. 0.64, p < 0.01). The calibration curve of predicted 1-, 3-, and 5-year OS showed satisfactory accuracy. The external validation cohort showed good performance of comprehensive nomogram as well. CONCLUSION: The novel nomogram by integrating the molecular markers and TNM staging system has better performance in predicting long-term prognosis in HCC patients than the TNM staging system alone.
Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Nomograms , Biomarkers, Tumor/genetics , DNA-Binding Proteins/genetics , Databases, Genetic , Female , Humans , Lectins, C-Type/genetics , Male , Membrane Proteins/genetics , Middle Aged , N-Acetylglucosaminyltransferases/genetics , Neoplasm Staging , Prognosis , Proportional Hazards Models , Survival Rate , Transcription Factors/genetics , TranscriptomeABSTRACT
Nuclear genomes of two isolates of Hirsutella thompsonii, a pathogen causing epizootics among mites, have been reported; in contrast, its mitochondrial genome (mitogenome) has remained unknown, limiting our understanding of its evolution. Herein, we annotated the first complete mitogenome of H. thompsonii, which encoded all standard fungal mitochondrial genes plus three free-standing ORFs. Transcriptional analyses validated the expression of most conserved genes and revealed some interesting transcription patterns of mitochondrial genes. Phylogenetic analyses confirmed its placement in Ophiocordycipitaceae. Comparison of five different isolates originally collected from different locations revealed mitogenome size variations (60.3-66.4 kb) mainly due to different numbers of introns. A total of 15 intron loci were identified, with 11 existing in all 5 isolates and 4 showing presence/absence dynamics. These introns were most likely obtained through horizontal transfer from other fungal organisms. Those common introns might have been in H. thompsonii mitogenomes since the divergence of the fungus from its putative sister species H. minnesotensis, whereas those dynamic introns might have experienced 1-2 gain or loss events. We also detected evidence of degeneration for some introns. Overall, our study shed new insights into the mitochondrial evolution of the acaropathogenic fungus H. thompsonii.
Subject(s)
Acari/microbiology , Genome, Mitochondrial , Hypocreales/genetics , Animals , Evolution, Molecular , Fungal Proteins/genetics , Genome, Fungal , Hypocreales/classification , Hypocreales/isolation & purification , Introns , Mitochondria/genetics , Open Reading Frames , PhylogenyABSTRACT
BACKGROUND: Magnetic compression anastomosis (magnamosis, MCA) has been verified safe and effective by us and others in animal bilioenteric anastomosis (BEA). The objective of the present study was to introduce clinical application of magnetic compression bilioenteric anastomosis (MC-BEA) with a unique device in series of patients. METHODS: Patients with obstructive jaundice with an indication of BEA were prospectively enrolled from 2012 to 2015. After dissection of bile ducts, the mother ring and drainage tube were placed in the proximal bile duct and the purse-string suture was tightened over the drainage tube. The drainage tube was introduced into the jejunal lumen at the anastomotic site and used to guide the daughter ring to assemble with the mother ring. All the patients were routinely followed up for magnets discharge or any complications associated. RESULTS: Forty-one patients were included. Thirty-four (82.9%) patients had a malignant primary disease, while seven (17.1%) had benign disease. The median time for MC-BEA was 10.5 min (interquartile range [IQR] 8.3-13.0 min). No perioperative morbidity or mortality associated with MC-BEA was observed. The median time for a patent bilioenteric anastomosis formation was 19.0 days (IQR 14.5-23.0 days), and the magnets were discharged with a median postoperative duration of 35.0 days (IQR 28.0-43.0 days). With a median follow-up of 547.5 days (range 223-1042 days), no patients had biliary fistula, while two (4.9%) developed anastomotic stricture at 4 months and 14 months after surgery, and underwent reoperation for reconstruction of BEA. CONCLUSIONS: MCA is a safe, effective, and time-saving modality for biliojejunostomy.
Subject(s)
Anastomosis, Surgical/methods , Bile Ducts/surgery , Jaundice, Obstructive/surgery , Jejunostomy/methods , Magnets , Aged , Anastomosis, Surgical/adverse effects , Drainage , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: Chicken erythrocytes are involved in immunity through binding of toll-like receptors (TLRs) with their ligands to activate downstream signaling and lead to cytokine production in erythrocytes. Some avian ß-defensins (AvBDs) are constitutively expressed in tissues and some others can be induced by various bacteria and viruses. However, the expression of AvBDs in erythrocytes has not yet been studied extensively. RESULTS: The transcripts of eight AvBDs (AvBD1 to AvBD7, and AvBD9) and liver-expressed antimicrobial peptide-2 (LEAP-2) were found in normal chicken erythrocytes. The expression levels of AvBD2, 4 and 7 were significantly increased (P < 0.01), whereas the levels of AvBD1, 6 and 9 were significantly decreased (P < 0.01) after Marek's disease virus (MDV) infection. The mRNA expression level of LEAP-2 was not significantly changed after MDV infection. Highest viral nucleic acid (VNA) of MDV in the feather tips among the tested time points was found at 14 days post-infection (d.p.i.). In addition, 35 MD5-related gene segments were detected in the erythrocytes at 14 d.p.i. by transcriptome sequencing. CONCLUSIONS: These results suggest that the AvBDs in chicken erythrocytes may participate in MDV-induced host immune responses.