[Objective] To analyze factors influencing the postoperative progression-free survival (PFS) in patients with renal cell carcinoma (RCC), construct a nomogram model for predicting PFS, and compare it with other predictive models. [Methods] A retrospective analysis was conducted on the general and clinical data of 263 RCC patients who underwent surgery at the Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, during Apr.2014 and Nov.2021.Patients were divided into the progression group (n=34) and non-progression group (n=229). The data of the two groups were analyzed to identify prognostic variables associated with PFS, and a nomogram model was constructed.The performance of this model was compared with that of the University of California, Los Angeles Integrated Staging System (UISS) score, tumor staging, tumor size, tumor pathological grade, and tumor necrosis scoring system (SSIGN score), and Leibovich score by plotting receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Calibration curve of the nomogram was used to validate the model's performance, and K-fold cross-validation was employed to assess its external validity. [Results] Multivariate Cox regression analysis revealed that age (HR=2.255, 95%CI: 1.032-4.926), T stage (HR=5.766, 95%CI: 2.351-14.142), pathological grade (HR=3.100, 95%CI: 1.445-6.651), and pathological necrosis (HR=2.656, 95%CI: 1.253-5.629) were independent risk factors of PFS (P<0.05). The nomogram model based on these four independent variables had AUCs (95%CI) of 0.750 (0.630-0.870), 0.803 (0.705-0.902), and 0.847 (0.757-0.937) for 1, 3, and 5 years, respectively, which were higher than those of UISS score, SSIGN score, and Leibovich score.The calibration curve of the nomogram showed good consistency between predicted and actual probabilities.In K-fold cross-validation, the average AUCs of the nomogram at 1, 3, and 5 years were 0.761, 0.808, and 0.842, indicating good external validity of the nomogram. [Conclusion] The nomogram based on age, T stage, pathological grade and pathological necrosis can accurately predict the risk of postoperative PFS in RCC patients at 1, 3, and 5 years, which can aid clinicians in the early identification of high-risk progression.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*

Objective:To explore the association between different paths of diabetic progression and dyslipidemia in a Nanjing adult population.Methods:From January 2017 to June 2018, 61, 098 local residents aged ≥18 years were selected from the Chronic Disease and Risk Factor Surveillance database in Nanjing using a five-stage stratified cluster random sampling method. Data were collected through interview surveys, physical measurements, and laboratory examinations. The relationship between different rates of diabetic progression and dyslipidemia was analyzed using complex weighting and multilevel models.Results:In all, 60, 283 participants were finally enrolled in the study. The weighted proportions of normal glucose regulation, pre-diabetes, and diabetes were 71.2%, 17.9%, and 10.9%, respectively. The overall weighted prevalence, awareness, treatment, and control of dyslipidemia were 29.8%, 41.6%, 28.9%, and 22.9%, respectively. The weighted proportion of patients with dyslipidemia combined with diabetes was 52.9%. The weighted prevalence of dyslipidemia in adults with normal glucose regulation, pre-diabetes, and diabetes was 24.0%, 38.8%, and 52.9%, respectively (all P<0.001). Compared to the normal glucose regulation group, subjects with pre-diabetes ( OR = 2.04, 95% CI: 1.95-2.13) or diabetes ( OR= 3.87, 95% CI: 3.66-4.10) had possibly gradually increased risks of dyslipidemia (all P<0.001). In addition, there was an increasing trend toward awareness, treatment, and control of dyslipidemia with increasing levels of glucose (all P<0.001). The weighted awareness of dyslipidemia in adults with normal glucose regulation, pre-diabetes, and diabetes was 36.3%, 42.8%, and 56.2%, respectively; the corresponding rates of treatment and control were 23.7%, 29.2%, and 43.7%, and 20.4%, 22.6%, and 30.1%, respectively. Conclusion:Diabetes and dyslipidemia have become the main chronic diseases in the Nanjing population.

Objective:To investigate the joint associations of smoking and insufficient physical activity with hypertension, diabetes and dyslipidemia in male adults.Methods:Based on the data from the 2017 Nanjing Chronic Diseases Risk Factors Surveillance Program, 61 098 Nanjing residents aged 18 and older was randomly recruited from 12 districts, using the multi-stage stratified cluster sampling method. Information about smoking behaviors, physical activity and chronic disease-related indicators within the first 12 months before the survey was obtained through questionnaires.Results:Among the 29 848 valid male samples, the proportions of non-smokers, current smokers and ex-smokers were 59.6%, 37.2% and 3.2%, and the proportions of those who had physically active<600 MET-min/w (insufficient physically active) and ≥600 MET-min/w (adequate physically active) were 18.8% and 82.2%, respectively. In non-smokers, current smokers and ex-smokers, the prevalence of hypertension was 24.7%, 34.0% and 43.8%, and the prevalence of diabetes was 8.8%, 12.3% and 16.5%, and the prevalence of dyslipidemia was 26.8%, 36.1% and 41.9%, respectively. Multivariate logistic regression analysis showed that current smokers had a higher risk of hypertension ( OR=1.164, 95% CI: 1.086-1.248), diabetes ( OR=1.324, 95% CI: 1.207-1.452), and dyslipidemia ( OR=1.291, 95% CI: 1.216-1.371) than non-smokers in male adults. Compared with people who had adequate physical activity, someone with insufficient physical activity had higher hypertension ( OR=1.452, 95% CI: 1.331-1.583), diabetes ( OR=1.170, 95% CI: 1.041-1.315) and dyslipidemia ( OR=1.245, 95% CI: 1.158-1.338). And current smokers with insufficient physical activity had the highest risk of hypertension ( OR=1.749, 95% CI: 1.550-1.974), diabetes ( OR=1.363, 95% CI: 1.165-1.595), and dyslipidemia ( OR=1.614, 95% CI: 1.461-1.782) in male adults. Conclusions:Smoking and insufficient physical activity are risk factors for hypertension, diabetes, and dyslipidemia. People who is characterized by smoking together with insufficient physical activity presents with increased risk on developing hypertension, diabetes, and dyslipidemia.

Objective:To study the effect of levosimendan on coronary microembolization (CME)-induced myocardial injury and LOX-1/p38MAPK pathway.Methods:Microspheres were injected into coronary anterior descending branch to construct swine CME model, swine was given levosimendan by continuous intravenous drip for 24 h before modeling, and myocardial-specific overexpression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) was achieved through coronary artery injection of adeno-associated virus (AAVs) at 2 weeks before modeling. Then, echocardiography was used to measure cardiac function; HE staining and HBFP staining were used to observe the pathological changes of myocardium and myocardial microinfarction area, respectively; ELISA was used to detect the serum level of cTnI; TUNLE staining was used to detect cardiomyocyte apoptotic index; the LOX-1, Bax, caspase-3 p12, Bcl-2, and p-p38 MAPK protein in myocardial tissue was observed by immunofluorescence method.Results:Compared to the sham group, the LVEF, LVFS, and CO value in the CME group were decreased, while the LVEDd value was increased significantly (all P<0.05); the area of myocardial micro-infarction, serum cTnI level and cardiomyocyte apoptotic rate in the CME group were increased significantly (all P<0.05); the protein levels of Bax, caspase-3 p12, LOX-1, and p-p38 MAPK were increased significantly, while the Bcl-2 level was decreased significantly ( P<0.05). Levosimendan pretreatment significantly improved cardiac dysfunction, reduced the area of myocardial micro-infarction and serum cTnI level, alleviated cardiomyocyte apoptosis, and significantly reduced the LOX-1 and p-p38 MAPK protein expression levels following CME (all P<0.05); while pretreatment with levosimendan and LOX-1 overexpression AAVs simultaneously abolished the effects of pretreatment with levosimendan alone (all P<0.05). Conclusion:Levosimendan alleviates CME-induced myocardial injury through inhibiting cardiomyocyte apoptosis mediated by LOX-1/p38 MAPK signaling pathway.

Objective:To analysis and compare the burden of ischemic heart disease (IHD) attributable to metabolic risks in population aged 25 years and older in 2011 and 2017 in Nanjing.Methods:The data were extracted from the Nanjing Chronic Disease and Risk Factor Surveillance (2011 and 2017), the Nanjing Mortality Surveillance (2011 and 2017) and the 2016 Global Burden of Disease Study (GBD). Using GBD′s Comparative Risk Assessment Theory, the attribution burden was estimated by comparing the observed health outcomes with the health outcomes that may be observed when exposed to counterfactual levels. Based on population attributable fractions, the deaths and life expectancy losses of ischemic heart disease due to high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high total cholesterol (TC), high body mass index (BMI) and combination of four risks were estimated in 2011 and 2017. The average population structure of the world′s population from 2000 to 2025 wasusedas the standard population for standardization.Results:The number of IHD deaths attributable to four metabolic risks combination was 3 204, andwhich resulted in a loss of life expectancy of 0.90 years in 2017. High SBP appeared as the major cause of IHD deaths and Years of Life Lost (YLL). In 2017, the world standardized mortality rate (25.60×10 －5, 19.94×10 －5 and 6.83×10 －5) and the standardized YLL rate (389.31×10 －5, 335.16×10 －5, 134.60×10 －5) of the population due to high systolic blood pressure, high total cholesterol and high body mass index were significantly lower than those in 2011 (31.75×10 －5, 26.74×10 －5, 7.45×10 －5 and 469.07×10 －5, 463.70×10 －5, 142.66×10 －5); the world standardized rate and the standardized YLL rate due to high blood sugar (11.90×10 －5 and 174.61×10 －5) were significantly higher than those in 2011 (9.67×10 －5 and 150.61×10 －5) (all P<0.05). Males appeared to have higher standardized rate of YLL of IHD deaths than females, due to having metabolism risks( P<0.05). Conclusion:Metabolic exposures especially high SBP are the important risk factors whichleadto IHD deaths in Nanjing.

Objective To master the current status of iodine nutrition of people in Nanjing after the adjustment of iodized salt standard,and to provide scientific basis for reasonable iodine supplementation and strategies for iodine nutrition control.Methods The probability proportional to size (PPS) sampling method was employed in the investigation.We firstly selected 30 streets in the whole city,and then chosen 50 children aged 8-10 years from each of 30 primary schools respectively,which was selected from 30 different streets to examine the size of thyroid gland by palpation and B-type ultrasound.We also collected urine and edible salt samples from 12 children aged 8-10 years from each primary school,to detect their urinary and salt iodine content.Moreover,20 pregnant women and 10 lactating women were picked out from each of 30 schools nearby to detect their urinary and salt iodine content.We also conducted a unique questionnaire survey in 30 fifth-grade students selected from each of 30 schools,and 5 housewives selected from these schools nearby to understand their knowledge of iodine deficiency disorders.Results The thyroid palpate swelling rate was 0.33％(5/1 500) in 1 500 children aged 8-10.The medians of urinary iodine level were 220.5 μg/L in 362 school-age children,196.7 μg/L in 600 pregnant women and 152.0 μg/L in 300 lactating women.A total of 1 260 samples of edible salt were tested.The coverage rate of iodized salt and the consumption rate of eligible iodized salt were 99.7％ (1 256/1 260) and 96.9％ (1 221/1 260),respectively.The mean iodine content of edible salt was (24.5 ± 4.5) mg/kg.A total of 900 fifth-grade students and 150 housewives were surveyed for health knowledge of iodine,and the eligible rate was 83.2％ (2 246/2 700) and 91.6％ (412/450),respectively.Conclusions After the adjustment of iodized salt content,iodine nutrition level of people in Nanjing has maintained appropriately.However,health education should be further strengthened.Improving the awareness rate of iodine deficiency knowledge,and guiding scientific iodine consciousness are our serious task in the future.

Objective To investigate the agitation effect of dexmedetomidine in the operation of radical hysterectomy by general anesthesia in patients.Methods 68 cases in this study who were under the operation of radical hysterectomy by general anesthesia in our hospital were selected, and randomly divided into the group A and the group B, 34 cases in each group.Group A received dexmedetomidine after tracheal intubation, and group B received physiological saline as the measurement of group A, hemodynamic and inflammatory factors were measured at different time points in anesthesia, the corresponding indexes and the degree of emergence delirium were compared.Results Compared with T1 , levels of HR and MAP increased, levels of SpO2 decreased at T3 and T4 in group B, levels of CRP, TNF-αincreased at T2 , T3 , T4 , T5 in group B, levels of CRP, TNF-αincreased at T3 , T4 , T5 in group A(P<0.05), and compared with the group A, levels of HR and MAP were higher at T3 and T4, levels of SpO2 were lower,levels of CRP, TNF-αwere higher at T2, T3, T4, T5in group B(P<0.05).The cough response score and agitation score in group B were higher than group A, and sedation score was lower than group A ( P <0.05 ) , the grade of emergence delirium in group A was better than group B ( P <0.05 ) . Conclusion Dexmedetomidine in the operation of radical hysterectomy by general anesthesia could reduce the emergence of agitation occurred, inhibit extubation reaction, but would not extend the anesthesia recovery time.

Objective To evaluate the value of serum kaliuretic peptide (KP) in predicting atrial fibrillation (AF) and its prognosis,by detecting serum KP levels in patients with severe sepsis.Methods Fifty-six patients with severe sepsis in Integrated Intensive Care Unit of Shajing Hospital of Shenzhen Affiliated to Guangzhou Medical University from January 2014 to August 2015 were collected as the case group.In addition 20 cases health checkup for the same period were collected as the control group.Serum KP were determined in all patients in the case group every day for 1 week after admission,meanwhile the APACHE-Ⅱ score was undertook,then according to heart guardianship and electrocardiogram whether occurrence of AF the case group were divided into AF group and non AF group.According to survival after 28 days again divided into survival group and death group,the relationship of serum KP with AF and the prognosis were analyzed.Serum KP was detected on the day of physical examination in the control group.Results (1) The incidence of AF was 32.1％(18/56) in 56 patients with severe sepsis.(2)Serum KP in admission to hospital in case group was significantly higher than that in the control group((234.2±73.5) pmol/L vs.(169.6±65.4) pmol/L;t =3.47,P =0.001).Serum KP in admission to hospital in AF group was significandy higher than that in the non AF group((306.0±35.6) pmol/L vs.(200.2±61.2) pmol/L;t =6.79,P =0.001).Serum KP in AF group before 1 day of the occurrence AF was significantly higher than of the admission to hospital ((339.2± 30.5) pmol/L vs.(306.0±35.6) pmol/L;P=0.007),serum KP on the day of occurrence AF was significantly higher than before 1 days of the occurrence AF((390.6±47.8) pmol/L vs.(339.2±30.5) pmol/L;P=0.006),there was no difference between the serum KP after 1 days of occurrence AF and on the day of occurrence AF(P=0.246),but began to gradually declining.Serum KP and APACHE-Ⅱ score in death group on admission to hospital were significantly higher than survival group((301.1±42.0) pmol/L vs.(199.8±61.5) pmol/L,(26.1±2.8) points vs.(19.9±4.3) points;t =6.44,5.67;P＜0.001).(3) Linear correlation analysis showed that serum KP on admission to hospital was positively correlated with the occurrence of AF(r=0.679,P=0.010).According to AF grouping,serum levels of KP on admission to hospital draw ROC curve,the serum KP of AUC was 0.908(95％ CI:0.831-0.984),when the KP value was 351.5 pmol/L,the sensitivity of the occurrence AF was 89.9％,specificity of 97.4％.(4)Linear correlation analysis showed that serum KP on admission to hospital was positively correlated with death(r=0.659,P =0.010),according to prognostic grouping,serum KP on admission to hospital and APACHE-Ⅱ score ROC curve was drew,the serum KP of AUC was 0.893 (95％ CI:0.811-0.974),when the KP value was 338.5 pmol/L,the sensitivity of death was 78.9％,specificity of 97.3％.Conclusion Early serum KP level can be used as an indicator to predict AF and prognosis in the patients with severe sepsis.