Relationship between initial red cell distribution width and ΔRDW and mortality in cardiac arrest patients.

AIMS: There has been a lack of research examining the relationship between red cell distribution width (RDW) and the prognosis of cardiac arrest (CA) patients. The prognostic value of the changes in RDW during intensive care unit (ICU) hospitalization for CA patients has not been investigated. This study aims to investigate the correlation between RDW measures at ICU admission and RDW changes during ICU hospitalization and the prognosis of CA patients and then develop a nomogram that predicts the risk of mortality of these patients. METHODS AND RESULTS: A retrospective cohort study is used to collect clinical characteristics of CA patients (>18 years) that are on their first admission to ICU with RDW data measured from the Medical Information Mart for Intensive Care IV Version 2.0 database. Patients are randomly divided into a development cohort (75%) and a validation cohort (25%). The primary outcome is 30 and 360 day all-cause mortality. ΔRDW is defined as the RDW on ICU discharge minus RDW on ICU admission. A multivariate Cox regression model is applied to test whether the RDW represents an independent risk factor that affects the all-cause mortality of these patients. Meanwhile, the dose-response relationship between the RDW and the mortality is described by restricted cubic spine (RCS). A prediction model is constructed using a nomogram, which is then assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). A total of 1278 adult CA patients are included in this study. We found that non-survivors have a higher level of RDW and ΔRDW compared with survivors, and the mortality rate is higher in the high RDW group than in the normal RDW group. The Kaplan-Meier survival curve indicates that patients in the normal RDW group had a higher cumulative survival rate at 30 and 360 days than those in the high RDW group (log-rank test, χ2  = 36.710, χ2  = 54.960, both P values <0.05). The multivariate Cox regression analysis shows that elevated RDW at ICU admission (>15.50%) is an independent predictor of 30 [hazard ratio = 1.451, 95% confidence interval (CI) = 1.181-1.782, P < 0.001] and 360 day (hazard ratio = 1.393, 95% CI = 1.160-1.671, P < 0.001) all-cause mortality among CA patients, and an increase in RDW during ICU hospitalization (ΔRDW ≥ 0.4%) can serve as an independent predictor of mortality among these patients. A non-linear relationship between the RDW measured at ICU admission and the increased risk of mortality rate of these patients is shown by the RCS. This study established and validated a nomogram based on six variables, anion gap, first-day Sequential Organ Failure Assessment score, cerebrovascular disease, malignant tumour, norepinephrine use, and RDW, to predict mortality risk in CA patients. The consistency indices of 30 and 360 day mortality of CA patients in the validation cohort are 0.721 and 0.725, respectively. The nomogram proved to be well calibrated in the validation cohort. DCA curves indicated that the nomogram provided a higher net benefit over a wide, reasonable range of threshold probabilities for predicting mortality in CA patients and could be adapted for clinical decision-making. CONCLUSIONS: Elevated RDW levels on ICU admission and rising RDW during ICU hospitalization are powerful predictors of all-cause mortality for CA patients at 30 and 360 days, and they can be used as potential clinical biomarkers to predict the bad prognosis of these patients. The newly developed nomogram, which includes RDW, demonstrates high efficacy in predicting the mortality of CA patients.

Observed and relative survival trends of lung cancer: A systematic review of population-based cancer registration data.

BACKGROUND: Using the published survival statistics from cancer registration or population-based studies, we aimed to describe the global pattern and trend of lung cancer survival. METHODS: By searching SinoMed, PubMed, Web of Science, EMBASE, and SEER, all survival analyses from cancer registration or population-based studies of lung cancer were collected by the end of November 2022. The survival rates were extracted by sex, period, and country. The observed, relative, and net survival rates of lung cancer were applied to describe the pattern and time changes from the late 1990s to the early 21st century. RESULTS: Age-standardized 5-year relative/net survival rate of lung cancer was typically low, with 10%-20% for most regions. The highest age-standardized relative/net survival rate was observed in Japan (32.9%, 2010-2014), and the lowest was in India (3.7%, 2010-2014). In most countries, the five-year age-standardized relative/net survival rates of lung cancer were higher in females and younger people. The patients with adenocarcinoma had a better prognosis than other groups. In China, the highest 5-year overall relative/net survival rates were 27.90% and 31.62% in men and women in Jiangyin (2012-2013). CONCLUSION: Over the past decades, the prognosis of lung cancer has gradually improved, but significant variations were also observed globally. Worldwide, a better prognosis of lung cancer can be observed in females and younger patients. It is essential to compare and evaluate the histological or stage-specific survival rates of lung cancer between different regions in the future.

The association between albumin corrected anion gap and ICU mortality in acute kidney injury patients requiring continuous renal replacement therapy.

The relationship between albumin corrected anion gap (ACAG) and mortality in acute kidney injury (AKI) patients who received continuous renal replacement therapy (CRRT) has not been investigated in any previous studies. This study aimed to investigate the relationship between ACAG at CRRT initiation and all-cause mortality among these patients in the intensive care unit (ICU). Patients diagnosed with AKI and treated with CRRT in the ICU from the Medical Information Mart for Intensive Care-IV version 1.0 (MIMIC IV) database and Huzhou Central Hospital were retrospectively enrolled. Participants were divided into two groups: the normal ACAG group (12-20 mmol/L) and high ACAG group (> 20 mmol/L). The Kaplan-Meier method and log-rank test were used to compare the survival rate between the two groups. Restricted cubic spine (RCS) and Cox proportional-hazards models were utilized to analyze the relationship between ACAG at CRRT initiation and ICU all-cause mortality of these patients. A total of 708 patients met the inclusion criteria in the study. The all-cause mortality of these patients during ICU hospitalization was 41.95%. Patients in the high ACAG group exhibited significantly higher ICU all-cause mortality rate than patients in the normal ACAG group (all P < 0.001). The Kaplan-Meier survival curves showed that the normal ACAG group had a higher ICU cumulative survival rate than the high ACAG group (log-rank test, χ12 = 13.620, χ22 = 12.460, both P < 0.001). In the multivariate COX regression analyses, patients with higher ACAG (> 20 mmol/L) levels at the time of CRRT initiation in the MIMIC IV database and Huzhou Central Hospital were significantly correlated with ICU all-cause mortality after adjusting multiple potential confounding factors with hazard ratios of 2.852 (95% CI 1.718-4.734) and 2.637(95% CI 1.584-4.389), respectively. In critically AKI patients who undergo CRRT, higher ACAG (> 20 mmol/L) level at the initiation of CRRT was significantly correlated with ICU all-cause mortality. Therefore, clinicians should pay more attention to those patients with a higher ACAG value.

Clinical efficacy of blastocyst culture supernatant transfer in hormone replacement freeze-thaw embryo transfer cycles: A prospective double-blind randomized controlled study.

OBJECTIVE: To investigate the clinical efficacy of blastocyst culture supernatant transfer in hormone replacement freeze-thaw embryo transfer (FET) cycles. METHODS: The present study was a prospective double-blind randomized controlled study. Patients who met the inclusion criteria for the first hormone replacement freeze-thaw single blastocyst transfer proposed from September 2017 to December 2020 were randomly grouped at the endometrial transformation day of the secretory phase (P + 0). Patients in Group A (the experimental group) received the blastocyst culture supernatant at P + 2 and a single blastocyst at P + 5. Patients in Group B (the control group) received the embryo culture at P + 2 and a single blastocyst at P + 5. The clinical outcomes were compared between the two groups. RESULTS: A total of 288 cycles were included in the present study, with 144 cycles in each group. The clinical pregnancy rate and live birth rate were higher in group A than in group B (54.9% vs 45.8%, and 50% vs 39.6%, respectively), and the differences were more pronounced in patients with the age of ≥35 years (51.7% vs 37.5%, and 44.8% vs 32.1%, respectively), but the differences were not statistically significant. CONCLUSION: Blastocyst culture supernatant transfer in hormone replacement FET cycles could improve the pregnancy outcomes.

Trends of stomach cancer survival: A systematic review of survival rates from population-based cancer registration.

OBJECTIVES: We aimed to describe the pattern and time trends of survival from stomach cancer worldwide from population-based cancer registers. METHODS: A systematic search of PubMed, Web of Science, EMBASE, SEER and SinoMed for articles published up to 31 December 2020 was conducted. All eligible survival analyses of stomach cancer were collected and evaluated by countries or regions, periods, sex and age groups. RESULTS: Our review included 76 articles on stomach cancer survival rates and found that these rates had improved globally with time, although this increase was unremarkable. The highest 5-year survival rate of 72.1% was observed in Japan (2004-2007). The 5-year relative and net survival, rates were relatively high in Korea and Japan, while they were fairly poor in Africa and India. Sex-specific survival rates were higher in women than in men in America, Europe and Oceania, whereas they were relatively low in Asia. The poorest age-specific 5-year relative and net survival rates were observed in patients aged over 75 years. CONCLUSIONS: Over the past decades, patient prognosis of stomach cancer has gradually improved worldwide and survival rates in developed regions were higher than those in developing regions. White men and Asian women had a poorer survival than white women and Asian men. Younger patients had better survival rates than those aged over 75 years globally.

Joint impact of BMI, physical activity and diet on type 2 diabetes: Findings from two population-based cohorts in China.

AIMS: Limited epidemiological data on the combined impact of several lifestyle factors on type 2 diabetes (T2D) incidence was reported in Chinese population. This study aimed to examine how combinations of BMI, physical activity and diet relate to T2D incidence and estimate corresponding population attributable risk in the general population. METHODS: A total of 56,691 male and 70,849 female participants aged 40-74 years old in two population-based cohorts from the Shanghai Men's and Women's Health Studies were used for analysis. The Cox regression model was used to estimate the association between lifestyle factors collected at baseline and T2D incidence. Multivariable-adjusted population attributable risks were calculated for specific combinations of lifestyle factors. RESULTS: There were 3315 male and 5925 female incident T2D, with corresponding density incidence rates of 6.39 and 6.04 per 1000 person-years. If the healthiest group of healthy lifestyle index (HLI) was used as a reference, the hazard ratios (95% confidence intervals) of T2D increased monotonically in men [2.04 (1.75, 2.38); 2.94 (2.53, 3.42); 4.31 (3.66, 5.07)] and women [1.85 (1.64, 2.08); 2.79 (2.49, 3.13); 4.14 (3.66, 4.67)]. One point increase of HLI was related to 35% and 35% lower risk in men and women. About 52.7% and 58.4% cases in men and women could have been avoided if participants had been adherent to a healthy lifestyle of maintaining healthy body weight, eating a healthy diet and keeping physically active. CONCLUSIONS: An increased number of healthy lifestyle factors were associated with a decreased risk of T2D in the Chinese population. Future interventions targeted at combined healthy lifestyle factors are needed to reduce the burden of T2D.

Dose-Response Association between Adiposity and Liver Cancer Incidence: A Prospective Cohort Study among Non-Smoking and Non-Alcohol-Drinking Chinese Women.

BACKGROUND: Based on a population with very low prevalence of smoking and alcohol drinking, we examined the associations between overall obesity and fat distribution in middle age, obesity in early adulthood, and adult weight gain with the risk of liver cancer incidence. METHODS: The associations between body mass index (BMI) at study enrollment and at age 20, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), adult weight gain, and annual average weight gain with the risk of liver cancer were estimated using Cox regression models. Multivariable-adjusted HRs and 95% confidence intervals (CIs) were calculated. RESULTS: After a mean follow-up time of 17.5 years, 241 liver cancer cases were identified from 69,296 participants. The HRs for per 5-kg/m2 increment of BMI, per 10-cm increment of WC and HC, and per 0.1-unit increment of WHtR in middle age were 1.29 (95% CI, 1.07-1.57), 1.23 (95% CI, 1.05-1.43), 1.30 (95% CI, 1.10-1.55), and 1.37 (95% CI, 1.07-1.75), respectively. The HRs for per 5-kg increment of absolute adult weight gain and per 0.5-kg/year increment of annual average weight gain were 1.15 (95% CI, 1.06-1.25) and 1.44 (95% CI, 1.08-1.92). CONCLUSIONS: Overall and abdominal obesity in middle age and weight gain through adulthood were positively associated with liver cancer risk among non-smoking and non-alcohol-drinking women. IMPACT: Based on a cohort of non-smoking and non-alcohol-drinking women, the current study confirmed the association between obesity in middle age and increased liver cancer risk and suggested weight gain through adulthood as a risk factor for liver cancer.

Population attributable risk of excess weight, abdominal obesity and physical inactivity for type 2 diabetes in Chinese men and women.

BACKGROUND: Given the high prevalence of type 2 diabetes mellitus (T2DM) in the Chinese population, it is necessary to estimate the T2DM incident attributable to obesity and physical inactivity. METHODS: We analyzed the data from the Shanghai Men's and Women's Health Studies, including 56,691 men and 70,849 women aged 40-74. The hazard ratios (HRs) and the population attributable risks (PARs) were calculated by Cox regression model and model-based estimation. RESULTS: A total of 3,315 male and 5,925 female cases were identified during 519,157 and 981,504 person-years, up to 31 December 2017. Excess weight, abdominal obesity were associated with the increased risks of T2DM both in women and men, while physical inactivity was only associated with an increased risk in men. A large proportion of T2DM incident cases can be attributed to excess body weight (women: 48.6%; men: 41.5%) and abdominal obesity (women: 50.4%; men: 30.3%). Physical activity was negatively associated with the risk of T2DM (Ptrend<0.01). The PARs adjusted for confounders were 3.6% for physical inactivity in men and 1.7% in women. CONCLUSIONS: Excess weight and abdominal obesity accounted for a large proportion of T2DM incident cases in men and women; a small part of T2DM cases were attributed to physical inactivity in men. Weight control is of great significance in curbing the epidemic of diabetes.

Gender differences of relationship between serum lipid indices and type 2 diabetes mellitus: a cross-sectional survey in Chinese elderly adults.

BACKGROUND: To investigate the gender differences of the relationships between clinical serum lipid indices and type 2 diabetes mellitus (T2DM) in Chinese elderly adults. METHODS: Between 2014 and 2016, participants selected from three communities in an urban district of Shanghai were measured for serum lipid indices of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), and triglyceride (TG). Age and multivariate adjusted logistic regression models were utilized to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of serum lipid indices on T2DM prevalence. RESULTS: In total, 4,023 male and 3,862 female participants were included in this study, with the T2DM prevalence proportions of 13.03% and 11.73%, respectively. In association analysis, the serum levels of LDL-c, HDL-c, TC were significant between non-T2DM individuals and T2DM patients in men, but the HDL-c and TG in women. LDL-c/HDL-c, TG/HDL-c, and TC/HDL-c ratios were associated with the T2DM prevalence only in women. In the multivariate analysis, a higher serum LDL-c level was positively associated with a reduced risk of T2DM prevalence in men with OR (95% CI) of 0.57 (0.39-0.85) (P=0.006). Higher ratios of LDL-c/HDL-c, TG/HDL-c, and TC/HDL-c were all more likely associated with the decreased risks of T2DM prevalence with the ORs ranging from 0.45 to 0.62 in men (all P<0.05), but not in women. CONCLUSIONS: High LDL-c concentration was significantly associated with a lower T2DM prevalence in men. A gender difference of the associations between the lipid ratios and T2DM prevalence was observed for LDL-c/HDL-c and TC/HDL-c ratios, which might be validated in female T2DM prevalence in the future.

Dietary fat intake and liver cancer incidence: A population-based cohort study in Chinese men.

To date, limited studies have focused on the association between dietary fat and liver cancer risk, especially in China. Our study aims to evaluate the association between dietary fat intake and liver cancer incidence risk in men. Dietary fat intake was obtained through a validated food frequency questionnaire in a Chinese prospective cohort. The Cox regression model was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After exclusion, 59 998 recruitments were finally analyzed with a total follow-up time of 714 339 person-years, 431 incident liver cancer cases were newly identified among them. The adjusted HRs (95% CIs) for the highest vs lowest quartile of total fat, saturated fat, monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) were 1.33 (1.01-1.75), 1.50 (1.13-1.97), 1.26 (0.96-1.65), and 1.41 (1.07-1.86), and the corresponding P-trend values were .008, .005, .034, and .005, respectively. In the secondary analysis among participants tested for hepatitis B virus, we found that higher intakes of saturated fat and PUFA were also associated with increased liver cancer risks. Besides, high risks of per standard deviation alterations of the total fat, saturated fat and MUFA were detected in liver cancer, and these results were similar to those concluded from the full-cohort analysis. In conclusion, dietary intakes of total fat, saturated fat, PUFA, and probably MUFA might increase liver cancer risks. Our study provides suggestive advice to public administration on dietary suggestions, and related measures taken from managing dietary fat intake might reduce liver cancer incidence.

Tea Drinking and Risk of Cancer Incidence: A Meta-Analysis of Prospective Cohort Studies and Evidence Evaluation.

Here we provide a comprehensive meta-analysis to summarize and appraise the quality of the current evidence on the associations of tea drinking in relation to cancer risk. PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched up to June 2020. We reanalyzed the individual prospective studies focused on associations between tea drinking and cancer risk in humans. We conducted a meta-analysis of prospective studies and provided the highest- versus lowest-category analyses, dose-response analyses, and test of nonlinearity of each association by modeling restricted cubic spline regression for each type of tea. We graded the evidence based on the summary effect size, its 95% confidence interval, 95% prediction interval, the extent of heterogeneity, evidence of small-study effects, and excess significance bias. We identified 113 individual studies investigating the associations between tea drinking and 26 cancer sites including 153,598 cancer cases. We assessed 12 associations for the intake of black tea with cancer risk and 26 associations each for the intake of green tea and total tea with cancer risk. Except for an association between lymphoid neoplasms with green tea, we did not find consistent associations for the highest versus lowest categories and dose-response analyses for any cancer. When grading current evidence for each association (number of studies ≥2), weak evidence was detected for lymphoid neoplasm (green tea), glioma (total tea, per 1 cup), bladder cancer (total tea, per 1 cup), and gastric and esophageal cancer (tea, per 1 cup). This review of prospective studies provides little evidence to support the hypothesis that tea drinking is associated with cancer risk. More well-designed studies are still needed to identify associations between tea intake and rare cancers.

Physcion, a tetra-substituted 9,10-anthraquinone, prevents homocysteine-induced endothelial dysfunction by activating Ca2+- and Akt-eNOS-NO signaling pathways.

BACKGROUND: Homocysteine (Hcy) induced vascular endothelial dysfunction is known to be closely associated with oxidative stress and impaired NO system. 1,8-Dihydroxy-3-methoxy-6-methylanthracene-9,10-dione (physcion) has been known to has antioxidative and anti-inflammatory properties. PURPOSE: The purpose of the present study was to define the protective effect of physcion on Hcy-induced endothelial dysfunction and its mechanisms involved. STUDY DESIGN AND METHODS: Hyperhomocysteinemia (HHcy) rat model was induced by feeding 3% methionine. A rat thoracic aortic ring model was used to investigate the effects of physcion on Hcy-induced impairment of endothelium-dependent relaxation. Two doses, low (L, 30 mg/kg/day) and high (H, 50 mg/kg/day) of physcion were used in the present study. To construct Hcy-injured human umbilical vein endothelial cells (HUVECs) model, the cells treated with 3 mM Hcy. The effects of physcion on Hcy-induced HUVECs cytotoxicity and apoptosis were studied using MTT and flow cytometry. Confocal analysis was used to determine the levels of intracellular Ca2+. The levels of protein expression of the apoptosis-related markers Bcl-2, Bax, caspase-9/3, and Akt and endothelial nitric oxide synthase (eNOS) were evaluated by western blot. RESULTS: In the HHcy rat model, plasma levels of Hcy and malondialdehyde (MDA) were elevated (20.45 ± 2.42 vs. 4.67 ± 1.94 µM, 9.42 ± 0.48 vs. 3.47 ± 0.59 nM, p < 0.001 for both), whereas superoxide dismutase (SOD) and nitric oxide (NO) levels were decreased (77.11 ± 4.78 vs. 115.02 ± 5.63 U/ml, 44.51 ± 4.45 vs. 64.18 ± 5.34 µM, p < 0.001 and p < 0.01, respectively). However, treatment with physcion significantly reversed these changes (11.82 ± 2.02 vs. 20.45 ± 2.42 µM, 5.97 ± 0.72 vs. 9.42 ± 0.48 nM, 108.75 ± 5.65 vs. 77.11 ± 4.78 U/ml, 58.14 ± 6.02 vs. 44.51 ± 4.45 µM, p < 0.01 for all). Physcion also prevented Hcy-induced impairment of endothelium-dependent relaxation in HHcy rats (1.56 ± 0.06 vs. 15.44 ± 2.53 nM EC50 for ACh vasorelaxation, p < 0.05 vs. HHcy). In Hcy-injured HUVECs, physcion inhibited the impaired viability, apoptosis and reactive oxygen species. Hcy treatment significantly increased the protein phosphorylation levels of p38 (2.26 ± 0.20 vs. 1.00 ± 0.12, p <0.01), ERK (2.11 ± 0.21 vs. 1.00 ± 0.11, p <0.01) and JNK. Moreover, physcion reversed the Hcy-induced apoptosis related parameter changes such as decreased mitochondrial membrane potential (MMP) and Bcl-2/Bax protein ratio, and increased protein expression of caspase-9/3 in HUVECs. Furthermore, the downregulation of Ca2+, Akt, eNOS and NO caused by Hcy were recovered with physcion treatment in HUVECs. CONCLUSION: Physcion prevents Hcy-induced endothelial dysfunction by activating Ca2+- and Akt-eNOS-NO signaling pathways. This study provides the first evidence that physcion might be a candidate agent for the prevention of cardiovascular disease induced by Hcy.

Non-catecholamine vasopressors in the treatment of adult patients with septic shock-evidence from meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Norepinephrine (NE) has currently been the first-choice vasopressor in treating septic shock despite generally insufficient for patients with refractory septic shock. The aim of this update meta-analysis was to assess the safety and efficacy of a combination of non-catecholamine vasopressors (vasopressin/pituitrin/terlipressin/selepressin/angiotensin II) and NE versus NE in managing adult septic shock patients. METHODS: We conducted this study of literatures published from the inception to April 30, 2020, using PubMed, Embase, and the Cochrane Library databases without language restriction. Randomized controlled trials comparing NE with non-catecholamine vasopressors among adult septic shock patients were included in this meta-analysis. Pooled effects of relative risk (RR) or standard mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. RESULTS: Twenty-three studies covering 4380 participants were finally enrolled. The combined analysis of non-catecholamine vasopressors resulted in a nonsignificant reduction in 90-day/ICU/hospital mortality except for a decreased in 28-day mortality (n = 4217; RR, 0.92; 95% CI 0.86-0.99; P = 0.02). This favorable result was subsequently verified by the subgroup analyses of low risk of bias studies (RR = 0.91, 95% CI = 0.84 to 0.98; P = 0.02) and catecholamine-resistant refractory shock patients group (RR, 0.84; 95% CI = 0.70-1.00; P = 0.048). The pooled analysis of non-catecholamine vasopressors showed a 14% higher success rate of shock reversal at 6 h, a 29% decreased risk of continuous renal replacement therapy, but a 51% increased risk of hyponatremia and a 2.43 times higher risk of digital ischemia. Besides, the pooled data showed that non-catecholamine vasopressors decreased heart rate (HR) (SMD, - 0.43; 95% CI - 0.66 - - 0.19; P < 0.001), serum creatinine (- 0.15; 95% CI - 0.29 - - 0.01; P = 0.04), and the length of mechanical ventilation (MV) (- 0.19; 95% CI - 0.31 - - 0.07; P < 0.01, but there was no significant difference in other parameters. CONCLUSIONS: Current pooled results suggest that the addition of NE to non-catecholamine vasopressors was associated with a marginally significant reduction in 28-day mortality. Moreover, they were able to shorten the length of MV, improved renal function, decreased HR, and increased the 6-h shock reversal success rate at the expense of increased the risk of hyponatremia and digital ischemia.

The value of 18F-PSMA-1007 PET/CT in identifying non-metastatic high-risk prostate cancer.

BACKGROUND: Clinical management decisions on prostate cancer (PCa) are often based on a determination of risk. 68Ga-prostate-specific membrane antigen (PSMA)-11-positron emission tomography (PET)/computer tomography (CT) is an attractive modality to assess biochemical recurrence of PCa, detect metastatic disease and stage of primary PCa, making it a promising strategy for risk stratification. However, due to some limitation of 68Ga-PSMA-11 the development of alternative tracers is of high interest. In this study, we aimed to investigate the value of 18F-PSMA-1007 in identifying non-metastatic high-risk PCa. METHODS: A total of 101 patients with primary non-metastatic PCa who underwent 18F-PSMA-1007 PET/CT were retrospectively analyzed. According to the European Association of Urology guidelines on PCa, patients were classified into intermediate-risk (IR) group or high-risk (HR) group. The maximum standardized uptake values (SUVmax) of the primary prostate tumor were measured on PET/CT images. The diagnostic performance of PET/CT for IR and HR PCa was calculated, and the relationship between the SUVmax of primary prostate tumor, prostate-specific antigen (PSA) level and Gleason score (GS) was analyzed. RESULTS: Of all 101 patients, 49 patients were classified into IR group and 52 patients were classified into HR group. There was a significant positive correlation between PSA level/GS and SUVmax (r = 0.561, r = 0.496, P < 0.001, respectively). Tumors with GS 6 and 7a showed significantly lower 18F-PSMA-1007 uptake compared to patients with GS 8 and 9 (P < 0.01). SUVmax in patients of HR was significantly higher than those of IR (median SUVmax: 16.85 vs 7.80; P < 0.001). In receiver operating characteristic curve analysis, the optimal cutoff value of the SUVmax for identifying high-risk PCa was set as 9.05 (area under the curve: 0.829; sensitivity: 90.4%; specificity: 65.3%). CONCLUSION: 18F-PSMA-1007 PET/CT showed the powerful diagnosis efficacy for high-risk PCa, which can be used as an objective imaging reference index for clinical reference.

Long-term liver cancer incidence and mortality trends in the Changning District of Shanghai, China.

OBJECTIVE: To evaluate the trends and estimate the long-term effects of age, period and birth cohort on the incidence and mortality rates of liver cancer (LC) in an urban district of Shanghai, China. METHODS: Crude and age-standardized rates of the incidence and mortality of LC were calculated from 1973 to 2013 annually by sex, and the direction and magnitude of the trends were estimated by the average annual percentage change (AAPC) using the Joinpoint Regression Model. An age-period-cohort (APC) model was also used to evaluate the non-linear effects of calendar time and birth cohort on LC incidence and mortality. RESULTS: In 1973-1977 and 2008-2013 the age-standardized rates of LC incidence and mortality (per 100 000) were 24.27 and 22.60 in men, and 7.50 and 7.26 in women, respectively. Declining trends of LC incidence and mortality rates were observed for both sexes (AAPC; P < 0.05 for both). The APC models indicated that the rates of LC incidence and mortality were significantly influenced both by calendar time and birth cohort effects. CONCLUSIONS: The incidence and mortality rates of LC have decreased in both sexes in the Changning District of Shanghai over the past four decades. Although obvious descending trends of LC incidence and mortality were detected, attention should also be paid to the LC burden for a long time in the future because of huge population size in China and the continuity of population aging.

Coffee drinking and cancer risk: an umbrella review of meta-analyses of observational studies.

BACKGROUND: Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias. RESULTS: Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10- 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies. CONCLUSIONS: There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.

Knockdown of KIAA1199 suppresses IL-1ß-induced cartilage degradation and inflammatory responses in human chondrocytes through the Wnt/ß-catenin signalling pathway.

The overproduction of proteolytic enzymes and dysregulation of extracellular matrix (ECM) metabolism have been shown to accelerate the degradation process of articular cartilage. The purpose of this study was to investigate the role of KIAA1199 and its association with the pathophysiology of osteoarthritis (OA). We found that the expression of KIAA1199 was significantly upregulated in OA cartilage compared with normal tissues. Serum levels of KIAA1199 were higher in OA patients than in non-OA patients. Furthermore, knockdown of KIAA1199 inhibited interleukin-1 beta (IL-1ß)-induced ECM metabolic imbalance by regulating the expression of A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 5; matrix metallopeptidase-13; aggrecan; and COL2A1. In addition, silencing of KIAA1199 significantly decreased the expression of inflammatory mediators such as prostaglandin E2, IL-6, and TNF-α. Mechanistic analyses further revealed that IL-1ß-induced activation of the Wnt/ß-catenin pathway was suppressed during KIAA1199 knockdown. Moreover, KIAA1199 expression was also upregulated in an in vivo rat OA model. Together, these results increase our understanding of the emerging role of KIAA1199 in the process of OA degeneration, and may lead to a novel molecular target to prevent cartilage degradation.

Monoamine neurotransmitters and fibroblast growth factor-2 in the brains of rats with post-stroke depression.

The aim of the present study was to investigate the changes in the levels of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and fibroblast growth factor-2 (FGF-2) in the brains of rats with post-stroke depression (PSD). A rat model of stroke was established by middle cerebral artery occlusion and the rats were randomly divided into two groups: Control and modification groups. The rats in the modification group had PSD, while the rats in the control group had experienced a stroke only. The PSD model was established by applying chronic mild stress to the individually housed rats. High-performance liquid chromatography was used to detect the levels of 5-HT, DA and NE, while western blotting was used to detect the FGF-2 protein expression levels in the frontal lobe and hippocampus. Quantitative polymerase chain reaction was also used to determine the mRNA expression levels of FGF-2 in the frontal lobes of the two groups. The levels of 5-HT, DA and NE in the frontal lobe and hippocampus of the rats in the PSD group were significantly lower than the levels observed in the rats in the stroke group (P<0.01). In addition, protein expression levels of FGF-2 in the frontal lobe of the rats in the PSD group were significantly lower when compared with the control group rats (P<0.01), however, the protein expression levels of FGF-2 in the hippocampus did not exhibit a statistically significant difference (P>0.05). The mRNA expression levels of FGF-2 in the frontal lobe of the rats in the modification group were significantly lower than the levels in the control group rats (P<0.01). Therefore, reduced levels of monoamine neurotransmitters and FGF-2 expression in the brains of rats with PSD are associated with the incidence of PSD.

Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress.

BACKGROUND: Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. MATERIAL AND METHODS: Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. RESULTS: In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. CONCLUSIONS: Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS.

Mini-dose GnRH-a long versus short protocol in patients ≥ 35 years old undergoing in vitro fertilization.

PURPOSE: To compare the clinical result of mini-dose GnRH-a long protocol with short protocol in older patients undergoing IVF. MATERIALS AND METHODS: This was a retrospective study. Four hundred and sixty-one women aged above 35-year-old in first cycle were assigned to two groups: GnRH-a short protocol (n=359); and mini-dose GnRH-a long protocol (n=102). Both groups were divided based on their age, into groups over and under 38 years old. Primary outcome include live birth rate per started cycle. Other clinical outcomes were good-quality embryo rate, clinical pregnancy rate. RESULTS: Patients treated with mini-dose GnRH-a protocol and those treated with short protocol showed similar live birth rate. In the mini-dose long protocol group aged 35-38 years old, patients showed significantly thicker endometrium at the day of hCG administration, higher number of good embryos obtained and higher good-quality embryo rate (56.3% versus 46.5%) compared with short protocol. The implantation rate and clinical pregnancy rate were higher versus short protocol group, but this result was not statistically significant. CONCLUSION(S): Mini-dose GnRH-a long protocol for older women is at least as effective as short protocol, especially in patients aged 35-38 years, with a better good-quality embryo rate and higher number of good embryos obtained, therefore mini-dose GnRH-a long protocol can be considered as an alternative protocol for patients above 35 years age.