Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).

Risk stratification of papillary thyroid cancers using multidimensional machine learning.

BACKGROUND: Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a challenge in the worldwide. Here, the authors first report a Preoperative Risk Assessment Classifier for PTC (PRAC-PTC) by multidimensional features including clinical indicators, immune indices, genetic feature, and proteomics. MATERIALS AND METHODS: The 558 patients collected from June 2013 to November 2020 were allocated to three groups: the discovery set [274 patients, 274 formalin-fixed paraffin-embedded (FFPE)], the retrospective test set (166 patients, 166 FFPE), and the prospective test set (118 patients, 118 fine-needle aspiration). Proteomic profiling was conducted by FFPE and fine-needle aspiration tissues from the patients. Preoperative clinical information and blood immunological indices were collected. The BRAFV600E mutation were detected by the amplification refractory mutation system. RESULTS: The authors developed a machine learning model of 17 variables based on the multidimensional features of 274 PTC patients from a retrospective cohort. The PRAC-PTC achieved areas under the curve (AUC) of 0.925 in the discovery set and was validated externally by blinded analyses in a retrospective cohort of 166 PTC patients (0.787 AUC) and a prospective cohort of 118 PTC patients (0.799 AUC) from two independent clinical centres. Meanwhile, the preoperative predictive risk effectiveness of clinicians was improved with the assistance of PRAC-PTC, and the accuracies reached at 84.4% (95% CI: 82.9-84.4) and 83.5% (95% CI: 82.2-84.2) in the retrospective and prospective test sets, respectively. CONCLUSION: This study demonstrated that the PRAC-PTC that integrating clinical data, gene mutation information, immune indices, high-throughput proteomics and machine learning technology in multicentre retrospective and prospective clinical cohorts can effectively stratify the preoperative risk of PTC and may decrease unnecessary surgery or overtreatment.

Machine Learning Models of Postoperative Atrial Fibrillation Prediction After Cardiac Surgery.

OBJECTIVES: This study aimed to use machine learning algorithms to build an efficient forecasting model of atrial fibrillation after cardiac surgery, and to compare the predictive performance of machine learning to traditional logistic regression. DESIGN: A retrospective study. SETTING: Second Affiliated Hospital of Zhejiang University School of Medicine. PARTICIPANTS: The study comprised 1,400 patients who underwent valve and/or coronary artery bypass grafting surgery with cardiopulmonary bypass from September 1, 2013 to December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two machine learning approaches (gradient-boosting decision tree and support-vector machine) and logistic regression were used to build predictive models. The performance was compared by the area under the curve (AUC). The clinical practicability was assessed using decision curve analysis. Postoperative atrial fibrillation occurred in 519 patients (37.1%). The AUCs of the support-vector machine, logistic regression, and gradient boosting decision tree were 0.777 (95% CI: 0.772-0.781), 0.767 (95% CI: 0.762-0.772), and 0.765 (95% CI: 0.761-0.770), respectively. As decision curve analysis manifested, these models had achieved appropriate net benefit. CONCLUSION: In the authors' study, the support-vector machine model was the best predictor; it may be an effective tool for predicting atrial fibrillation after cardiac surgery.

Association between lifestyle and dietary preference factors and conventional adenomas and serrated polyps.

Introduction: Both conventional adenoma (AD) and serrated polyp (SP) were known precursor lesions of colorectal cancer (CRC). Modifiable lifestyle factors were significantly associated with CRC risk, but whether these factors were related to the risk of different precursors of CRC needed to be clarified. This study aimed to evaluate the risks of AD and SP caused by lifestyle factors and compare the risk differences between AD and SP. Methods: The study population was from the CRC screening cohort in Hangzhou, China. A total of 458,457 eligible individuals volunteered to undergo initial screening including the fecal immunochemical test (FIT) and the CRC risk assessment. Finally, 13,993 participants who had undergone colonoscopy tests and had been diagnosed at designated hospitals were selected in this study. All participants were required to fill out a questionnaire during the initial screening for collecting their information. The generalized estimate equation (GEE) model was used to assess the association between lifestyle factors/dietary preferences and AD/SP. Results: The body mass index (BMI) and smoking were positively associated with the risks of only SP (BMI: OR = 1.50, 95%CI: 1.23-1.84; smoking: OR = 1.29, 95%CI: 1.07-1.55), only AD (BMI: OR = 1.53, 95%CI: 1.28-1.82; OR = 1.24, 95%CI: 1.11-1.39), and synchronous SP and AD (BMI: OR = 1.97, 95%CI: 1.40-2.75; smoking: OR = 1.53, 95%CI: 1.27-1.85). In the case-group comparison, smoking was more strongly associated with the risk of synchronous SP and AD than only AD. Alcohol drinking was positively associated with the risk of AD (OR = 1.28, 95%CI: 1.14-1.44), but no statistically significant difference was observed in risks in the case-group comparison. Furthermore, whole-grain intake was associated with a decreased risk of only AD (OR = 0.78, 95%CI: 0.65-0.93). However, white meat intake was positively associated with risks of only SP when compared with AD cases (OR = 1.60, 95%CI: 1.15-2.23). Conclusion: The current study identified common risk factors such as BMI and smoking as well as different risks of certain factors (e.g., alcohol drinking and whole-grain intake) for SP and AD. However, there were still some factors, especially diet-related factors, that have not been fully elucidated in their association with the two lesions. Further research is needed in future to confirm and develop prevention strategies for different lesions.

Local infiltration of HYR-PB21, a sustained-release formulation of bupivacaine, provides analgesia and reduces opioid requirement after haemorrhoidectomy: a randomised controlled trial.

BACKGROUND: HYR-PB21 is a new sustained-release formulation of bupivacaine indicated for controlling postoperative pain. The objectives of this study were to investigate the analgesic efficacy and safety profile of HYR-PB21 in patients after haemorrhoidectomy. METHODS: This was a multicentre, randomised, double-blind, positive-controlled trial. Patients were assigned randomly to receive a single dose of HYR-PB21 (150 mg or 300 mg) or bupivacaine HCl (75 mg) after surgery for prolapsing haemorrhoids. Postoperative pain was evaluated using a numeric rating scale at rest to calculate a cumulative pain score. Total rescue opioid usage and the proportion of subjects receiving rescue opioid were also assessed. RESULTS: We enrolled 72 patients with haemorrhoidectomy, and 71 patients completed the study. The average cumulative pain score through 72 h after surgery in the 300 mg HYR-PB21 group (87 scores) was lower than in the bupivacaine HCl group (166 scores) in an intention-to-treat analysis (P<0.001). There was a dose-response effect in reducing total opioid usage and the proportion of rescue opioid use between the 150 mg and 300 mg HYR-PB21 groups, with bupivacaine HCl as a reference group. The HYR-PB21 groups did not show more adverse effects than the bupivacaine HCl group. CONCLUSIONS: Local infiltration of a single dose of HYR-PB21 sustained-release bupivacaine had better efficacy in controlling postoperative pain, with similar adverse effects, compared with a single dose of bupivacaine HCl in patients after haemorrhoidectomy. CLINICAL TRIAL REGISTRATION: ChiCTR2000041318 (Chinese Clinical Trial Registry).

Hemoglobin concentration and iron supplement during pregnancy were associated with an increased risk of gestational diabetes mellitus.

BACKGROUND: Hemoglobin (Hb) measurement is a conventional test during perinatal visits. Hb concentration is related to iron supplement. However, studies focusing on Hb levels, iron supplement, and pregnancy outcomes are scarce. This study aimed to determine whether Hb levels and iron supplement were associated with the risk of gestational diabetes mellitus (GDM). METHODS: A running hospital-based cohort was conducted from August, 2011. The demographic data and medical information were collected individually through questionnaires and patient medical records. Multiple linear regression was applied for the association between Hb levels, iron supplement, and blood glucose. Multiple logistic regression was used for evaluating odds ratios between Hb levels, iron supplement, and GDM. RESULTS: Hb levels during first (T1) and second trimester (T2) of pregnancy were significantly and positively associated with blood glucose and GDM risk. After adjusting for age, prepregnancy body mass index, and other risk factors, pregnant women with Hb ≥ 11 g/dL and iron supplement had higher postprandial blood glucose at 1 hour (Hb ≥ 11 g/dL in T2 and iron supplement in T1: ß = 0.860，P = <0.001; Hb ≥ 11 g/dL in T2 and iron supplement in T2: ß = 0.960，P < 0.001; Hb ≥ 11 g/dL in T1 and iron supplement in T2: ß = 1.133, P = 0.033) and GDM risks (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.05-2.24; OR = 1.92, 95% CI: 1.13-3.35; OR = 2.15, 95% CI: 1.07-4.34, respectively), compared with those with Hb < 11 g/dL and without iron supplement. CONCLUSION: High Hb concentration and iron supplements without anemia increased postprandial blood glucose and risks for GDM. It indicates that pregnant women with good Hb levels should not be advised to take iron supplements during pregnancy.

Uric acid fluctuation had no effect on renal function among gout patients.

BACKGROUND AND AIMS: To investigate the effects of serum uric acid (SUA) level and its fluctuation on renal dysfunction in gout patients. METHODS AND RESULTS: Data on gout patients was collected from Huzhou city electronic medical record system data sharing platform, and information about relevant diagnoses, prescriptions, biochemical indexes and imaging characteristics was extracted. The gout patients with baseline normal renal function were enrolled in this analysis, and the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was defined as renal dysfunction. The generalized estimating equation and Cox regression analysis were used. A total of 1009 patients with gout were enrolled. Compared with the reference group (normal baseline SUA with endpoint SUA to be < 6 mg/dL), endpoint SUA ≥ 10 mg/dL was associated with an increased risk of renal dysfunction (baseline normal SUA group: HR [95% CI] = 3.28 [1.21, 8.91]; baseline high SUA group: HR [95% CI] = 3.01 [1.43, 6.35]). Subgroup analysis of 771 SUA stable gout patients demonstrated that SUA levels at 8-10 (excluding 10), and ≥10 mg/dL were significantly associated with an increased risk for renal dysfunction, with HR [95%CI] to be 1.99 [1.05, 3.77], and 2.98 [1.38, 6.43], respectively. CONCLUSION: Regardless of the baseline SUA level, SUA >10 mg/dL was a significant risk factor for renal dysfunction. SUA between 6 and 10 mg/dL was a potential risk factor for renal dysfunction. No significant correlation of SUA fluctuation and renal function was found.

Iron overload is related to elevated blood glucose levels in obese children and aggravates high glucose-induced endothelial cell dysfunction in vitro.

INTRODUCTION: This study was performed to investigate the role of iron overload in the early stage of hyperglycemia-induced vascular functional impairment. RESEARCH DESIGN AND METHODS: A total of 196 obese children were enrolled, and data regarding ferritin levels, blood glucose levels, intima-media thickness of carotid arteries, liver function and fibrosis index, hemoglobin, blood pressure, blood lipids, and inflammation indicators were collected. Ferritin levels were compared with a control group, which consisted of 148 healthy non-obese children who were age-matched and gender-matched. Endothelial cells were cultured in high glucose medium and supplemented with ferric citrate with or without iron remover (deferoxamine), a reducing agent (N-acetyl-cysteine), or a nuclear factor-κB (NF-κB) inhibitor (BAY 11-7082). Apoptosis, oxidative stress, nitric oxide levels, and endothelin content were evaluated. DNA microarray analysis was performed to analyze the expression of genes in the NF-κB signaling pathway. RESULTS: Obese children have significantly higher ferritin levels compared with the control group. Ferritin level was positively correlated with hemoglobin and was related to metabolic disorders, including impaired glucose tolerance, higher blood pressure, dyslipidemia, and impaired hepatic function. Endothelial cells treated with ferric citrate showed a significantly higher rate of apoptosis, higher levels of oxidative stress, and impaired vasomotor function under high glucose conditions. The above effects were rescued by treatment with an iron remover, reducing agent, or NF-κB inhibitor. Further, detection of phosphorylated-p65 distribution in cells confirmed activation of the NF-κB pathway. DNA microarrays and subsequent gene oncology enrichment analyses revealed the main processes activated in cells. CONCLUSION: Increased ferritin levels are related to impaired glucose tolerance and other metabolic disorders in obese children. At the cellular level, iron overload aggravated the endothelial cell dysfunction caused by high glucose.

HYR-PB21-LA, a potential extended-release bupivacaine formulation, produces long-lasting local anesthesia in rats and guinea pigs.

BACKGROUND: Effective postoperative pain management plays a key role in enhancing recovery of patients after surgery. Bupivacaine hydrochloride is one of the most commonly local anesthetics used for the postoperative pain control. However, the relatively short anesthesia duration of bupivacaine preparations limited their clinical application. METHODS: Both guinea pig pin-prick study and rat tail-flick test were performed to evaluate the local anesthesia efficacy of HYR-PB21-LA, a new microparticle suspension injection of bupivacaine pamoate. RESULTS: In the pin-prick test, the complete cutaneous trunci muscle reflex inhibitions were observed at 30 min in all treatment groups containing bupivacaine. In comparison with 6.7 mg/mL HYR-PB21-LA, both 10 and 20 mg/mL HYR-PB21-LA groups had significantly higher area under effect time curve (AUEC) values (p<0.001 and p<0.0001) and slower offset time (p<0.0001). Significantly higher AUEC (p<0.0001) and slower offset time (p<0.0001) were also found in 10 mg/mL HYR-PB21-LA treatment group compared with bupivacaine liposome injectable suspension (liposomal bupivacaine). In the rat tail-flick test, significantly increased local anesthesia effect was lasted for 5 hours after 2.5 mg/mL HYR-PB21-LA administration, which was fivefold longer than bupivacaine hydrochloride. The longer lasted efficacy of significantly increased local anesthesia was also observed in 5 mg/mLHYR-PB21-LA than those in liposomal bupivacaine (8 hour vs 1 hour). CONCLUSIONS: The results demonstrated that the HYR-PB21-LA produced longer local anesthesia effect than current clinical preparations of bupivacaine in two animal models. These findings raise the potential clinical value of HYR-PB21-LA as a long-lasting local anesthesia for controlling postsurgical pain in humans.

Does fibrosis have an impact on survival of patients with hepatocellular carcinoma: evidence from the SEER database?

BACKGROUND: Liver fibrosis is involved in hepatocellular carcinoma (HCC), but its effect on the survival of patients with HCC remains controversial. This study aims to explore whether the severity of liver fibrosis has an impact on HCC overall survival (OS) and disease-specific survival (DSS) in Surveilance, Epidemiology, and End-Results (SEER) database. METHODS: A total of 11,783 HCC patients diagnosed between 2004 and 2014 from SEER database were enrolled. Cox proportional hazard regression models were used to estimate crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for fibrosis group associated with survival. Decision curve analysis (DCA) was also performed to compare the effect of fibrosis with other clinicopathological characteristics for survival outcome. RESULTS: Patients with high fibrosis score (5-6) had a greater proportion than those with low fibrosis score (0-4) (80.3% vs. 19.7%). Fibrosis score was an independent prognostic factor for OS (HR = 1.09, 95%CI: 1.02-1.16), but not for DSS (HR = 1.05, 95%CI: 0.98-1.13) by multivariate Cox proportional hazard models. Additionally, there was no significant effect of liver fibrosis on OS and DSS with stratification of TNM stage and therapy. Findings of DCA showed that fibrosis was less associated with survival outcome in comparison with other tumor characteristics. CONCLUSIONS: The effect of fibrosis on HCC survival was less important than that of other clinicopathological characteristics (like TNM stage or tumor size).

High Serum Iron level is Associated with Increased Mortality in Patients with Sepsis.

Iron is an essential nutrient for bacterial survival and thus higher iron levels may precipitate bacterial infections. We investigated the association between the serum iron level and prognosis in patients with sepsis by using the single-centre Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis patients with iron parameters measured on ICU admission were included and stratified according to quartiles of serum iron levels. A total of 1,891 patients diagnosed with sepsis according to the Sepsis-3 criteria were included in this study, 324 of whom were septic shock. After adjusting for confounding variables, higher iron quartile was associated with an increase in 90-day mortality in the Cox regression analysis. Moreover, a stepwise increase in the risk of 90-day mortality was observed as the quartiles of serum iron levels increased in the patients with sepsis. In conclusion, higher serum iron levels were independently associated with increased 90-day mortality in this large cohort of patients with sepsis.

The Relationship of TPOAb and TGAb with Risk of Thyroid Nodules: A Large Epidemiological Study.

Objective: The association between thyroid hormones, thyroid autoantibodies, and thyroid nodules are still not clear. The cross-sectional study, conducted in Hangzhou, China in 2010, aimed to identify the relationship of thyroid hormones and autoantibodies with thyroid nodules. Methods: Information regarding social demography was collected by a questionnaire. Thyroid hormones (triiodothyronine, thyroxin, free triiodothyronine, free thyroxin, thyrotropin), thyroid autoantibodies (thyroid peroxidase antibody, antithyroglobulin antibody), and thyroid nodules (diagnosed by ultrasonography) was measured in 1271 adults. The association of thyroid hormones and thyroid autoantibodies with thyroid nodules was evaluated using multiple logistic regression models. Results: The prevalence of thyroid nodules among males and females was 29.49% and 33.15%, respectively. The thyroid hormone level in the thyroid nodules group was significantly higher than the non-nodules group (all p values < 0.05), except reversely in TSH (thyroid stimulating hormone) (p = 0.0532) and TGAb (thyroglobulin antibody) (p = 0.0004). High levels of TPOAb (thyroid peroxidase antibody) (OR (Odds Ratio) = 1.51, 95% CI (confidence interval): 0.99-2.30) and TGAb (OR = 2.86, 95% CI: 1.49-5.51) were associated with increased risk of thyroid nodules, compared with corresponding low levels. However, following sub-analyses in two genders, the similar associations were only observed in females (TPOAb: OR = 1.63, 95% CI: 0.99-2.68; TGAb: OR = 3.13, 95% CI: 1.53-6.40). Conclusions: The present study indicated that thyroid autoantibodies were positively associated with the risk of thyroid nodules in Chinese coastal adults.

Intraoperative tranexamic acid is associated with postoperative stroke in patients undergoing cardiac surgery.

BACKGROUND: Stroke is a devastating and potentially preventable complication of cardiac surgery. Tranexamic acid (TXA) is a commonly antifibrinolytic agent in cardiac surgeries with cardiopulmonary bypass (CPB), however, there is concern that it might increase incidence of stroke after cardiac surgery. In this retrospective study, we investigated whether TXA usage could increase postoperative stroke in cardiac surgery. METHODS: A retrospective study was conducted from January 1, 2010, to December 31, 2015, in 2,016 patients undergoing cardiac surgery, 664 patients received intravenous TXA infusion and 1,352 patients did not receive any antifibrinolytic agent. Univariate and propensity-weighted multivariate regression analysis were applied for data analysis. RESULTS: Intraoperative TXA administration was associated with postoperative stroke (1.7% vs. 0.5%; adjusted OR, 4.11; 95% CI, 1.33 to 12.71; p = 0.014) and coma (adjusted OR, 2.77; 95% CI, 1.06 to 7.26; p = 0.038) in cardiac surgery. As subtype analysis was performed, TXA administration was still associated with postoperative stroke (1.7% vs. 0.3%; adjusted OR, 5.78; 95% CI, 1.34 to 27.89; p = 0.018) in patients undergoing valve surgery or multi-valve surgery only, but was not associated with postoperative stroke (1.7% vs. 1.3%; adjusted OR, 5.21; 95% CI, 0.27 to 101.17; p = 0.276) in patients undergoing CABG surgery only. However, TXA administration was not associated with postoperative mortality (adjusted OR, 1.31; 95% CI, 0.56 to 3.71; p = 0.451), seizure (adjusted OR, 1.13; 95% CI, 0.42 to 3.04; p = 0.816), continuous renal replacement therapy (adjusted OR, 1.36; 95% CI, 0.56 to 3.28; p = 0.495) and resternotomy for postoperative bleeding (adjusted OR, 1.55; 95% CI, 0.55 to 4.30; p = 0.405). No difference was found in postoperative ventilation time (adjusted B, -1.45; SE, 2.33; p = 0.535), length of intensive care unit stay (adjusted B, -0.12; SE, 0.25; p = 0.633) and length of hospital stay (adjusted B, 0.48; SE, 0.58; p = 0.408). CONCLUSIONS: Based on the 5-year experience of TXA administration in cardiac surgery with CPB, we found that postoperative stroke was associated with intraoperative TXA administration in patients undergoing cardiac surgery, especially in those undergoing valve surgeries only. This study may suggest that TXA should be administrated according to clear indications after evaluating the bleeding risk in patients undergoing cardiac surgery, especially in those with high stroke risk.

Prognostic role of survivin in renal cell carcinoma: A system review and meta-analysis.

BACKGROUND: Survivin plays an important role in cancer pathogenesis, which has been suggested to be related to poor prognosis in renal cell carcinoma (RCC). We performed a meta-analysis to quantify the prognostic value of survivin in renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: Relevant articles exploring the relationship between survivin expression and survival of RCC patients published up to 10 November 2015 were retrieved in PubMed, Web of science and Cochrane databases. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated by a random-effects model. RESULTS: A total of 1583 patients from 10 studies were included. The high expression of survivin was associated with poor Overall Survival (OS) in two studies (Pooled HRs=2.77, 95%CI: 1.46-5.26, I(2)=0.0%, P=0.329). Further, meta-analysis of seven studies showed that elevated survivin expression predicted shorter cancer-specific survival (CSS) of RCC (HR=2.85, 95% CI: 2.25-3.61, I(2)=17.6%, P=0.295). Additionally, subgroup analysis showed that survivin over-expression was associated significantly with worse CSS regardless of different source of survivin, sample size, follow-up duration, race and detection method. CONCLUSIONS: A higher survivin expression seems to represent an unfavorable and robust prognostic factor for clinical outcomes in RCC patients.

Tissue microRNA-21 expression predicted recurrence and poor survival in patients with colorectal cancer - a meta-analysis.

OBJECTIVE: MicroRNA-21 (miR-21) has been shown to play an important role in cancer prognosis. We performed a meta-analysis to evaluate the prognostic effect of miR-21 from tissues and serum on survival of the patients with colorectal cancer (CRC). METHODS: Relevant studies were identified by searching PubMed, Embase, and Cochrane Library. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of total and subgroup analyses, for overall survival (OS) and disease-free survival (DFS), were calculated to investigate the association between miR-21 expression and CRC prognosis. RESULTS: Our analysis included eleven studies (3,669 subjects). In addition, four studies explored the association between miR-21 and DFS, and ten studies focused on the prognostic value of miR-21 for OS. Our results indicated that increased miR-21 expression of tissues predicted both poor DFS and OS in patients with CRC (DFS: HR =1.59, 95% CI =1.20-2.10; OS: HR =1.53, 95% CI =1.23-1.90). Consistent results were observed among colon cancer and quantitative real-time polymerase chain reaction subgroups. CONCLUSION: Meta-analysis indicated that miR-21 predicted recurrence and poor survival in patients with CRC. miR-21 may be more suitable to predict cancer prognosis in colon cancer patients.

Exposure to 50Hz-sinusoidal electromagnetic field induces DNA damage-independent autophagy.

As electromagnetic field (EMF) is commonly encountered within our daily lives, the biological effects of EMF are of great concern. Autophagy is a key process for maintaining cellular homeostasis, and it can also reveal cellular responses to environmental stimuli. In this study, we aim to investigate the biological effects of a 50Hz-sinusoidal electromagnetic field on autophagy and we identified its mechanism of action in Chinese Hamster Lung (CHL) cells. CHL cells were exposed to a 50Hz sinusoidal EMF at 0.4mT for 30min or 24h. In this study, we found that a 0.4mT EMF resulted in: (i) an increase in LC3-II expression and increased autophagosome formation; (ii) no significant difference in the incidence of γH2AX foci between the sham and exposure groups; (iii) reorganized actin filaments and increased pseudopodial extensions without promoting cell migration; and (iv) enhanced cell apoptosis when autophagy was blocked by Bafilomycin A1. These results implied that DNA damage was not directly involved in the autophagy induced by a 0.4mT 50Hz EMF. In addition, an EMF induced autophagy balanced the cellular homeostasis to protect the cells from severe adverse biological consequences.

Effects of electromagnetic fields exposure on plasma hormonal and inflammatory pathway biomarkers in male workers of a power plant.

PURPOSE: The potential health risks of electromagnetic fields (EMFs) have currently raised considerable public concerns. The aim of this study was to evaluate the effects of EMF exposure on levels of plasma hormonal and inflammatory pathway biomarkers in male workers of an electric power plant. METHODS: Seventy-seven male workers with high occupational EMF exposure and 77 male controls with low exposure, matched by age, were selected from a cross-sectional study. Moreover, high EMF exposure group was with walkie-talkies usage and exposed to power frequency EMF at the work places for a longer duration than control group. A questionnaire was applied to obtain relevant information, including sociodemographic characteristics, lifestyle factors, and EMF exposures. Plasma levels of testosterone, estradiol, melatonin, NF-κB, heat-shock protein (HSP) 70, HSP27, and TET1 were determined by an enzyme-linked immunosorbent assay. RESULTS: EMF exposure group had statistically significantly lower levels of testosterone (ß = -0.3 nmol/L, P = 0.015), testosterone/estradiol (T/E2) ratio (ß = -15.6, P = 0.037), and NF-κB (ß = -20.8 ng/L, P = 0.045) than control group. Moreover, joint effects between occupational EMF exposure and employment duration, mobile phone fees, years of mobile phone usage, and electric fees on levels of testosterone and T/E2 ratio were observed. Nevertheless, no statistically significant associations of EMF exposures with plasma estradiol, melatonin, HSP70, HSP27, and TET1 were found. CONCLUSIONS: The findings showed that chronic exposure to EMF could decrease male plasma testosterone and T/E2 ratio, and it might possibly affect reproductive functions in males. No significant associations of EMF exposure with inflammatory pathway biomarkers were found.

Effects of electromagnetic fields on serum lipids in workers of a power plant.

This study aimed to evaluate the effects of electromagnetic fields (EMF) exposure on levels of serum lipids in workers of an electric power plant. A cross-sectional study was carried out in an electric power plant in Zhejiang province, China, from August to September 2011. All participants were divided into two groups with high occupational EMF exposure and low occupational EMF exposure. The occupational EMF exposure included radiofrequency EMF and extremely low-frequency EMF. Occupational EMF exposure was associated with an increased level of low-density lipoprotein cholesterol (LDL-c; ß = 0.17 mmol/L, P = 0.022). High EMF exposure group with longer employment duration, longer daily EMF exposure duration, and more mobile phone or electric fee per month had significantly higher levels of total cholesterol, LDL-c, or triglyceride than the corresponding reference group. However, significantly decreased level of high-density lipoprotein cholesterol was only observed in high EMF exposure group with more mobile phone fee per month. Similar results were also found in 544 participants with available data of serum lipids in 2010. The findings showed that chronic EMF exposure was associated with the change of serum lipid levels. EMF exposure might modulate the process of lipid metabolism.

Effects of electromagnetic fields from mobile phones on depression and anxiety after titanium mesh cranioplasty among patients with traumatic brain injury.

OBJECTIVE: To explore the effects of radiofrequency-electromagnetic fields (RF-EMFs) from mobile phones on depression and anxiety after titanium mesh cranioplasty among patients with traumatic brain injury (TBI). METHODS: Two hundred and twenty patients with TBI and titanium mesh cranioplasty who were hospitalized from 2008-2012 were recruited in this study. From November-December 2012, the relevant information was surveyed including socio-demographic characteristics, lifestyle variables, injury-related information, RF-EMF exposure of mobile phone, Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS). Associations of RF-EMFs exposure after titanium mesh cranioplasty with SAS and SDS were respectively estimated by multivariable linear regression models. RESULTS: The patients with long durations of mobile phone use (ß = -6.6, p = 0.002), long individual call duration (ß = -5.3, p = 0.012), more daily calls (ß = -3.6, p = 0.027), invariably answer call immediately (ß = -3.9, p = 0.022) and high comprehensive exposure level (ß = -4.8, p = 0.003) had a lower score of depression compared with those without a mobile phone. Moreover, an ipsilateral and contralateral answering phone enhanced the protective effect on depression. Individuals with a long duration of mobile phone use had a lower score of anxiety (ß = -4.2, p = 0.008), while those with a bilateral answering phone had higher anxiety (ß = 3.9, p = 0.012) in comparison to those without a mobile phone. CONCLUSION: RF-EMFs after cranioplasty were significantly associated with the lower risk of depression and anxiety status among patients with TBI. Chronic and frequent RF-EMFs exposure may improve psychiatric disorders among patients with TBI.

Relationship of anthropometric measurements to thyroid nodules in a Chinese population.

OBJECTIVE: Previous studies have found that overweight and obesity are related to numerous diseases, including thyroid cancer and thyroid volume. This study evaluates the relationship between body size and the presence of thyroid nodules in a Chinese population. METHODS: A total of 6793 adults and 2410 children who underwent thyroid ultrasonography were recruited in this cross-sectional study in Hangzhou, Zhejiang Province, China, from March to October, 2010. Sociodemographic characteristics and potential risk factors of thyroid nodules were collected by questionnaire. Height and weight were measured using standard protocols. Associations of height, weight, body mass index (BMI) and body surface area (BSA) with the presence of thyroid nodules were evaluated using multiple logistic regression models. RESULTS: After adjustment for potential risk factors, an increased risk of thyroid nodule incidence was associated with height (OR 1.15, 95% CI 1.02 to 1.30), weight (OR 1.40, 95% CI 1.24 to 1.58), BMI (OR 1.26, 95% CI 1.11 to 1.42) and BSA (OR 1.43, 95% CI 1.27 to 1.62) in all adults, but most obviously in women. In children, similar associations were observed between risk of thyroid nodule incidence and weight, BMI and BSA, but not height. BSA was the measurement most significantly associated with thyroid nodules in both adults and children. CONCLUSIONS: This study identified that the presence of thyroid nodules was positively associated with weight, height, BMI and BSA in both women and girls. It suggests that tall, obese individuals have increased susceptibility to thyroid nodules. TRIAL REGISTRATION NUMBER: NCT01838629.