Diabetes mellitus and the risk of gastrointestinal cancer in women compared with men: a meta-analysis of cohort studies.

BACKGROUND: The increasing epidemic proportions of diabetes mellitus (DM) are a major cause of premature illness and death. However, whether DM confers the same excess risk of gastrointestinal cancer for women as it does for men remains controversial. The purpose of this study was to estimate the relation between DM and gastrointestinal cancer in women compared with men after accounting for other major risk factors based on cohort studies. METHODS: We performed a meta-analysis of cohort studies published through May 2017 from PubMed, Embase, and the Cochrane Library. Studies with cohort designs were stratified by sex and reported the relation between DM and esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), hepatocellular carcinoma (HCC), or pancreatic cancer (PC) risk. The ratio of relative risk (RRR) between men and women was employed to measure the sex differences in the relation between DM and gastrointestinal cancer with a random effects model with inverse variance weighting. RESULTS: We included 38 cohort studies reporting data on 18,060,698 individuals. The pooled RRR indicated DM women was associated with an increased risk of GC (RRR: 1.14; 95%CI: 1.06-1.22; p < 0.001), while the risk of HCC was lower (RRR: 0.88; 95%CI: 0.79-0.99; p = 0.031) as compared with DM men. Further, there was no evidence of sex differences in the RRR between participants who had DM compared with those without DM for EC (p = 0.068), CRC (p = 0.618), and PC (p = 0.976). In addition, the pooled RRR showed a statistically significant association between DM and the risk of CC in women compared with men (RRR: 0.93; 95%CI: 0.86-1.00; p = 0.050), and there was no evidence of sex differences for RC among participants with DM compared to those without DM (p = 0.648). Finally, the sex differences of the comparison between DM and non-DM for gastrointestinal cancer risk at different sites were variable after stratification for different effect estimates. CONCLUSIONS: The findings of this study suggested female-to-male RRR of DM was increased for GC, while reduced for HCC and CC. However, there were no sex differences for the relation between DM and the risk of EC, CRC, PC, and RC.

Influence of Iron Supplementation on DMT1 (IRE)-induced Transport of Lead by Brain Barrier Systems in vivo.

OBJECTIVE: To investigate the potential involvement of DMT1 (IRE) protein in the brain vascular system in vivo during Pb exposure. METHODS: Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the mRNA. RESULTS: Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1 (IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1 (IRE) mRNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1 (IRE). CONCLUSION: These results suggest that Pb is transported into the brain through DMT1 (IRE), and the ERK MAPK pathway is involved in DMT1 (IRE)-mediated transport regulation in brain vascular system in vivo.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma.

OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

Impact of Sleep Duration on Depression and Anxiety After Acute Ischemic Stroke.

Background: Abnormal sleep duration predicts depression and anxiety. We seek to evaluate the impact of sleep duration before stroke on the occurrence of depression and anxiety at 3 months after acute ischemic stroke (AIS). Methods: Nationally representative samples from the Third China National Stroke Registry were used to examine cognition and sleep impairment after AIS (CNSR-III-ICONS). Based on baseline sleep duration before onset of stroke as measured by using the Pittsburgh Sleep Quality Index (PSQI), 1,446 patients were divided into four groups: >7, 6-7, 5-6, and <5 h of sleep. Patients were followed up with the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) for 3 months. Poststroke anxiety (PSA) was defined as GAD-7 of ≥5 and poststroke depression (PSD) as PHQ-9 of ≥5. The association of sleep duration with PSA and PSD was evaluated using multivariable logistic regression. Results: The incidences of PSA and PSD were 11.2 and 17.6% at 3 months, respectively. Compared to a sleep duration of >7 h, 5-6 h, and <5 h of sleep were identified as risk factors of PSA [odds ratio (OR), 1.95; 95% confidence interval (CI), 1.24-3.07; P < 0.01 and OR, 3.41; 95% CI, 1.94-6.04; P < 0.01) and PSD (OR, 1.47; 95% CI, 1.00-2.17; P = 0.04 and OR, 3.05; 95% CI, 1.85-5.02; P < 0.01), while 6-7 h of sleep was associated with neither PSA (OR, 1.09; 95% CI, 0.71-1.67; P = 0.68) nor PSD (OR, 0.92; 95% CI, 0.64-1.30; P = 0.64). In interaction analysis, the impact of sleep duration on PSA and PSD was not affected by gender (P = 0.68 and P = 0.29, respectively). Conclusions: Sleep duration of shorter than 6 h was predictive of anxiety and depression after ischemic stroke.

[Impact of electroacupuncture on liver lipid metabolism and hepatic Sirt1 and PPARγ expression in abdominal obese rats].

OBJECTIVE: To observe the impact of electroacupuncture (EA) on liver lipid metabolism and expression of hepatic sirtuin 1(Sirt1) and peroxisome proliferator activated receptor γ(PPARγ) of abdominal obese rats induced by high-fat diet. METHODS: Eighteen male SD rats were divided into blank control, model and EA groups (n＝6 per group). The abdominal obesity model was established by feeding the rats with high-fat diet for 12 weeks. EA (2 Hz/15 Hz, 1.5 mA) was applied to bilateral "Daimai"(GB26) for 20 min every time, once every other day for 8 weeks. Rats of the model group were also restrained for 20 min. The body mass and abdominal circumference were measured every week, and the contents of serum cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), aspartate aminotransferase (AST) were detected by using an automated biochemical analyzer. Histopathological changes of the liver tissues were observed under microscope after oil red "O" staining. The expression of hepatic Sirt1 and PPARγ mRNAs and proteins were detected using quantitative real time PCR and Western blot, separately. RESULTS: After modeling, the body weight and abdominal circumference, and serum TC, TG, ALT and AST contents, and expression of hepatic PPARγ mRNA and protein were significantly increased (P<0.001, P<0.01, P<0.05), and the expression levels of hepatic Sirt1 mRNA and protein obviously down-regulated (P<0.05, P<0.01) in the model group. Following EA intervention, the increased body weight and abdominal circumference, and serum TC, TG, ALT and AST contents, and hepatic PPARγ mRNA and protein expression were remarkably suppressed (P<0.05, P<0.01), and the decreased hepatic Sirt1 mRNA and protein were remarkably up-regulated (P<0.001，P<0.05). The lipid droplets in hepatocytes were reduced in the EA group relevant to the model group. CONCLUSION: EA intervention can significantly improve the liver lipid metabolism of abdominal obese rats, which is possibly related with its effect in up-regulating the expression of hepatic Sirt1 mRNA and protein, and in down-regulating the expression of hepatic PPARγ mRNA and protein.

[Acupuncture improves hepatic lipid metabolism by suppressing oxidative stress in obese nonalcoholic fatty liver disease rats].

OBJECTIVE: To investigate the effect of acupuncture of "Daimai"(GB26) on abdominal fat accumulation, lipid metabolism and hepatic oxidative stress in abdominal obese non-alcoholic fatty liver disease (NAFLD) rats. METHODS: male SD rats were divided into 3 groups: normal diet (normal, n＝8), high fat diet control (model) and acupuncture (n＝8/group in the latter 2 groups). The abdominal obese NAFLD model was established by feeding the rats with high fat diet for 12 weeks. EA (2 Hz/15 Hz, 1.5 mA) was applied to bilateral GB26 for 20 min, once every other day for 8 weeks. Rats of the model group were also restrained for 20 min as those in the EA group. The body mass and abdominal circumference were measured weekly, the isolated adipose tissues around the bilateral kidney and epididymis and the fresh liver were weighed. The contents of serum cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), glutamic oxaloacetic aminotransferase (AST) were detected by using an automatic biochemical analyzer. The abdominal visceral fat distribution was acquired by CT scanning. The oxidative stress indexes of the homogenated liver tissues, such as malondialdehyde (MDA) was assayed using sodium thiobarbital (TBA) method, and the activity of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) were assayed by using hydroxylamine method and colorimetric method respectively. The histopathological changes of the liver were observed after staining with hematoxylin-eosin (HE). RESULTS: Following modeling, the body mass and waist circumference, visceral fat weight of bilateral kidneys and testis (visceral fat weight), liver weight, serum ALT, AST, TG and TC and liver MDA contents, were significantly higher in the model group (P<0.001，P<0.05), while hepatic T-SOD and GSH-PX activity was considerably lower in the model group than those in the normal group (P<0.001). After acupuncture intervention, the levels of all the above-mentioned indexes (modeling induced both increase and decrease) were reversed relevant to the model group (P<0.05, P<0.01). The results of CT scanning showed that the fat accumulation area in the abdomen was 8.67 cm2, 18.51 cm2 and 13.75 cm2 in the normal, model and acupuncture groups, respectively, presenting a decrease after acupuncture. H．E. staining displayed that the degree of hepatic steatosis (including vague hepatic lobule boundary, disordered arrangement of hepatic cord, hepatocellular swelling, diffuse fatty degeneration, unequal-sized lipid droplets in the hepatocytes, nucleus excursion and dissolution after modeling) was improved after acupuncture. CONCLUSION: Acupuncture can reduce body weight and abdominal fat accumulation in abdominal obese NAFLD rats, which may be related to its effects in inhibiting oxidative stress (lowering MDA level and increasing the activity of T-SOD and GSH-PX) and improving hepatic lipid metabolism.

DPP-4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high-glucose conditions, potentially through the SIRT1/HIF-1/VEGF pathway.

BACKGROUND: Vascular disease in diabetes, for example, stroke, presents a significant public health burden. Recently, the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin has been found to counteract stroke among diabetic patients, showing great promise in drug repurposing and indication expansion. However, the molecular basis of this protection mechanism remains unknown. METHODS: The expression and localization of DPP-4 in rat brain microvascular endothelial cells (rBMVECs) were assessed with immunofluorescent staining and Western blotting. The effects of DPP-4 inhibitors on cell proliferation and migration of rBMVECs were determined using MTT and transwell assays, separately. The influence of DPP-4 inhibition on the expression of molecular markers (eg, VEGF, eNOS, HIF-1α. SIRT1) was examined at both mRNA and protein levels with qRT-PCR and Western blotting, individually. RESULTS: DPP-4 inhibitors (40 nmol/L linagliptin, 30 µmol/L berberine) offer protection from hypoxia/high glucose induced impairments in the proliferation and migration of rBMVECs. Treatment with DPP-4 inhibitors counteracted the attenuating effects of hypoxic/high-glucose conditions on the expression of VEGF, eNOS, HIF-1α, and SIRT1, which can be completely eliminated by the inhibition of SIRT1 with 1 mmol/L nicotinamide. CONCLUSIONS: The protection of rBMVECs from hypoxia/high-glucose induced impairment by DPP-4 inhibitors may be mediated by the SIRT1/HIF-1α/VEGF pathway.

Short-term Preoperative Octreotide for Thyrotropin-secreting Pituitary Adenoma.

BACKGROUND: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin (SST) analogs work by interacting with somatostatin receptors (SSTRs). This study aimed to evaluate short-term preoperative octreotide (OCT) use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue. METHODS: We reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment. RESULTS: OCT treatment (median time: 7.9 days, range: 3-16 days; median total dose: 1.8 mg, range: 0.9-4.2 mg) led to significant decrease in all patients' thyroid hormone levels (FT3 [nmol/L]: 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]: 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [µU/ml]: 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]). All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTR5, but 3/8 that expressed low SSTR5 presented a significantly higher TSH suppression rate (P = 0.036). Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens. CONCLUSIONS: OCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.

Effects of intensive glucose lowering in treatment of type 2 diabetes mellitus on cardiovascular outcomes: A meta-analysis of data from 58,160 patients in 13 randomized controlled trials.

BACKGROUND: Previous trials indicated that intensive glucose lowering in treatment of patients with type 2 diabetes mellitus (T2DM) was associated with a higher incidence of mortality. We therefore conducted a meta-analysis to evaluate the benefits and harms of intensive glucose lowering therapy in treatment of T2DM patients on major cardiovascular outcomes. METHODS: Randomized controlled trials (RCTs) were obtained from searches of PubMed, EmBase, and the Cochrane Library electronic databases until Feb. 2016. Relative risk (RR) was used to measure the treatment effect by random-effect model. Meta-regression, sensitivity analyses, subgroup analyses, and publication biases were also conducted. RESULTS: Thirteen RCTs were included with 58,160 T2DM patients and reported 5719 major cardiovascular events (MACEs), 6569 deaths, 2057 cardiac death cases, 3201 myocardial infarction (MI) cases, 1835 stroke cases, and 1778 congestive heart failure cases. Intensive glucose lowering therapy significantly reduced risk of MACEs (RR: 0.92; 95%CI: 0.85-1.00; P=0.042), and MI (RR: 0.90; 95%CI: 0.82-0.98; P=0.020) compared with conventional glucose control therapy. Furthermore, intensive glucose lowering therapy has no significant effect on the incidence of total mortality (RR: 0.98; 95%CI: 0.91-1.07; P=0.693), cardiac death (RR: 1.00; 95%CI: 0.87-1.04; P=0.999), stroke (RR: 0.94; 95%CI: 0.84-1.06; P=0.333), and congestive heart failure (RR: 1.19; 95%CI: 0.96-1.48; P=0.108). CONCLUSION: T2DM patients who received intensive glucose lowering therapy are associated with a reduced risk of MACEs and MI, whereas it has no significant effect on the risk of total mortality, cardiac death, stroke, and congestive heart failure. These effects might differ when stratified by baseline characteristics in T2DM patients.

Treatment of Middle Cranial Fossa Arachnoid Cysts: A Systematic Review and Meta-Analysis.

OBJECTIVE: To review the literature and analyze the efficacy and safety of 3 surgical methods (neuroendoscopic fenestration, microsurgical fenestration, and cystoperitoneal shunting) for middle cranial fossa arachnoid cysts (MCFACs). METHODS: We searched MEDLINE, PubMed, and Cochrane Central electronic databases and collected studies of patients with MCFACs treated with 1 of 3 surgical methods. Eligible studies reported the rate of clinical symptoms improvement (RCSI), rate of cyst reduction (RCR), rate of total complications (RTC), rate of short-term complications (RSTC), rate of long-term complications (RLTC), and other parameters. RESULTS: Eighteen studies met the criteria. MCFACs were divided into 3 groups on the basis of surgical method: RCSI in group I (237 patients, neuroendoscopic fenestration) was 90% (95% confidence interval [CI]: 83%-95%); RCR: 76% (95% CI: 67%-84%); RTC: 28% (95% CI: 22%-34%); RSTC: 23% (95% CI: 17%-30%); and RLTC: 6% (95% CI: 3%-11%). RCSI in group II (144 patients, microsurgical fenestration) was 87% (95% CI: 75%-96%); RCR: 87% (95% CI: 70%-97%); RTC: 49% (95% CI: 30%-68%); RSTC: 44% (95% CI: 21%-68%); RLTC: 3% (95% CI: 0%-12%). RCSI in group III (93 patients, cystoperitoneal shunting) was 93% (95% CI: 66%-99%); RCR: 93% (95% CI: 66%-99%); RTC: 20% (95% CI: 5%-42%); RSTC: 10% (95% CI: 0%-31%); RLTC: 15% (95% CI: 9%-23%). RLTC differed significantly between the 3 groups (P = 0.005); RTC and RSTC between group I and group II (P = 0.002). CONCLUSIONS: All 3 surgical methods are effective for MCFACs, but considering safety, neuroendoscopic fenestration may be the best initial procedure.