Gastroesophageal reflux disease and non-alcoholic fatty liver disease: a two-sample Mendelian randomization combined with meta-analysis.

Accumulating evidence from observational studies have suggested an association between gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, due to that such studies are prone to biases, we imported Mendelian randomization (MR) to explore whether the causal association between two diseases exsit. Hence, we aimed to analysis the potential association with MR. The single nucleotide polymorphisms (SNPs) of GERD were retrieved from the genome-wide association study dataset as the exposure. The SNPs of NAFLD were taken from the FinnGen dataset as the outcome. The relationship was analyzed with the assistance of inverse variance weighted, MR-Egger, and weighted median. We also uitilized the MR-Egger intercept, Cochran's Q test, leave-one-out analysis, MR-PRESSO, and Steiger directionality test to evaluate the robustness of the causal association. The meta-analysis were also implemented to give an overall evaluation. Finally, our analysis showed a causal relationship between GERD and NAFLD with aid of MR and meta-analysis (OR 1.71 95% CI 1.40-2.09; P < 0.0001).

Small cell lung cancer with panhypopituitarism due to ectopic adrenocorticotropic hormone syndrome: A case report.

BACKGROUND: Small cell lung cancer (SCLC) accounts for 15% of lung cancers, and it commonly expresses peptide and protein factors that are active as hormones. These secreting factors manifest as paraneoplastic disorders, such as ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). The clinical features are abnormalities in carbohydrate metabolism, hypokalemia, peripheral edema, proximal myopathy, hypertension, hyperpigmentation, and severe systemic infection. However, it is uncommon that EAS has an influence on hypothalamus-pituitary function. CASE SUMMARY: A 62-year-old man presented with complaints of haemoptysis, polyuria, polydipsia, increased appetite, weight loss, and pigmentation. Following a series of laboratory and imaging examinations, he was diagnosed with SCLC, EAS, hypogonadism, hypothyroidism, and central diabetes insipidus. After three rounds of chemotherapy, levels of ACTH, cortisol, thyroid hormone, gonadal hormone, and urine volume had returned to normal levels. In addition, the pulmonary tumor was reduced in size. CONCLUSION: We report a rare case of SCLC complicated with panhypopituitarism due to EAS. We hypothesize that EAS induced high levels of serum glucocorticoid and negative feedback for the synthesis and secretion of antidiuretic hormone from the paraventricular nucleus, and trophic hormones from the anterior pituitary. Therefore, patients who present with symptoms of hypopituitarism, or even panhypopituitarism, with SCLC should be evaluated for EAS.

Xuezhikang () reduced renal cell apoptosis in streptozocin-induced diabetic rats through regulation of Bcl-2 family.

OBJECTIVE: To investigate the effect of Xuezhikang (, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism. METHODS: Sixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK (1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion (UAE) measurement. Periodic acid-Schiff (PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C (Cyt C) and caspase-9 concentration were detected by Western blot. RESULTS: Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months (P<0.05 or P<0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent. CONCLUSIONS: Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.

Central obesity and metabolic risk factors in middle-aged Chinese.

OBJECTIVE: Central obesity is considered to be a central component of metabolic syndrome. Waist circumference (WC) has been widely used as a simple indicator of central obesity. This study is aimed to evaluate the sensitivity of WC cut-off values for predicting metabolic risk factors in middle-aged Chinese. METHODS: The study involved 923 subjects aged 40-65 years. The metabolic risk factors were defined according to the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. WC cut-off 85-90 cm and ⋝90 cm were used as cut-off values of central pre-obesity and central obesity in males, respectively, while WC 80-85 cm and ⋝85 cm were used as cut-off values of central pre-obesity and central obesity in females. RESULTS: First, WC values corresponding to body mass index (BMI) 24 kg/m2 and visceral fat area (VFA) 80 cm2 were 88.55 cm and 88.51 cm in males, and 81.46 cm and 82.51 cm in females respectively. Second, receiver operating characteristic curves showed that the optimal WC cut-off of value was 88.75 cm in males, higher than that in females (81.75 cm). Third, the subjects with higher WC values were more likely to have accumulating metabolic risk factors. The prevalence of metabolic risk factors increased linearly and significantly in relation to WC levels. CONCLUSION: WC cut-off values of central pre-/central obesity are optimal to predict multiple metabolic risk factors.

[A comparison of clinical effectiveness of different neuropathy scoring systems in screening asymptomatic diabetic peripheral neuropathy].

OBJECTIVE: To evaluate the clinical effectiveness in screening asymptomatic diabetic peripheral neuropathy (ADPN) by the Michigan neuropathy screening instrument (MNSI) and the Toronto clinical scoring system (TCSS). METHODS: MNSI, TCSS and neural electrophysiological test (NET) were conducted in 232 neurologically asymptomatic type 2 diabetes patients. By using the results of NET as the golden criteria for diagnosis of ADPN, we evaluated the effectiveness of the two different scoring system by the receiver operator characteristic curve. The sensitivity, specificity, positive and negative predictive values, accuracy, Youden indexes and kappa values on different diagnostic cut-off points of MNSI and TCSS were analyzed. The correlation between the two different scoring system and the risk factors of diabetic peripheral neuropathy (DPN) were also analyzed. RESULTS: The area under the ROC curve of MNSI and TCSS were 0.792, 0.704, respectively. The sensitivity, specificity, accuracy, Youden indexes and kappa values of MNSI over 2 and TCSS over 2 were 66.2%vs 73.3%, 90.4% vs 63.7%, 78.3% vs 68.5%, 0.566 vs 0.370, and 0.588 vs 0.345, respectively. MNSI was better than TCSS in the effectiveness of diagnosing ADPN and consistence with the result of NET. Moreover, MNSI was associated with the most related risk factors of DPN including age, glycosylated hemoglobin (HbA1c), HbA1c × disease duration, islet function and HDL-C. CONCLUSIONS: MNSI could be used as a relatively simple and reliable method for clinical and epidemiological screening and assessment of ADPN.

Recurrent Hashimoto's encephalopathy, showing spontaneous remission: a case report.

Hashimoto's encephalopathy (HE) is a rare condition associated with Hashimoto's thyroiditis (HT). It is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, non-specific radiological examinations or electroencephalogram abnormalities, and responsiveness to corticosteroid treatment. We describe the case of a man with HE who showed decreased mentality, cognitive impairment, dysarthria, and gait disturbance. The initial attack was improved rapidly by corticosteroid treatment. When the symptoms recurred in 7 months, the patient achieved spontaneous remission without corticosteroid treatment. The recognition of the condition was essential for the prognosis and treatment of this rare disease.

[Clinical features and risk factors of renal damage in elderly and non-elderly patients with type 2 diabetes mellitus].

OBJECTIVE: To investigate the clinical features and risk factors of renal damage in the elderly and non-elderly patients with type 2 diabetes mellitus. METHODS: The data were collected from a survey of 10-year retrospective study of chronic complications of hospitalized type 2 diabetics organized by Chinese Diabetes Society. A total of 1351 patients of type 2 diabetes were selected and divided into an elderly group (>or=60 year) and a non-elderly group (<60 year). The patients were also divided into three groups according to urinary albumin excretion rate (AER): normoalbuminuria group (AER<30 mg/24 h), microalbuminuria group (30or=300 mg/24 h). eGFR was estimated by the equation from the MDRD study. Clinical and laboratory parameters of all patients were analyzed. RESULTS: (1) The proportions of renal insufficiency in both normoalbuminuria and microalbuminuria groups of type 2 diabetes in the elderly patients were significantly higher than those in the non-elderly patients (26.7% vs 15.8%, P<0.01; 30.5% vs 21.3%, P<0.05 respectively); (2) in type 2 diabetic patients with renal insufficiency and normoalbuminuria, the diabetes duration (7.7 vs 3.8 years), systolic blood pressure [(146+/-24) mm Hg vs (134+/-23) mm Hg], diastolic blood pressure [(84+/-13) mm Hg vs (80+/-11) mm Hg], proportion of hypertension (37.8% vs 21.1%), diabetic retinopathy (34.1% vs 23.9%), cardiovascular diseases (31.6% vs 11.3%) and cerebrovascular disease (24.4% vs 9.9%) were significantly higher in the elderly group than in the non-elderly group (P<0.05 or 0.01); (3) multiple logistic regression analysis revealed that the duration of diabetes (OR=1.046, P=0.013) and systolic blood pressure (OR=1.014, P=0.002) were independently associated with renal insufficiency in the elderly type 2 diabetic patients with normoalbuminuria, whereas systolic blood pressure (OR=1.042, P=0.000) and 2-hour postprandial blood glucose (OR=1.048, P=0.002) were independent risk factors for renal insufficiency of non-elderly patients. CONCLUSION: The elderly type 2 diabetic patients are likely to suffer renal insufficiency initially from a lower glomerular filtration rate than the non-elderly patients. Systolic blood pressure is the main risk factor in both elderly and non-elderly type 2 diabetes with normoalbuminuria and a decreased renal function. Controlling blood pressure may delay the decline of renal function.

[Renal insufficiency and its associated factors in type 2 diabetic patients with normoalbuminuria.].

OBJECTIVE: To investigate the prevalence of renal insufficiency and its associated factors in type 2 diabetes mellitus with normoalbuminuria using estimated glomerular filtration rate (eGFR). METHODS: We retrospectively analyzed 10-year data of chronic complications in type 2 diabetics in-patient from the Chinese Diabetes Society. eGFR was estimated using the equation from Modification of Diet in Renal Disease (MDRD) study. The clinical characteristics as well as associated factors for low eGFR were analyzed among the normoalbuminuric type 2 diabetic patients. RESULTS: A total of 1351 type 2 diabetic patients were included, 755 patients with normoalbuminuria, 466 patients with microalbuminuria and 130 patients with macroalbuminuria respectively. Among the patients, 310 (22.9%) had low eGFR (GFR < 60 mlxmin(-1) x 1.73 m(-2)), 19.7% (149/755) in the patients with normoalbuminuria, 21.9% (102/466) in microalbuminuria and 45.4% (59/130) in macroalbuminuria. Patients with normoalbuminuria and low eGFR suffered more chronic complications than those with normoalbuminuria and normal eGFR, mainly retinopathy, cerebrovascular diseases and sensory neuropathy. Stepwise logistic regression analysis revealed that age (OR = 1.042, P < 0.001), diabetic duration (OR = 1.038, P = 0.045), systolic blood pressure (OR = 1.017, P < 0.001) were independently associated with renal impairment among the patients with normoalbuminuria. Body mass index (OR = 0.868, P < 0.001) and HbA1c (OR = 0.898, P = 0.021) were also related with renal insufficiency. CONCLUSION: A considerable proportion in type 2 diabetic patients without albuminuria may exist renal impairment, and eGFR estimation could benefit the evaluation of renal function in such patients.

[Correlation between the amplitude of glucose excursion and plasma 8-iso prostaglandin F2alpha level in subjects with different types of glucose regulation].

OBJECTIVE: To investigate the effect of glucose excursion on oxidative stress that is expressed by plasma 8-iso prostaglandin F2alpha (8-iso) level. METHODS: Continuous glucose monitor system (CGMS) was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), mean 1 h preprandial glucose value (1 h-prePG) and 3 h post-prandial glucose value (3 h PPG) over 24 h period, area under the ROC curve when the blood glucose within 24 h > 5.6 mmol/L (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE) on 33 individuals with normal glucose regulation (NGR), 25 subjects with impaired glucose regulation (IGR), and 25 patients with newly diagnosed type 2 diabetes mellitus (T2DM) for 3 days. Plasma 8-iso level was determined by EIA. RESULTS: The plasma 8-iso level of the T2DM patients was 230 ng/L, significantly higher than that of the subjects with IGR (199 ng/L, P < 0.05) and that of the NGR subjects (156 ng/L, P < 0.01). Patients with T2DM also had higher levels of glycated hemoglobin (HbA1c), MBG, SDBG, 1 h pre-PG and 3 h PPG, MAGE, and MODD than those of the NGR and IGR subjects (P < 0.05 or 0.01). The plasma 8-iso level and parameters of glucose excursion of the IGR subjects were all significantly higher than those of the NGR individuals (P < 0.05 or 0.01). Plasma 8-iso level was positively correlated with MAGE, MBG, SDBG, 1 h pre-PG, 3 h PPG, MODD, and HbA1c in all groups. Further analysis showed that the relationship between plasma 8-iso level and MAGE remained significant after adjustment for the other parameters of glucose excursion in multiple linear regression analysis (multiple R(2) = 0.55 for the model including MAGE). Standardized regression coefficients were 0.694 (P = 0.000) for MAGE. CONCLUSION: Glucose excursion exhibits a stronger triggering effect on oxidative stress than chronic sustained hyperglycemia in the subjects with IGR and T2DM.

Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats.

BACKGROUND: The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type IV (C-IV) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy. METHODS: In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone [20 mg.kg(-1).d(-1)] in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-IV were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques. RESULTS: Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P < 0.05, vs control). By contrast, MMP-2 expression in the interstitium increased, but not significantly (P > 0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P > 0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-IV in the glomeruli and the interstitium (P < 0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-IV accumulation. CONCLUSIONS: These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-IV degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-IV degradation, has curative effects on diabetic nephropathy.

[TGF-beta1mRNA levels in renal cortex and peripheral blood mononuclear cells of diabetic rats].

OBJECTIVE: To investigate the effect of hyperglycemia and pioglitazone on TGF-beta(1) gene expression in peripheral blood mononuclear cells (PBMC) and renal cortex, and the correlation of TGF-beta(1)mRNA levels between PBMC and renal cortex in STZ induced diabetic rats. METHODS: Fifty-four Sprague-Dawley rats were randomly divided into three groups: 18 normal control rats (group C), 18 diabetic rats (group D) and 18 diabetic rats treated with pioglitazone (20 mg x kg(-1)x d(-1), group DP). Six rats from each group were sacrificed at 2, 4, 8 weeks. TGF-beta(1)mRNA levels of PBMC and renal cortex were examined by RT-PCR+Slit hybridization analysis. RESULT: TGF-beta(1)mRNA level of renal cortex in group D was significantly higher than that in group C at each time point (P<0. 05); TGF-beta(1)mRNA level of PMBC in group D was slightly higher than that of group C at 4 weeks, and significantly higher at 8 weeks (P=0.01). There was positive correlation of TGF -beta(1)mRNA level between PBMC and renal cortex before (r=0.83, P=0.02) and after pioglitazone treatment at 8 weeks (r=0.82, P=0.03). CONCLUSION: TGF-beta(1)mRNA level of PBMC may reflect the change of TGF-beta(1) gene expression of renal cortex in diabetic rats.