BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Type 2 diabetes (T2D) is often accompanied with an induction of retinaldehyde dehydrogenase 1 (RALDH1 or ALDH1A1) expression and a consequent decrease in hepatic retinaldehyde (Rald) levels. However, the role of hepatic Rald deficiency in T2D progression remains unclear. In this study, we demonstrated that reversing T2D-mediated hepatic Rald deficiency by Rald or citral treatments, or liver-specific Raldh1 silencing substantially lowered fasting glycemia levels, inhibited hepatic glucogenesis, and downregulated phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) expression in diabetic db/db mice. Fasting glycemia and Pck1/G6pc mRNA expression levels were strongly negatively correlated with hepatic Rald levels, indicating the involvement of hepatic Rald depletion in T2D deterioration. A similar result that liver-specific Raldh1 silencing improved glucose metabolism was also observed in high-fat diet-fed mice. In primary human hepatocytes and oleic acid-treated HepG2 cells, Rald or Rald + RALDH1 silencing resulted in decreased glucose production and downregulated PCK1/G6PC mRNA and protein expression. Mechanistically, Rald downregulated direct repeat 1-mediated PCK1 and G6PC expression by antagonizing retinoid X receptor α, as confirmed by luciferase reporter assays and molecular docking. These results highlight the link between hepatic Rald deficiency, glucose dyshomeostasis, and the progression of T2D, whilst also suggesting RALDH1 as a potential therapeutic target for T2D.

BACKGROUND: The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS: A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS: The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.
Humans ; Cohort Studies ; Longitudinal Studies ; Diabetes Mellitus, Type 2/diagnosis* ; Maillard Reaction ; Glycated Hemoglobin ; Cardiovascular Diseases

Objective:To understand the current situation of smartphone addiction and mental health of medical freshmen, and conduct research on the relationship between smartphone addiction and mental health, so as to provide evidence for the prevention and intervention of smartphone addiction among medical freshmen.Methods:A stratified random sampling method was used to select 279 freshmen in the medical profession of Binzhou Medical University as the research objects, and the revised smartphone addiction scale (SAS-C) and mental health symptom self-rating checklist scale (SCL-90) were selected for testing. SPSS 19.0 was used for t test. Results:A percentage of 29.71 medical freshmen had smartphone addiction problems, which was generally above average. The SCL-90 total scores and the scores of somatization, interpersonal sensitivity, depression, anxiety, hostility, psychosis and other factors in the smartphone addiction group were significantly higher than those in non-smartphone addiction group. The total score of smartphone addiction in medical professional freshmen was significantly correlated with the total score of SCL-90. In addition to the interference factors of daily life, other factors had positive correlation with various factors of SCL-90. Interpersonal sensitivity and obsessive-compulsive symptoms had a significant predictive effect on smartphone addiction (β=0.24, 0.26, P < 0.01), which were important variables affecting mobile phone addiction of medical freshmen. Conclusion:Many medical freshmen have the problem of smartphone addiction, which may cause a series of psychological problems, especially obsessive-compulsive symptoms, interpersonal sensitivity, anxiety and psychosis.

Objective: To explore the effect of high mobility group box-1 protein (HMGB1) on the balance of Th17/Treg in patients with immune thrombocytopenia (ITP). Methods: A total of 30 patients who were first diagnosed as ITP in the Fifth People's Hospital of Datong from July 2017 to April 2018 were selected as the case group, and another 30 healthy volunteers in the corresponding period were taken as the control group. The proportion of Th17 and Treg cells was detected by using flow cytometry, and the concentration of HMGB1, interleukin (IL)-17 and transforming growth factor β (TGF-β) in plasma was tested by using enzyme-linked immunosorbent assay (ELISA). Isolated peripheral blood mononuclear cells (PBMC) were cultured in vitro. After the treatment with recombinant human HMGB1 (rhHMGB1), real-time polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression changes in Treg cell transcription factor intracellular forkhead helix transcription factor 3 (Foxp3) and Th17 cell transcription factor retinoid related orphan receptor γt (RORγt). The differences of indicators in Treg cell transcription factor peripheral blood between the case group and the control group were compared, and the balance correlation between HMGB1 and Th17/Treg was analyzed. Results: Compared with the healthy control group, the proportion of Th17 cells and the expression level of HMGB1 and IL-17 in peripheral blood of ITP patients were increased (all P < 0.01), while the proportion of Treg cells and the level of TGF-β were decreased (all P < 0.01). The proportion of Th17 cells and the expression level of IL-17 and HMGB1 in peripheral blood of ITP patients were positively correlated with the concentration of HMGB1 (all P < 0.01); the proportion of Treg cells and the level of TGF-β were negatively correlated with the expression level of HMGB1 (all P < 0.01). In vitro experiments, the expression of intracellular RORγt mRNA was increased compared with the negative control group (1.50±0.24 vs. 0.93±0.22, t = 9.612, P < 0.01), and the expression of Foxp3 mRNA was decreased compared with the negative control group after the stimulation of PBMC by rhHMGB1 (0.72±0.19 vs. 1.08±0.18, t = 7.387, P < 0.01). Conclusion The high level of HMGB1 in the peripheral blood of ITP patients induces Th17/Treg imbalance and aggravates inflammatory reactions, which may be an important cause of ITP.

Objective:To analyze the constitution and clinical characteristics of patients with thyroid diseases in Lanzhou, and to provide experience and basis for clinical treatment and prevention of thyroid diseases.Methods:The data of inpatients with thyroid diseases of Anning Branch of General Hospital of Lanzhou Military Region from October 2008 to October 2018 were collected, and the differences of age, gender, occupation, thyroid disease classification and composition, and thyroid hormone levels were analyzed.Results:A total of 375 inpatients data with thyroid diseases were collected, including 114 males and 261 females, accounting for 30.4% and 69.6%, respectively. Thyroid nodules, hypothyroidism, hyperthyroidism, goiter, thyroiditis, thyroid adenoma and thyroid cancer accounted for 12.3% (46/375), 22.9% (86/375), 10.4% (39/375), 7.5% (28/375), 5.9% (22/375), 40.0% (150/375) and 1.1% (4/375), respectively. There were significant differences in hypothyroidism and thyroid adenoma between different genders ( P < 0.05). There were significant differences in hypothyroidism, hyperthyroidism and thyroid adenoma between different age groups( P < 0.05). There were significant differences in hypothyroidism and thyroid adenoma between different occupations ( P < 0.05). The diagnostic coincidence rates of thyroid stimulating hormone (TSH), free triiodothyroine (FT 3) and free thyroine (FT 4) of inpatients with hyperthyroidism were 43.6% (17/39), 79.5% (31/39) and 89.7% (35/39), respectively. The diagnostic coincidence rates of TSH, FT 4 and FT 3 of inpatients with hypothyroidism were 60.5% (52/86), 44.2% (38/86) and 2.3% (2/86), respectively. The patients with thyroid nodules, thyroiditis, goiter and thyroid adenoma mainly had elevated FT 3 and decreased T 3 levels. Conclusions:Thyroid adenoma and hypothyroidism are the main thyroid diseases in Lanzhou. The incidence in women and aged ≥50 years old people is high, and hyperthyroidism tends to be younger. Therefore, it is necessary to strengthen the physical examination and screening of thyroid diseases.

This article reported a case of malignant pheochromocytoma and paraganglioma with cranial metastasis. The patient was a 25-year-old man. At the age of 10, he was diagnosed with retroperitoneal paraganglioma. He received radiotherapy after partial resection of the tumor. At the age of 15, when he consulted for headache and hypertension, a space occupying lesion was found on the right adrenal without further diagnosis and treatment. His headache and hypertension were aggravated at the age of 25. Then he visited our medical center and diagnosed with right adrenal pheochromocytoma. He undertook an operation to remove the right adrenal lesion, and his blood pressured could be controlled in the normal range with oral antihypertensive medication. One year after the surgery, a cranial lesion with positive 131I-metaiodobenzylguanidine imaging was found following the increase of norepinephrine and dopamine in both blood and urine. The diagnosis of malignant pheochromocytoma with cranial metastasis was confirmed. The cranial lesion was treated with cyberknife therapy for 4 times, and the lesion was slightly reduced. Four year after the removal of right adrenal tumor, he developed multiple bone metastasis in the right ribs and left ilium, and then he received 131I-metaiodobenzylguanidine radiotherapy. Additionally, the results of gene test indicated a pathogenic mutation of SDHB. During the follow-up period of one year after the treatment, his blood pressure fluctuated to about 140/90mmHg with 10mg of phenoxybenzamine once a day. The case is a malignant pheochromocytoma with multiple bone metastasis characterized by a long course with an ideal prognosis in a way. Consequently, we suggested the diagnostic pathway with genetic testing based on clinical phenotype to approach more timely diagnosis and reasonable evaluation of the prognosis in pheochromocytoma and paraganglioma. Furthermore, clinicians should pay more attention to the long-term surveillance.

Objective To analyze the relationships of high mobility group box 1 protein (HMGB1) with regulatory T cells (Treg), T helper 17 cells (Th17) and cytokine secrtion in peripheral blood of gravidas with preeclampsia(PE),and to investigate the mechanism of HMGB1 in regulating Th17/Treg ratio via receptor for advanced glycation end products (RAGE)-IL-6 pathway. Methods Forty gravi-das with mild(20 cases) and severe(20 cases) PE were recruited as experimental groups,20 heathy gravi-das in the third trimester of pregnancy were enrolled as control group. Concentrations of HMGB1,IL-6,IL-17 and TGF-β in peripheral blood of all subjects were determined by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR(RT-PCR) was used to detect the expression of RAGE at mRNA lev-el in peripheral blood mononuclear cells(PBMCs). The percentages of Treg and Th17 cells were determined by flow cytometry. RT-PCR was performed to analyze changes in the expression of RAGE,IL-6,Foxp3 and RORγt at mRNA level after the PBMCs isolated from 20 garvidas with PE were cultured in vitro and stimula-ted with recombinant human HMGB1 (rhHMGB1). Results The levels of HMGB1,IL-6,Th17 and IL-17 in peripheral blood of gravidas with PE were significantly higher than those in the normal pregnancy group. Moreover,HMGB1 level was positively correlated with IL-6 level and ratios of Th17/Treg and IL-17/TGF-β in preeclamptic pregancies. In vitro stimulation of PBMCs with rhHMGB1 significantly enhanced the expres-sion of RAGE,IL-6 and RORγt at mRNA level, but suppressed the expression of Foxp3 at mRNA level. Conclusion Enriched HMGB1 in plasma shifts the Th17/Treg balance towards Th17 dominance via the RAGE-IL-6 pathway, which exacerbates inflammation and participates in the onset of preeclampsia during pregnancy.

Objective To understand the status quo of stressors and mental health of undergradu-ates of local medical colleges in internship and provide relevant countermeasures so as to provide scientific reference for psychological health counseling for them. Methods The stress source scale and mental health symptom self-rating scale for medical students in internship (SCL-90) coded by Chang Lirong et al was adopted to investigate. The questionnaire survey was conducted on the stress and mental health status of 390 interns in Binzhou Medical College, and 384 valid questionnaires were collected, with the effective rate of recovery as 98.46%. The questionnaire results were analyzed by sample t test, variance analysis and Pearson correlation analysis. Results A total of 24.1% of students in local medical schools were under moderate pressure (1.17±0.63). The highest pressure source was examination and employment (1.58±0.74), and the other followed were knowledge and skills (1.43 ±0.68), interpersonal relationships (1.11 ±0.54), patients (1.06±0.53), medical conditions (1.00±0.53) and work load (0.95±0.52) respectively. The scores of various stressors were significantly and positively correlated with most of the mental health factors. Conclusion The undergraduates of local medical colleges and universities are generally under stress in internship, which would affect their mental health. It is suggested that the interns should be guided from the aspects of employment, study and psychology so as to help them relieve their stress and develop good psychological qualities.

Objective Using middle cerebral artery occlusion (MCAO) model to observe protective effect of effective components of bezoar on brain damage.To discuss the anti-cerebral ischemia mechanism and compare the efficacy of effective components of bezoar from the endoplasmic reticulum stress intervention angle.Methods Rats were stratified randomly divided into sham group,model group,Qingkailing group (positive drug,3 mL/kg),taurine group,ursodeoxycholic acid (UDCA,78 mg/kg) group,taurine-conjugated ursodeoxycholic acid (TUDCA,100 mg/kg) group.Through establish MCAO model in rats,observed the scores of the neurologic impairment,measured infarct volume by TTC.Immunohistochemistry and Western blotting were Used to detect the content of P-PERK,P-EIF2α,and ATF4.Results Compared with sham group,neurologic impairment scores of model group significantly reduced (P ＜ 0.01).Compared with model group,Qingkailing group,UDCA group,and TUDCA group significantly improved neurological function in rats (P ＜ 0.05,0.01).Compared model group,all the treatment groups could significantly reduce the volume of cerebral infarction (P ＜ 0.01).Compared with sham group,expression of P-PERK,P-EIF2α,and ATF4 was significantly increased (P ＜ 0.01).Compared with model group,all the treatment groups reduced the expression of P-PERK,P-EIF2α,and ATF4 in varying degrees,effect of Qingkailing and TUDCA were more obvious.Conclusion The effective components ofbezoar alleviate cerebral ischemia reperfusion injury in rats by inhibiting endoplasmic reticulum stress,the effect of TUDCA is better than that of taurine and UDCA.