Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1β (IL-1β) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1β and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1β level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.
Rats ; Animals ; Diabetic Retinopathy/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mitogen-Activated Protein Kinase 3/metabolism* ; Interleukin-1beta/metabolism* ; Methylene Blue/pharmacology* ; Phosphorylation ; Rats, Sprague-Dawley ; MAP Kinase Signaling System ; Diabetes Mellitus, Experimental/drug therapy* ; Superoxide Dismutase/metabolism*

Objective: To investigate the assessment and treatment strategy of patients with renal cell carcinoma. Methods: The clinical data of 43 patients with renal cell carcinoma and bone metastases admitted to the First Affiliated Hospital of Nanjing Medical University from January 2006 to December 2018 were retrospectively analyzed. The follow-up time was 6 years, with an average age of 55.4 years (21-87 years). There were 29 males, 14 females, 22 cases of limb bone metastasis, 12 cases of spinal metastasis, 9 cases of multiple bone metastasis, 21 cases of Fuhrman grade 1 and 2, 19 cases of T₁, and 20 cases of N₀. All patients were confirmed by postoperative pathological examination or imaging data suggesting that bone metastasis are from renal cell carcinoma. Forty-three patients underwent primary renal surgery, and molecular targeted therapy was used after the operation. The treatment process was smooth, no obvious discomfort, and postoperative pathology showed clear cell carcinoma.22 patients with limb bones metastasis and 12 patients with spinal metastasis included in the study all met the indications for secondary surgery after the disease assessment. After communicating with the patient, 13 patients with limbs metastasis and 6 patients with spinal metastasis received local treatment, including complete resection of the extremities and spinal fixation, the remaining 15 patients and 9 patients with multiple bone metastasis were treated conservatively. There were 19 patients in the local treatment group, 13 patients with limbs bone metastasis, 6 patients with spinal bone metastasis, the average age was 54.9 years, the average diameter of the primary tumor was 4.7 cm. There were 24 patients in the conservative treatment group, 9 patients with limbs metastasis, 6 patients with spinal metastases and 9 cases with multiple bone metastasis, with an average age of 56 years and a primary tumor diameter of 5.6 cm. Limb metastatic lesions were evaluated according to the patient's general condition, bone pain, fracture risk, and bone metastasis. Spinal lesions were evaluated according to Tokuhashi score, Harrington score, Tomita score, vertebral stability assessment, and molecular targeted therapy. Aminokinase inhibitors, conservative treatment with local radiotherapy and bisphosphonate treatment. Results: During the follow-up period, the 1-year overall survival rate of the local treatment group was 100.0%, the 2-year overall survival rate was 89.4%, and the 5-year overall survival rate was 73.7%. The 1-year overall survival rate of the conservative treatment group was 87.5%, and the 2-year overall survival rate was 62.5%. The 5-year overall survival rate was 16.7%. The 2-year and 5-year survival rates of the local treatment group were statistically different (P=0.044, P=0.000) compared with the conservative treatment group. For patients with limb bone metastasis, the 5-year survival rate was significantly higher in patients receiving topical treatment than in the conservative treatment group (P=0.011). For spinal metastasis, spinal pain in the local treatment group was alleviated to varying degrees. No spinal instability and spasticity were observed after follow-up. In the spine patients who received conservative treatment, 3 patients developed paraplegia, which was statistically different from local treatment (P=0.046). Another 9 patients with multiple bone metastases did not undergo local surgery, and all died after multiple organ failure. Conclusions At the same time of molecular targeted therapy, according to the evaluation results, selective treatment of bone metastases with secondary surgical indications, including complete resection of the extremities and spinal fixation, can significantly improve the survival and quality of life of those patients.

Objective To summarize the current status and trend of hypoglycemic agents of diabetic inpatients in different departments of Chinese PLA General Hospital.Methods The clinical data of diabetic patients admitted to Chinese PLA General Hospital from January 2000 to May 2014 were collected(those hospitalized in the department of endocrinology were excluded).A total of 10 041 patients were selected by stratified random sampling.The type of hypoglycemic agents in different departments and the variation on anti-hyperglycemic drugs with time were retrospectively analyzed.Results Of all the patients in non-endocrinological wards, 50.2% were treated with insulin, 36.9% with metformin, 21.3% with α-glycosidase inhibitor, and 18.9% with sulfonylureas.Metformin, α-glucosidase inhibitors, pre-mixed 30R, and insulin glargine were more commonly used than other anti-hyperglycemic agents, accounting for 36.9%, 21.0%, 14.0%, 8.7%, respectively.Metformin, sulfonylureas, α-glucosidase inhibitor, and different types of insulin were more widely applied in internal medicine while insulin therapy was more frequently used in surgical department.During the past 15 years, the proportions of insulin, glinides, α-glucosidase inhibitor, and thiazolidinediones application were gradually increased, while the proportions of sulfonylureas and metformin treatment were on the decline trend.Conclusion Most of the inpatients were treated with oral antidiabetic drugs.Metformin, α-glucosidase inhibitor, pre-mixed 30R, and insulin glargine were the most frequently prescribed agents for the inpatients.

Objective To analyze the clinical characteristics of dengue fever (DF) in Guangzhou Higher Education Mega Center (HEMC) in the year of 2014. Methods A retrospective analysis was carried out in the clinical data of 487 cases of DF patients. Results The incidence of DF accounted for 27.18% ( 527/1939) of the total emergeney fever cases. In 487 DF cases with detailed data, 261 were male, and 226 were female; 312 were young aged, 88 were middle aged, and 87 were old aged. For the systemic symptoms, fever accounted for 87.5%, headache 48.3%, and muscular soreness 47.6%. Cough ( 16.6%) , pharynx pain ( 16.8%) and running nose ( 10.9%) were common in respiratory symptoms; poor appetite ( 14.4%) and nausea ( 10.3%) were common in gastrointestinal symptoms. The abnormal laboratory parameters were mainly shown as WBC count ( 48.25%) and PLT count ( 41.68%) , following by creatine kinase ( CK, 39.49%) , aspartate aminotransferase ( AST, 34.12%) , and lactate dehydrogenase ( LDH, 31.96%) . Less cases had abnormal renal function. The distribution of Chinese medical syndrome types was shown as damp-heat blockage (65.7%), syndrome involving Weifen and Qifen simultaneously (23.6%), and Qi-yin deficiency (10.7%). Conclusion In the year of 2014, DF in Guangzhou HEMC occurred mainly among the youth people, the incidence of male DF was similar to that of the female DF, and DF cases usually have the primary symptoms of fever, aversion to cold, headache and muscular soreness. Bleeding is seldom seen in the DF patients, a few cases are complicated with the damage in the blood, liver and myocardium, and most of them have good prognosis.

Objective To analyze the relationship between obesity and arterial stiffness among population of different glucose tolerance status. Methods A cross-sectional study recruited the population aged 40 years or older from ShiJingShan district in Beijing. 9080 subjects were included by measured weight, waist circumference (WC), body mass index (BMI), waist/hip ratio (WHR) and WC/height ratio (WHtR) and hemodynamic indexes and the aortic stiffness (using brachial-ankle pulse wave velocity(baPWV). They were divided into 3 groups based on the results of OGTT and diabetes history: normal glucose tolerance group ( NGT group) ,impaired glucose regulation group ( IGR group) and diabetes mellitus group ( DM group) . The association between baPWV and different obese indexes was analyzed by multi-ple linear regression. Results According to the criterion of WC, WHR and WHtR, baPWV of central obesity group was significantly higher than the normal group(P<0. 01). There was no statistically significant differences based on BMI in DM group(P>0. 05), but it was of sta-tistically significant differences in NGT group and IGR group. Central obese indexes( WC、WHR、WHtR) showed a positive correlation to PWV in the studied groups(P<0. 05). BMI was only positively correlated with baPWV in NGT group, there was no significant correlation in IGR and DM group(P>0. 05). After adjusting for age, gender and cardiovascular risk factors, the multiple regression analysis found that for every 0. 1 point increase in WHR and WHtR, the PWV increased 40. 6 cm/s and 55. 3cm/s respectively. Conclusion There is a positive correlation between central obese indexes (WC、WHR、WHtR) and arterial stiffness, and the central obese indexes correlated with arterial stiffness better than BMI.

Objective To analyze the clinical characteristics and prognosis of patients with insulin autoimmune syndrome (IAS) and to get better understanding of IAS by literatures reviewing.Methods Nine cases of IAS who were diagnosed in the General Hospital of the People's Liberation Army from 2001 to 2011 were analyzed.Results All patients had hypoglycemic syndrome and episodes of hypoglycemia during both postprandial and fasting states.Most cases (8/9) were accompanied with autoimmune diseases,including 6 cases of Graves' disease treated with methimazole.The biochemical data showed extremely elevated serum insulin level (9/9) during hypoglycemic episode.For most patients,the tests of insulin autoantibodies were positive (7/9) while results of imaging examinations were negative(8/9).After removal of possible offending medications and with diet treatment,hypoglycemic episodes were ameliorated in 5 of 9 cases.For severe patients,acarbose (1/9) and prednisone (3/9)therapy were useful.During the period of follow-up,four cases experienced no episode of hypoglycemia and 3 cases with markedly reduced episodes.Conclusions IAS is characterized by hypoglycemic episodes,elevated blood insulin levels,and positive insulin autoantibodies.It is strongly related with autoimmune disease and is able to be induced by methimazole.Most patients undergo remission after diet treatment,drug withdrawal,and oral prednisone.

Impaired eady phase insulin secretion is an important reason for leading to postprandial hyperglycemia.Nateglinide is a rapid-acting insulin secretagogue,which reduces postprandial blood glucose of type 2diabetic patient by restoring early phase insulin secretion.The efficacy and safety have been fully verified by clinical administration and it is more widely used to treat type 2 diabetic patients.Both sulfonylureas and glinides were named insulin secretagogue agents and regarded as alternative first-line drugs in the 2010 Chinese Guideline for treatment of type 2 diabetes.AACE/ACE Consensus statement claimed that glinides would be one of the important choices after metformin.In order to further guide the clinical application of nateglinide,16 national specialists in the field of endocrinology and metabolism of China discussed,drafted,and edited this consensus.The current consensus combined clinical evidences at home and abroad.systematically reviewed and summarized tlle results of these studies about nateglinide.It will provide guiding recommendations and reference concerning how to reasonably and effectively use nateglinide in the clinical practice.

Objectives To investigate the relationship between albuminuria and all-cause mortality and cardiovascular mortality in middle-to-old-aged Chinese population. Methods A total of 2500 residents aged more than 40 years old were selected using random cluster sampling in Shougang community, Beijing, and 2315 of them took part in the survey finally. Morning urinary samples were collected. Urinary albumin and creatinine were measured. Albumin to creatinine ratio (ACR) was calculated and used as an index of albuminuria. The subjects were grouped according to ACR: normoalbuminuria (NO, ACR＜ 30 mg/g), microalbuminuria (MI, ACR 30-299 mg/g), and macroalbuminuria (MA, ACR ≥ 300 mg/g). Albuminuria (AL) group consisted of MI group and MA group. Cardiovascular risk factors were also investigated. Then all-cause mortality and cardiovascular mortality were collected after 4 years. The Cox model was used to analyze the relationship between albuminuria and all-cause mortality after adjusting for confounders. Results The prevalence of microalbuminuria and macroalbuminuria was 7.6% and 1.4% respectively. After 4 years follow-up,the cardiovascular mortality was 2.7/1000 person-years in NO group, 19.9/1000 person-years in MI group, and 11.5/1000 person-years in MA group and the all-cause mortality was 6.6/1000,25.9/1000 and 57.5/1000 person-years respectively. After adjusting for age, gender, smoking, body mass index, serum lipids, hypertension, diabetes mellitus, cardiovascular disease at baseline and serum creatinine, the hazard ratio (HR) of cardiovascular mortality in AL group was 5.26 [95% confidence intervals (CI) 2.26-12.24] compared with NO group; the HR of all-cause mortality was 3.34 (95% CI 1.82-6.15). Among patients without cardiovascular disease at baseline, the corresponding HRs were 6.92 (95%CI 1.80-26.58) and 2.85 (95%CI 1.22-6.65) respectively.Conclusion In the population studied, albuminuria is an independent risk factor for all-cause mortality and cardiovascular mortality.