BACKGROUNDEarly intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve beta-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship between the glycemic remission and beta-cell function and assess the variables predictive of long-term near-normoglycemic remission.

METHODSEighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion (CSII) and followed up longitudinally. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, hemoglobin A1c (HbA1c) and insulin were measured at baseline, after CSII and at 2-year visit. The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group.

RESULTSThe duration to be diagnosed of the patients (from the time that patients began to have diabetic symptoms until diagnosis) in the remission group was shorter than that in the non-remission group (1.00 month vs 4.38 months, P = 0.040). The increase of the acute insulin response (AIR) was maintained after 2 years in the remission group compared with AIR measured immediately after intervention (413.05 pmol*L(-1)*min(-1) vs 408.99 pmol*L(-1)*min(-1), P = 0.820). While AIR in the non-remission group significantly declined (74.71 pmol*L(-1)*min(-1) vs 335.64 pmol*L(-1)*min(-1), P = 0.030). Cox model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio (OR) 1.019, P = 0.038, while fasting plasma glucose (FPG) and post-breakfast plasma glucose (PPG) after CSII were the risk factors (OR 1.397, P = 0.024 and OR 1.187, P = 0.035, respectively).

CONCLUSIONThe near-normoglycemic remission is closely associated with long-term maintenance of beta-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII.

Adult ; Aged ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; pathology ; Female ; Follow-Up Studies ; Humans ; Hyperglycemia ; pathology ; Hypoglycemic Agents ; therapeutic use ; Insulin ; therapeutic use ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Young Adult

Objective:To explore the clinical diagnosis and treatment of invasive gastrointestinal fungal infection plus pulmonary infection after renal transplantation.Methods:Clinical data were analyzed retrospectively for one patient with invasive fungal infection plus pulmonary infection after renal transplantation. The middle-aged female recipient underwent allogeneic kidney transplantation due to end-stage uremia. After successful kidney transplantation, there was postprandial epigastric pain not relieved by proton pump inhibitor. Gastroscopy after admission suggested that the nature of gastric mucosal lesions was to be determined. Pathological examination and special staining confirmed mucor.Results:After clarifying her conditions, the doses of such immunosuppression as tacrolimus, mycophenolate mofetil and prednisone were tapered and discontinued when necessary and using amphotericin B liposome plus posaconazole alleviated the digestive tract symptoms. Chest tightness, fever, shortness of breath after activities hinted at pulmonary infection after renal transplantation. Treatment was guided by the results of sputum culture.Conclusions:Mucor infection is rare in digestive tract complicated with pulmonary infection after renal transplantation. Clinicians should actively search for etiological evidence, seek multidisciplinary consultations for a definite diagnosis and provide empirical anti-infection treatments. Due attention is to be paid for double infection caused by anti-infection treatments and anti-infection treatment strategy should be timely adjusted and the dosage of immunosuppressant based upon immune monitoring.

Background Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve β-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship between the glycemic remission and p-cell function and assess the variables predictive of long-term near-normoglycemic remission. Methods Eighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion (CSII) and followed up longitudinally. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, hemoglobin A1c (HbA1c) and insulin were measured at baseline, after CSII and at 2-year visit. The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group. Results The duration to be diagnosed of the patients (from the time that patients began to have diabetic symptoms until diagnosis) in the remission group was shorter than that in the non-remission group (1.00 month vs 4.38 months, P=0.040). The increase of the acute insulin response (AIR) was maintained after 2 years in the remission group compared with AIR measured immediately after intervention (413.05 pmol·L~(-1)·min~(-1) vs 408.99 pmol·L~(-1)·min~(-1), P=0.820). While AIR in the non-remission group significantly declined (74.71 pmol·L~(-1)·min~(-1) vs 335.64 pmol·L~(-1)·min~(-1), P=0.030). Cox model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio (OR) 1.019, P=0.038, while fasting plasma glucose (FPG) and post-breakfast plasma glucose (PPG) after CSII were the risk factors (OR 1.397, P = 0.024 and OR 1.187, P = 0.035, respectively). Conclusion The near-normoglycemic remission is closely associated with long-term maintenance of p-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII.

OBJECTIVETo study the effect of Notoginsenoside Rgl on p38 mitogen activated protein kinase (p38MAPK) expression in pulmonary artery smooth muscle cells (PASMCs) cultured in hypoxia hypercapnia.

METHODSSD rat PASMCs was primary cultured, the cells of passage 2- 5 were divided into six groups: normoxic group (N group), hypoxia hypercapnia group (H group), dimethyl sulfoxide (DMSO) control group (HD group), Rg1 treated group (Rg low dose, Rg middle dose and Rg high dose group). Western blot was used to detect the expression of p-p38MAPK protein, and RT-PCR to determine the expression of p38MAPK mRNA.

RESULTSWestern blot and RT-PCR analysis indicated that the expression of p-p38MAPK protein and p-p38MAPK mRNA were significantly higher in HD group than those in N group (P < 0.01). Whereas, in Rg1 treated groups, the level of p-p38MAPK markedly decreased (P < 0.01) in dose-dependent manner.

CONCLUSIONNotoginsenoside Rg1 has protective effects on PASMCs under hypoxia hypercapnia condition, which may be related to inhibiting expression of p38MAPK.

Animals ; Cell Hypoxia ; Cells, Cultured ; Ginsenosides ; pharmacology ; Hypercapnia ; metabolism ; Male ; Muscle, Smooth, Vascular ; cytology ; drug effects ; Myocytes, Smooth Muscle ; drug effects ; Pulmonary Artery ; cytology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

OBJECTIVETo determine the sperm mtDNA content, mtDNA4977bp deletion and ROS in the seminal plasma of normal and leukocytospermia men, and to investigate the correlation of the changes of sperm mtDNA with the increase of leukocytes and reactive oxgygen species (ROS) in the seminal plasma.

METHODSSeventy-eight semen samples from leukocytospermia patients and 31 from healthy donors were divided into 3 layers, supernatant fluid, 30% sperm and 80% sperm, by Percoll gradient centrifugation, their sperm mtDNA content and mtDNA4977bp deletion quantitatively analyzed by real-time PCR, and the level of ROS determined by flow cytometry.

RESULTSThe ROS in the seminal plasma and the sperm mtDNA contents of the three layers were all significantly higher in the leukocytospermia group than in the healthy control (P < 0.01). In the supernatant fluid and 80% layers, mtDNA4977bp deletion showed no obvious difference between the control and the leukocytospermia group, but was significantly higher in the 30% layer of the latter (P < 0.01). The ROS level was found positively correlated with the mtDNA content in the 30% (r = 0.347, P < 0.01) and the 80% layer (r = 0.456, P < 0.01), but not in the supernatant layer.

CONCLUSIONThe increase of leukocytes and ROS may be one of the causes of the enhanced sperm mtDNA content, but has no significant impact on the mtDNA4977bp deletion.

Adult ; DNA, Mitochondrial ; genetics ; metabolism ; Flow Cytometry ; Humans ; Infertility, Male ; genetics ; metabolism ; physiopathology ; Leukocytes ; chemistry ; metabolism ; Leukocytosis ; genetics ; metabolism ; physiopathology ; Male ; Polymerase Chain Reaction ; Reactive Oxygen Species ; metabolism ; Sequence Deletion ; Sperm Count ; Spermatozoa ; cytology ; metabolism

BACKGROUNDFamitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).

METHODSThe data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent.

RESULTSA total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg, 20 mg and 30 mg, respectively. Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD). Progressive disease was found in 3 (12.5%) patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% CI 7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% CI 8.7-57.3) months. The adverse drug reactions mainly included hypertension (54.1%), hand-foot skin reactions (45.8%), diarrhea (33.3%), mucositis (29.2%), neutropenia (45.8%), thrombocytopenia (29.2%), hyperlipidemia (41.7%) and proteinuria (41.7%). The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%.

CONCLUSIONSFamitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.

Adult ; Aged ; Carcinoma, Renal Cell ; drug therapy ; Female ; Humans ; Indoles ; adverse effects ; therapeutic use ; Kidney Neoplasms ; drug therapy ; Male ; Protein Kinase Inhibitors ; Pyrroles ; adverse effects ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective: To assess the early experience and clinical value of left anteriolateral minor thoracotomy minimally invasive directly coronary artery bypass (MIDCAB) for treating multi-vessel lesion coronary artery disease (CAD) with bilateral internal mammary artery (BITA). Methods: Our research included in 2 groups: MIDCABG group, n=38 consecutive patients received left anteriolateral minor thoracotomy MIDCAB with BITA in our hospital from 2015-05 to 2017-01 and Control group, n=236 patients received conventional off-pump coronary artery bypass (OPCAB) by the same surgeon at same period. Peri-operative condition and relevant complications were compared between 2 groups. Results: In MIDCAB group, the success rate for harvesting BIMA was 94.7% (36/38), the mean time for harvesting right internal mammary artery (RIMA) and LIMA were (42.3±10.5) min and (35.2±8.3) min respectively; a total of 78 grafts were made in 38 patients with the mean of (2.05±0.31) graft/patient, no patient was switching to conventional CABG during the operation. Compared with Control group, MIDCAB group had reduced post-operative mechanical ventilation time (8.9±3.8) h vs (23.6±15.9) h, ICU stay time (29.3±20.8) h vs (56.5±38.3) h and hospital stay time (11.3±3.2) d vs (15.7±4.2) d, all P<0.05; while the incidence of peri-operative MACCE including death, myocardial infarction (MI), revascularization, cerebrovascular accident and poor incision healing were similar between 2 groups, P>0.05. No occlusion of anastomotic stoma was found by post-operative coronary angiography in neither group. The patients were followed-up for the average of 3 months, no death, angina or MI occurred. Conclusion: Through left anterolateral small incision, we can successfully get bilateral internal mammary artery and complete beating heart multi branch CABG.

Objectives: To explore the feasibility and safety of "2-staged" hybrid coronary revascularization using bilateral internal thoracic artery (BITA) for the treatment of multivessel coronary artery disease. Methods: Data of 65 patients who underwent "2-staged" hybrid technique (HCR) using BITA (BITA-HCR group) in our heart center because of multivessel coronary artery lesions during 2014.05-2017.05 were retrospectively analyzed. Results were compared with 96 patients who underwent "2-staged" HCR with single ITA (SITA-HCR group) by the same surgeon over the same time period. Results: There was no significant difference of preoperative characteristics between two groups. Operation time was significantly longer [(204.6±28.7) min vs (147.9±31.6) min, P<0.05], number of distal anastomoses was significantly higher [(2.2±0.5) vs (1.0±0.0), P<0.05], number of stents was significantly lower [(1.90±0.67) vs (2.40±0.49), P<0.05] in BITA-HCR group than in SITA-HCR group. Bleeding volume [(520.1±120.3) ml vs (532.2±350.3)ml, P>0.05], mechanical ventilation time [(7.7±3.2) h vs (6.9±2.3) h, P>0.05] and blood transfusion required [5(7.7%)vs 8(8.3%), P>0.05] were similar between the two groups. Conclusions: The "2-staged" hybrid procedure using BITA is safe and feasible for the revascularization of multiple coronary artery lesions.

Objective To establish a hanging drop 3D cell culture model of human colon cancer cell (HT29) in 48-well cell culture plate,at the same time,through the comparison of several cell viability detection methods to determine the appropriate one for this cell culture way.Methods HT29 cells of 2 375,3 164,4 218,5 625,7 500 and 10 000/well were seeded in the bottom of the 48-well culture plate to form droplets.After 2 d of inversion culture,the cell spheroids were formed and incubated in medium for another 3 d.The volume of cell spheroids were measured,and the absorbance (A) values were detected through APH assay,MTT assay,MTT assay after digestion,CCK-8 assay and CCK-8 assay after digestion.The results were compared among different methods.Results After 5 d of culture,the cell spheroids were formed perfectly at the density of 2 375-10 000/well,and the volumes were in good linear with the original cell inoculation number at the density of 2 375-7 500/well.The A values of APH assay,MTT assay after digestion and CCK-8 assay after digestion increased with the increase of cell inoculation amount;But the cell ball digestion process was complex,and the cell viability was damaged.However,the A values of MTT and CCK-8 assay increased slowly.Conclusion The method of a hanging drop 3D cell culture model in 48-well culture plate combining with APH assay to detect cell viability is economical,accurate and easy to operate.