D-D4FC (?-D-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine),a new anti-HIV drug,is on its PhaseⅡ clinical trials in America,France and Germany. Our lab has synthesized D-D4FC successfully using N-deoxyribosyltransferase from Lactobacillus helveticto catalyzing the ribose transfer from D4T (?-D-2′,3′-unsaturated thymidine) to 5-FC (5-fluorocytidine).The yield of D-D4FC reached 25%.We discovered the reaction could also be done by using intact cells.The yield could increase to 50% in 12.5 hours and more convenient to industrial continuous process.In this paper,the conditions including pH,buffer,substrates concentration,cells amount,reaction time and a possible catalytic mechanism were studied and discussed.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Chronotherapy ; Female ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Remission Induction ; Taxoids ; administration & dosage ; adverse effects

Adenoma, Pleomorphic ; surgery ; Adult ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; surgery

Coloboma ; Humans ; Infant, Newborn ; Male ; Optic Nerve ; abnormalities

OBJECTIVETo study the effects of low concentration dopamine(DA) on hydrogen peroxide-induced apoptosis in cultured rat cardiomyocytes as well as the possible molecular mechanisms.

METHODSCultured neonatal rat cardiomyocytes were randomly divided into the following groups: control group (control), hydrogen peroxide group (H2O2), pretreated with low concentration dopamine ( DA + H2O2), dopamine receptor l(DR1) antagonist group (DR1 + DA + H2O2), dopamine receptor 2(DR2) antagonist group (DR2 + DA + H2O2). The cell apoptosis was then assessed by MTT and flow cytometry. The cellular ultrastructure changes were observed by transmission electron micro- scope. The activity of lactate dehydrogenase(LDH )and superoxide dismutase (SOD) in cell medium was analyzed by colorimetry. The protein expressions of Cytochrone c, Caspase 3 and Caspase 9 were obtained by Western blot.

RESULTSCompared with hydrogen peroxide group, low concentration dopamine(10 µmol/L) decreased the apoptosis rate and the expression of protein of apoptosis related protein, enhanced SOD activity, decreased LDH activity. DR1 antagonist SCH-23390 treatment inhibited dopamine induced cardiac protective effect. DR2 antagonist haloperido treatment had no changes compared with dopamine group.

CONCLUSIONAbove findings indicate that low concentration dopanine inhibits apoptosis induced by hydrogen peroxide in neonatal rat cardiomyocytes, which is partly associated with the activation of DR1.

Animals ; Apoptosis ; Benzazepines ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cells, Cultured ; Dopamine ; pharmacology ; Hydrogen Peroxide ; L-Lactate Dehydrogenase ; metabolism ; Myocytes, Cardiac ; drug effects ; Rats ; Rats, Wistar ; Receptors, Dopamine D1 ; metabolism ; Superoxide Dismutase ; metabolism

Objective To study the roles of the contact heat evoked potential (CHEP) in evaluating the small nerve fibers of cranial and spinal in elderly diabetic patients,and to analyze the feature of the small fibers in order to provide scientific foundations for early diagnosis of diabetic neuropathy (DN).Methods Totally 50 diabetic patients and 40 healthy subjects were included in this study.The diabetic patients were divided into the normal nerve conduction group (n=17) and the abnormal nerve conduction group (n=33).CHEP was determined and thermal stimuli was given to the area of eyelid,forearm and peroneal.Sensory and motor nerve conduction velocity in the upper and lower limbs were tested in all diabetic patients.Results Compared with the healthy group,the N wave latencies were prolonged and the N-P amplitudes were reduced in the area of eyelid,forearm and peroneal in diabetic patients (all P＜0.01).Compared with the healthy group,the logarithm of N-P amplitudes were reduced in areas of forearm and peroneal [(1.70±0.10) vs.(1.60±0.14),(1.65±0.078) vs.(1.54±0.15),both P＜0.05] and N wave latencies were prolonged in eyelid area [(343.1±18.2) ms vs.(385.4±26.5) ms,P＜0.05] in normal nerve conduction group.Compared to group with normal nerve conduction velocity,the logarithm of N-P amplitudes was reduced in peroneal area [(1.54±0.15) vs.(1.44±0.15),P＜0.05] in abnormal nerve conduction group.Conclusions CHEP can detect the early impairment of the small fibers in elderly diabetic patients.The early smallfiber impairments in diabetic neuropathy may be axon-oriented in spinal nerves and myelin-oriented in cranial nerves.

Objective To investigate motor nerve function status in rats with diabetes mellitus by motor unit number estimation (MUNE), and discuss it′s early diagnostic value in diabetic peripheral neuropathy (DPN). Methods Diabetic rat model (DM group) was induced by streptozotocin. The MUNE of gastrocnemius muscle and motor nerve conduction (MCV, CMAP) of the sciatic nerve were measured at the 4th, 8th and 12th week after onset of hyperglycemia in the DM group and the control group (normal SD rats). The ultrastructure of sciatic nerve was observed by electron microscope. Results At the 4th week, MUNE of gastrocnemius muscle was significantly decreased in DM group compared to that of the control group (275.88 ± 87.87 vs 369.71 ± 75.64,P<0.05). There were no significant differences in MCV and CMAP of sciatic nerve be?tween two groups. The electron microscopy observation showed that most nerve fibers were normal;a small amount of axonal atrophy, and myelin lamellar structure was separated in DM group. At the 8th week, compared with the control group, MUNE were reduced in gastrocnemius muscle in DM group (357.49±72.68 vs 221.26±92.41, P<0.01). There were no significant dif?ferences in MCV and CMAP of the sciatic nerve between DM group and control group. The electron microscope observation showed that part of nerve fibers were normal, the myelin focal plate layer was loose and separated, axonal atrophy, the axonal membrane and myelin sheath inner layer was separated with big gap. At the 12th week, MUNE of gastrocnemius muscle (127.87±19.80 vs 366.85±51.25), sciatic nerve MCV [(35.06±4.43) m/s vs (50.47±6.07) m/s] and CMAP [(2.91±1.37) mV vs (5.98±2.14) mV] were significantly decreased in DM group than those of control group (P<0.01). The electron microscopy observation showed severely damaged myelin flex and axonal squeeze. Conclusion MUNE is much earlier in detecting ear?ly motor nerve dysfunction in DM than conventional motor nerve conduction test.

Objective To assess the function of motor nerve fiber in patients with diabetic peripheral neuropathy (DPN) by single-fiber conduction studies.Methods According to the diagnostic standard of DPN issued in Toronto meeting in 2009,on the basis of the result of peroneal nerve conventional conduction study,a total of 65 patients with DPN in the Department of Endocrinology and the Department of Neurology of Tianjin Third Central Hospital from October 2012 to October 2013 were enrolled into the study,from whom 33 had abnormal sensory conduction (sensory-diabetic peripheral neuropathy group,S-DPN group),32 had abnormal sensory motor conduction (sensory motor-diabetic peripheral neuropathy group,SM-DPN group).Single-fiber conduction velocity (SF-CV) and single-fiber distal motor latency (SF-DML)were detected in all subjects.The obtained results were compared with the data from 34 healthy volunteers (control group).The relationship of SF-CV,SF-DML and the duration of diabetes mellitus,fasting glucose,HbA1 c was also studied in DPN patients.Results The SF-CV ((43.1 ± 3.6) m/s) was decreased in S-DPN group compared with control group ((47.5 ± 3.3) m/s,t =5.077,P ＜ 0.01).There were no significant differences in SF-DML ((3.6 ± 0.7) ms),motor nerve conduction velocity (MCV (49.5 ± 2.6)m/s) and DML ((3.4 ± 0.6) ms) in S-DPN group compared with that of control group ((3.4 ± 0.5) ms,(50.9 ± 3.5) m/s,(3.2 ± 0.5) ms,respectively).SM-DPN group had lower SF-CV ((35.2 ± 3.6)m/s,t =9.119,14.219),MCV ((40.9 ± 3.2) m/s,t =11.131,13.025) and increased SF-DML ((4.5±0.7) ms,t=5.692,7.231),DML ((4.2 ±0.7) ms,t=5.561,6.975) compared with the other two groups (P ＜0.01).SF-CV in DPN patients was negatively related to the diabetic duration (r =-0.340,P =0.006),while SF-DML had no correlation with duration of DM,fasting blood glucose and HbAlc.Conclusions Detection of SF-CV is easy to find early motor nerve dysfunction in DPN patients.SF-CV is decreased with the increasing duration of diabetes.

Objective The international multidisciplinary lung adenocarcinoma classification was published by IASLC/ ATS/ERS in 2011.This study aimed to explore the clinicopathologic characteristics of lung adenocarcinoma based on IASLC/ATS/ERS classification and validate its clinical diagnostic and therapeutic value.Methods 2 056 cases of surgical resection from Shanghai Chest Hospital were classified according to the new classification and clinical information were retrospectively reviewed.The clinicopathologic characteristics based on new classification were analyzed statistically.Results Our data indicated that women were in high risk of lung adenocarcinoma; The average age of onset was 59-year-old; the female patients were younger than the male patients (58.7 years vs 60.2 years,P ＜ 0.01) ; Average tumor diameter was 2.6 centimeter; right lung was more popular than left and superior lobe than the inferior one.Acinar predominant subtype and papillary predominant subtype were frequently observed.Micropapillary predominant subtype and solid predominant subtype were identified to be more aggressive than other histopathologic subtypes.Most patients were classified as stage Ⅰ(71.7％),which were predominantly stage Ⅰa (53.1％).Conclusion The new classification is superior to reflect the clinicopathologic characteristics of lung adenocarcinoma and satisfy clinical needs,especially contributing to change and update the surgical strategy of early stage lung adenocarcinoma.

Objective To explore the effect of endoscopic sinus surgery combined with postoperative nasal irrigation on the symptoms improvement and prognosis for patients with allergic fungal sinusitis.Methods The clinical data of 145 patients with allergic fungal sinusitis who had received treatment in our hospital from January 2010 and January 2014 were reviewed.According to different treatment methods,they were divided into two groups,65 cases in the control group was treated with conventional surgical treatment,80 cases in the obeservation group was treated with endoscopic sinus surgery combined with postoperative treatment.The therapeutic conditions of two groups were compared. Results The symptom scores of patients with polyps,edema,rhinorrhea in two groups were decreased compared with those before treatment, and the obeservation group decreased more significantly (P <0.05,P <0.01).After the operation,patients with nasal mucociliary transport rate of two groups were higher compared with postoperative 6 months and 9 months,and the obeservation group improved more significantly (P <0.05).In addition,two groups of postoperative SNOT-20 scores (physiological problems,limitations and affective outcomes)treatment were lower than those before,and the obeservation group decreased significantly than that of the control group (P <0.05,P <0.01).Con-clusion Endoscopic sinus surgery combined with postoperative nasal irrigation can effectively alleviate the symptoms and improve the prog-nosis in the treatment of allergic fungal sinusitis.