In the first half of 2014, the U.S. Food and Drug Administration (FDA) approved 46 new drugs, including 10 new molecular entities and 10 new biologic license applications. According to the prescription information for professionals, this article introduces the description, mechanism of action and clinical studies, briefly describs the box warning, indications and usage, dosage and administration, dosage form and strength, contraindications, warning and precautions, adverse reactions, drug interaction and use in special population of these new drugs. In addition, the “first events” in the history of new drug research, development and approval are also discussed.

In the first half year of 2015, the U.S. Food and Drug Administration(FDA) approved 11 new molecular entities and 5 new biologic license applications. According to the prescription information for professionals, this article introduces the description, mechanism of action and clinical studies; briefly describes the box warning, indications and usage, dosage and administration, dosage form and strength, contraindications, warning and precautions, adverse reactions, drug interaction and use in special population of these new drugs. In addition, the first and critical events in the history of new drug reaserch and development are emphasized.

In the first half year of 2016,the U.S. food and drug administration(FDA)approved 9 new molecular entities and 8 new biologic license applications. According to the prescription information for professionals,this article introduces the description, mechanism of action and clinical studies;briefly describes the box warning,indications and usage,dosage and administration,dos?age form and strength,contraindications,warning and precautions,adverse reactions,drug interaction and use in special population of these new drugs. In addition,the first and critical events in the history of new drug development and reaserch are emphasized.

In the second half of 2016,the U.S. Food and Drug Administration(FDA)approved 7 new molecular entities and 3 new Biologic License Application(BLA), the lowest number in recent years. According to the prescription information for profes-sionals,this article introduced the description,mechanism of action and clinical studies and briefly describes the boxed warning,indi-cations and usage,dosage and administration,dosage form and strength,contraindications,warning and precautions,adverse reac-tions,drug interaction and the use in the special population. In addition,the first and critical events in the history of new drug develop-ment and reaserch were emphasized.

96% and with the same bio-activity as unlabeled Huwen toxin-1; Radioactivity detected in epidural space was 38% of injected radioacti vity at 10 min after epidural injection, which demonstrated successful administr ation into epidural space; The maximum serum concentration after epidural or iv administration of [ 125 I]labeled Huwentoxin-1 were determined to be (0 70?0 04) MBq?L -1 and (4 98?0 58) MBq?L -1 , respectively, a t the maximum serum concentration times of 30 min and 2 min. Terminal T 1/2 after epidural or iv administration were (10 36?0 27) h or (11 03?1 16) h, respectively. Cls was (1 29?0 07) L?h -1 ?kg -1 or (1 25? 0 23) L?h -1 ?kg -1 , respectively. Bioavailability after epidural a dministration was(95?5)%. CONCLUSION Concentration-time cur ves of [ 125 I] labeled Huwentoxin-1 after two routes were different. The degradation profiles after epidural and iv injection supported the using of HWTX-1 as analgesic by epidural administration.

BACKGROUND: Nitric oxide (NO) is synthesized by catalysis of nitric oxide synthase (NOS). Three distinct isoforms of NOS have been detected in different structures of the guinea pig cochlea. However, there are still rather controversies about the definite localization and expression of NOS isoforms in guinea pig cochlea.OBJECTIVE: To investigate localization and expression of three NOS isoforms in the cochlea of guinea pigs, and to explore the effect of NO on auditory physiology and pathophysiology of inner ear.DESIGN: An observed and controlled study.SETTING: Department of Physiology, Jinzhou Medical College; Department of Orthopedics, the Second Affiliated Hospital of Jinzhou; Department of Otorhinolaryngology, Jinzhou Central Hospital.MATERIALS: The study was performed in Hearing Research Laboratory of China Medical University from May to November 2000. Ten healthy male albino guinea pigs, with body mass of 250-300 g, with sensitive Preyer's reflexes and normal drum membrane and external auditory canal,were selected.METHODS: After anesthesia, guinea pigs were decapitated and the temporal bones were removed immediately. The round and oval windows were opened, perfused with 40 g/L paraformaldehyde, and the specimens were immersed in the same fixative solution for 2 hours. Decalcification of the cochleae was performed in 100 g/L EDTA solution for 1 week. Then the specimens were placed in 250 g/L sucrose solution overnight and embedded in OCT. Cryostat (20 μm) sections were prepared for immunohistochemistry.MAIN OUTCOME MEASURES: Localization and expression of three NOS isoforms in the cochlea of guinea pigs.RESULTS: All data of ten guinea pigs was entered the final analysis without any loss. [1] Neuronal-type nNOS and endothelial-type eNOS immunoreactivity were localized in inner and outer hair cells of the organ of Corti, as well as in spiral ganglion cells. In addition, staining for nNOS and eNOS were also seen in the marginal cells of stria vascularis, spiral ligament cells, and in nerve fibers. [2] Inducible-type iNOS immunoreactivity was also detected in above each structure of the guinea pig cochlea under physiological conditions.CONCLUSION:NO may play an important role in neurotransmission,blood flow regulation, and cytotoxicity.

Objective To investigate the relationship between dynamic changes of plasma D-dimer and survival rate of the esophageal carcinoma patients pre-and post-operation.Methods 30 cases of normal control group,160 cases of esophageal cancer group( including operation cases n =112),with the gold standard method for the determination of plasma D-dimer.Results There was a link between the level of D-dimer,TNM staging,lymph node metastasis and tumor size in esophageal carcinoma patients.Compared with the preoperation,the plasma D-dimer is significantly elevated 2 years later( t =7.35,P ＞ 0.05 ).Conclusion Before or after the operation,dynamic changes of plasma D-dimer had a relationship with short-term survival rate.

Objective To analyze the epidemiological and clinical characteristics of an outbreak of tsutsugamushi disease in Taizhou region of Jiangsu Province,and to clarify new changes of endemic focus of tsutsugamushi disease in Jiangsu Province.Methods The definition of tsutsugamushi infected cases was determined,field epidemiological investigation with analysis of clinical features and polymerase chain reaction (PCR) results to diagnose tsutsugamushi disease were combined.Some of the positive samples were conducted genotyping by amplification and sequencing.Results The outbreak occurred from October to November,2011.The endemic focus located on the plain with humid climate and abundant rainfall.Fifteen cases of tsutsugamushi disease were found,including 6 PCR confirmed cases,5 clinically diagnosed cases,and 4 suspected cases.The main clinical symptoms were fever in 15 cases,skin rash in 14 cases,lymphadenectasis in 3 cases,skin eschar or ulcer in 12 cases,and liver dysfunction in 3 cases.None of the patients developed severe complications,and all recovered rapidly after the treatment.Comparing the sequencing results of positive samples with standard strains,the homology of base sequences was 99.00％ with that of Kawasaki.Conclusions The outbreak of tsutsugamushi disease in Jiangsu Province in 2011 is of autumn type in transitional endemic focus,and the pathogen is Kawasaki Orientia tsutsugamushi.

OBJECTIVE To study the pharmacokinetics of heat shock protein 65-mucin 1 (HSP65-MUC1) recombinant fusion protein vaccine in Macaca mulatta monkeys and tumor-bearing mice. METHODS HSP65-MUC1 was labeled by radioactive isotope 125I. M. mulatta monkeys were randomly divided into sc and iv administration groups. Simultaneously, sc administration group was designed as a multiple dose group in which M. mulatta monkeys were sc given [ 125I] HSP65-MUC1 40 μg·g-1, once every 2 weeks for a total of 3 times. Size exclusion chromatography ( SEC) was used to determine concentrations of HSP65-MUC1 in serum samples. The tumor-bearing mice were randomly divided into 0.5, 1.5, 4, 8 and 24 h groups. Mice were sc given [125I] HSP65-MUC1 550 μg·kg-1, tissues were collected and tissue distribution of [125I] HSP65-MUC1 in tumor-bearing mice was studied using trichloroacetic acid (TCA) precipitation method. RESULTS The absolute bioavailability of [125I]HSP65-MUC1 was 38.33% after M. mulatta monkeys were sc given [125I]HSP65-MUC1. In multiple dose group, concentrations of [125I]HSP65-MUC1 after the third dose administration was compared to that of the first dose administration. The accumulation factor (AUC3/AUC1) was 1.17 ±0.25. Distribution of [ 125I]HSP65-MUC1 was significantly different compared with general polypeptide and protein drugs after sc in tumor-bearing mice. The concentration in lymph nodes was the highest. The concentration in other immune tissues, such as thymus and spleen, were not relatively high, but their declined tendency was slow after reaching the peak concentration (cmax ). However, the concentrations in the serum and some other tissues with a large blood volume, such as the heart, liver, and lung, were relatively low and declined quickly after reaching cmax. Its level in the tumor was not very high. [125 I] HSP65-MUC1 was excreted mainly by the kidneys. CONCLUSION The bioavailability of [125I]HSP65-MUC1 is 38.33% after sc administration in M. mulatta. After multiple-dose administration, the vaccine does not accumulate in the body, whose concentration is the highest in lymph nodes after [1251] HSP65-MUC1 was sc given in tumor-bearing mice, but is not very high in tumor. Besides, the vaccine declined tendency is slow after reaching cmax in immune tissues such as thymus and spleen compared with other tissues with a large blood volume.

Objective To establish a mouse model of biliogenic severe acute pancreatitis (SAP) by using a self-made device for retrograde injection of sodium taurocholate into common bile duct,and to investigate the improvement of the device on retrograde injection of sodium taurocholate into common bile duct and its safety.Methods Thirty-six adult male ICR mice were randomly divided into biliogenic SAP model group and sham group,with 18 mice in each group.A 40 U disposable insulin syringe,a 200 μL tips and a 25 μL micro-syringer were used as basic materials for making the mouse common bile duct injection device [National Utility Model Patent (ZL 2014 2 0694365.4)].In model group,3.5％ sodium taurocholate (1 mL/kg) was injected retrogradely into the common bile duct of mice,whilst in sham group,the mice underwent the injection of equal amount of normal saline instead.Six mice in each group were sacrificed at 6,24 and 48 hours after operation,and the abdominal aortic blood was collected.Serum amylase (AMY),alanine aminotransferase (ALT),creatine kinase-MB (CK-MB),serum creatinine (SCr),oxygenation index (PaO2/FiO2) as well as serum Ca2+ were.determined.Pathological change in pancreas was observed under conventional light microscopy after hematoxylin and eosiu (HE) staining,and the impairment was evaluated by a widely used score system.Results The injection device was easily placed into mouse common bile duct under macroscopic observation.Six hours after operation,the levels of serum AMY,ALT and SCr in model group were significantly higher than those in sham group,and peaked at 24 hours,and they slightly decreased at 48 hours,which were still significantly higher than those of the sham group [24-hour AMY (U/L):7 325 ± 1 154 vs.1 737 ± 197,24-hour ALT (U/L):176.0±5.0 vs.38.3 ± 2.0,24-hour SCr (tmol/L):46.3 ± 1.5 vs.17.8 ±0.6,all P ＜ 0.01].The level of CK-MB at 6 hours in the model group was significantly higher than that of the sham group,and peaked at 48 hours (U/L:749.8±42.2 vs.383.3±35.5 at 6 hours,3 340.1 ± 203.6 vs.704.6 ± 63.5 at 48 hours,both P ＜ 0.01).PaO2/FiO2 at 6 hours after the operation in model group was significantly lower than that of sham group,then it began to rise at the similar level in sham group at 48 hours [mmHg (1 mmHg =0.133 kPa):327.5±33.8 vs.424.8±31.0 at 6 hours,P ＜ 0.01;429.8 ±41.8 vs.464.7±43.3 at 48 hours,P ＞ 0.05].Ca2+ level in model group was continuously decreased after operation,and it was significantly lower than that of sham group at 48 hours (mmol/L:1.58 ± 0.14 vs.2.45 ± 0.21,P ＜ 0.01).The pancreatic edema was obvious after operation in sham group,with the observation time prolongation,the changes were gradually improved;pancreatic focal necrosis was found at 6 hours after operation in model group,and it was secondary aggravated,and pancreatic lobule structure disappearance and inflammatory cells extensive infiltration was found at 48 hours.Pathological score of the model group was significantly higher than that of sham group at each time point,and peaked at 48 hours (13.3 ±0.3 vs.3.0±0.1,P ＜ 0.01).Conclusion It is a highly efficient and low-cost way to induce biliogenic SAP in mice by retrograde injection of 3.5％ sodium deoxycholate into common bile duct via the self-made injection device,and the model conformed to the clinical characteristics of biliogenic SAP.