奥利司他胶囊有区分力溶出度检测法的建立及溶出曲线相似性评价

目的建立有区分能力的奥利司他胶囊溶出度检测法,评价国内6家企业与进口奥利司他胶囊溶出曲线的相似性。方法采用HPLC法,色谱柱为Thermo Hyersil GOLD C_(18)(150 mm×4.6 mm,5μm)柱,流动相为乙腈-水(85∶15),流速为1.0 mL·min^(-1),检测波长为195 nm,柱温为30℃,进样量为20μL。考察不同浓度十二烷基硫酸钠、不同浓度氯化钠及不同pH溶出介质对溶出曲线的影响,筛选出最佳溶出条件,并采用溶出曲线相似因子法评价溶出曲线的相似性。结果奥利司他在5.989~179.697μg·mL^(-1)范围内线性关系良好(r=0.999 8),平均回收率为100.4%,RSD为1.1%(n=9)。筛选出的最佳溶出条件如下:以含1.0%十二烷基硫酸钠、0.5%氯化钠、pH 6.0的磷酸盐缓冲溶液为溶出介质,在桨法、75 r·min^(-1)、介质1 000 mL的条件下开展溶出试验。国内仅1家企业产品与参比制剂的溶出曲线相似,其余5家企业产品与参比制剂相比溶出行为均不一致。结论该法能有效区分不同企业生产的奥利司他胶囊的溶出行为,对我国开展奥利司他胶囊仿制药质量与疗效一致性评价具有一定的参考意义。

Mechanisms of salt rejection at the ice-liquid interface during the freezing of pore fluids in the seasonal frozen soil area

Seasonal frozen soil accounts for about 53.50%of the land area in China.Frozen soil is a complex multiphase system where ice,water,soil,and air coexist.The distribution and migration of salts in frozen soil during soil freezing are notably different from those in unfrozen soil areas.However,little knowledge is available about the process and mechanisms of salt migration in frozen soil.This study explores the mechanisms of salt migration at the ice-liquid interface during the freezing of pore fluids through batch experiments.The results are as follows.The solute concentrations of liquid and solid phases at the ice-liquid interface(C*_(L),C*_(S))gradually increased at the initial stage of freezing and remained approximately constant at the middle stage.As the ice-liquid interface advanced toward the system boundary,the diffusion of the liquid phase was blocked but the ice phase continued rejecting salts.As a result,C*_(L)and C*_(S)rapidly increased at the final stage of freezing.The distribution characteristics of solutes in ice and the liquid phases before C*_(L)and C*_(S)became steady were mainly affected by the freezing temperature,initial concentrations,and particle-size distribution of media(quartz sand and kaolin).In detail,the lower the freezing temperature and the better the particle-size distribution of media,the higher the solute proportion in the ice phase at the initial stage of freezing.Meanwhile,the increase in concentration first promoted but then inhibited the increase of solutes in the ice phase.These results have insights and scientific significance for the tackling of climate change,the environmental protection of groundwater and soil,and infrastructure protection such as roads,among other things.

Spatiotemporal expression of Nogo-66 receptor after focal cerebral ischemia

Ng R, the receptor for the neurite outgrowth inhibitor Nogo-66, plays a critical role in the plasticity and regeneration of the nervous system after injury such as ischemic stroke. In the present study, we used immunohistochemistry to investigate the regional expression of Ng R in rat brain following middle cerebral artery occlusion（MCAO）. Ng R protein expression was not observed in the center of the lesion, but was elevated in the marginal zone compared with control and sham-operated rats. The cerebral cortex and hippocampus（CA1, CA2, and CA3） showed the greatest expression of Ng R. Furthermore, Ng R expression was higher in the ipsilesional hemisphere than on the control side in the same coronal section. Although time-dependent changes in Ng R expression across brain regions had their own characteristics, the overall trend complied with the following rules： Ng R expression changes with time showed two peaks and one trough; the first peak in expression appeared between 1 and 3 days after MCAO; expression declined at 5 days; and the second peak occurred at 28 days.

Novel compound heterozygous mutation of SLC12A3 in Gitelman syndrome co-existent with hyperthyroidism:A case report and literature review

BACKGROUND Gitelman syndrome(GS)is a rare inherited autosomal recessive tubulopathy,characterized clinically by hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis,and is caused by an inactivating mutation in SLC12A3.GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism.It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia,which is difficult to correct.CASE SUMMARY A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo.However,the patient’s serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism.GS was confirmed by whole exome and Sanger sequencing.Gene sequencing revealed compound heterozygous mutations of c.488C>T(p.Thr163Met),c.2612G>A(p.Arg871His),and c.1171_1178dupGCCACCAT(p.Ile393fs)in SLC12A3.Protein molecular modeling was performed to predict the effects of the identified missense mutations.All three mutations cause changes in protein structure and may result in abnormal protein function.All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed.CONCLUSION We have identified a novel compound heterozygous mutation in SLC12A3.The present study provides new genetic evidence for GS.

Microstructure and corrosion behaviors of friction stir-welded Q235 low-carbon steel joint

Friction stir welding(FSW)was used to prepare Q235 low-carbon steel joint,and the microstructure of different zones of the joint was characterized.The electrochemical corrosion behavior of different macroscopic zones of the joint was evaluated in 3.5 wt.%NaCl solution.The results showed that the retreated-side heat-affected zone(HAZRS)and the advanced-side heat-affected zone(HAZAS)did not undergo phase transformation during FSW,and their microstructures were similar to those of the base material(BM),which was mainly composed of blocky ferrite and pearlite.The retreated-side thermo-mechanical affected zone(TMAZRS),the stirring zone(SZ),and the advanced-side thermo-mechanical affected zone(TMAZAS)underwent phase transformation,and the microstructure was mainly composed of proeutectoid ferrite and pearlite.The order of the corrosion resistance of different micro-zones from high to low was:HAZRS>BM>HAZAS>TMAZRS>SZ>TMAZAS.The corrosion mechanism for BM,HAZRS,and HAZAS was mainly the dissolution of ferrite.By contrast,the corrosion mechanism for TMAZRS,SZ,and TMAZAS was mainly galvanic corrosion between proeutectoid ferrite and pearlite.

Thermal Stability of WB_2 and W–B–N Films Deposited by Magnetron Sputtering

The work is mainly to study the thermal stability including the phase stability, microstructure and tribo-mechanical properties of the AlB_2-type WB_2 and W–B–N(5.6 at.% N) films annealed in vacuum at various temperatures, which are deposited on Si and GY8 substrates by magnetron sputtering. For the WB_2 and W–B–N films deposited on Si wafers, as the annealing temperature increases from 700 to 1000 °C, a-WB(700 °C) and Mo_2B_5-type WB_2(1000 °C) are successively observed in the AlB_2-type WB_2 films, which show many cracks at the temperature ≥ 800 °C resulting in the performance failure; by contrast, only slight α-WB is observed at 1000 °C in the W–B–N films due to the stabilization eff ect of a-BN phase, and the hardness increases to 34.1 GPa fi rst due to the improved crystallinity and then decreases to 31.5 GPa ascribed to the formation of α-WB. For the WB_2 and the W–B–N films deposited on WC–Co substrates, both the WB_2 and W–B–N films react with the YG8(WC–Co) substrates leading to the formation of CoWB, CoW_2B_2 and CoW_3B_3 with the annealing temperature increasing to 900 °C; a large number of linear cracks occur on the surface of these two films annealed at ≥ 800 °C leading to the fi lm failure; after vacuum annealing at 700 °C, the friction performance of the W–B–N films is higher than that of the deposited W–B–N films, while the wear resistance of the WB_2 films shows a slight decrease compared with that of the deposited WB_2 films.