Advances in characterization of pharmaceutical polymorphisms by vibrational spectroscopy / 药学学报

The determination and characterization of solid drug form polymorphisms plays an important role in drug quality control, selection of the production process and clinical efficacy evaluation. Vibrational spectroscopy is a powerful method for the characterization of drug polymorphisms. In this paper we review recent research and application advances in the polymorphic characterization of active pharmaceutical ingredients (APIs) and drug cocrystals/salts by using Fourier transform infrared (FTIR) and Raman spectroscopy to elucidate the characteristics of APIs and drug complexes. This may provide theoretical support for structural analysis during the development process for drugs.

Effects of Electroacupuncture on Learning-memory and P35/P25-Cyclin-dependent Kinase 5-Tau Phosphorylation Signal Pathway in Prefrontal Cortex of Rats with Alzheimer's Disease / 中国康复理论与实践

Objective:To observe the effect of electroacupuncture at Baihui (DU20) and Shenshu (BL23) acupoints on learning-memory ability and expression of the relative protein of P35/P25-cyclin-dependent kinase 5 (CDK5)-Tau phosphorylation signaling pathway in the prefrontal cortex (PFC) in rats with Alzheimer's disease (AD), so as to reveal its potential mechanisms in treating AD. Methods:Male adult Sprague-Dawley rats were randomly divided into normal control group, sham group, model group and treatment group with six rats in each group. The AD model was constructed by bilateral hippocampal injection of Aβ25-35 in latter two groups. Equal amount of normal saline was injected into the sham group. The treatment group was acupunctured at Baihui and Shenshu once a day for ten days. All the rats were tested with Morris Water Maze. Immunohistochemistry staining and Western blotting were used to detect the related protein of P35/P25-CDK5-Tau protein phosphorylation in the PFC. Results:Compared with the normal control group and the sham group, the escape latency and escape length increased (P < 0.05) and the times crossing the platform reduced (P < 0.05) in the model group; compared with the model group, the escape latency and escape length reduced (P < 0.05), and the times crossing the platform increased (P < 0.05) in the treatment group. The optical density of P35/P25 and CDK5 were significantly higher in the model group than in the normal control group and the sham group (P < 0.01), and they were lower in the treatment group than in the model group (P < 0.001). The relative expression of P35/P25, CDK5, Tau[pS199] and Tau[pS202] were higher in the model group than in the normal control group and the sham group (P < 0.05), and the expression of the above proteins was lower in the treatment group than in the model group (P < 0.05). Conclusion:Electroacupuncture could improve the learning-memory and spatial exploration ability, which associate with inhabiting the P35/P25-CDK5-Tau protein phosphorylation signaling pathway in the PFC to delay the development of AD.

Advances in drug-drug complexes based on the crystal engineering design / 药学学报

Drug-drug complexes play important roles in improving the physicochemical properties of drugs including the solubility, dissolution rate and stability of the active pharmaceutical ingredients (APIs). In this paper, the design, synthesis, characterization, changes in physicochemical and pharmacologic properties, structural polymorphisms and the research and development pipelines of a variety of drug-drug cocrystals/salts synthesized based on the crystal engineering design are reviewed. This may provide theoretical support for the development of the new solid-state combinational drugs.

Clinicopathological study of pituicytoma and its rare ependymal variant / 临床与实验病理学杂志

Purpose To study the clinicopathological, immunophynotypic features of pituicytoma and its rare ependymal variant with discussion of its diagnosis and differential diagnosis. Methods 7 cases of pituicytoma, including 6 conventional pituicytomas and 1 ependymal variant tumor, were evaluated by HE staining and immunohistochemistry, and the relevant literatures were reviewed. Results Microscopically, the tumors were composed of closely packed plump spindle cells arranged in short fascicle and storiform pattern in 6 conventional pituicytomas, and whorl and papillary architecture with obvious perivascular rosette formation in the ependymal variant tumor. Immunohistochemically, all tumor cells were diffuse positive for S-100 and TTF-1, but negative for IDH1 R132H, Olig-2, CD34, NF, Syn, CgA, and pituitary hormones. Ki-67 proliferation index was less than 2％ in all cases. GFAP and EMA were only focally positive in conventional pituicytomas, whereas GFAP was diffuse positive in ependymal variant tumor with EMA dot-like staining in more than half of tumor cells. Conclusion Pituicytoma is a rare low grade glioma derived from neurohypophysis. To study helps recognition of extending morphological spectrum of pituicytoma and its new variant, which is important for its differential diagnosis consideration and clinical therapy.

Role of mesangial cells and podocyte axis in the renal tubulointerstitial lesions of IgA nephropathy / 临床与实验病理学杂志

Purpose To investigate the role of mesangial cells and podocyte axis in the renal tubulointerstitial lesion in IgA nephropathy. Method Forty cases of IgA nephropathy diag-nosed by renal biopsy were analyzed. The expression of WT-1, a specific marker of podocyte surface, TNF-a and IL-6 in renal tissue was observed by immunohistochemistry, and the activity of TNF-a and IL-6 in urine was detected by enzyme-linked immu-nosorbent assay (ELISA). Results The glomerular mesangial proliferation score was negatively correlated with the expression of WT-1 in IgA nephropathy (r =-0.763, P＜ 0.05), and positively correlated with the expression of renal tissue TNF-a and IL-6, urine TNF-a and IL-6 activity levels in IgA nephropathy (r =0.674, r=0.853, r =0.819, r=0.763, all P＜0.05). With the aggravation of renal tubulointerstitial lesions in IgA nephropathy, the expression of WT-1 decreased gradually, while the expression of TNF-a and IL-6 in renal tissue increased gradually, and the activity of TNF-a and IL-6 in urine increased gradually (P＜ 0.05). The expression of WT-1 was negatively correlated with renal tissue IL-6 expression, TNF-α expression, urine IL-6 activity level, and urine TNF-a activity level (r =-0.603, r =-0.564, r =-0.563, r =-0.544, all P＜0.05), and it was positively correlated with the urine osmotic pressure (r = 0.821, P＜ 0.05 ) and positively correlated with the degree of renal tubular interstitial damage (r = 0.793, P＜0.01). Conclusion The cytokines produced by mesangial cell proliferation of IgA nephropathy play a role in podocyte and in-duce podocyte apoptosis and aggravate tubulointerstitial injury.

Clavuridins A and B, two new trinor-guaiane sesquiterpenes isolated from the Xisha soft coral Clavularia viridis / 中国天然药物

In the present study, two new trinor-guaiane sesquiterpenes, named clavuridins B (1), and A (2), along with three known sesquiterpenes (3-5), were isolated from the Xisha soft coral Clavularia viridis. Their structures and absolute configurations were determined on the basis of spectroscopic analysis, X-ray diffraction analysis with Cu Kα radiation and by comparison with related model compounds. Compounds 1 and 3-5 were evaluated for their cytotoxic activity.

Correlations of IL-4R gene polymorphism and serum IgE levels with asthma predictive index / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the correlations of IL-4R gene polymorphism and serum IgE levels with asthma predictive index (API) in children.</p><p><b>METHODS</b>One hundred and sixty-seven children with positive API, 187 children with negative API and 203 healthy children (control group) were enrolled. PCR and DNA sequencing were used to identify genotypes of the Arg551Gln locus in IL-4R gene. Serum IgE levels were measured using ELISA.</p><p><b>RESULTS</b>There was no significant difference in the genotype frequencies of the Arg551Gln locus in IL-4R gene among the positive API, negative API and control groups. Serum IgE levels in the positive API group were significantly higher than in the negative API and control groups (P<0.01). In the positive API group, the children aged less than 2 years had significantly lower serum IgE levels than those aged over 2 years (P<0.01).</p><p><b>CONCLUSIONS</b>There is no correlation between the Arg551Gln polymorphism in IL-4R gene and API results. API positivity is correlated with elevated serum IgE levels. An older age (>2 years) may be a risk factor for increased serum IgE levels in children with positive API.</p>

Role of autophagy in acute myeloid leukemia therapy / 癌症

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

Association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>A neonatal rat model of HPH was established as an HPH group, and normal neonatal rats were enrolled as a control group. The mean pulmonary arterial pressure (mPAP) was measured. The percentage of medial thickness to outer diameter of the small pulmonary arteries (MT%) and the percentage of medial cross-section area to total cross-section area of the pulmonary small arteries (MA%) were measured as the indicators for pulmonary vascular remodeling. The immunohistochemical reaction intensities for HIF-1α, ET-1 and iNOS and their mRNA expression in lung tissues of neonatal rats were measured. Correlation analysis was performed to determine the relationship between pulmonary vascular remodeling and mRNA expression of HIF-1α, ET-1 and iNOS.</p><p><b>RESULTS</b>The mPAP of the HPH group kept increasing on days 3, 5, 7, 10, 14, and 21 of hypoxia, with a significant difference compared with the control group (P<0.05). The HPH group had significantly higher MT% and MA% than the control group from day 7 of hypoxia (P<0.05). HIF-1α protein expression increased significantly on days 3, 5, 7 and 10 days of hypoxia, and HIF-1α mRNA expression increased significantly on days 3, 5 and 7 days of hypoxia in the HPH group compared with the control group (P<0.05). ET-1 protein expression increased significantly on days 3, 5 and 7 days of hypoxia and ET-1 mRNA expression increased significantly on day 3 of hypoxia in the HPH group compared with the control group (P<0.05). Both iNOS protein and mRNA expression were significantly higher on days 3, 5 and 7 days of hypoxia than the control group (P<0.05). Both MT% and MA% were positively correlated with HIF-1α mRNA expression (r=0.835 and 0.850 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>Pulmonary vascular remodeling is developed on day 7 of hypoxia in neonatal rats. HIF-1α, ET-1 and iNOS are all involved in the occurrence and development of HPH in neonatal rats.</p>

Investigation on the difference of intolerance to food between southern and northern middle-aged Chinese and its association with eating habits / 中国应用生理学杂志

<p><b>OBJECTIVE</b>The aim of the present study was to investigate the difference of intolerance to food between southern and northern middle-aged Chinese, and furthermore analyze its association with eating habits in both study population.</p><p><b>METHODS</b>ELISA was applied to determine the serum concentrations of specific IgG of 14 food anaphylactogen in 1568 healthy subjects from totally 9 districts in both southern and northern China. Life style questionnaire was also applied to investigate the daily intake of six categorizes of food associated with food intolerance.</p><p><b>RESULTS</b>45.8% of all subjects were found to be intolerant to certain food. 62.3% of subjects from southern China and 40.4% of subjects from northern China were found to be intolerant to certain food, the difference between southern and northern Chinese was statistically significant. Top three foods intolerant by southern Chinese were crab, egg, and cold fish, while top three food intolerant by northern Chinese were egg, crab, and milk. The differences of intolerance to crab, cold fish, soy bean, rice, and tomato between southern and northern Chinese were statistically significant. Investigation on eating habits revealed that cereals and fish were the major food consumed by subjects in our study. There was no certain association between food intolerance and eating habits.</p><p><b>CONCLUSION</b>Considering that there are differences between southern and northern Chinese, southern and northern Chinese should pay attention to their daily food in order to avoid food allergy.</p>

Evaluation of emergency tourniquets for prehospital use in China / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>Massive hemorrhage is life-threatening during armed conflicts. Tourniquets are important medical devices used to reduce severe bleeding in trauma. The aim of this study was to empirically evaluate the current tourniquets used in China and provide information to emergency nurses in selecting the appropriate tourniquet.</p><p><b>METHODS</b>Five tourniquets were self-applied by 20 healthy participants. The blood flow distal to the tourniquet site was assessed using vascular Doppler ultrasound. Application time, pain, numbness, and other parameters were evaluated.</p><p><b>RESULTS</b>The bladder tourniquet and windlass tourniquet effectively occluded arterial blood flow with success rates higher than 75% in both the upper and lower extremities. The Cargo-strap was the fastest to apply, taking (7.22+/-2.30) s for the upper extremity and (6.48+/-2.40) s for the lower extremity. The rubber tube was the most painful, and the improvised tourniquet was the least efficient. The success rates were higher in the lower extremity than in the upper extremity (P less than 0.05, X(2) equal to 5.714).</p><p><b>CONCLUSIONS</b>The bladder tourniquet and the windlass tourniquet are efficient tourniquets, although the windlass is superior with respect to portability and pain. The Cargo-strap and rubber tourniquets have several disadvantages that reduce their suitability for field use. The improvised tourniquet is not recommended because of low efficiency and severe pain during implementation.</p>