The protective effect of Qizhi hypoglycemic tablet on foot ulcer in streptozotocin-induced diabetes in rats / 药学学报

This study aimed to determine the protective effect of Qizhi hypoglycemic tablet (QZHGT) on foot ulcer in diabetic rats and explore its possible mechanism. Diabetes was induced by streptozotocin injection in rats. The rats received QZHGT (780 mg·kg-1), metformin hydrochloride tablet (Metf, 200 mg·kg-1) or glibenclamide tablet (Glib, 1.5 mg·kg-1) alone via intragastric administration once a day for three months. Food ulcer was prepared by foot skin excision after drug therapy lasted for two months, and the dynamic changes in food ulcer healingwere determined. During the experiment, blood glucose, serum levels of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), factor Ⅲ (FⅢ) and four coagulation parameters [thrombin time (TT), activated partial thromboplatin time (APTT), prothrombin time (PT), fibrinogen (FIB)] were detected. Finally, the protective mechanisms of QZHGT against diabetes and foot ulcer were analyzed by network pharmacology, and immunohistochemistry was used to confirm the expression of transforming growth factor-β (TGF-β) and nuclear factor κB (NF-κB) in pancreatic tissue. All animal procedures were approved by the Animal Experimentation Ethics Committee of Henan University (permission number HUSAM 2016-288). The results showed that the lasting hyperglycemia, polydipsia, polyphagia, polyuria and body weight lost took place in model rats compared to those in normal rats. These model rats also showed an increase in serum VEGF and iNOS, FⅢ, TT, APTT and PT, and a reduction in FIB and wound healing. Metf or Glib significantly improved hyperglycemia, polydipsia, polyphagia, polyuria and emaciation, but failed to ameliorate hypercoagulation and wound healing. QZHGT showed a similar effect on polydipsia, polyphagia, polyuria and emaciation to Metf or Glib, although it was inferior to them in hypoglycemic action. Importantly, QZHGT significantly improved hypercoagulation and wound healing, and attenuated serum VEGF and iNOS. Network pharmacology revealed that QZHGT decreased hyperglycemia through "insulin resistance pathway", improved coagulation status through "HIF-1 signaling pathway", prevented diabetic foot ulcers through "VEGF signaling pathway", "MAPK signaling pathway" and "NF-κB signaling pathway". Immunohistochemistry showed that QZHGT could inhibit the expression of TGF-β and NF-κB in pancreatic tissue to maintain islet function in diabetic rats. In summary, these data suggest that QZHGT can prevent pancreatic injury for adjunctive hypoglycemia and diabetic foot ulcer treatment, and is a better preventive and therapeutic drug for diabetic foot ulcer.

Effect of Leukodepleted Blood Transfusions on the Balance of Th1/Th2 Cells in Peripheral Blood of Patients with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of leukodepleted blood transfusions on peripheral blood Th1/Th2 cell balance in patients with acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>Fifty-seven ALL patients in our hospital from March 2016 to August 2017 were selected, 31 of them received routine blood transfusion were enrolled in group A, and 26 patients received depleted-blood leukotransfusion were enrolled in group B, 36 cases in normal physical examination at the same period were enrolled in control group. And the basic clinical characteristics of patients were recorded; the ratio of Th1/Th2 cells in peripheral blood of patients was analyzed by flow cytometry;the serum levels of IL-2, IFN-γ, IL-4, IL-10 were detected by ELISA method; the mRNA levels of T-bet and GATA-3 in lymphocytes were detected by RT-PCR;the protein levels of T-bet and GATA-3 in lymphocyte were detected by Western blot.</p><p><b>RESULTS</b>The Th1/Th2 ratio in peripheral blood of ALL patients significantly related with patient age and risk grade (P<0.05).After treatment,the change of Th1/Th2 ratio in group A showed no statistical difference from Th1/Th2 ratio before treatment (P>0.05), while the Th1/Th2 ratio in group B increased (P<0.05);the levels of IL-2, IFN-γ, IL-4 and IL-10 secreted from Th1 and Th2 cells of ALL patients in A group were not changed significantly(P>0.05), while the levels of IL-2 and IFN-γ secreted from Th1 cells of ALL patients in group B increased, the levels of IL-4 and IL-10 secreted from Th2 cells in group B decreased with statistical difference (P<0.05); the RT-PCR and Western blot showed that the expression levels of T-bet mRNA and T-bet protein in group A were lower than those in control group, while the expression levels of T-bet mRNA and T-bet protein in group B were higher than those in group A (P<0.05); the expression levels of mRNA and GATA-3 protein in group A were higher than those in control group, the expression levels of mRNA and GATA-3 protein in group B were lower than those in group A (P<0.05).</p><p><b>CONCLUSION</b>The leukoreduced blood transfusion helps to improve the balance of Th1/Th2 cells in peripheral blood and improve the immune function of patients, which may closely relate with the expression levels of T-bet and GATA-3.</p>

Significance and Clinical Application of the Establishment of RhD/C/c/E/e Blood Group Base in Chinese Nanyang City / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To understand the regularity of Rh blood typing of valunteary blood donors in Chinese Nanyang city, and to estabbish a Rh DC/c/E/e antigen negative donor base so as to provide the help for clinical emergent blood transfusion to patients and ensure the safety of blood transfusion.</p><p><b>METHODS</b>The Rh D blood group of blood samples from 81462 voluntary blood donors in Chinese Nanyang city in 2014 was identified by serologic method; after first screening and confirmation, the RhE/e/C/c typing of Rh D negative samples was performed; the detailed infornation of donors was registered seriously by using unified creteria; the data base and base in kind of RhE/e/C/c types of valuntary donors were established by means of compater-mamayement system.</p><p><b>RESULTS</b>300 cases (0.37%) were RhD negative blood donors, and the Rh antigen was Ccdee and ccdee in 83%.</p><p><b>CONCLUSION</b>The proportion of RhD negative donors accounts for 4% of Chinese Nanyang peoples, the RhE/e/C/c types of RhD negative donors are ccdee (50.67%)>Ccdee (33.00%)>ccdEe(5.67%)>CCdee (5.33%)>CcdEe(5.33%). The establisment of RhE/e/C/c subbase can show importent significance for clinical blood transfusion.</p>

Cataract-causing mutation S228P promotes βB1-crystallin aggregation and degradation by separating two interacting loops in C-terminal domain

β/γ-Crystallins are predominant structural proteins in the cytoplasm of lens fiber cells and share a similar fold composing of four Greek-key motifs divided into two domains. Numerous cataract-causing mutations have been identified in various β/γ-crystallins, but the mechanisms underlying cataract caused by most mutations remains uncharacterized. The S228P mutation in βB1-crystallin has been linked to autosomal dominant congenital nuclear cataract. Here we found that the S228P mutant was prone to aggregate and degrade in both of the human and E. coli cells. The intracellular S228P aggregates could be redissolved by lanosterol. The S228P mutation modified the refolding pathway of βB1-crystallin by affecting the formation of the dimeric intermediate but not the monomeric intermediate. Compared with native βB1-crystallin, the refolded S228P protein had less packed structures, unquenched Trp fluorophores and increased hydrophobic exposure. The refolded S228P protein was prone to aggregate at the physiological temperature and decreased the protective effect of βB1-crystallin on βA3-crystallin. Molecular dynamic simulation studies indicated that the mutation decreased the subunit binding energy and modified the distribution of surface electrostatic potentials. More importantly, the mutation separated two interacting loops in the C-terminal domain, which shielded the hydrophobic core from solvent in native βB1-crystallin. These two interacting loops are highly conserved in both of the N- and C-terminal domains of all β/γ-crystallins. We propose that these two interacting loops play an important role in the folding and structural stability of β/γ-crystallin domains by protecting the hydrophobic core from solvent access.

Simulation calculation on biomechanical properties of lumbar disc herniation / 医用生物力学

Objective To establish a numerical calculation and analysis model of lumbar disc herniation so as to provide a method of detecting and assessing the mechanical mechanism of lumbar disc herniation. Methods Based on CT of a healthy adult, the vertebra and intervertebral disc of lumbar 4~5 segment were reconstructed by Mimics 10.01 software and Geomagic 10.0 software, respectively. By adding the lumbar attaching ligaments and transforming the corresponding material properties of the extruded disc in Ansys software, the finite element model of L4~5 was established to create the intact disc and extruded disc model. The finite element method was employed to simulate the biomechanical properties of the two models under the loads of axial compression, flexion, lateral bending, extension and rotation. Results After the lumbar disc was extruded, the stress distribution on the disc and the ability of load transfer were changed. The stress was concentrated at the posterior lateral of annulus fibrous. Under the same loads, the maximum deformation of the extruded disc was larger than that of the intact disc. The contact forces of the facet joints in the extruded disc model were larger than that in the intact disc model. Conclusions After the lumbar disc was extruded, the load-bearing capacity was decreased and the stress level of the articular process was increased, and the loads on the facet joints were also enhanced, leading to the decline of stability in the lumbar vertebrae.

A novel mutation in the myocilin gene identified in a Chinese primary open angle glaucoma family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the possible myocilin molecular genetic defect underlying POAG in China and to identify the pathogenic mutation causing the disease.</p><p><b>METHODS</b>The majority of 1 branch of a large Chinese POAG family were personally examined by two senior ophthalmologists. The diagnoses were made by both doctors according to the signs of elevated intraocular pressure, glaucomatous optic neuropathy and glaucomatous visual field defect. All coding sequences of the myocilin gene plus the flanking sites were amplified by polymerase chain reaction (PCR) using genomic DNA from all examined family members followed by sequencing of the PCR products. One hundred normal control subjects were screened by single strand confirmational polymorphism analysis for the mutation.</p><p><b>RESULTS</b>This Chinese pedigree exhibited autosomal dominant mode of inheritance. The onset age ranged from 26 to 59 years. A novel disease-causing missense mutation T455K in the third exon of the myocilin gene was identified in all affected family members, all glaucoma suspects and 4 individuals who have not shown apparently signs of glaucoma. None of the subjects without the mutation had glaucoma. Affected individuals with the T455K mutation showed variable onset between 26 and 59 years of age. Filtering surgery was performed on all of 7 affected family members. The T455K mutation in myocilin gene was not found in the normal controls. A previously reported polymorphism IVS2+35(A to G)was detected in 4 individuals.</p><p><b>CONCLUSION</b>The novel myocilin sequence alteration T455K that is highly associated with the development of glaucoma and locates in a very conserved residue is proven to be a disease-causing missence mutation. All affected individuals and all POAG suspects in this family are identified to have this mutation. The mutation in this family is associated with a phenotype characterized by mix-onset open angle glaucoma and associated with a high penetrance. It is important for the mutation screening and periodical checkups of presymptomatic individuals belonging to the family of a POAG patient with T455K mutation.</p>