Effects of post-traumatic stress disorder on the excitability of glutamatergic and GABAergic neurons in dorsal and ventral hippocampus in mice / 生理学报

The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.

Prediction of superantigen active sites and clonal expression of staphylococcal enterotoxin-like W / 中华流行病学杂志

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.

DYRK1-mediated phosphorylation of endocytic components is required for extracellular lumen expansion in ascidian notochord

BACKGROUND: The biological tube is a basal biology structure distributed in all multicellular animals, from worms to humans, and has diverse biological functions. Formation of tubular system is crucial for embryogenesis and adult metabolism. Ascidian Ciona notochord lumen is an excellent in vivo model for tubulogenesis. Exocytosis has been known to be essential for tubular lumen formation and expansion. The roles of endocytosis in tubular lumen expansion remain largely unclear. RESULTS: In this study, we first identified a dual specificity tyrosine-phosphorylation-regulated kinase 1 (DYRK1), the protein kinase, which was upregulated and required for ascidian notochord extracellular lumen expansion. We demonstrated that DYRK1 interacted with and phosphorylated one of the endocytic components endophilin at Ser263 that was essential for notochord lumen expansion. Moreover, through phosphoproteomic sequencing, we revealed that in addition to endophilin, the phosphorylation of other endocytic components was also regulated by DYRK1. The loss of function of DYRK1 disturbed endocytosis. Then, we demonstrated that clathrin-mediated endocytosis existed and was required for notochord lumen expansion. In the meantime, the results showed that the secretion of noto-chord cells is vigorous in the apical membrane. CONCLUSIONS: We found the co-existence of endocytosis and exocytosis activities in apical membrane during lumen formation and expansion in Ciona notochord. A novel signaling pathway is revealed that DYRK1 regulates the endocytosis by phosphorylation that is required for lumen expansion. Our finding thus indicates a dynamic balance between endocytosis and exocytosis is crucial to maintain apical membrane homeostasis that is essential for lumen growth and expansion in tubular organogenesis.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA / 中华肝脏病杂志

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Regulatory factor X5 promotes hepatocellular carcinoma progression by transactivating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta and suppressing apoptosis / 中华医学杂志(英文版)

BACKGROUND@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*METHODS@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*RESULTS@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*CONCLUSION@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

Regulatory factor X5 promotes hepatocellular carcinoma progression by transactivating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta and suppressing apoptosis / 中华医学杂志(英文版)

Background@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*Methods@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*Results@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*Conclusion@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

A new alkaloid isolated from leaves of Carthamus tinctorius / 中草药

Objective To study the alkaloids from leaves of Carthamus tinctorius. Methods The alkaloids were isolated and purified by silica gel, MCI, Sephadex LH-20 column chromatographies, and semi-preparative HPLC, and their structures were elucidated by physical and spectroscopic analysis. Results A new β-carboline alkaloid, 4,9-dimethoxy-1-ethyl-β-carboline (1) along with one known analogue 4-methoxy-1-ethyl-β-carboline (2), were isolated from the leaves of C. tinctorius. Compounds 1 and 2 showed the cytotoxicity against HepG2 cell lines with IC50 values of (15.2 ± 0.58) μmol/L and (17.4 ± 0.33) μmol/L, respectively. Conclusion Compounds 1 and 2 are firstly obtained from Carthamus genus, and compound 1 is a new compound named carthine A. Both compounds 1 and 2 exhibited cytotoxicity against HepG2 cell lines.

A new coumarin isolated from root barks of Zanthoxylum schinifolium / 中草药

Objective: To study the anti-inflammatory components from the root barks of Zanthoxylum schinifolium. Methods: The compounds were isolated and purified by silica gel, MCI, Sephadex LH-20 column chromatographies, and semi-preparative HPLC, and their structures were elucidated by physical and spectroscopic analysis. The anti-inf1ammatory activity was evaluated by the levels of NO in LPS-induced RAW264.7 tested by Griess reagent. Results: Four coumarins, namely zantholin A (1), 7-methoxycoumarin (2), isoscopoletin (3), and esculetin (4), were isolated from the root barks of Z. schinifolium. Compounds 1-4 exhibited anti-inflammatory activities on inhibition of lipopolysaccharide (LPS)-induced NO production in RAW 264.7 macrophages with IC50 values of (0.21 ± 0.03), (0.92 ± 0.16), (0.15 ± 0.02), and (0.26 ± 0.04) μmol/L, respectively. Conclusion: Compound 1 is a new compound, a rare terpenylated coumarin named zantholin A, and compounds 3 is obtained from this plant for the first time. All compounds exhibited anti-inflammatory activities.

Clinical comparison between a percutaneous hydraulic pressure delivery system and balloon tamp system using high-viscosity cement for the treatment of osteoporotic vertebral compression fractures

OBJECTIVES: Osteoporotic vertebral compression fractures (OVCFs) affect the elderly population, especially postmenopausal women. Percutaneous kyphoplasty is designed to treat painful vertebral compression fractures for which conservative therapy has been unsuccessful. High-viscosity cement can be injected by either a hydraulic pressure delivery system (HPDS) or a balloon tamp system (BTS). Therefore, the purpose of this study was to compare the safety and clinical outcomes of these two systems. METHODS: A random, multicenter, prospective study was performed. Clinical and radiological assessments were carried out, including assessments of general surgery information, visual analog scale, quality of life, cement leakage, and height and angle restoration. RESULTS: Using either the HPDS or BTS to inject high-viscosity cement effectively relieved pain and improved the patients' quality of life immediately, and these effects lasted at least two years. The HPDS using high-viscosity cement reduced cost, surgery time, and radiation exposure and showed similar clinical results to those of the BTS. In addition, the leakage rate and the incidence of adjacent vertebral fractures after the HPDS treatment were reduced compared with those after treatment using the classic vertebroplasty devices. However, the BTS had better height and angle restoration abilities. CONCLUSIONS: The percutaneous HPDS with high-viscosity cement has similar clinical outcomes to those of traditional procedures in the treatment of vertebral fractures in the elderly. The HPDS with high-viscosity cement is better than the BTS in the treatment of mild and moderate OVCFs and could be an alternative method for the treatment of severe OVCFs.

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.

Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.

Analysis of Medical Service Capacity of Otorhinolaryngology in County-level Hospitals in Ningxia / 中国医院管理

Objective To investigate the status quo of Otolaryngology services in county-level hospitals in Ningxia,to know its developmentbottlenecks and shortcomings,and to provide suggestions for promotion of Otolaryngotogy medical service ability in county-level hospitals in Ningxia.Methods By cluster sampling method,and through questionaire survey,investigating and analyzing the actuality of Otorhinolaryngology in county-level hospitals in Ningxia.Results The current status of Otorhinolaryngology in county-level hospitals in Ningxia was lower than the standard of county-level hospitals.The number of personnel and equipment is seriously insufficient.Few medical technology can be carried out.The number of outpatients and discharged patients increases.The number of outgoing patients increases.Conclusion The medical service ability of Otorhinolaryngology in county-level hospitals in Ningxia is low.It is suggested to formulate development plans and to innovate development way;to develop human resources,and to upgrade technical level;to use information platform,and to joint construction of academic alliances.

Relationship Between Plasma Jagged1 Protein Level and Coronary Collateral Circulation in Patients With Coronary Artery Disease / 中国循环杂志

Objective: To explore the relationship between plasma Jagged1 protein level and coronary collateral circulation (CCC) formation in patients with coronary artery disease(CAD). Methods: According to coronary angiography (CAG) examination, our research was categorized in 2 groups: CAD group, n=89 patients with at least one of left anterior descending (LAD), left circumflex(LCX) or right coronary artery(RCA) stenosis ≥ 95％ and Control group, n=30 subjects without abnormal findings by CAG. Based on Rentrop grading system, CAD group was further divided into 2 subgroups: Good CCC subgroup, n=42 patients with Rentrop grade ≥ 2 and Poor CCC subgroup, n=47 patients with Rentrop grade≤1. Plasma levels of Jagged1 protein,vascular endothelial growth factor (VEGF) were measured by ELISA and the relevant correlation study was conducted by multivariate regression analysis. Results: Compared with Control group, CAD group had increased plasma levels of Jagged1 protein (38.74±10.60)ng/L vs (23.04±8.97)ng/L and elevated VEGF (113.98±30.80)pg/L vs (72.73±14.55)pg/L. Compared with Poor CCC subgroup, Good CCC subgroup presented increased Jagged1 protein (46.77±8.49)ng/L vs (31.56±6.26)ng/L and elevated VEGF (128.10±20.24) pg/L vs (92.43±21.09)pg/L. Correlation study showed that Jagged1 protein was positively related to VEGF in CAD patients (r=0.730, P<0.01); multivariate regression analysis indicated that Jagged1 protein (OR=1.318, P=0.000) and VEGF (OR=1.043, P=0.043) were the independent predictors for CCC processing.Conclusion: CAD patients with good CCC had the higher plasma Jagged1 protein level than the patients with poor CCC which implied that Jagged1 protein played important role in CCC processing, such finding may provide a new direction for treating CAD patients in clinical practice.

Humoral immunity evaluation and virual challenge of lysosomal targeted hantavirus envelope glycoprotein DNA vaccine / 中国免疫学杂志

Objective:To build the DNA vaccine encoding hantavirus glycoprotein fused with lysosome-associated membrane protein (LAMP) and assess its immune response.Methods:BALB/c mice were immuned with the previous experimental expressing purified recombinant plasmids pVAX-Gn,pVAX-Gc,pVAX-LAMP/Gn,pVAX-LAMP/Gc,and inactivated vaccine.Indirect ELISA and neutralization test was used to detect specific antibody and neutralizing antibody in the serum of mice.The mice were tested to detect the protective effects in vivo.Results:Indirect ELISA results showed that the pVAX-LAMP/Gc group was the highest,followed by pVAX-Gc,pVAX-LAMP/Gn,and PVAX-Gn,and inactivated vaccine group.In neutralization test,there were significantly higher serum antibodies in LAMP group than those in conventional DNA group,which were higher than the inactivated vaccine group.The mice immuned had good protective effect in vivo without the specific antigen of hantavirus in vivo.Conclusion:Chimeric DNA vaccines induced higher levels of antibody in BALB/c mice and produced better protective efficacy,which illustrate the targeting strategy is expected to be an effective way to improve the DNA vaccine efficacy.

Evaluation of early macular retinal microcirculation in diabetic patients using optical coherence tomography angiography / 眼科新进展

Objective To observe the early changes in the area of the foveal avascular zone (FAZ) and macular vascular density (MVD) in diabetic patients using optical coherence tomography angiography (OCTA) and its clinical significance.Methods This was a retrospective study.Totally 33 patients with diabetes mellitus were enrolled,including 13 patients with no-diabetic retinopathy (NDR group) and 20 patients with nonproliferative diabetic retinopathy (NPDR group) according to the international clinical grading criteria of diabetic retinopathy.Additional 26 healthy subjects with matched age were enrolled in the control group.All the subjects underwent the 3 mm ×3 mm scanning of macular retina by OCTA for obtaining 4 levels of macular vascular density map.And the area of the FAZ and the MVD were measured.Results The area of FAZ was(0.392 ± 0.028) mm2 in the NDR group and (0.410 ± 0.019) mm2 in the NPDR group,respectively,and the difference was statistically significant compared with the control group (0.314 ± 0.025) mm2 (all P =0.000),and there was statistically significant difference between the NDR group and NPDR group (P =0.010).The MVD in the superficial retinal layer,deep retinal layer,outer retinal layer and choroidal capillary layer was 0.500 ±0.012,0.553 ±0.007,0.393 ±0.005,0.651 ±0.006 in the NDR group,and 0.484 ± 0.012,0.522 ± 0.007,0.397 ± 0.007,0.642 ± 0.007 in the NPDR group,respectively,and the difference was statistically significant compared with the control group (0.518 ±0.014,0.572 ±0.008,0.385 ±0.005,0.666 ±0.007) (all P =0.000);there were statistically significant differences in MVD between the NDR group and NPDR group in the superficial retinal layer,deep retinal layer and choroidal capillary layer (all P =0.000),but not in the outer retinal layer (P =0.065).Conclusion OCTA suggested that the early retinal microcirculation impairment in the macula in patients with diabetes,which changes with the progression of the disease.

Efficacy of intravitreal ranibizumab combined with laser photocoagulation for the treatment of macular edema induced by ischemic branch retinal vein occlusion / 眼科新进展

Objective To observe the therapeutic efficacy of intravitreal ranibizumab combined with laser photocoagulation for the treatment of macular edema associated with ischemic branch retinal vein occlusion (BRVO).Methods Together 60 patients (60 eyes) with BRVO in Anshan City Central Hospital were included and divided into three groups,20 patients with intravitreal ranibizumab treatment as A group,20patients with retinal laser photocoagulation treatment as B group,and another 20 patients with intravitreal ranibizumab combined with retinal laser photocoagulation therapy as C group,followed by the preoperative observation of the best corrected visual acuity (BCVA),slit lamp,fundus and intraocular pressure examination,fundus fluorescein angiography (FFA),optical coherence tomography (OCT).One day after the surgery,BCVA,slit lamp and intraocular pressure examination were conducted,and 1 month,2months,3 months after the surgery,observation of BCVA,slit lamp,fundus and intraocular pressure examination were performed.Then,OCT was used to determine the status of macular edema.And finally,BCVA and central macular thickness (CMT) in the three groups were statistically analyzed by observing the above indicators.Results The BCVA at 1 month,2 months,and 3 months after treatment was higher than before treatment in all three groups,and the differences were statistically significant (all P ＜ 0.05).The BCVA of A group was 0.26 ±0.14 and 0.26 ±0.14 at 2 and 3 months after treatment,respectively,which was significantly better than that of B group (0.39 ±0.10 and 0.40 ±0.10) (all P ＜0.05).At 3 months after treatment,the BCVA in C group was 0.14 ±0.11,which was significantly higher than that in A group (0.26 ±0.14) (P＜0.05).The BCVA of C group was 0.30 ±0.13,0.20 ±0.12,0.14 ± 0.11 at 1 month,2 months and 3months after treatment,respectively,which was better than that of B group (0.43 ±0.10,0.39 ± 0.10,0.40 ± 0.10),and the differences were statistically significant (all P ＜0.05).The postoperative CMT was significantly reduced when compared with preoperation in all three groups (all P ＜ 0.05).The CMT at 1 month,2 months and 3 months after treatment in C group was (318.85 ± 71.48)μm,(287.15 ± 56.71) μm and (255.05 ± 60.90)μm,respectively,which was better than that in A group [(347.00 ± 67.59) μm (305.10 ± 47.44) μm and (282.40 ± 36.26) μm],and B group [(417.05 ± 63.94) μm,(394.80 ±57.18) μm,and (375.90 ± 55.10) μm],with significant differences (all P ＜ 0.05).At 2 months and 3 months after treatment,CMT in A group was better than that in B group,and the difference was statistically significant (P ＜ 0.05).Conclusion The efficacy of retinal laser photocoagulation combined with intravitreal ranibizumab in the treatment of BRVO macular edema is better than simple retinal laser photocoagulation and simple intravitreal ranibizumab.

Study on alkaloids from Ervatamia hainanensis / 中草药

Objective: To study the alkaloids from Ervatamia hainanensis. Methods: The alkaloids were isolated and purified by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC, and their structures were elucidated by physical and spectroscopic analysis. Results: Twelve alkaloids were obtained and identified as coronaridine (1), 19-epi-heyneanine (2), 9,10-dimethoxycoronaridine (3), vobasine (4), vobasine N(4)-oxide (5), 3-oxo-19-epi-heyneanine (6), strictamine (7), deacetylakuammiline (8), pandine (9), rhazicine (10), rhazicine N(4)-oxide (11), and rhazimine (12). Conclusion: Compounds 8 and 10-12 are isolated from the genus Ervatamia Stapf for the first time, while compounds 3 and 5-7 are firstly obtained from E. hainanensis.

Exogenous hydrogen sulfide inhibits high-glucose-induced injuries via regulating leptin/leptin receptor signaling pathway in human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate whether exogenous hydrogen sulfide (H2S) inhibits the high-glucose (HG)-induced injury by modulating leptin/leptin receptor (LEPR) signal pathway in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>HUVECs were treated with 40 mmol/L glucose for 3-24 h, and the cell viability was examined by CCK-8 assay. The changes of cell morphology and the number of apoptotic cells were assessed by Hoechst 33258 nuclear staining followed by photofluorography. The intracellular levels of reactive oxygen species (ROS) was detected by DCFH-DA staining followed by photofluorography. Mitochondrial membrane potential (MMP) was determined by Rhodamine 123 (Rh123) staining and photofluorography. The expression levels of leptin and LEPR protein were measured by Western blotting.</p><p><b>RESULTS</b>s The expression of leptin and LERP in HUVECs began to significantly increase at 3 h after HG exposure and reached the peak levels at 9 h (P<0.01). Pretreatment of HUVECs with 400 µmol/L sodium hydrosulfide (H2S donor) for 30 min inhibited HG-induced increase in leptin and leptin receptor expressions in HUVECs (P<0.01). Pretreatment of HUVECs with 400 µmol/L NaHS for 30 min or 50 ng/mL leptin antagonists (LA) for 1 h obviously alleviated HG-induced injury by increasing cell viability, decreasing cell apoptosis and lowering accumulation of intracellular ROS and MMP loss (P<0.01).</p><p><b>CONCLUSION</b>Exogenous H2S protects against HG-induced injury by inhibiting leptin/LEPR pathway in HUVECs.</p>

Monitoring the progression of renal fibrosis by T2-weighted signal intensity and diffusion weighted magnetic resonance imaging in cisplatin induced rat models / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diffusion weighted imaging (DWI), with the applying of intravoxel incoherent motion model, has showed promising results in obtaining additional information about microperfusion and tubular flow associated with morphologic changes in chronic kidney diseases. The study aims to evaluate the potential of T2-weighted signal intensity (SI) and DWI with mono- and bi-exponential models to reflect the serial changes on cisplatin (CP) induced rat renal fibrosis models.</p><p><b>METHODS</b>Magnetic resonance exams were performed prior to and 2 nd day, 4 th day, 6 th day, 8 th day, 2 nd week, 3 rd week and 4 th week after CP injection at a 3.0T with an animal coil. Besides T2-weighted images (T2WI), DWI of 13 b values from 0 to 1500 s/mm 2 was acquired. Apparent diffusion coefficient (ADC), fluid fraction f, pure diffusivity D and pseudodiffusivity DFNx01 values were calculated. The regions of interest were placed on cortex (CO), outer stripe of the outer medulla (OM) and inner stripe of the outer medulla (OM), parameters were measured and compared among different time points. Five rats were scarified at each time point for pathological examination.</p><p><b>RESULTS</b>OM revealed remarkable hyperintense and broadened before it became an obscure thread, while CO demonstrated moderate hyperintense and IM didn't show significant change on T2WI. On all three stripes, ADC values decreased firstly then kept increasing since the 4 th day; f values decreased on all stripes; D values had a tendency to increase with fluctuations but the changes didn't achieve statistical significance; DFNx01 values increased at the 2 nd day then tended to be steady thereafter. Pathological findings revealed tubules epitheliums swelling followed by inflammation cells infiltration, interstitial fibrosis was observed since the 2 nd week.</p><p><b>CONCLUSIONS</b>All of T2-weighted SI, ADC, and biexponential models parameters vary during fibrotic process; biexponential model is superior to monoexponential model in separating changes of microperfusion together with tubular flow from pure diffusion.</p>

Preparation of curcumin-loaded long-circulating liposomes and its pharmacokinetics in rats / 中国中药杂志

Curcumin has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin are major challenge in its development as a useful drug. To overcome many of these problems, curcumin-loaded long-circulating liposomes (Cur-LCL) were prepared by the ethanol injection method. Morphology of Cur-LCL was observed by transmission electron microscope, mean particle size and Zeta potential were detected by laser particle size analyzer, entrapment efficiency and drug loading were evaluated by ultracentrifugation. The drug release behavior in vitro and pharmacokinetic behavior in rats of Cur-LCL were investigated with curcumin (Cur) and curcumin liposomes (Cur-Lips) as control. The results showed that the mean diameter of Cur-LCL was 110 nm, the Zeta potential was -5.8 mV. The entrapment efficiency and drug loading of Cur-LCL was 80.25%, 2.06%, respectively. The release behavior in vitro studied by dialysis in PBS buffer showed significant sustained release profile that 48.95% Cur were released from Cur-LCL in 7 h, 88.92% in 24 h. The pharmacokinetic parameters showed that compared with Cur and Cur-Lips, the t(1/2beta) of Cur-LCL was extended to 13 and 1.8-fold, respectively. Besides, the AUC values was significantly increased (P < 0.01), and the clearance was evidently decreased (P < 0.01). These results from in vitro and in vivo indicated that Cur-LCL were able to realize controlled drug release and increase circulation time.

Antifungal azoles exacerbate vinblastine-related hyponatremia in ALL children / 中国实验血液学杂志

The purpose of this study was to investigate the clinical characteristics and the treatments of patients with vinblastine-related hyponatremia which was aggravated by azole antifungal agents in children with acute lymphoblastic leukemia(ALL). A total of 93 children treated with vinblastine in our department during April 2013 to March 2014 were enrolled in this study and were divided into 3 groups:VDLD, VDLD with azoles antifungal, VDLD with non azoles antifungal. The incidence and severity of hyponatremia were statistically analysed. The results showed that (1) the incidence of hyponatremia in VDLD group was 93.1%(67/72),100%(13/13) in VDLD with azoles antifungal group, and 75%(6/8) in VDLD with non-azoles antifungal, there was no statistically difference between these three groups. (2) Incidence of moderate to severe hyponatremia (Na<129 mmol/L) in VDLD with azoles antifungal group was(9/13,69.2%),which was significartly higher than those in VDLD group (22/72, 30.6%) and in VDLD with non azoles antifungal group (1/8, 12.5%). However, the difference between VDLD group and VDLD with non azoles antifungal group were not statistical significant. (3) the lowest serum sodium level in VDLD with azoles antifungal group (124.0 ± 8.6 mmol/L) was significantly lower than that in VDLD group (130.8 ± 3.8 mmol/L)and VDLD+non azoles antifungal group(132.9 ± 4.9 mmol/L). Otherwise, the difference was not statistically significant between VDLD group and VDLD with non azoles antifungal group. (4) four children with severe hyponatremia showed convulsions and coma which all belong to VDLD with azoles antifungal group. The children with hyponatremia were restricted intake of fluid, adjusted the liquid tension, supplied hypertonic sodium and given diuretic, the serum sodium value gradually picked up in these children. In 4-11 months' follow-up, no hyponatremia happened again in these children. It is concluded that the incident of hyponatremia in children treated with vinblastine is high, but most of them seldom showed clinical characteristics. The combination of antifungal azoles with vinblastine can increase the incidence and severity of hyponatremia. Therefore, combined administration of azole antifungals with vinblastine should be avoided.