Biological Connotation of Pathogenesis of Ulcerative Colitis with Liver Depression and Spleen Deficiency Based on Bile Acid-intestinal Flora Axis / 中国实验方剂学杂志

Ulcerative colitis （UC） is one of the chronic refractory inflammatory bowel diseases characterized by abdominal pain， diarrhea， and mucus， pus and blood in the stool. In recent years， with changes in human life style and improvements of the diagnosis， the incidence and prevalence of UC have been increasing. The pathogenesis of UC is closely related to intestinal mucosal immune dysfunction， intestinal flora disturbance， and abnormal bile acid secretion. Patients with UC have abnormal bile acid secretion and intestinal flora imbalance. A large number of studies have found that abnormal bile acid secretion inhibits immune function， affects signal transduction， and destroys the intestinal mucosal barrier. Intestinal flora disturbance has an important impact on the occurrence and development of inflammation， immune homeostasis， and stress. Bile acids indirectly or directly affect the structure and function of intestinal flora， and at the same time， they produce secondary bile acids under the modification of intestinal flora， entering the liver through enterohepatic circulation. Therefore， the complex dialogue mechanism of bile acid-intestinal flora axis is closely related to the occurrence and development of UC. Based on the basic theory of traditional Chinese medicine（TCM） and clinical research， it is found that emotion is an important factor that induces this disease， spleen and stomach weakness is the root of the disease， and liver depression and spleen deficiency are the key pathogenesis of UC. Combined with modern medicine and molecular biology research， it is believed that abnormal secretion of bile acids is a microscopic manifestation of liver depression in TCM， and intestinal flora disturbance is the biological basis of spleen deficiency. In the pathogenesis of UC， the imbalanced bile acid-intestinal flora axis is consistent with the pathogenesis of liver depression and spleen in TCM. The exploration of the biological connotation of the pathogenesis of UC with liver depression and spleen deficiency from the perspective of bile acid-intestinal flora axis can better explain the scientific nature of its pathogenesis， which provides new clinical solutions and reliable references for studying the pathogenesis of UC with liver depression and spleen deficiency and finding representative prescriptions to prevent and treat this disease.

Research progresses of biomarkers in early detection of diabetic nephropathy / 中国医师杂志

Although significant progress has been made in the diagnosis and treatment of diabetic nephropathy (DN) patients over the past decades,the mortality rate for DN patients has not been significantly reduced.If effective drug intervention is carried out at the early stage of DN,DN pathophysiological progress will be significantly delayed or hindered.Therefore,it is urgent to develop and apply clinically effective biomarkers for diagnosing early DN.In this paper,biomarkers commonly used in the early detection of diabetic nephropathy and the potential biomarkers involved in the pathogenesis and progression of DN are reviewed.It is expected to provide new ideas and directions for further understanding and development of early biomarkers.

A clinical analysis of micafungin treatment of pulmonary invasive fungal infection in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation / 中华儿科杂志

Objective@#To investigate the efficacy and safety of micafungin (MCF) for pulmonary invasive fungal disease (PIFD) in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation.@*Method@#Twenty-five neutropenic PIFD children with acute leukemia or post hematopoietic stem cells transplantation in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were selected from January 2012 to June 2015, including 12 males and 13 females, age range 2-15 (average 6.2±2.0) years. There were 12 cases of acute leukemia (AL) after chemotherapy, 4 cases of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 9 cases of β-thalassemia major after allo-HSCT. All children received MCM for the treatment of PIFD, the dosage of MCM was 3-4 mg/ (kg·d) , once a day. The children received 2 to 6 courses of treatment, individually with a course of 7 days. 1, 3-β-D glucan assay (G test), galactomannan antigen test (GM test), high-resolution CT and the biochemical indexes for organ functions were closely monitored.@*Result@#Twenty-five cases were diagnosed as PIFD, including 2 patients diagnosed as proven, 6 as probable and 17 as possible. Of the 25 cases, 1 was confirmed aspergillus by biopsy pathology and 1 was candida albicans by blood culture. The G and GM test with positive results was 5 and 2 respectively. Chest CT scans of the 25 cases had obvious lesions: air crescent sign and cavitation in 4 cases, diffuse ground glass change in 9 cases, double lung scattered patchy, small nodules and cord like high density shadow in 7 cases, unilateral or bilateral chest wall wedge-shaped consolidation edge in 5 cases and pleural effusion in 5 patients. The effective rate of MCF in treatment of PIFD was 68% (17/25), including 13 cases cured, 4 cases improved, 4 cases were improved clinically and in 4 cases the treatment was ineffective. Eight cases were effective in MCF monotherapy group (12 cases) and nine were effective in MCF combined therapy group(13 cases), respectively. Side-effects including allergies, gastrointestinal side effects, electrolyte disturbances, impairment of liver and kidney function, and myelosuppression were not found in those children treated with MCF.@*Conclusion@#Micafungin is effective and safe in the treatment of pulmonary invasive fungal disease in pediatric patients with acute leukemia or post hematopoietic stem cell transplantation.

Combination antifungal therapy for invasive fungal disease in children with hematologic disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate antifungal combination strategy in children with hematologic diseases and invasive fungal disease( IFD).</p><p><b>METHODS</b>A retrospective clinical study was performed based on 67 childhood patients with hematologic diseases and IFD who firstly accepted combination antifungal therapy for ≥ 7 days during January 2012 and December 2014. Of them, 11 cases received combination of echinocandin with azole, 10 cases received combination of echinocandin with amphotericin B, and 46 cases received combination of azole with amphotericin B.</p><p><b>RESULTS</b>Overall response rate was 79.1%. Univariate analysis revealed that granulocyte recovery (P=0.031), status of underling disease (P=0.023) and the duration of the therapy (P=0.046) were significantly associated with efficacy. Multivariate analysis showed that the independent prognostic factor was the duration of combination antifungal therapy (OR=0.229, 95% CI 0.061- 0.863, P=0.029). The response rates of echinocandin combined with azole, echinocandin combined with amphotericin B and azole combined with amphotericin B were 81.8%, 60.0% and 82.6%, respectively (P>0.05), and 12-week survival rates were 81.8%, 80.0% and 86.5%, respectively (P>0.05). The drug- related adverse reactions occurred 59 times in 34 patients. BUN increasing, hypokalemia and abnormal liver functions were considered the main side effects.</p><p><b>CONCLUSION</b>For IFD in children with hematologic disease, to extend the duration of treatment (≥ 14 days) could significantly improve the curative effect. Combinations of echinocandin with azole, echinocandin with amphotericin B and azole with amphotericin B can be used as a combination treatment options. Combination of Azole with amphotericin B is efficacious, safe and economic treatment option considering efficacy, survival rate, cost and dosage form.</p>

Synthesis and anti-myocardial ischemia activities of novel Danshensu derivatives / 药学实践杂志

Objective To design and synthesize novel Danshensu derivatives in order to improve their stability and cardio-protective effect against myocardial ischemia .Methods Novel Danshensu derivatives were synthesized chiefly viaesterification , methoxy phenol hydroxyl protection ,nitration and amine solution reaction .All the target compounds were evaluated their bio-logical effects on anti-myocardial ischemia with H9c2 cells in vitro .Results 15 compounds were synthesized and further con-firmed by 1 H NMR and MS .Pharmacological studies showed that few synthetic derivatives at 5μmol/L performed a higher bi-ological effect than Danshensu .Conclusion Most derivatives didn't show the best activity at the chosen concentration gradient that a further pharmacological trial need to be done .

Preparation and characterization of salinomycin sodium loaded nano liposomes / 药学实践杂志

Objective To prepare and characterize salinomycin sodium‐loaded nano liposomes(SLN) .Methods The nano liposomes were prepared by a thin‐film dispersion method .The formula of SLN was optimized by regulating the cholesterol ratio of the nano liposomes ,using the encapsulation efficacy (EE) of SLN as the primary outcome measure .Results Transmission e‐lectron microscope (TEM) showed that SLN was round and had a good dispersion .Dynamic laser scatter (DLS) showed that SLN was of a desired size of 99 nm ,and zeta potential of -33 .5 mV .EE of SLN was 85 .7% and drug loading of 6 .7% .Ac‐cording to the formulation of nano liposomes ,the concentration of salinomycin sodium in water was greatly improved by 15 folds .Additionally ,the nano liposomes were observed to exhibit sustained release characteristics .Conclusion Salinomycin sodi‐um‐loaded nanoliposomes of a desired size of about 100 nm were obtained ,which were well dispersion ,and high EE and drug loading .Solid pharmaceutics foundation for the activity examination of SLN was provided in this research .

A comparison study of synthesizing methods of thiolated dxooru bicin / 药学实践杂志

Objective To investigate the optimal method for synthesizing thiolated doxorubicin .Methods Thiolated doxorubi-cin was synthesized through two different methods .Doxorubicin was reacted with 2-iminothiolane (2-IT) and S-acetylthioglycolic acid N-hydroxysuccinimide ester (SATA),respectively.The synthesized thiolated doxorubicin was further characterized by HPLC and MS -ESI techniques .Several factors including molar ratios as well as reaction time were evaluated .Results The results showed that thiolat-ed doxorubicin could be synthesized via both of the two methods successfully .Thiolated doxorubicin could be stable when doxorubicin was reacted with SATA .But the crude thiolated doxorubicin could be cyclized easily when doxorubicin was reacted with 2-IT.Conclu-sion Thiolated doxorubicin prepared with SATA is more feasible than that with 2-IT.

Influence of serum complement and IgG on rituximab-dependent NK cell-mediated cytotoxicity to Raji cells / 白血病·淋巴瘤

Objective To determine the influence of serum complement and IgG on rituximabdependent NK cell-mediated cytotoxicity to Raji cells in vitro.Methods FcγR Ⅲ a (CD16a) polymorphism of NK cells were detected by nest-PCR. Effects of serum IgG on FcγRⅢ a expression of NK cells in vitro were analyzed by flow cytometry.The target cells(Raji cells) were stained with DIO,cultured with effector cells(NK cells) and rituximab with or without serum IgG/complement,and finally stained with propidium iodide (PI),then these cells were tested by flow cytometry and the cytotoxic index was calculated as well. Results The cytotoxic indexes of the ADCC +CDC groups were higher than those of ADCC groups, but the serum IgG groups were lower than the ADCC groups. In FcγRⅢa-158Ⅴ/Ⅴ groups, the cytotoxic indexs of the ADCC+ CDC groups,the serum IgG groups and the ADCC groups were (94.25±1.79) ％,(59.79±0.66) ％ and(69.05± 2.38) ％,respectively,and the differences among the groups were statistically significant (P＜ 0.05).In FcγRⅢ a-158Ⅴ/F groups,the cytotoxic indexs of these three groups were (66.71±5.57) ％,(18.13±2.99) ％ and (39.63±3.86) ％, respectively, and the differences among the groups were also statistically significant (P＜ 0.05).Conclusions Complement may enhance the rituximab-mediated NK cell cytotoxicity to Raji cells, whereas,serum IgG may weaken the cytotoxicity against Raji cells. It is clued up that for patients treated by tumorspecific monolonal antibody (MAb), combined infusion of fresh frozen plasma could promote its anti-tumor effect,however,MAb combined with IVIG may impair its anti-tumor effect.

Inhibition of leukemia mediated by vascular endothelial growth factor receptor 2 short hairpin RNA gene silencing / 中国组织工程研究

BACKGROUND: Vascular endothelial growth factor receptor 2 (VEGFR2) is primarily involved in vascular endothelial growth factor (VEGF)-mediated signal transduction and plays a critical role in the pathological angiogenesis that occurs in a number of diseases, including leukemia. Besides, VEGF secreted by leukemia cells also induces its own expression which leads to an enhanced production of VEGFR2 which contributes to the survival and proliferation of leukemia cells.OBJECTrVE: To evaluate the inhibitive effect of Lenti6/shVEGFR2 on the VEGFR2 expression and leukemia growth in mouse.DESIGN: A randomized, parallelized, controlled and open trial.SETTING: Department of Pediatrics, the Second Affiliated Hospital of Sun Yat-sen University; Biotechnology Research Center, Sun Yat-sen University.MATERIALS: The experiment had been done in the laboratories for Medical Research Center of the Second Affiliated Hospital, Sun Yat-sen University and Biotechnology Research Center, Sun Yat-sen University from May 2004 to January Lentiviral RNAi Expression System was purchased from Invitrogen, Co.,Ltd.; human VEGFR2 Mcb (PE) was purchased from R&D; CD31 immunohistochemistry kit was purchased from Boster, Co.,Ltd.; CD33-PE fluorescence labeled antibody was purchased from BD, Co.,Ltd.transiently and expression clone (Lenti6/shVEGFR2) was constructed, then cotransfected with ViraPowerTM Packaging Mix pU6/shVEGFR2 entry clone and transducting with Lenti6/shVEGFR2 expression clone, the effect on the development of intravenous xenograft leukemia mouse model, the distribution of microvessels in mouse bone marrow was observed after leukemia model mouse injected with recombinant lentivirus (group B); leukemia model mouse injected with recombinant lentivirus and endothelial cell (group C); leukemia model mouse injected with endothelial cell (group D). Through detecting changes of CD33 positive cells and microvessel density (MVD) in bone marrow, observing peripheral blood cell (PBC)smear and slice of liver, spleen, the effect of Lenti6/shVEGFR2 recombinant lentivirus on mouse leukemia was evaluated.mediated with lentivirus on VEGFNEGFR2 paracrine and autocrine loops in leukemia mouse.effective in inhibiting HL60 cell. pU6/shVEGFR2 entry clone constructed according to it had cell inhibitory rate as high as after transfection of pU6/shVEGFR2 entry clone and transduction of Lenti6/shVEGFR2 expression clone: 48 hours after transfection of pU6/shVEGFR2 entry clone and transduction of Lenti6/shVEGFR2 expression clone, the cell growth inhibitive rates were similar. However, the cell growth inhibitive rate of entry clone descended rapidly after 48 hours (P＜0.01); which of expression clone changed slowly, reaching the peak at 96 hours, dropped slightly, having no significance mouse: The amount of HL60 cells in bone marrow of groups A, B and C detected with flow cytometry were (25.8%±4.9)%, (14.3%±5.1)%, (8.4±2.6)%, respectively (P＜0.05); MVD in group C was obviously less than that in group D (P＜0.05); The amount of HL60 cells in leukemia model mouse injected with recombinant lentivirus and endothelial cell was the lowest as compared with the other groups.

Hospital Infection of Inpatients with Indwelling Catheter:Objective Monitoring and Analysis / 中华医院感染学杂志

OBJECTIVE To investigate the incidence of hospital infection in patients with indwelling catheter and its risk factors, the inpatients were monitored and the measures were taken to prevent the patients from infection. METHODS Monitoring 617 patients with indwelling catheter, retrospective survey and analysis study were available , including a plan to detect microbe, to study the medical history and to examine the patients. RESULTS Eighty nine patients with 106 cases-times of urinary tract infection happened, and its incidence rate was 14.42 percent with the highest rate in all the hospital infection cases. The main risk factors of urinary tract infection included inserting catheter, unclean operation, delayed removing of catheter and unreasonable application of antibiotic . CONCLUSIONS Controlling the indication, shortening the time of indwelling catheter, keeping urinary aseptic manipulation and rational application of antibiotic are effective measurement for the patients with indwelling catheter.

Corrosion rate measurements of biomedical TiNi shape memory alloy and cobalt alloys / 生物医学工程学杂志

The corrosion rates of TiNi, CoCrNiW and CoCrNiMo were measured in Tyrode's solution with potentiodynamic linear polarization, fore-point weak polarization, Cao Chunan weak polarization, transient linear polarization and atomic absorption spectroscopy. Results indicated that corrosion rates of these three alloys were very low due to their excellent corrosion resistance and the corrosion resistance of CoCrNiMo was the best. Corrosion rates of TiNi, CoCrNiW and CoCrNiMo were 0.691, 0.0595, 0.0490 micron/a and 0.0528, 0.0383, 0.0387 micron/a, respectively. The results measured by the first three methods were about ten times of those by the latter two methods, this was related to the applicability of each method and the alloy surface state. Transient linear polarization technique can determine low corrosion rate conveniently and quickly. Atomic absorption spectroscopy method, determining directly the concentration of ion in solution, and thus provide reference for material biocompatibility. And these two methods are properly used in measuring corrosion rates for biomedical materials.

Serious central nervous system involvement in childhood systemic lupus erythematosus / 中国小儿急救医学

Objective　To study the characteristics of serious central nervous system(CNS) involvement in childhood systemic lupus erythematosus.Methods　We made a comparison on the level of ANA、dsDNA and positive rate of Sm、C3 between primary and secondary CNS involvement and analysed the clinical manifestations between two groups.Results　The level of ANA、dsDNA and ositive rate of Sm、C3 were not related with SLE encephalopathy;EEG was useful to the diagnosis of SLE.Conclusion　The differiential diagnosis between primary and secondary CNSD in volvement of SLE must be analysed according to clinical manifestations and other laboratory findings.

Xaf1 regulates TNFR signal pathway and induces apoptosis / 中国病理生理杂志

AIM:Xaf1-Saos inducible cell lines,which contain "gene switch" system were used to detect the effect of Xaf1 on tumor necrosis factor receptor(TNFR) signal pathway and to investigate the mechanism of cooperation between Xaf1 and TNF-? in inducing cell apoptosis.METHODS:Xaf1 on TNFR1 expression was measured by RT-PCR and Western blotting.The effect of NF-?B on Xaf1 induced apoptosis was detected by DNA content flow cytometry after co-transfection.DNA binding activity of NF-?B was identified by gel mobility shift assay and transcription activity of NF-?B was analyzed by luciferase assay and RT-PCR.SAPK/JNK activity was checked by SAPK/JNK assay.RESULTS:Xaf1 did not modulate TNFR1 at protein and mRNA levels.Increased NF-?B activity in cells inhibited Xaf1 induced apoptosis.Expression of Xaf1 impaired modestly TNF-? induced NF-?B DNA binding activation and transcription activation,also modestly reduced SAPK/JNK activity.CONCLUSION:Xaf1 inhibits TNFR signal pathway,partly contributing to cooperation with TNF-? to induce apoptosis.

Lethal effect of VEGFR_2 shRNA on HL60 cells in vitro using lentiviral vector / 中国病理生理杂志

AIM: To look for harmfulless anti-leukemia drug with selective high performance, lethal effect of small hairpin RNA (shRNA) on VEGFR2 gene expression of tumor cell line HL60 in vitro.METHODS: The most effective VEGFR2 siRNA was designed and screened. The shRNA oligo was designed and pU6/VEGFR2 entry clone was constructed. HL60 was transfected transiently and vascular endothelial growth factor receptor 2(VEGFR2) expression was tested with MTT assay, RT-PCR and Western blotting. The expression clone was constructed and cotransfected with ViraPowerTM Packaging Mix into 293FTTM cells to produce Lentiviral vectors harboring Lenti6/shVEGFR2. The virion supernatant was added into HL60 cells and VEGFR2 gene inhibitory effect was determined. RESULTS: The inhibitory rates of VEGFR2 siRNA c were high. VEGFR2 expression in HL60 was inhibited by using pU6/VEGFR2 entry clone constructed with shRNA and pENTRTM/U6. For HL60 cells, the inhibitory rate was 84.9%. The expression of VEGFR2 mRNA and protein decreased significantly. 48 hours after transfection of pU6/shVEGFR2 entry clone and transduction of Lenti6/shVEGFR2 expression clone, the cell inhibitory rates were similar. Cell growth inhibitory rate of entry clone descended rapidly after this time point, the expression clone changed slowly, reaching the peak at 96 hours, dropped slightly, having no significance deviation. CONCLUSION: in vitro, VEGFR2 shRNA using lentiviral vector blocks VEGF/VEGFR2 self-secretion in HL60 cells, which inhibits leukemia development.