Mechanism of curcumin inhibiting choroidal neovascularization in brown Norway rat / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the mechanism of curcumin inhibiting the choroidal neovascularization(CNV)of brown Norway(BN)rats.METHODS: CNV model of 36 BN rats was established through laser photocoagulation induction, and they were divided into 6 groups with 6 rats in each group. Normal group was fed normally with no intervention, while 532nm laser photocoagulation was used to establish a experimental CNV model in BN rats. Rats after modeling were respectively intervened for 14d and divided into model group, ranibizumab group, curcumin low [100mg/(kg·d)], medium [200mg/(kg·d)], and high [400mg/(kg·d)] dose group. The model group was given intragastric administration of saline for 14d, ranibizumab(10mg/mL, 0.2mL/dose)was injected at 2d after photocoagulation with 5μL once for rats in ranibizumab group, and different concentrations of curcumin were intragastrically administrated to the rats in low, medium and high groups for 14d. Fundus photography, fundus fluorescein angiography(FFA)and indocyanine green angiography(ICGA)examination were performed at 14d after photocoagulation. Ocular histopathological specimens of rats with CNV were made, and the central thickness of CNV were observed by HE staining. Ocular histopathological specimens were made, and the expressions of AKT/p-AKT/HIF-1α/VEGF signaling pathway-related proteins were observed by immunohistochemistry. The mRNA relative expressions of AKT/HIF-1α/VEGF factor in CNV tissues were detected by RT-qPCR, and the protein expressions of AKT/p-AKT/HIF-1α/VEGF factor in CNV tissues were detected by Western-blot.RESULTS: CNV generation rates in the model group, the ranibizumab group, and the low, medium and high-dose curcumin groups were 78.18%, 73.21%, 77.19%, 75.86%, 74.55%, respectively, which were higher than 70%. The average absorbance were 182.12±6.59, 119.22±8.03, 166.45±8.33, 164.34±5.69, 149.22±6.45, respectively; the ranibizumab group was significantly lower than the model group(P<0.05); the low-dose, medium-dose and high-dose groups were significantly higher than the ranibizumab group(P<0.05), and the curcumin high-dose group was significantly lower than the model group(P<0.05). HE staining showed that the retinal tissue structure of BN rats in normal group was clear and neatly arranged. The central thickness of CNV in the ranibizumab group was significantly reduced at 14d after photocoagulation compared with the model group(P<0.05); While the curcumin high-dose group was significantly reduced compared with the model group(P<0.05), but increased when compared with ranibizumab group(P<0.05). Immunohistochemistry results showed that AKT, p-AKT, HIF-1α, and VEGF factors were negatively expressed in the retinal tissue structure of BN rats in the normal group, and no brown-yellow reactants were found. The expression of AKT, p-AKT, HIF-1α, and VEGF factors in the model group were higher than that in the normal group at 14d after photocoagulation(P<0.05); the ranibizumab group was lower than the model group(P<0.05). While the expression of the curcumin high-dose group was significantly decreased compared with the model group(P<0.05), but significantly increased when compared with ranibizumab group(P<0.05). The mRNA results showed that the relative expression levels of AKT, HIF-1α and VEGF mRNA in the model group at 14d after photocoagulation were higher than those of the normal group(P<0.05); the ranibizumab group was lower than the model group(P<0.05). While curcumin high-dose group was significantly decreased compared with the model group(P<0.05), but significantly increased when compared with ranibizumab group(P<0.05). Western-blot results showed that there was no significant difference in the relative expression of AKT protein among each experimental groups at 14d after photocoagulation. The relative expression of p-AKT protein in the model group was significantly higher than that in the normal group(P<0.05); the ranibizumab group was significantly lower than the model group(P<0.05); the curcumin high-dose group was significantly lower than the model group(P<0.05). The relative expression levels of HIF-1α protein were significantly higher in the model group than in the normal group(P<0.05), and the ranibizumab group was lower than in the model group(P<0.05). The relative expression levels of HIF-1α protein was lower in the curcumin high-dose group than in the model group(P<0.05)but higher than ranibizumab group(P<0.05). The relative expression level of VEGF protein was significantly lower in the curcumin medium/high-dose group than in the model group(P<0.05).CONCLUSION: Curcumin at 400mg/(kg·d)has an inhibitory effect on CNV in BN rats. The mechanism may be closely related to inhibiting the activation of AKT/p-AKT/HIF-1α/VEGF signaling pathways.

Evolution Characteristics and Clinical Significance of Blood Separation in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the evolution of blood separation results by gel extraction of multiple myeloma (MM) patients, and to evaluate the clinical value of abnormal blood separation results for the evaluation of disease and prognosis.@*METHODS@#The clinical data of 5 patients diagnosed newly MM patients with abnormal blood separation of gel collection vessels in our hospital were retrospectively analyzed, and the changes of blood separation results and blood index levels were followed up with the improvement of treatment effect, and the correlation of different blood index levels was analyzed.@*RESULTS@#In 5 patients with newly diagnosed MM, the blood separation result showed floating phenomenon after centrifugation, which divided into three layers and the order from top to bottom is separator gel, serum, and red blood cells(RBC). With partial remission of clinical symptoms, the blood separation results were still abnormal, which were divided into three layers from top to bottom: serum, RBC and separator gel. Finally, with complete remission of the disease, blood separation results returned to normal, from top to bottom: serum, separator gel, RBC. With the blood separation results from abnormal to normal, the blood routine indicators: Hb, Hct levels gradually increased, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) gradually decreased; biochemical indexes: TP, GLB, Ig and β2-MG levels gradually decreased. Tumor load related indicators: serum IL-6, TNF-α, IL-17 levels gradually decreased, and IL-35 levels gradually increased; and the differences were statistically significant (P<0.05). Pearson correlation analysis showed that serum β2-MG was positively correlated with IL-6, TNF-α and IL-17 levels (r=0.710, 0.756, 0.581, P<0.05), and negatively correlated with IL-35 level (r=-0565, P<0.05).@*CONCLUSION@#Abnormal blood separation exists in MM patients, and there are significant differences in blood, tumor load and immune balance related indexes in patients with different blood separation results, which provides partial experimental basis for evaluation of disease, efficacy and prognosis with different blood separation results.

Advances on the research and treatment of autoimmune disease-related chronic wounds / 中华烧伤杂志

Autoimmune disease is a disease caused by the body's immune system being misdirected to attack the host itself. Patients with this type of diseases are in poor general condition, and are affected by vascular and skin tissue lesions, and therapeutic drugs. Once the skin is broken, chronic wounds that do not heal could easily develop. This type of wounds is difficult to treat and requires joint diagnosis and treatment of multidisciplinary physicians. Therefore, this article reviews the advances on research and treatment of autoimmune disease-related chronic wounds in order to provide reference for their clinical treatment.

Design, synthesis, and activity study of α-conotoxin A10LPnIA fluorescent probe / 药学学报

italic>α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems, and is closely related to a variety of neurological diseases and inflammation response. α-Conotoxin [A10L]PnIA, as an antagonist targeting α7 nAChR, plays an important role in studying the physiological and pathological processes involved in α7 nAChR. [A10L]PnIA was labeled with fluorescein 5-carboxytetramethylrhodamine, and the active peptide ([A10L]PnIA-F) was obtained by a two-step oxidative folding procedure in vitro. The Xenopus oocyte expression system and the two-electrode voltage clamp technique were used to identify the potency of [A10L]PnIA-F fluorescent peptide, and its cytotoxicity was detected by mouse macrophages and CCK8 method. The molecular weight of [A10L]PnIA-F fluorescent peptide was identified by mass spectrometry as 2 077.28 Da, which was consistent with the theoretical value. Electrophysiological determination of its half-maximal inhibitory concentration (IC50) for α7 nAChR is 17.32 nmol·L-1, which is consistent with [A10L]PnIA (IC50, 13.84 nmol·L-1). The cytotoxicity test results showed that within the concentration range of 5 nmol·L-1 to 10 μmol·L-1, there was no significant inhibition on the growth of mouse macrophages. The results showed that the α-conotoxin fluorescent probe [A10L]PnIA could provide pharmacological tools for the research of α7 nAChR-related neurophysiological and pathological mechanisms.

Meta analysis of whether cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy can improve survival in patients with colorectal cancer peritoneal metastasis / 中华胃肠外科杂志

Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.

Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules () / 中国结合医学杂志

OBJECTIVE@#To examine the clinical effects of Yisui Shengxue Granules () in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels.@*METHODS@#A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin (Hb), red blood cells (RBCs), reticulocytes (Ret), and fetal hemoglobin (HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0.@*RESULTS@#Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group (P<0.01 or P<0.05). Meanwhile, HbF increased from the 2nd to the 3rd month (P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor (IGF1R) and Janus kinase 3 (JAK3) revealed the most relations with other genes (degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2 (PLCG2) and mitogen-activated protein kinase 10 (MAPK10) showed a stronger intermediary role (betweenness centrality=0.04).@*CONCLUSIONS@#JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis. (Registration No. NCT01549080).

Establishment of HPLC fingerprint of Compound Shiwei Tablets and application of its preparation process / 中草药

Objective To establish an HPLC fingerprint determination method of Compound Shiwei Tablets (CST), and apply it to the quality control during its preparation. Methods Agilent 5 TC C18 (2) (250 mm × 4.6 mm, 5 μm) column was used for HPLC with a gradient elution of acetonitrile-0.2% phosphoric acid in mobile phase at a flow rate of 1.0 mL/min. The wavelength was 235 nm, the column temperature was 25 ℃, and the injection volume was 10 μL. A total of 14 batches of CST and three batches of CST intermediates (extracts and granules) were measured. Results A common pattern of HPLC fingerprints of CST was established, and 18 common peaks were demarcated and five of them were identified. The relative peak retention time RSD of each batch was 0.990. The similarity between the same batch of CST intermediate and its preparation was > 0.990, and the correlation was good. Conclusion The established HPLC fingerprint of CST is simple, effective, and reproducible, and can be applied to the quality control of intermediates in the preparation process of the preparations, which provides a basis for the overall quality control of CST.

Determination of three saponins in Compound Shiwei Tablets and study on transfer rate in its preparation process / 中草药

Objective: High performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method was used to establish the determination method for the three kinds of saponins (astragaloside I, II, and IV) in Compound Shiwei Tablets (CST), and investigate the three saponins components’ s transfer rate in the preparation process of CST in order to improve the quality control method of CST. Methods: A HPLC-ELSD method was operated on the column of Agilent 5-HC C18 (2) (250 mm × 4.6 mm, 5 μm), with acetonitrile-water as the mobile phase for gradient elution, at a flow rate of 1.0 mL/min, with column temperature of 30 ℃ and injection volume of 20 μL. The ELSD parameters were as follow: the carrier gas flow rate was 1.5 L/min, the drift tube temperature was 90 ℃. Determinate the content of astragaloside I, II, and IV in products, granules and extracts of CST, and calculate the transfer rate of three saponins in the preparation process of CST. Results: A method for the determination of astragaloside I, II, and IV in CST was established. Under this condition, all three components reached baseline separation with good linear relationship. The average recovery rates were 99.58%, 99.31% and 99.51%, and RSD values were 3.0%, 2.5% and 2.5%, respectively. Astragaloside I had lower transfer rate during the preparation process, and the transfer rate of astragaloside IV was the higher in the preparation process, both of which were greater than 100%. Conclusion: This study established a method for simultaneous determination of three kinds of saponins of astragaloside I, II, and IV in CST. The method has good reproducibility and strong specificity, which is simple and easy,and can be used to inspect the transfer rates of three kinds of saponins in the preparation process and improve the quality control standard of saponins in CST, and provide reference for the quality control of other traditional Chinese medicine preparations containing astragalus.

Acupoint puncture combined with Ilizarov technique for the treatment of elderly paitents with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To explore the clinical effect of acupoint puncture combined with Ilizarov technique in the treatment of knee osteoarthritis in the elderly.@*METHODS@#From March 2015 to February 2016, 76 patients with primary knee osteoarthritis were treated with tibial osteotomy acupoint puncture grouop and Ilizarov technique anatomical puncture group, including 24 males and 52 females, aged 56 to 75 years old with an average of 61.4 years old, and a course of 3 to 17 years with an average of 5.2 years. Among them, 38 cases were treated with external fixation of acupoint puncture needle and 38 cases were treated with external fixation of anatomical puncture needle. Preoperative full-length X-ray of both lower limbs showed tibial varus deformity, narrowing of medial knee joint space and enlargement of lateral knee joint space. The force line of the affected knee and lower limb was moved inward by body surface measurement, and the KSS knee function score was decreased. Symptoms included medial knee pain, flexion and extension, and conservative treatment for more than 2 years.@*RESULTS@#The lower limb force lines of both groups were corrected and the osteotomy ends healed well. No nonunion of osteotomy, inadequate correction of lower limbs or recurrence of deformity were found. Seventy-five patients were followed up for 3, 6, 12 and 24 months after operation. There was no significant difference in knee joint mobility between the two groups before operation and on 6, 12, 24 months after operation(=1.346, >0.05). There were significant difference in KSS pain and total score between the two groups at 3 months after operation, acupoint puncture group was better than anatomical puncture group(0.05).@*CONCLUSIONS@#The acupoint puncture group formed a potential acupuncture effect in the acupoint area by continuously tightening the steel needle on Ilizarov ring external fixator during the post-operative adjustment. Within three months after wearing external fixator, the knee pain symptoms of knee osteoarthritis were relieved rapidly, continuously and effectively, which was significantly better than that of the anatomical puncture group.

Research progress on inhibition of ocular neovascularization by traditional Chinese medicine monomers / 国际眼科杂志(Guoji Yanke Zazhi)

@#Overview of the status application of traditional Chinese medicine monomers in ocular neovascular diseases. Through retrieving related domestic and overseas research state for more than ten years, summarizing, analyzing and summarizing, overviewing the research progress of traditional Chinese medicine monomer in inhibiting intraocular neovascularization, and expounding the potential advantages of traditional Chinese medicine in the field of intraocular angiogenesis research, providing information for treating and researching of neovascular diseases.

Analysis of Effects of Different Doses of Rosuvastatin Calcium on Serum Lipids in Elderly Patients with Coronary Heart Disease and Hyperlipidemia / 现代生物医学进展

Objective:To investigate the effects of different doses of rosuvastatin on lipid levels in elderly patients with CHD complicated with hyperlipidemia.Methods:120 elderly patients with coronary heart disease admitted in our hospital were retrospectively chosen.By lipid examination,they were all hyperlipidemia.According to the dose of rosuvastatin,they were divided into three groups,and 40 cases in each group.They were given 5 mg,10 mg and 20 mg treatment,respectively.After 2 months,the changes of blood lipid level and the clinical effective rate were compared before and after the treatment.Results:①The blood lipid levels HDL-C [(1.17 ± 0.62) mmol / L] was significantly higher than the other two groups.LDL-C [(3.67 ± 0.83) mmol / L],TC [(4.36 ± 0.96) mmol / L] and TG [(1.68 ± 0.94) mmol / L] were significantly lower than those of the other two groups (P ＜0.05).②The effective rate of treatment in the 20mg group (97.5％) was significantly higher than that in the 5mg group (87.5％) and the 10mg group(85.0％).Conclusions:Rosuvastatin can treat coronary heart disease complicated with hyperlipidemia in elderly patients.The dosage of 20 mg can improve the blood lipid level of the patients,is an effective and convenient method,and with high therapeutic efficiency.

Clinical analysis of 24 cases of aortic dissection during pregnancy / 中华妇产科杂志

plus stented elephant trunk implantation (Bentall+Sun′s surgery), aortic root replacement (Bentall surgery), stent implantation, thoracic and abdominal aorta replacement. The aortic operation time of the 19 patients were 5 gestational weeks to 1 month after delivery. The relation between aortic operation and the termination of pregnancy: 4 patients underwent aorta surgery after termination of pregnancy, 9 patients had cesarean section and aorta surgery at the same time, 6 patients underwent aorta surgery before cesarean section. ②5 patients did not receive arota surgery, 2 patients of type A dissection and 1 patient of type B dissection died before the surgery;2 cases of type B dissection underwent conservative treatment. The termination time of pregnancy was 6-37 gestational weeks, with the average of (26 ± 10) weeks. (3)Maternal and fetal outcomes:20 patients survived after treatment (83%,20/24) and 4 patients died (17%,4/24). 10 cases were live births, including 4 full-term infants and 6 preterm premature infants. The birth weight of the neonates was 1 080-3 800 g, with the average of (2 302±764) g. Three of them were very low birth weight infants and 1 was low birth weight infant;3 neonates had mild asphyxia. The neonates were followed up for 0.5 to 10 years, with the average time of (1.4 ± 1.7) years. So far the infants′ development was good.Conclusions Pregnancy with aortic dissection is pernicious. Early identification, prompt diagnosis and prompt interventing of the vascular surgery are necessary to the safety of mother and fetus.

Influence of Helicobacter pylori Infection on Diagnostic Performance of Serum Pepsinogens / 胃肠病学

Background:Serum pepsinogens (PGs),as a serologic marker for gastric mucosal lesions,can reflect the functional status of gastric mucosa. Helicobacter pylori (Hp)infection can cause pathological changes in gastric mucosa,and has been reported to influence the serum level of PGs. Aims:To explore the influence of Hp infection on diagnostic performance of serum PGs for gastric mucosal lesions. Methods:The endoscopic findings,biopsy pathology (including Giemsa staining) and serum PGs test in 1216 cases of patients from July 2014 to June 2015 at the First Affiliated Hospital of Jiaxing University were collected. Patients were categorized according to the pathological diagnosis and Hp status,and the results of serum PGs test were analyzed between different groups. Results:When patients were classified by gastric mucosal lesion,no significant differences were found in serum levels of PGⅠ,PGⅡ,ratio for PGⅠ/ Ⅱ (PGR)and proportion of PG-positive (PGⅠ≤70 μg/ L and PGR < 3. 0)patients of different mucosal lesion groups with Hp-positive status (P >0. 05),whereas significant differences were observed in serum levels of PGⅠ,PGⅡ,PGR and proportions of patients with PGⅠ≤70 μg/ L or PGR < 3. 0 of different mucosal lesion groups with Hp-negative status (P < 0. 05). When patients were classified by Hp status,PGⅠ level and PGR were lower and PGⅡ level and proportion of PG-positive patients were higher in Hp-positive patients than in Hp-negative patients in any of the gastric mucosal lesion groups (P < 0. 05 in part of the comparisons). Conclusions:Hp infection is strongly associated with the alterations in serum PGs test,which narrows the differences in PGs between groups with different gastric mucosal lesions and expands that within the same mucosal lesion, subsequently decreasing PGR and increasing the proportion of PG-positive patients. Patients negative for Hp infection may need new cut-off value of serum PGs test to improve the sensitivity for diagnosis of gastric mucosal lesion.

Involvement of TLR4/NLRP3 inflammasome in contrast medium-induced inflammation and injury in renal tubular epithelial cells / 中国病理生理杂志

AIM: To investigate whether Toll-like receptor 4 ( TLR4 ) and Nod-like receptor protein 3 (NLRP3) inflammasome were involved in contrast medium (CM)-induced inflammation and injury in renal tubular epithe-lial cells.METHODS: Iopromide was used to injure NRK-52E cells in the study.The cell viability was measured by CCK-8 assay.The protein levels of TLR4, NLRP3, apoptosis-associated speckle-like protein (ASC), caspase-1 and cleaved caspase-3 were determined by Western blot .The releases of interleukin ( IL )-1βand IL-18 were detected by ELISA .The apoptotic rate was evaluated by Hoechst staining , and mitochondrial membrane potential ( MMP) was analyzed by JC-1 staining.siRNA was transfected into the NRK-52E cells to silence NLRP3 expression.RESULTS:CM decreased the viability of NRK-52E cells (P<0.05).CM also elevated the protein levels of cleaved caspase-3, TLR4, NLRP3, IL-1βand IL-18 (P<0.05).Silencing NLRP3 attenuated CM-induced releases of inflammatory cytokines .Moreover, treat-ment with TLR4 inhibitor TAK-242 or knockdown of NLRP3 by siRNA transfection both attenuated cell apoptosis and loss of MMP caused by CM .CONCLUSION:TLR4/NLRP3 inflammasome takes part in the pathogenesis of CM-induced acute kidney injury , and mediates CM-induced injury and inflammation in renal tubular epithelial cells .

Clinical treatment of infective endocarditis with vegetations in pregnant women and the outcomes of gestation / 中华妇产科杂志

Objective To investigate the clinical treatment of infective endocarditis with vegetations in pregnant women and the outcomes of the gestation. Methods Nine cases of pregnant women diagnosed as infective endocarditis with vegetations in Beijing Anzhen Hospital, Capital Medical University from January 2001 to October 2015 were enrolled in retrospective analysis. Consultations were held by doctors from department of obstetrics, anesthesiology, cardiology, cardial surgery and extracorporeal circulation to decide the individualized treatment plan for the 9 cases of pregnant women after admissions. Clinical treatments including general treatment, anti-infection treatment, cardiac surgery, and termination of pregnancy surgery were completed through collaboration among related departments. The clinical characters, therapeutic regimens, maternal and neonatal outcomes of the 9 cases were analyzed. Results (1)Clinical characters: the ages of the 9 cases of pregnant women were from 25 to 36 years old. The onset gestational ages were from 19 to 36 weeks. Clinical symptoms: fever, cough, sputum and progressive anemia were the main symptoms. Patients had cyanosis of lips, could not lie on the back or even be orthopnea, when heart failure happened. Heart murmur was audible and splenomegaly was touched in physical examination. Blood cultures were positive. Basic heart disease types: 7 cases of congenital heart diseases included 2 cases of aortic insufficiency, 1 case of mitral insufficiency, 1 case of patent ductus arteriosus, 1 case of right ventricular outflow tract stenosis and 2 cases of ventricular septal defect.Two cases of rheumatic heart diseases included 1 case of mitral stenosis, 1 case of mitral stenosis after artificial disc changed and jammed. According to endocardial vegetations attached position there were 3 cases of mitral valve vegetations, 2 cases of pulmonary valve vegetations, 3 cases of aortic vegetations and 1 case of right ventricular outflow tract neoplasm. Preoperative heart function classification:1 case of levelⅡ, 3 cases of levelⅢ, 5 cases of levelⅣ.(2)Treatments:general treatment included oxygen uptake, rest in bed, cardiac strengthen and diuretic therapy, etc. Combined and adequate antibiotics were applied in anti-infection treatment according to drug sensitive test. Nine cases of pregnant women were all performed surgical treatment of heart diseases and removal of the endocardial vegetations. Caesarean sections were performed for 2 cases in second trimester and for 7 cases in last trimester. Cardiac surgery and caesarean section were operated in 6 cases at the same time among 22-34 weeks of pregnancy. Cardiac surgery were respectively operated in 2 cases 11 days and 32 days after the caesarean section at 33, 37 weeks of pregnancy. While Cardiac surgery was operated (at 26 weeks of pregnancy) before the caesarean section (at 37 weeks of pregnancy) in another 1 case. (3) Maternal and neonatal outcomes:7 cases of pregnant women were rescued successfully, while 2 cases of pregnant women were death. Postoperative heart function classification: 1 case of level Ⅰ, 2 cases of levelⅡ, 4 cases of levelⅢand 2 cases of levelⅥ. Neonatal survivals were 6 cases including 2case of full-term infants, 4 cases of preterm infants. Stillbirth or neonatal death were 3 cases, which included 2 cases performed caesarean section in second trimester and 1 case of very low weight infant who was given up treatment by family because of severe asphyxia. Followed up periods were from 1 to 7 years with an average time of (2.0 ± 1.6) years. Infants and young children grew and developed well during the period of follow up. Conclusions The risk is extremely high of pregnancy with infective endocarditis with vegetations. But there is still a way to save the maternal and neonatal life by using a multidisciplinary collaboration formulation and implementation of individualized treatment plan and selecting the appropriate time for heart surgery and the termination of pregnancy.

Expression and Significance of Notch1 in Human Gastric Cancer / 胃肠病学

Background:Gastric cancer(GC)is the fourth commonly seen cancer in the world. The role of Notch signaling pathway in the pathogenesis of tumors has become a focus in related studies,however,the underlying mechanism of Notch1 in GC has not yet been fully understood. Aims:To investigate the expression and significance of Notch1 in human GC tissue. Methods:A total of 115 patients with GC admitted at Jiaxing First Hospital from October 2011 to July 2014 were enrolled. Expression of Notch1 in cancerous tissue and para-cancer noncancerous tissue was determined by immunohistochemistry. The correlation between expression of Notch1 and clinicopathological characteristics of GC was analyzed. Results:Expression rate of Notch1 in cancerous tissue was significantly higher than that in para-cancer noncancerous tissue(73. 9% vs. 3. 5% ,P < 0. 001). Notch1 expression in cancerous tissue was significantly correlated with depth of vascular involvement,lymph node metastasis and TNM stage of GC(P < 0. 05). Conclusions:Notch1 as a cancer-promoting gene is involved in the pathogenesis of GC,and has a close association with tumor invasion and metastasis.

Efficacy assessment of 33 cases of peroral endoscopic myotomy in different achalasia subtypes by esophageal high-resolution manometry / 中华消化杂志

Objective To explore the symptomatic improvement of different achalasia (AC)subtypes after peroral endoscopic myotomy (POEM) procedure.Methods A total of 33 patients received POEM for the first time were enrolled.Patients were evaluated by high-resolution manometry (HRM)and subtyped by Chicago classification criteria.The total scores of symptoms were evaluated by Eckardt scale before and after POEM.Solid food dysphagia,liquid dysphagia,reflux and chest pain were scored by five-point Likert scales and compared by Wilcoxon paired test.Multiple linear regression analysis was performed to analyze key factors affecting the prognosis of symptoms.Results Among 33 AC patients,there were 20 females and the mean age was (44.0± 13.3) years.According to Chicago criteria,four patients had subtype Ⅰ AC,25 patients had subtype Ⅱ AC,and four patients with subtype Ⅲ achalasia.Before operation,the total Eckardt score was 7.5(6.3,10.0),which declined to 1.5 (1.0,3.0) after operation,and the difference was statistically significant (Z=-4.795,P ＜ 0.01).There was no statistically significant difference in the incidence of solid food/liquid dysphagia,reflux and chest pain among subtypies.Solid food dysphagia was the main symptom of each AC subtypes.POEM could improve all the symptoms of subtype Ⅱ AC except for chest pain.Before and after POEM,solid food dysphagia score was 16.0 (12.0,16.0) and 2.0 (1.0,12.0),liquid dysphagia score was 2.0 (0.0,5.0) and 0.0(0.0,0.0),reflux score was 9.0 (6.0,9.0) and 0.0 (0.0,1.0),respectively,and the differences were statistically significant (Z =-3.929,-3.470,1.841;all P＜ 0.01).The results of multiple linear regression analysis indicated that female and 4 s integrated relaxation pressure (4 s IRP) of 10 mL continuous swallows were positively correlated with symptom scores of solid food dysphagia (β 3.950,P=0.048;β=0.376,P=0.005);While 4 sIRP in solid food swallow was negatively correlated with symptom scores of solid food and liquid dysphagia (β=-0.244,P =0.008;β=-0.118,P =0.037).Conclusion For patients with AC,clinical symptoms could be significantly improved by single treatment of POEM,but there are certain differences in the symptomatic improvement among different subtypes.

Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus / 华中科技大学学报（医学）（英德文版）

The relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor (InsR) and insulin resistance (IR) in patients with gestational diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG (5.61±0.78 mmol/L), FINS (15.42±5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR) (1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively) (P0.05). TP of InsR with insulin stimulation was significantly decreased in GDM group (0.20±0.05) as compared with normal pregnancy group (0.26±0.06) (P0.05). It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.

Therapeutic effect of peroral endoscopic myotomy on esophageal achalasia / 中华消化内镜杂志

Objective To evaluate the efficacy and safety of peroral endoscopic myotomy (POEM) for achalasia.Methods A total of 40 achalasia patients who underwent POEM at our hospital were enrolled.The outcomes of Eckardt score,Barium contrast imaging,esophageal manometry as well as esophagogastroscopy were assessed before and at 6th day,1 month,3 months and 6 months after POEM respectively.Results All 40 patients successfully underwent POEM,with the mean operation time 57.2 ± 18.4 minutes.lntraoperative mediastinal and subcutaneous emphysema occurred on two patients.All patients had significant symptom relief after POEM (Eckardt score ≤ 3).The patients had a mean follow-up of 13.3 months.Two patients had symptom relapse,and treatment success rate (Eckardt score ≤3) was 90％ in 6-month follow up.According to high-resolution manometry (HRM),the resting lower esophageal sphincter (LES) pressures were 30.6 and 15.8 mmHg (P =0.001),and intergrated relaxation pressure(IRPs) were 28.1 and 12.2 mmHg (P =0.000) before and after POEM,respectively.The diameter of the esophageal lumen was 4.2 cm and 3.1 cm before and after POEM (P＜0.001).Conclusion POEM is safe and effective in a short term with less complications.Further follow-up studies are needed to evaluate long-term outcomes.

Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus / 华中科技大学学报（医学）（英德文版）

The relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor (InsR) and insulin resistance (IR) in patients with gestational diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG (5.61±0.78 mmol/L), FINS (15.42±5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR) (1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively) (P<0.01). The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group (7.56±2.31 mU/L and 0.47±0.26 respectively) (P<0.01). There was no significant difference in the InsR expression level among the three groups (P>0.05). TP of InsR with insulin stimulation was significantly decreased in GDM group (0.20±0.05) as compared with normal pregnancy group (0.26±0.06) (P<0.01). TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group (0.31±0.06) (P<0.01). TP of InsR with insulin stimulation was negatively related with HOMA-IR in GDM group (r=-0.525, P<0.01). There was no correlation between the protein expression of InsR and HOMA-IR in GDM group (r=-0.236, P>0.05). It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.