Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics / 中国中药杂志

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.

Naringin Inhibits Colorectal Carcinogenesis by Inhibiting Viability of Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To explore the therapeutic effect of naringin on colorectal cancer (CRC) and the related mechanism.@*METHODS@#Cell counting kit-8 (CCK-8) assay and annexin V-FITC/PI assay were used to detect the effect of naringin (50-400 µg/mL) on cell proliferation and apoptosis of CRC cells, respectively. The scratch wound assay and transwell migration assay were used to assess the effect of naringin on CRC cell migration. Four-week-old male nude mice were injected with HCT116 cells subcutaneously to establish the tumor xenograft model. Naringin was injected intraperitoneally at 50 mg/(kg·d), with solvent and 5-fluorouracil treatment as control. The width and length of the tumors were measured and recorded every 6 days, and tumor tissues were photographed and weighed on the last day of the 24-d observation period. Immunohistochemical staining for caspase-3, proliferating cell nuclear antigen and TUNEL assay were used to evaluate the effect of naringin on cell proliferation and apoptosis in tumor tissues. The body weight, food and water intake of mice were recorded, and the major organs in different treatment groups were weighed on the last day and stained with hematoxylin and eosin for histological analysis. Meanwhile, the routine blood indicators were recorded.@*RESULTS@#CCK-8 and annexin V-FITC/PI results confirmed that naringin (100, 200, and 400 µg/mL) could inhibit proliferation and promote apoptosis. The scratch wound assay and transwell migration assay results confirmed the inhibitory activity of naringin against CRC cells migration. In vivo results demonstrated the inhibitory effect of naringin on tumor growth with good bio-compatibility.@*CONCLUSION@#Naringin inhibited colorectal carcinogenesis by inhibiting viability of CRC cells.

Treatment and prognosis analysis of 488 patients with FIGO 2018 stage Ⅲc squamous cervical cancer / 中华妇产科杂志

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

Effect of Danggui-Chuanxiong herb pair on JAK-STAT signaling pathway in rats with cerebral ischemia/reperfusion injury / 中国药理学通报

Aim To explore the regulatory effect of Danggui-chuanxiong herb pair (GX) on JAK-STAT signaling pathway in rats with cerebral ischemia/reper-fusion injury (I/R). Methods The I/R injury rat model was constructed by modified suture occlusion method. After 24 hours of perfusion, Zea Longa scoring method was used to score the neurological function, TTC staining to detect the cerebral infarct volume of rats, HE staining to observe the pathological changes of brain tissues, the biochemical method to determine the MDA, SOD, GSH-Px expression, ELISA to detect the expression of NF-κB, VEGF, ICAM-1 and PAH in brain tissues, and immunohistochemical method to detect JAK2, p-STAT3, AKT And ERK1/2 expression of the brain tissue ischemic penumbra area. Results Compared with sham group, model rats had severe neurological damage, larger cerebral infarction, necrosis, edema, inflammation, disorder of nerve cell arrangement, abnormal cell enlargement, vacuole-like changes, neuron reduction and other pathologies in brain tissues. The expression JeveJs of MDA, NF-κB, VEGF, PAI-1 and ICAM-1 in brain tissues of model group significantly increased, and the expression levels of GSH-Px and SOD were significantly reduced. Compared with model group, the neurological scores of rats in GX

Study on effect of Schisandra Chinensis Fructus-Glycyrrhizae Radix Et Rhizoma containing serum on lipid accumulation in hepatocytes andits mechanism / 中国药理学通报

Aim To study the effect of drug-containing serum of Schisandra Chinensis Fructus and compatible with Glycyrrhizae Radix Et Rhizoma -on lipid accumulation in hepatocytes and explore the related mechanism. Methods SD rats were given Schisandra Chinensis Fructus (SF, 3.9 g • kg"1), Schisandrae Chinensis Fructus-Glycyrrhizae Radix Et Rhizoma (SG, 1 : 1, 1 '• 1. 5, the extract 3. 9 g • kg"1 in crud of Schisandrae Chinensis Fructus), once per day, the drug-containing serum was prepared after seven days of continuous administration. Conventional cultivation of human normal hepatocytes (L02 cells) in vitro, cells were divided into blank control group, SF group, and SG(1 : 1 and 1 : 1.5) group. After 48 hours' treatment , lactate dehydrogenase ( LDH) release was detected by the kit, the levels of intracellular triglyceride (TG) and total cholesterol (TC) were detected by biochemical method. The mRNA expression levels of PPAR-a, PPAR-7, Fabpl/2, SREBPlc, ACCa and FAS were detected by the real-time reverse tran scrip- tion polymerase chain reaction ( RT-PCR ). Results The biochemical results showed that compared with the blank group, the content of TG and TC in SF group increased significantly (P < 0. 05 ) , the mRNA expres sion of PPAR-a and PPAR-7 in SF group was significantly reduced, and the mRNA expression of SREBPlc and ACCa markedly increased ( P < 0.05, P < 0.01). When compared with SF group, the levels of TG and TC in SG (1 : 1) group were significantly reduced (P <0. 05) , the mRNA expressions of Fabpl/2 and FAS in SG (1 : 1) group were significantly reduced, while the mRNA expression of SREBPlc significantly increased ( P < 0. 05, P < 0. 01 ). TC content in SG (1 : 1.5) group significantly decreased (P < 0.05 ) and the mRNA expression of PPAR-7, SREBP1 c in SG (1 : 1.5) significantly increased, but the Fabpl/2 and FAS markedly decreased (P <0. 05, P < 0. 01). Conclusions SF containing serum can significantly increase the content of TG and TC in hepatocytes , and the SG containing serum can significantly improve the elevated TG and TC contents and reduce lipid accumulation. The mechanism may be related to the regulation of mRNA expression of PPAR-a, PPAR- 7, Fabpl/2, SREBPlc, ACCa and FAS.

Efficacy of drug coated balloon versus conventional balloon in the treatment of coronary de novo bifurcation lesions: a meta-analysis / 中华心血管病杂志

Objective: To systematically evaluate the efficacy of drug coated balloon (DCB) versus conventional balloon in the treatment of coronary de novo bifurcation lesions. Methods: The databases of PubMed, Embase, Cochrane Library, Web of science, CNKI (China National Knowledge Infrastructure), Wanfang database, VIP, China Biology Medicine disc, Chinese clinical trial registry, American clinical trial registry and cardiovascular related websites until September 2020 were retrieved for collecting the randomized controlled trials (RCT) comparing DCB versus conventional balloon in the treatment of coronary de novo bifurcation lesions. The risk of bias of included studies was assessed using the Cochrane risk assessment tool. The meta-analysis was performed by using Revman 5.3 and Stata 14.0 software. Results: Seven RCTs with a total of 613 patients were included in this meta-analysis. Among the included studies, 4 articles reached the low risk of bias, and the other 3 articles reached the medium risk of bias. The results of meta-analysis showed that there was no significant difference in the major adverse cardiac events (RR=0.65, 95%CI 0.39-1.08, P=0.10), myocardial infarction (RR=0.68, 95%CI 0.25-1.80, P=0.43), target lesion revascularization (RR=0.94, 95%CI 0.53-1.67, P=0.83) between DCB group and conventional balloon group. Late lumen loss of side branch was less in the DCB group than that in the conventional balloon group (WMD=-0.25, 95%CI -0.41--0.09, P<0.01) and the risk of side branch restenosis was also lower in the DCB group than that in the conventional balloon group (RR=0.47, 95%CI 0.22-0.98, P<0.05). However, subgroup analysis showed that the conclusions of domestic studies and foreign studies on late lumen loss and side branch restenosis were inconsistent. The meta-analysis based on domestic literature showed that the risk of side branch restenosis after DCB treatment was lower compared with conventional balloon group (RR=0.29, 95%CI 0.15-0.57, P<0.05), while this parameter derived from foreign literatures remained unchanged between two groups (P=0.53). The meta-analysis results of domestic literature showed that late lumen loss in DCB group was less than that in conventional balloon group (WMD=-0.32, 95%CI -0.51--0.13, P<0.05), but this phenomenon was not observed in foreign literatures (P=0.30). Conclusions: The use of DCB in the treatment of coronary de novo bifurcation lesions has the potential to reduce the rate of restenosis and late lumen loss of side branch compared with conventional balloon group. However, due to the limitation on quantity, quality and results of published studies, more high-quality and large scale RCTs are still needed to confirm these findings.

Effects of shikonin on colon cancer xenografts in nude mice based on serum metabolomics / 药学学报

To investigate the antitumor activity of shikonin against human colorectal cancer, the IC50 value towards four different human colon cancer cells was detected by MTT assay. In addition, a SW620 xenograft model was established and both the tumor volume and tumor inhibitory rate were calculated to evaluate the antitumor activity of shikonin in vivo. To further explore the mechanism of shikonin, metabolomics combined with multivariate statistical analysis was performed to analyse the profile of metabolites in mouse serum. The results show that shikonin can significantly inhibit the proliferation of four different colon cancer cell lines and exerted a high antitumor activity in vivo. The tumor inhibitory rate at low dose and high dose were 38.35% and 42.16%, respectively. In addition, a total of 38 potential biomarkers related to the antitumor effects of shikonin were identified through metabolomics analysis, including tryptophan, proline and methionine. The study revealed that the mechanism was related to disordered amino acid metabolism in colon cancer, especially in tryptophan metabolism. Our study suggests that shikonin could exert an antitumor effect by regulating amino acid metabolism in colon cancer and provides a theoretical foundation for further exploration and the eventual clinical application of shikonin.

Establishment of an accurate C57BL6/J mouse model of acute radiation-induced enteritis based on small animal radiation research platform / 中华放射肿瘤学杂志

Objective:To establish an accurate C57BL6/J mouse model of acute radiation-induced enteritis based on small animal radiation research platform (SARRP).Methods:Forty-eight female mice were randomly divided into the following four groups: blank control group, 6 Gy irradiation group, 9 Gy irradiation group and 12 Gy irradiation group. Based on the SARRP, the mice in the irradiation groups were exposed to a single fraction dose of 6 Gy, 9 Gy and 12 Gy at a dose rate of 4Gy/min, respectively. The general condition, body weight and pathological changes of the small intestine of mice were observed.Results:After CT scanning, the target area and normal tissues were delineated. According to the dose distribution of the target area and the protection of spinal cord, the AP-PA field irradiation scheme at the isocentric level was adopted. The average irradiation time in the 6, 9 and 12 Gy groups was 163, 252 and 328 seconds, respectively. The survival rates of mice in the 6, 9 and 12 Gy groups were 100%, 100% and 50% 15 days after irradiation.The body weight of mice in the 6 Gy ( P=0.035), 9 Gy ( P=0.002) and 12 Gy groups ( P<0.001) was decreased significantly on the 5 th day after irradiation, and gradually increased on the 10 th day. With the increase of irradiation dose, the villus and gland injury was aggravated. Compared with the blank control group, the villus length in the 9 and 12 Gy groups was significantly shorter (both P<0.001), and the intestinal wall thickness in the irradiation groups was significantly thinner (all P<0.001). Conclusion:SARRP can provide accurate target location, planned screening and accurate dose delivery in the establishment of C57BL6/J mouse model of acute radiation-induced enteritis. The C57BL6/J mouse model of acute radiation-induced enteritis can be successfully established by a single fraction total-abdominal irradiation of 6-9 Gy.

Preparation and in vitro evaluation of arsenic trioxide-loaded glioma targeting drug delivery system iRGD/TGN-PEG-PAMAM/ATO / 中草药

Objective To construct a glioma targeting delivery system, PAMAM G5 were modified with the oligopeptide of blood brain barrier (BBB) targeting TGN and tumor targeting oligopeptide iRGD to solve the problem of non-specificity in distribution and difficulty in permeating BBB of ATO, in order to have better anti-glioma effect. Methods The physical and chemical properties of nanocarriers were investigated by 1H-NMR and transmission electron microscopy (TEM); The encapsulation efficiency and in vitro release were analyzed by inductively coupled plasma emission spectrum (ICP) and dialysis bag method; The effects of iRGD and TGN on cellular uptake of the carriers were analyzed by laser confocal and flow cytometry. The cytotoxicity of nanocarriers on brain microvascular endothelial cells (HBMEC) and glioma cells (U87), the inhibition effect on U87 cells of drug delivery systems after acrossing the BBB model in vitro were investigated by MTT method. Results The iRGD/TGN-PEG-PAMAM was synthesized successfully. The TEM results showed that iRGD/TGN-PEG-PAMAM was regular in shape and uniform in size. The particle size of iRGD/TGN-PEG-PAMAM/ATO was (24.87 ± 0.84) nm and the potential was (17.26 ± 1.64) mV. The synthesized carrier had less toxicity to HBMEC and U87 cells. The encapsulation efficiency of iRGD/TGN-PEG-PAMAM/ATO delivery system was (71.92 ± 1.17)%. The in vitro release showed that ATO had a slow release trend after entrapment, and it was more favorable for ATO release under acidic conditions. The cell uptake indicated that iRGD/TGN modification was more beneficial for U87 cell to uptake the drug delivery system. The in vitro inhibition effect on U87 cells after acrossing the BBB model showed iRGD/TGN-PEG-PAMAM/ATO had better inhibition effect on U87 cells. Conclusion The iRGD/TGN-PEG-PAMAM/ATO targeting drug delivery system has good inhibition effect on U87 cells effect after acrossing the BBB model in vitro, which provides a new strategy for the treatment of glioma.

Changes of CD4+CD28null cells and oxidative stress in patients with polycystic ovary syndrome / 中华内分泌外科杂志

Objective To investigate the relationship between CD4+CD28na cells,oxidative stress markers malondialdehyde(MDA) and superoxide dismutase(SOD) and the pathogenesis of polycystic ovary syndrome(PCOS).Methods Thirty-two patients with PCOS(PCOS group) and 28 healthy women(control group) were selected.Six ml of peripheral venous blood were taken from each person,3 ml of which were separated and serum was collected.Sex hormone level,C-reactive protein (CRP),SOD and MDA were detected.Peripheral blood mononuclear cells (PBMCs) were isolated from the other 3 ml blood by centrifugation,and CD4+CD28null T cell subsets were detected by flow cytometry.The characteristics of each detected index of PCOS patients and healthy controls were compared.Results The proportion of CD4+CD28null T cells in the peripheral blood of the PCOS group was significantly higher than that of the control group (P＜0.05).The serum CRP and MDA in PCOS group were both significantly higher than that in the control group,and SOD was significantly lower than the control group(P＜0.05).Correlation analysis showed that the expression of CD4+CD28null T cells in the PCOS group was positively correlated with CRP(P＜0.05) and MDA(P＜0.05) and negatively correlated with SOD (P＜0.05).Conclusions Our study shows a disorder of immunoregulatory mechanism represented by abnormal increase of CD4+CD28null T cell expression and an imbalance of oxidative stress in patients with PCOS.The further study of relationship between these two pathophysiological patterns and PCOS may help to elucidate its pathogenesis.

The role of Tom70 in cardiac microvascular endothelial cell damage induced by high fat and high glucose / 解放军医学杂志

Objective To investigate the effect of high glycolipid on mouse cardiac microvascular endothelial cells (MCMECs),clarify the role of Tom70 (translocase of the outer mitochondrial membrane 70,Tom70) in it,and explore the related mechanism.Methods MCMECs cultured with normal glucose medium were divided into normal glucose group (NG,5.5mmol/L),high glucose group (HG,25mmol/L) and HG combined with high fat group (HG+HF,glucose concentration 25mmol/L,500μmol/L,16h).Then,the expression of Tom70 in MCMECs was knocked down by siRNA,and the HG+HF group was further divided into vehicle group,Scramble siRNA group and Tom70-siRNA group.To further confirm the specific mechanism of Tom70 in MCMEC injury induced by high glycolipid,Tom70-siRNA group was subgrouped into N-acetylcysteine (NAC)-free group and NAG-containing group.Accordingly,the apoptosis levels were measured by flow cytometer,the generation of nitric oxide (NO) was detected by ELISA kit,the expressions of Tom70 were determined by immunofluorescence and qRT-PCR,and the levels of reactive oxygen species (ROS) by DHE staining and ELISA kit.Results The apoptosis level increased after exposure to HG,and the generation of NO decreased (P＜0.05),while merging HF could aggravate these injuries (P＜0.05).Moreover,HG inhibited the expressions of Tom70 and promoted the production of ROS in MCMECs (P＜0.05).Compared with HG alone,and combination with HF significantly inhibited the expression of Tom70,and significantly increased the production of ROS (P＜0.05).Most importantly,compared with the vehicle group and Scramble siRNA group,the intracellular ROS content and apoptosis rate increased in the Tom70-siRNA group,while generation of NO was significantly decreased (P＜0.01).In contrast,these damage effects mentioned above were partially reversed by the application of antioxidants NAC (P＜0.05).Conclusions High fat can further aggravate the damage on diabetic MCMECs and Tom70 could exert its effect against cardiac microvascular endothelial injury induced by diabetes via inhibiting oxidative stress.

Efficient Water Splitting Catalyzed by Cobalt Phosphide Nanobead-chain Like Nanoarrays Supported on Three Dimensional Nickel Foam / 分析化学

The research for efficient and low-cost electrocatalysts for water splitting are essential for the exploitation and application of hydrogen energy. Transitional metal phosphides are considered as one of the most promising bifunctional water splitting electrocatalysts. Herein, we reported a facile two-step method (firstly hydrothermal preparation, then phosphorization under low temperature) to synthesize the bead-chain like nanoarrays of CoP supported on three dimensional Nickel foam (CoP/NF). The as-prepared CoP/NF could act as an efficient bifunctional catalyst for overall water splitting. The catalyst exhibited remarkable activity for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in alkaline media,delivering a current density of 10 mA/cm2at an overpotential of 281 mV for OER and 95 mV for HER, respectively. Efficient water splitting in alkaline system was realized by applying a two-electrode system with the CoP/NF acting as both the anode and cathode. The applied potential was 1.63 V to obtain the current density of 10 mA/cm2,and good stability was also testified.

Silencing Filamin A Inhibits the Invasion and Migration of Breast Cancer Cells by Up-regulating 14-3-3σ / 华中科技大学学报（医学）（英德文版）

Filamin A and 14-3-3-σ are closely associated with the development of breast cancer.However,the exact relationship between them is still unknown.The present study aimed to examine the interaction of filamin A with 14-3-3-σ in the invasion and migration of breast cancer.RNA interference technology was employed to silence filamin A in MDA-MB-231 cells.Real-time PCR and Western blotting were used to detect the expression of filamin A and 14-3-3-σ at mRNA and protein levels,respectively.Double immunofluorescence was applied to show their colocalization morphologically.Wound healing assay and Trans-well assay were used to testify the migration and invasion of MDA-MB-231 cells in filamin A-silenced cells.The results showed that silencing filamin A significantly increased the mRNA and protein levels of 14-3-3σ.In addition,double immunofluorescence displayed that filamin A and 14-3-3σ were predominantly colocalized in the cytoplasm of MDA-MB-231 cells.Silencing filamin A led to the enhanced fluorescence of 14-3-3σ.Furthermore,cell functional experiments showed that silencing filamin A inhibited the migration and invasion of MDA-MB-231 cells in vitro.In conclusion,silencing filamin A may inhibit the invasion and migration of breast cancer cells by upregulating 14-3-3σ.

Silencing Filamin A Inhibits the Invasion and Migration of Breast Cancer Cells by Up-regulating 14-3-3σ / 华中科技大学学报（医学）（英德文版）

Filamin A and 14-3-3-σ are closely associated with the development of breast cancer.However,the exact relationship between them is still unknown.The present study aimed to examine the interaction of filamin A with 14-3-3-σ in the invasion and migration of breast cancer.RNA interference technology was employed to silence filamin A in MDA-MB-231 cells.Real-time PCR and Western blotting were used to detect the expression of filamin A and 14-3-3-σ at mRNA and protein levels,respectively.Double immunofluorescence was applied to show their colocalization morphologically.Wound healing assay and Trans-well assay were used to testify the migration and invasion of MDA-MB-231 cells in filamin A-silenced cells.The results showed that silencing filamin A significantly increased the mRNA and protein levels of 14-3-3σ.In addition,double immunofluorescence displayed that filamin A and 14-3-3σ were predominantly colocalized in the cytoplasm of MDA-MB-231 cells.Silencing filamin A led to the enhanced fluorescence of 14-3-3σ.Furthermore,cell functional experiments showed that silencing filamin A inhibited the migration and invasion of MDA-MB-231 cells in vitro.In conclusion,silencing filamin A may inhibit the invasion and migration of breast cancer cells by upregulating 14-3-3σ.

Clinical Study of Acute Vasoreactivity Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.</p><p><b>METHODS</b>We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.</p><p><b>RESULTS</b>The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).</p><p><b>CONCLUSIONS</b>The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.</p>

Effect of perilipin-5 on apoptosis of cardiac microvascular endothelial cells induced by high fat and high glucose in mice / 解放军医学杂志

Objective To investigate the effects and mechanisms of perilipin-5 (Plin5) on the apoptosis of mouse cardiac microvascular endothelial cells induced by high fat and high glucose.Methods The mouse cardiac microvascular endothelial cells (MCMECs) cultured with high glucose medium were respectively given 0,100,300 and 500μmol/L palmitic acid for 24 hours.In order to explore the effects and mechanisms of Plin5 on MCMECs injuries induced by high fat and high glucose,MCMECs exposed to 300μmol/L palmitic acid for 24 hours were divided into control group,Scra siRNA group and Plin5 siRNA group.The control group was only treated with transfection reagent,the Scra siRNA group was given treatment of transfection reagent and garbled RNA,the Plin5 siRNA group was given treatment of transfection reagent and Plin5 specific siRNA.In order to further confirm the specific mechanism of Plin5 in high fat/glucose inducing MCMECs injury,MCMECs in Plin5 siRNA group were divided into vehicle group and N-acetyl cysteine (NAC) group,and given the same intervention of high fat.The apoptotic rate was detected by flow cytometry,qRT-PCR and Western blotting were respectively used to detect the mRNA and protein expression of Plin5,and the intracellular reactive oxygen species (ROS) level was tested by DHE staining and ELISA kit.Results The apoptotic rate of MCMECs was increased in a fat concentration-dependent manner (P＜0.05).Compared with 0μmol/L palmitic acid group,the intracellular ROS content and the expression of Plin5 increased significantly in 300μmol/L palmitic acid group (P＜0.05).Compared with the control group and the Scra siRNA group,the intracellular ROS content and apoptotic rate increased significantly in Plin5 siRNA group under the action of 300μmol/L palmitic acid (P＜0.05).Compared with the vehicle group,the intracellular ROS content and apoptotic rate decreased remarkably in NAC group (P＜0.05).Conclusion With inhibition of oxidative stress,Plin5 may reduce the apoptosis of MCMECs induced by high fat and high glucose.

Mechanism of IL-38 inhibits LPS/TLR4 induced inflammation in patients with rheumatoid arthritis / 中国免疫学杂志

Objective:To investigate the proteins association of IL-38 and TLR4 in rheumatoid arthritis (RA) and its mechanism in RA pathogenesis.Methods:Forty-one rheumatoid arthritis patients(observation group) and forty-five patients with post-traumatic synovial membrane resection (control group) in our hospital from Jan 2013 to Feb 2016 were selected as study subjects.Peripheral blood mononuclear cells (PBMCs),synovial tissues and serum from patients with RA and controls were collected.The expression of IL-38 and TLR4 in PBMCs and synovial tissues were detected by real-time polymerase chain reaction (realtime-PCR).The protiens of IL-38 and TLR4 in synovial tissues and fluid from RA patients and controls were detected by enzyme-linked immunosorbent assay (ELISA) or Western blot assay,respectively.RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or IL-38.The production of inflammatory cytokines including IL-6,IL-8 as well as TNF-α were detected by real-time-PCR and ELISA,respectively.The activation of nuclear factor-κB(NF-κB) signaling were determined by nuclear transfer reagent kit for NF-κB and Western blot.Results: Compared with control group,the expression of IL-38 in PBMCs,synovial tissue,serum and synovial fluid of patients with RA increased significantly,meanwhile,TLR4 was significantly increased in PBMCs and synovium of RA patients.Moreover,IL-38 was negatively associated with TLR4 in RA,suggested by Pearson′s correlation analysis.When RAW264.7 cells were stimulated by LPS with or without IL-38 in vitro,IL-38 could suppress LPS-mediated expression of TLR4 and the production of IL-6,IL-8 and TNF-α in RAW264.7 cells.IL-38 can inhibit the activation of NF-κB signaling pathway,so we hypothesized that IL-38 may inhibit the expression of inflammatory factor which induced by LPS/TLR4 signaling via inhibiting the activation of NF-κB signaling pathway.Conclusion: IL-38 can attenuates rheumatoid arthritis through inhibiting LPS/TLR4 induced inflammation in rheumatoid arthritis,and the mechanism may be through inhibiting the activation of NF-κB signaling pathway.

Research progress of human's attitude angle measurement methods based on inertial sensors / 医疗卫生装备

Multiple methods of attitude measureinent based on inertial measurement unit (IMU) were summarized.The single sensor's means of attitude measurement and it's relative merits were introduced.What's more,the combined method applied to attitude measurement were highlightedly mentioned.In addition,the ways of attitude measurement with multi-sensors units were listed.It also gave useful recommendations for better selection with regard to specific application.The prospect of IMU applied on human bodies was analysed.

A randomized study of intensity-modulated radiation therapy versus three dimensional conformal radiation therapy for pelvic radiation in patients of post-operative treatment with gynecologic malignant tumor / 中华妇产科杂志

Objective To study the difference between intensity-modulated radiation therapy (IMRT) and three dimensional conformal radiation therapy (3D-CRT) for pelvic radiation of post-operative treatment with gynecologic malignant tumor. Methods A prospective investigation study was conducted on 183 patients of post-operative patients with whole pelvic radiation therapy of cervical cancer or endometrial cancer in Zhejiang Cancer Hospital [IMRT group (n=85) and 3D-CRT group (n=98)] from Oct. 2015 to Oct. 2016. The two groups received same dose (45 Gy in 25 fractions). Comparison of two groups with radiation dosimetry:the score according to the Radiation Therapy Oncology Group (RTOG) acute radiation injury grading standards before and after radiotherapy reaction, the score from functional assessment of cancer therapy scale-cervix (FACT-Cx) scale and expanded prostate cancer index composite for clinical practice (EPIC-CP) scale were also analyzed. Results (1) There were no significant effect with age, culture level, family economic condition and ratio of radiochemotherapy between two groups (all P>0.05). (2) Dosimetric comparison for IMRT vs 3D-CRT:the average dose of planning target volume (PTV) decreased(46.1 ± 0.4) vs(46.4 ± 0.5)Gy, V45 dose percentage increased(95.2 ± 1.0)%vs (93.3 ± 2.0)%, intestinal bag dose of V40 decreased(24.4 ± 6.8)%vs (36.5 ± 15.9)%, rectal V40 dose percentage decreased(73.9 ± 12.3)%vs (85.4 ± 8.4)%, and lower rectal V45 dose percentage(32.8 ± 13.4)%vs (71.5 ± 13.7)%, bladder V40 dose percentage decreased(55.5 ± 13.0)% vs (84.4 ± 13.0)%. Bone marrow V20 lower:(67.9 ± 5.4)% vs (79.5 ± 6.6)%, V10 lower:(82.1 ± 6.0)% vs (86.3 ± 6.6)%; there were significant differences (all P0.05). (3) Acute radiation injury classification for IMRT vs 3D-CRT:big or small intestine:Ⅱ-Ⅲreaction [13%(11/85) vs 24% (24/98); χ2=3.925, P=0.048], there was significant difference. Bladder: Ⅲ reaction [19% (16/85) vs 26% (25/98); χ2=1.171, P=0.279], there was no significant difference. Radiochemotherapy of bone marrow suppression:Ⅲ-Ⅳreaction (14/20), the incidence rate [26%(14/54) vs 31%(20/65);χ2=0.339, P=0.562], the difference was not statistically significant. (4) Quality of life scale by FACT-Cx scale in IMRT vs 3D-CRT:there were no significant difference before radiotherapy (82 ± 16 vs 85 ± 16;t=1.279, P=0.203), while there was significant difference after radiotherapy (76 ± 14 vs 71 ± 18;t=-2.160, P=0.032). EPIC-CP scale score:before radiotherapy they were (16±7 vs 15±6;t=-0.174, P=0.862) ,but after radiotherapy (18±7 vs 22± 7; t=3.158, P=0.002), there was significant difference between them. Before and after radiotherapy, the increased EPIC-CP scale of the IMRT group vs 3D-CRT group were 3 ± 4 and 6 ± 4, the 3D-CRT group was significantly higher, the difference was statistically significant (t=5.500, P=0.000). Conclusion IMRT has shown that there are a significant benefit for the post-operative patients with cervical cancer and endometrial cancer compared to 3D-CRT.

Serum Bilirubin and 6-min Walk Distance as Prognostic Predictors for Inoperable Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers (such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]) combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH.</p><p><b>METHODS</b>From June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance (6MWD) results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period.</p><p><b>RESULTS</b>During the follow-up, 22 patients (29%) died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin (hazard ratio [HR] = 7.755, P < 0.001), elevated N-terminal of the prohormone brain natriuretic peptide (HR = 1.001, P = 0.001), decreased 6MWD (HR = 0.990, P < 0.001), increased central venous pressure (HR = 1.074, P = 0.040), and higher pulmonary vascular resistance (HR = 1.001, P = 0.018) were associated with an increased risk of mortality. Serum concentrations of total bilirubin (HR = 4.755, P = 0.007) and 6MWD (HR = 0.994, P = 0.017) were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia (≥23.7 μmol/L) had markedly worse survival than those with normobilirubinemia.</p><p><b>CONCLUSION</b>Elevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH.</p>