Mechanism of Yantiao Fang regulating the Rho/ROCK signaling pathway in apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis / 中国比较医学杂志

Objective To investigate the effect of Yantiao Fang on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating the Rho/ROCK signaling pathway.Methods Seventy BALB/c mice were randomly divided into normal,sham,and model groups.Except for normal and sham groups,mice were subjected to cecal ligation and perforation to establish a mouse model of acute gastrointestinal injury caused by sepsis.The mouse models were randomly divided into model,Low,Medium,and High dose of Yantiao Fang,and ROCK inhibitor groups.Histopathological changes of the ileum were observed by HE staining.Serum levels of IL-1β,IL-6,TNF-α,and IL-10 were measured by ELISA.PCNA and Ki-67 expression was detected by immunohistochemistry.Cleaved caspase3 and Bax expression was detected by Western blot.ROCK and MLC mRNA expression in the ileum was measured by RT-qPCR.Results Compared with normal and sham groups,Chiu's pathological score,proinflammatory factor(IL-1β,IL-6,and TNF-α)levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were increased in the model group(P＜0.05).Moreover,anti-inflammatory mediator IL-10 and expression of PCNA and Ki-67 in the ileum were decreased in the model group(P＜0.05).Compared with the model group,histopathological changes of the ileum in all Yantiao Fang groups were improved by various degrees with the increase in dose.Chiu's pathological score,IL-1β,IL-6,and TNF-α serum levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were decreased in Yantian Fang groups(P＜0.05).The IL-10 level and expression of PCNA and Ki-67 in the ileum were increased in Yantian Fang groups(P＜0.05).Conclusions Yantiao Fang may inhibit apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury due to sepsis by regulating the Rho/ROCK signaling pathway,thereby alleviating intestinal tissue inflammation and ultimately preventing intestinal mucosal tissue injury.

Symptom experience and response of multiple myeloma patients based on symptom management theory model:a qualitative study / 中国实用护理杂志

Objective:To further explore the symptom experience and coping strategies of patients with multiple myeloma, so as to provide reference for the formulation of symptom management programs.Methods:Objective sampling method was used to conduct semi-structured in-depth interviews on 15 patients with multiple myeloma in Hematology Department of Nanjing Drum Tower Hospital from December 2021 to June 2022 and the model of symptom management theory was used as the framework to construct an interview outline. The Colaizzi 7-step analysis method was used to analyze data and extract themes.Results:Three main themes were summarized: symptom experience (obvious symptom perception, poor symptom assessment ability, negative symptom response); symptom management strategy (vague knowledge of symptom management, hope to get professional guidance, expect to get continuity of management); symptom management outcomes (recurrent anxiety, reordering, adaptive behavior).Conclusions:Patients with multiple myeloma have diverse and complex real symptom experience in different periods. Medical staff should pay attention to patients′ symptom response and coping needs and develop a systematic symptom management plan, so as to help them create better self-management and improve their quality of life.

Effect of Jiawei Taoren Chengqi Decoction on autophagy in rats with mechanical ventilation-induced lung injury / 天津医药

Objective To explore the impact of Jiawei Taoren Chengqi Decoction on autophagy in rats with mechanical ventilation-induced lung injury(VILI)through adenylate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Sixty SPF male rats were randomly grouped into the sham operation group,the model group,the low-dose Jiawei Taoren Chengqi Decoction group(TCM-L group,2.85 g/kg),the high-dose Jiawei Taoren Chengqi Decoction group(TCM-H group,8.55 g/kg)and the high-dose Jiawei Taoren Chengqi Decoction + AMPK inhibitor Compound C group(TCM-H+CC group,Jiawei Taoren Chengqi Decoction 8.55 g/kg+ Compound C 250μg/kg),12 in each group.Oxygenation index(OI)was measured immediately after intubation and at 1 h,2 h and 4 h after mechanical ventilation.Bronchoalveolar lavage fluid(BALF)was collected after mechanical ventilation,levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-18 in BALF were detected by enzyme-linked immunosorbent assay(ELISA).Rats were sacrificed,and lung tissue was taken to measure the wet/dry weight(W/D)ratio.HE staining was used to observe pathological changes of lung tissue in each group of rats.Lung injury scores were carried out.Morphology of alveolar epithelial cells was observed by transmission electron microscopy.RT-qPCR was applied to detect mRNA expression levels of AMPK and mTORC1 in rat lung tissue.Western blot assay was applied to detect expression levels of AMPK,p-AMPK,mTORC1,p-mTORC1 and autophagy-related proteins in rat lung tissue.Results Compared with the sham group,the pathological damage of lung tissue was serious,lung W/D,levels of TNF-α,IL-1β and IL-18 in BALF,lung injury score,mTORC1 mRNA expression level,and p-mTORC1 protein expression were increased in the model group(P＜0.05).OI values at 2 h and 4 h of mechanical ventilation,AMPK mRNA expression level,p-AMPK,LC3-II/LC3-I and Beclin-1 protein expression in lung tissue were decreased(P＜0.05).Compared with the model group,the pathological damage of lung tissue was alleviated in the Chinese medicine-H group,and the trend of changes in related indexes was opposite to the above(P＜0.05).Autophagosomes in alveolar epithelial cells were increased.Compound C attenuated the protective effect of Jiawei Taoren Chengqi Decoction on VILI rats(P＜0.05).Conclusion Jiawei Taoren Chengqi Decoction may promote autophagy and reduce VILI in rats by activating AMPK/mTOR signaling pathway.

Research advance in bone marrow metastasis in children′s neuroblastoma / 国际儿科学杂志

Neuroblastoma is the most common extracranial solid tumor for infants and young children.About 50% of patients have extensive metastasis before diagnosis, and the neuroblastoma can metastasize to bone marrow, bone, lymph node, orbit, liver and skin.Bone marrow is the most common site of neuroblastoma metastasis and recurrence.Once neuroblastoma metastasize or relapse, their survival rate will reduce significantly.The mechanism of neuroblastoma bone marrow metastasis has not been elucidated.The drug resistance of tumor cells, the interaction of bone marrow microenvironment, and the regulation of cell signaling pathways may play important roles in regulating tumor cell bone marrow metastasis.This review summarizes the research progress of bone marrow metastasis in neuroblastoma, which helps us to better understand the mechanism of interaction between neuroblastoma and the bone marrow microenvironment, and to provide new ideas for the diagnosis and treatment of patients.

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

Oligomycin A promotes radioresistance in HT29 colorectal cancer cells and its mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Radiotherapy is one of the main therapies for colorectal cancer, but radioresistance often leads to radiotherapy failure. To improve the radioresistance, we explore the effect of oligomycin A, the H@*METHODS@#The effects of different concentrations of oligomycin A on the survival rate and glycolysis of HT29 colorectal cancer cells at different time points were investigated via MTT and glycolysis assay. siRNA-PFK1 was synthesized in vitro and transfected into HT29 cells. The effects of oligomycin A on radiosensitivity of HT29 colorectal cancer cells were measured via MTT and colony formation assay. Western blotting was used to detect the effect of oligomycin A on the expression of glycolytic enzyme PFK1. We compared difference between the effects of siRNA-PFK1 group and oligomycin A combined with siRNA-PFK1 group on cell survival and glycolysis. After 4 Gy X-ray irradiation, the effects of cell survival and glycolysis between the siRNA-PFK1 group and the oligomycin A combined with siRNA-PFK1 group were compared.@*RESULTS@#Compared with the 0 μmol/L oligomycin A group, the cell survival rate of HT29 cells treated with 4 μmol/L oligomycin A was significantly increased (@*CONCLUSIONS@#Oligomycin A can promote the radioresistance of HT29 colorectal cancer cells, which may be related to up-regulation of the PFK1 expression and increase of cell glycolysis.

Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 therapeutic option

The cell entry of SARS-CoV-2 has emerged as an attractive drug repurposing target for COVID-19. Here we combine genetics and chemical perturbation to demonstrate that ACE2-mediated entry of SARS-CoV and CoV-2 requires the cell surface heparan sulfate (HS) as an assisting cofactor: ablation of genes involved in HS biosynthesis or incubating cells with a HS mimetic both inhibit Spike-mediated viral entry. We show that heparin/HS binds to Spike directly, facilitates the attachment of viral particles to the cell surface to promote cell entry. We screened approved drugs and identified two classes of inhibitors that act via distinct mechanisms to target this entry pathway. Among the drugs characterized, Mitoxantrone is a potent HS inhibitor, while Sunitinib and BNTX disrupt the actin network to indirectly abrogate HS-assisted viral entry. We further show that drugs of the two classes can be combined to generate a synergized activity against SARS-CoV-2-induced cytopathic effect. Altogether, our study establishes HS as an attachment factor that assists SARS coronavirus cell entry, and reveals drugs capable of targeting this important step in the viral life cycle.

Clinical observation for NAPD regimen in the treatment of 67 cases of recurrent refractory non-Hodgkin's lymphoma / 中南大学学报(医学版)

To explore the clinical efficacy and toxicity of the NAPD regimen(vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory non-Hodgkin' s lymphoma.
 Methods: A total of 67 patients identified with recurrent refractory non-Hodgkin's lymphoma were enrolled for this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and side effects were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), 1, 2 or 4 years of OS and PFS rates were analyzed. The prognosis was evaluated with univariate and multivariate analysis.
 Results: The ORR was 53.8% after two cycles, including 5(7.5%) complete responses and 31(46.3%) partial responses. The clinical benefit rate (CBR) was 88.7% (59/67). The median OS was 22 (1.5-140.0) months. 1, 2 or 4 years of OS rates were 70.9%, 49.0%, and 35.0%, respectively. The median PFS was 14 (1.5-140.0) months; and 1, 2 or 4 years of PFS rates were 57.5%, 38.3%, and 29.8%, respectively. The main side effect was myelosuppression. The rates of Grade III/IV leukopenia and thrombocytopenia were 13.4% (9 cases) and 3.0% (2 cases), respectively. Gastrointestinal toxicity was at Grade I or II and 6% patients displayed gastrointestinal toxicity at Grade III/IV. No severe cardiac and hepatorenal functional toxicity was observed.
 Conclusion: The NAPD regimen for recurrent refractory non-Hodgkin's lymphoma is effective, and its toxicity is well tolerated. It is a salvage chemotherapy regimen and be of worth to be verified.

Effects of metformin treatment on expression and activity of AMP-activated protein kinase α in skeletal muscle in type 2 diabetes / 中国医师杂志

Objective@#To investigate the effects of metformin treatment on fatty acid metabolism and expression and activity of AMP-activated protein kinase (AMPK)α in skeletal muscle in type 2 diabetes.@*Methods@#A total of 30 cases with or without type 2 diabetes mellitus (T2DM) who received selective surgery were enrolled from department of orthopaedics. These patients were divided into three groups: DM group, DM+ MET group and NC group. Blood samples were drawn from an antecubial vein for measurement of plasma glucose, insulin, lipid and free fatty acid (FFA). Insulin sensitivity index (ISI) was calculated. Skeletal muscle was freezed in liquid nitrogen during orthopaedics surgery and was kept at -70 ℃ until assay. Skeletal muscle tissue was analysed en bloc for triglyceride, long chain fatty acyl-CoA (LCACoAs), AMPKα1 and AMPKα2 mRNA expression [quantitative real-time polymerase chain reaction (qRT-PCR)], as well as protein expression of AMPKα1, AMPKα2 and phosphorylated AMPKα (p-AMPKα) (Western blot).@*Results@#⑴ Compared with NC group, HbA1c, fasting blood glucose (FBG), fasting insulin (FINS), FFA and triglyceride(TG) were increased in DM group, while metformin treatment decreased FFA and TG; ISI was reduced in DM group than that in NC group, but ISI was higher in DM+ MET group compared with DM group (P<0.05 or P<0.01). ⑵ The contents of triglyceride and LCACoAs in skeletal muscle in DM group were higher than those in NC group, while those in DM + MET group were lower than those in DM group (P<0.05 ). ⑶ No alternations of mRNA levels and protein levels of AMPKα1 were detected among three groups (P>0.05). Compared with NC group, AMPKα2 mRNA expression and protein levels of AMPKα2 and p-AMPKα in skeletal muscle were decreased in DM group, while metformin treatment increased protein level of p-AMPKα (P<0.05).@*Conclusions@#Compared with NC group, muscle lipid accumulation and insulin resistance always exist in T2DM patients. Metformin treatment may increase activity of AMPKα, resulting in a decrease in lipid accumulation in skeletal muscle and increase insulin sensitivity in T2DM patients.

Effects of metformin treatment on expression and activity of AMP-activated protein kinase α in skeletal muscle in type 2 diabetes / 中国医师杂志

Objective To investigate the effects of metformin treatment on fatty acid metabolism and expression and activity of AMP-activated protein kinase (AMPK)α in skeletal muscle in type 2 diabetes.Methods A total of 30 cases with or without type 2 diabetes mellitus (T2DM) who received selective surgery were enrolled from department of orthopaedics.These patients were divided into three groups:DM group,DM + MET group and NC group.Blood samples were drawn from an antecubial vein for measurement of plasma glucose,insulin,lipid and free fatty acid (FFA).Insulin sensitivity index (ISI) was calculated.Skeletal muscle was freezed in liquid nitrogen during orthopaedics surgery and was kept at-70 ℃ until assay.Skeletal muscle tissue was analysed en bloc for triglyceride,long chain fatty acyl-CoA (LCACoAs),AMPKα1 and AMPKα2 mRNA expression [quantitative real-time polymerase chain reaction (qRT-PCR)],as well as protein expression of AMPKα1,AMPKα2 and phosphorylated AMPKα (p-AMPKα) (Western blot).Results (1) Compared with NC group,HbA1c,fasting blood glucose (FBG),fasting insulin (FINS),FFA and triglyceride(TG) were increased in DM group,while metformin treatment decreased FFA and TG;ISI was reduced in DM group than that in NC group,but ISI was higher in DM + MET group compared with DM group (P ＜0.05 or P ＜0.01).(2) The contents of triglyceride and LCACoAs in skeletal muscle in DM group were higher than those in NC group,while those in DM + MET group were lower than those in DM group (P ＜0.05).(3) No alternations of mRNA levels and protein levels of AMPKα1 were detected among three groups (P ＞ 0.05).Compared with NC group,AMPKα2 mRNA expression and protein levels of AMPKα2 and p-AMPKα in skeletal muscle were decreased in DM group,while metformin treatment increased protein level of p-AMPKα (P ＜ 0.05).Conclusions Compared with NC group,muscle lipid accumulation and insulin resistance always exist in T2DM patients.Metformin treatment may increase activity of AMPKα,resulting in a decrease in lipid accumulation in skeletal muscle and increase insulin sensitivity in T2DM patients.

NAPD regimen for patients with recurrent refractory diffuse large B-cell lymphoma / 中南大学学报(医学版)

To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
 Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
 Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
 Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.

Effect of combined clopidogrel-aspirin treatment for acute cerebral ischemic infarction on a correlation between cerebral microbleeds and hemorrhagic transformation / 中华老年医学杂志

Objective To investigate effects of combined clopidogrel-aspirin treatment for acute cerebral ischemie infarction on a correlation between cerebral microbleeds (CMBs)and hemorrhagic transformation(HT),so as to provide a new evidence for acute phase treatment of ischemic stroke with CMBs.Methods One hundred and forty-eighty patients with acute cerebral infarction meeting the inclusion criteria were consecutively admitted to our hospitals.All patients underwent susceptibility weighted imaging(SWI) to detect CMBs.Patients were classed into two groups:with and without CMBs and subdivided into brain lobe group,deep group and mixed group.The influence of CMBs or not and CMBs different positions on the post-infarction HT was compared.Logistic regression analysis was used to assess the relationship between HT and the related risk factors.Results The 142 patients finally were included in the study,with 64 patients without CMBs and 78 with CMBs.The detection rates of CMBs were 54.9％.Hypertensive prevalence rate(x2 =6.96,P =0.010)and the levels of uric acid (t =2.04,P =0.040) were higher in CMBs group than group without CMBs.The incidence rate of HT was 12.5 ％ (8 cases)in no CMBs group,and 21.8％(17 cases)in the CMBs group(x2 =2.09,P=0.150).6 in 15 patients(40.0％)patients experienced HT in lobar CMBs group;6 patients (12.5 ％)experienced HT in 48 patients with deep CMBs group;5 patients(33.3％)experienced HT in 15 patients with mixed CMBs group.There was statistically significant difference in HT incidence rate(x2 =6.52,P=0.038)among the 3 groups.Lobar CMBs are more vulnerable for HT.Logistic regression analysis showed that atrial fibrillation(OR=6.48,95 ％ CI:2.45-17.19,P =0.000) and hyperglycemia (OR =1.02,95 ％ CI:1.43 1.94,P =0.020) were risk factors for HT,instead of CMBs(OR=1.95,95％CI:0.78-4.87,P=0.150).Conclusions CMBs do not increase the risk of hemorrhage transformation in cerebral ischemic infarction patients at acute stage with combined antithrombotic treatment.While,the double antithrombotic treatment used in patients with the lobar CMBs should be careful.

TGF-β1 induces activation ofHSC-T6 cells and epithelial-mesenchymal transition in rats / 基础医学与临床

Objective To observe the effect of TGF-β1 on activation and epithelial mesenchymal transition(EMT) in rat hepatic stellate cell-T6.Methods Adopt the MTT method to screen the optimum concentration of TGF-β1 in vitro HSC-T6 cultured.After the HSC-T6 stimulation by TGF-β1 of 10 μg/L for 24 hours, the morphology of the cells was observed under inverted phase contrast microscope, the expression of F-actin which on behalf of cotoskeletal structure was detected by immunofluorescence staining;the expression of α-SMA and N-cadherin,vimentin,E-cadherin was measured by RT-qPCR;The changes of α-SMA,N-cadherin,vimentin and E-cadherin were assessed by Western blot after different concentrations (0,5 and 10 μg/L) of TGF-β1 interventing HSC-T6 for 24 h.Results The optimal cell survival rate was recorded when 10 μg/L TGF-β1 dealt withcells for 24 h.After HSC-T6 were treated with TGF-β1,cells stretched, pseudopodia increased and turn into stellate, cells connections were looser, so that represented a significantly activated state.F-actin filaments gathered to form stress and distributed along the long axis of the cells;The expression of α-SMA mRNA and vimentin mRNA in experimental group was significantly higher while E-cadherin mRNA was obviously lower than the control group(P<0.05).TGF-β1 made the protein expression of α-SMA and N-cadherin, vimentin in dose-dependent increased while E-cadherin was decreased.Conclusions TGF-β1 may induce activation and epithelial-mesenchymal transition of HSC-T6.

Effect of Hedan tablet combined with fluvastatin on serum LDL and heart rate variability in coronary atherosclerotic heart disease / 中国生化药物杂志

Objective To investigate the effect of Hedan tablet combined with fluvastatin on serum LDL and heart rate variability in patients with coronary atherosclerotic heart disease (CHD).Methods 110 patients with coronary heart disease who were treated from March 2015 to June 2016 in our hospital were selected and randomly divided into observation group and control group, with 55 cases in each group.The patients in the observation group were treated with Hedan tablet combined with fluvastatin, and the control group was treated with fluvastatin.The changes of heart rate variability, blood lipids and inflammatory factors were compared before and after treatment, and the clinical curative effect was observed.Results After treatment, the total effective rate of the observation group was 96.4%, significantly higher than the control group 85.5%, the difference was statistically significant (P<0.05).The SDNN of the observation group was (85.42 ±9.11) ms and the SDANN was (49.11 ±5.13) ms, was significantly higher than those in the control group (76.87 ±8.12) ms, (44.16 ±4.76) ms.In the observation group, TC was (4.14 ±0.45) mmol/L, TG was (1.26 ±0.16) mmol/L, LDL was (2.08 ±0.31) mmol/L, significantly lower than the control group (4.78 ±0.51) mmol/L, (1.42 ±0.18) mmol/L, (2.43 ± 0.27) mmol/L, and HDL levels was (1.51 ±0.18) mmol/L, significantly higher than those in the control group (1.35 ±0.15) mmol/L, the difference was statistically significant (P<0.05), and the levels of inflammatory factors in the observation group were significantly lower than those in the control group, the difference was statistically significant (P<0.05).Conclusion Hedan tablets combined with fluvastatin in treating coronary atherosclerotic heart disease can effectively reduce serum LDL levels, improve heart rate variability, significantly improve the treatment effect.

Curative efficacy of benazepril combined with atorvastatin on plasma NT-proBNP and its efficacy in chronic cardiac failure / 中国生化药物杂志

Objective To study curative efficacy of benazepril combined with atorvastatin on N-terminal pro-brain natriuretic peptide (NT-proBNP) and its efficacy in the treatment of chronic cardiac failure. Methods 90 patients of chronic heart failure were selected as research objects. The control group were treated with benazepril, while the observation group were treated with benazepril combined with atorvastatin, 45 cases in each group. Then before and after treatment of 6 months, the cardiac function of left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic dimension (LVESD), left ventricular eject fraction (LVEF), C-reactionprotein (CRP), interleukin- 6 (IL-6, tumor necrosis factor α (TNF-α) and plasma NT-proBNP levels were compared between two groups, and the efficacy was observed. Results After treatment, LVEDD and LVESD in observation group were lower than those in control group, the LVEF was higher than that in control group(P<0.05). The CRP,IL-6 and TNF-αlevels in observation group were lower than those in control group(P<0.05). The plasma NT-proBNP level in observation group was significantly lower than that in control group(P<0.05). The total effective rate of observation group was statistically higher than that that in the control group 95.55%(43/45)vs. 77.77%(35/45)(P<0.05). Conclusion Benazepril combined with atorvastatin in the treatment of chronic heart failure is significant, can reduce plasma NT-proBNP levels, improve the inflammatory factor.

Baicalein attenuates acute lung injury induced by intestinal ischemia/reperfusion via inhibition of nuclear factor-κ B pathway in mice / 中华危重病急救医学

Objective To investigate the effects of baicalein (Bai) on acute lung injury (ALI) induced by intestinal ischemia/reperfusion (I/R) and its mechanism in mice.Methods Twenty-four male C57BL/6J mice were divided into three groups by random number table:namely sham group,I/R group and Bai+I/R group,with 8 mice in each group.Intestinal I/R induced lung injury model was reproduced by clamping superior mesenteric artery for 90 minutes,followed by reperfusion.Bai (100 mg/kg) was intraperitoneally injected 1 hour before ischemic challenge in the Bai+I/Rgroup.The mice in sham group underwent the similar procedure with I/R group but without vascular occlusion.All mice were sacrificed at 4 hours of reperfusion,and blood was collected from inferior vena cava and lung tissues were harvested.Lung tissues were stained with hematoxylin-eosin (HE),and histological changes were examined under light microscope for pathological score.Lung wet/dry (W/D) ratio was calculated.Lung cell apoptosis was determined by TdT-mediated dUTP nick end labeling (TUNEL) technique.Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay (ELISA).The mRNA expressions of TNF-α and IL-6 in lung tissues were determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).The protein expression levels of cytoplasmic inhibitory factor-α of nuclear factor-κB (IκB-α) and nucleus NF-κB were determined by Western Blot.Results Under light microscope,a normal lung tissue structure was shown in the sham group and no evidence of obvious lung injury was found.In the I/R group,the alveolar structure was seriously damaged.The alveolar wall was widened and there was significant interstitial edema and leukocytes infiltration.In the Bai+I/R group,pathological damage was significantly decreased as indicated by reduced lung tissue edema and leukocytes infiltration.Compared with the sham group,the lung pathological scores,W/D ratio and cellular apoptosis in the I/R group were significantly increased.Bothserum TNF-α and IL-6 contents and lung TNF-α and IL-6 mRNA expressions were significantly increased.Furthermore,I/R significantly resulted in a decrease of IκB-α in the cytoplasm and an increase of NF-κB in the nucleus.Notably,Bai treatment significantly attenuated ALI induced by intestinal I/R injury.Compared with the I/R group,the lung pathological scores and W/D ratio in the Bai+I/R group were significantly decreased (lung pathological score:4.59±1.17 vs.6.27±1.34,W/D ratio:3.79±0.28 vs.4.32±0.57),cellular apoptosis was significantly decreased [(4.85 ± 2.47)％ vs.(8.15 ± 2.33)％],both serum TNF-α and IL-6 contents and lung TNF-α and IL-6 mRNA expressions were significantly decreased [serum TNF-α (pg/L):124.18±30.49 vs.167.72 ± 38.65,IL-6 (ng/L):1.65 ± 0.69 vs.2.43 ± 0.57;lung TNF-α mRNA (2-△△Ct:4.75 ± 2.38 vs.7.69 ± 2.32,IL-6 mRNA (2-△△ Ct):16.45 ±4.39 vs.27.69 ± 6.82],additionally,Bai pretreatment significantly increased cytoplasmic IκB-α protein expression (gray value:0.47 ± 0.11 vs.0.27 ± 0.09),while decreased nuclear NF-κB protein expression (gray value:0.57 ± 0.13 vs.1.07 ± 0.14,all P ＜ 0.05).Conclusion Bai could attenuate intestinal I/R injury induced ALI via the inhibition of inflammation and apoptosis.

Clinical effects of α-lipoic acid combined with epalrestat in elderly patients with diabetic peripheral neuropathy / 中华老年医学杂志

Objectives To examine the clinical effects of α-lipoic acid(ALA)combined with epalrestat in elderly patients with diabetic peripheral neuropathy(DPN)and its influence on plasma levels of high-sensitivity C-reactive protein(hs-CRP)and homocysteine(Hcy).Methods A total of 120 DPN patients aged over sixty years were randomly divided into the control group and the treatment group with 60 cases in each group.The control group received 0.6 g ALA in 250 ml saline given by an intravenous drip once a day and the treatment group was additionally given 50 mg epalrestat orally three times a day.Both groups were treated for two weeks.Improvement in clinical symptoms,nerve conduction velocity,and peripheral blood levels of hs-CRP and Hcy were compared between the two groups before and after treatment.Results TSS scores of all items and the total scores of the two groups decreased after treatment,with greater margins seen in the treatment group than in the control group(each P＜0.05).NCV increased in both groups after treatment (each P＜ 0.05),with greater increase in the treatment group(each P＜0.05).Levels of hs-CRP and Hcy were significantly reduced (each P＜0.05).A statistically significant difference was observed in hs-CRP(t =2.620,P=0.010) but not in Hcy(t =0.380,P =0.700)between the two groups.Conclusions ALA combined with epalrestat can significantly improve the symptoms of patients with DPN,with better outcomes than ALA alone,and effectively decrease the peripheral blood level of hs-CRP.

TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence

Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor, but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres and continued cell proliferation. Expression of hTERT prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data suggest that BMP7 induces breast cancer cell aging by a mechanism involving BMPRII receptor- and Smad3-mediated repression of the hTERT gene.

Analysis of insular lobe sensory and threshold stimulation intensities based on stereo-electroencephalograph / 中华神经医学杂志

Objective To explore the insula sensory features and analyze its electrophysiological characteristics based on stereo-electroencephalograph (SEEG).Methods The clinical data of 16 drug-refractory epilepsy patients,admitted to our hospital from December 2013 to June 2016,were retrospectively analyzed.All patients were implanted with SEEG electrodes;totally,34 electrodes (257 contacts) located in insular lobe.Micro current stimulation was performed every adjacent two contacts to get the sensory mapping and the stimulus threshold of the insula.Results Of all the 257 contacts,160 presented clinical symptoms (positive contacts);there were 149 contacts with sensory manifestations,of which 72 were on the left side and 77 on the right.Sensory symptoms of insula mainly included both somatic sensation and visceral sensation.The threshold of somatosensory was (4.9±2.9) mA,and the threshold of visceral sensation was (6.0±2.9) mA,without significant difference (P＞0.05).No significant difference was noted between the left insula sensory ([6.2±3.1] mA) and the right insula sensory ([5.7±2.8] mA,P＞0.05).It showed sensation abnormal of larynx,lingua,face and limb when the middle and posterior short gyrus,as well as anterior and posterior long gurus,respectively,were stimulated;insula sensory showed anatomy distribution,with different stimulated sensitivities.The sensory function showed parallel distribution with the insular gyrus from the middle short gyrus to posterior long gurus,as laryngeal-lingual-facial (nasal and lips)-limb sensation,and the thresholds of the five insular gurus were (6.0±3.1) mA,(4.7±1.5) mA,(8.0±2.9) mA,(5.1±2.4) mA and (4.5±2.6) mA,respectively,with statistically significant differences (P＜0.05).Conclusions The sensitivity of somatic sensation and visceral sensation of the insula monitored by SEEG is similar,as well as the left and right side.The sensory threshold and sensory fan-shaped distribution play important roles in conforming insular symptoms and location for clinician.

Study on effects of citric acid induced acid load on salivary secretion / 国际检验医学杂志

Objective To investigate the effects of citric acid on the related indexes of salivary secretion under acid loading in or‐der to optimize the citric acid load method .Methods The saliva samples were collected from 10 young healthy volunteers at 1-90 s before ,at 91-120 s during and at 121-210 s after citric acid loading .The indexes were detected in saliva with mixed loading and after loading .The salivary alpha‐amylase(sAA ) activity ,pH value ,saliva flow rate ,total protein concentration in various groups were detected .The ratio values before and after the acid loading were compared among the groups .Results (1)The sAA activity , saliva pH value and total protein concentrations after acid loading were significantly increased compared before loading (P<0 .05) , moreover the ratio of after loading and before loading was greater than 1(P<0 .05);(2) however in the citric acid mixing ,the sAA activity ,saliva pH value and total protein concentration were decreased compared with before acid loading ,its ratio was less than 1 (P<0 .05) .Conclusion Citric acid affects the secretion result of acid loading saliva secretion ,it is suggested that the saliva under acid loading is separated treated and analyzed .