Role of PIAS-regulated SUMOylation of PPARγ in endogenous protective mechanism against endotoxin-induced acute lung injury in mice / 中华麻醉学杂志

Objective:To evaluate the role of small ubiquitin-associated modifier (SUMO) E3 ligase (PIAS)-regulated SUMOylation of peroxisome proliferator-activated receptor γ (PPARγ) in the endogenous protective mechanism against endotoxin-induced acute lung injury (ALI) in mice.Methods:Experiment Ⅰ Twenty-four clean-grade wild type male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), ALI group, ALI+ PPARγ inducer TZD group (ALI+ T group) and ALI+ TZD+ SUMOylation inhibitor anacardic acid group (ALI+ T+ A group). Lipopolysaccharide (LPS) 15 mg/kg was injected into the tail vein to develop the ALI model. In ALI+ T+ A group, anacardic acid 5 mg/kg was intraperitoneally injected at 1 h before LPS administration. In ALI+ T group and ALI+ T+ A group, TZD 50 mg/kg was intraperitoneally injected at 30 min before LPS administration. The mice were sacrificed at 12 h after LPS administration, and the lung tissues were obtained to examine the pathological changes which were scored and to determine the wet/dry (W/D) weight ratio, and expression of PIAS1, PIAS2, PIAS3 and PIASy protein and mRNA (by Western blot or polymerase chain reaction). Experiment Ⅱ Mouse alveolar macrophages (MH-S cells) were cultured in vitro and divided into 4 groups ( n=5 each) using a random number table method: control group (C group), LPS group, LPS+ PIAS2 siRNA group (L+ P group) and LPS+ Con siRNA group (L+ C group). Cells were routinely cultured in group C. Cells were stimulated with 10 μg/ml LPS to develop the model of endotoxin challenge. PIAS2 siRNA 50 nmol/L and Con siRNA 50 nmol/L were transfected at 48 h before LPS was added in L+ P group and L+ C group, respectively. The cells were collected at 24 h of incubation with LPS to determine the cell viability, levels of M1 and M2 alveolar macrophages (by flow cytometry), expression of PIAS2 and PPARγ (by Western blot), co-expression of PPARγ-SUMO1 (by immunoprecipitation) and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) mRNA (by polymerase chain reaction). The ratio of M1/M2 was calculated. Results:Experiment Ⅰ Compared with C group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was up-regulated in the other three groups ( P<0.05). Compared with ALI group, the lung injury scores and W/D ratio were significantly decreased, and the expression of PIAS2 protein and mRNA was up-regulated in ALI+ T group and ALI+ T+ A group ( P<0.05). Compared with ALI+ T group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was down-regulated in ALI+ T+ A group ( P<0.05). There was no significant difference in the expression of PIAS1, PIAS3 and PIASy protein and mRNA in lung tissues among the four groups ( P>0.05). Experiment Ⅱ Compared with C group, the cell viability was significantly decreased, the expression of PPARγ and co-expression of PPARγ-SUMO1 was up-regulated, the levels of M1 and M2 macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was up-regulated, and the expression of IL-10 mRNA was down-regulated in the other three groups, and PIAS2 expression was significantly up-regulated in L group and L+ C group ( P<0.05). Compared with L group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and PPARγ-SUMO1 co-expression were down-regulated, the M1 macrophage level and M1/M2 ratio were increased, TNF-α mRNA expression was up-regulated, and the expression of IL-10 mRNA was down-regulated in L+ P group ( P<0.05), and no significant change was found in the parameters mentioned above in L+ C group ( P>0.05). Compared with L+ C group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and co-expression of PPARγ-SUMO1 were down-regulated, the level of M1 alveolar macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was down-regulated, and the expression of IL-10 mRNA was up-regulated in L+ P group ( P<0.05). Conclusions:PIAS2-regulated SUMOylation of PPARγ is the endogenous protective mechanism against endotoxin-induced ALI in mice, which may be related to inhibition of macrophage polarization into M1 type and alleviation of inflammatory responses.

Research progress of anti-acute marrow leukemia drugs by targeting FLT3 / 药学学报

Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.

Microscopic identification for roots from 4 medicinal plants of Actinidia genus / 药学实践杂志

Objective To perform microscopic identification for the roots of Actinidia macrosperma C.F. Liang, Actinidia valvata Dunn, Actinidia arguta (Sieb. & Zucc) Planch. ex Miq., Actinidia chinensis Planch., and provide the basis for judging medicinal materials exactly. Methods The powder microscopic characteristics of 4 medicinal plants of Actinidia genus were observed by microscopic identification method. Results Taking the morphological characteristics of calcium oxalate clusters, starch granules and ducts as the main differences, a key table was compiled to identify the roots of these four medicinal plants. Conclusion The microscopic identification method could effectively distinguish 4 Chinese herbs of Actinidia genus, and which is worth further studying.

Eleutheroside B induces apoptosis and autophagy of lung cancer cells by regulating PI3K/Akt/mTOR pathway / 中国中药杂志

This study investigated the effect of eleutheroside B on apoptosis and autophagy of lung cancer A549 and H460 cells and its molecular mechanism. MTT assay was used to detect the cytotoxicity of eleutheroside B at 5, 10, 15, 20, 25, 30, 35, 40, and 45 mmol·L~(-1) on lung cancer cells. Trypan blue exclusion assay was used to detect the effect of eleutheroside B on the survival rate of lung cancer A549 and H460 cells at different time. Colony formation assay was used to detect the effect of eleutheroside B on the proliferation of lung cancer A549 and H460 cells. AO/EB fluorescence double staining and Hoechst 33342 fluorescence staining were used to detect the effect of eleutheroside B on apoptosis of lung cancer A549 and H460 cells, and Western blot was used to detect apoptosis-related proteins to explore the apoptosis-related molecular mechanism. AO fluorescence staining and Western blot were used to detect the expression of autophagic vesicles and autophagy-related proteins P62 and LC3. The results showed that compared with the control group, eleutheroside B inhibited the growth of lung cancer A549 and H460 cells in a concentration-dependent manner. The optimal effect time of eleutheroside B on lung cancer A549 and H460 cells was 24 h, and the optimal concentrations were 28.64 and 22.16 mmol·L~(-1), respectively. Eleutheroside B could inhibit the colony formation of A549 and H460 cells. Compared with the control group, eleutheroside B could promote the formation of apoptotic bodies and induce cell apoptosis, as well as induce the expression of mitochondrial pathway-related proteins. Under the effect of eleutheroside B, the acidic autophagy vacuole in lung cancer cells increased, LC3Ⅱ expression increased, P62 protein expression decreased, and PI3K, p-Akt, and p-mTOR protein expression decreased in the PI3K/Akt/mTOR pathway. Studies have shown that eleutheroside B can inhibit the growth of lung cancer cells, reduce colony formation, induce apoptosis of lung cancer cells through mitochondrial pathway, and induce autophagy. The mechanism may be related to the PI3K/Akt/mTOR pathway.

Relationship between HO-1 and PPARγ during alveolar macrophage polarization in a mouse model of endotoxin-induced acute lung injury / 中华麻醉学杂志

Objective:To evaluate the relationship between heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor γ (PPARγ) during alveolar macrophage polarization in a mouse model of endotoxin-induced acute lung injury (ALI).Methods:Thirty clean-grade male C57BL/6 mice (24 wide-type mice and 6 HO-1 knockout mice), aged 6-8 weeks, weighing 18-22 g, were studied.Wide-type mice were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), ALI group, ALI+ HO-1 agonist hemin group (ALI+ H group), and ALI+ hemin+ PPARγ antagonist T0070907 group (ALI+ H+ T group).HO-1 knockout mice in which the ALI model was developed served as ALI+ HO-1 -/- group.ALI model was developed by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals.T0070907 1.5 mg/kg was intraperitoneally injected at 1 h before LPS administration in ALI+ H+ T group, and hemin 50 mg/kg was intraperitoneally injected at 30 min before LPS administration in ALI+ H group and ALI+ H+ T group.Mice were sacrificed at 12 h after LPS administration, and lung tissues were obtained to measure the wet to dry weight ratio (W/D ratio), to observe pathological changes which were scored, and to determine the F4/80+ /CD86+ labeled M1 alveolar macrophages and the F4/80+ /CD206+ labeled M2 alveolar macrophages (by flow cytometry), contents of M1 macrophage-related genes inducible nitric oxide synthase (iNOS) and M2 macrophage-related genes Arginase-1 (Arg-1) (by enzyme-linked immunosorbent assay), and the expression of HO-1 and PPARγ (by Western blot). Results:Compared with C group, the lung injury score, W/D ratio, levels of CD86 and CD206, and contents of iNOS and Arg-1 were significantly increased, and PPARγ expression was up-regulated in the other four groups ( P<0.05), and HO-1 protein expression was up-regulated in ALI, ALI+ H and ALI+ H+ T groups ( P<0.05).Compared with ALI group, the lung injury score, W/D ratio, and levels of CD86 and iNOS were significantly increased, the levels of CD206 and Arg-1 were decreased, and the expression of HO-1 and PPARγ was down-regulated in ALI+ HO-1 -/- group, the lung injury score, W/D ratio and levels of CD86 and iNOS were significantly decreased, the levels of CD206 and Arg-1 were increased, and the expression of HO-1 and PPARγ was up-regulated in ALI+ H group ( P<0.05), and no significant change was found in the parameters mentioned above in ALI+ H+ T group ( P>0.05).Compared with ALI+ H group, the lung injury score, W/D ratio and levels of CD86 and iNOS were significantly increased, the levels of CD206 and Arg-1 were decreased, the expression of PPARγ was down-regulated ( P<0.05), and no significant change was found in the expression of HO-1 in ALI+ H+ T group ( P>0.05). Conclusions:HO-1 can up-regulate the expression of PPARγ, inhibit the polarization of alveolar macrophages toward M1 phenotype and promote the polarization toward M2 phenotype, thus playing an endogenous protective role in endotoxin-induced ALI in mice.

Clinical observation of electroacupuncture combined with Qingyi Xianxiong Decoction in the treatment of acute respiratory distress syndrome due to severe acute pancreatitis / 中华危重病急救医学

Objective:To observe the clinical effect of electroacupuncture combined with Qingyi Xianxiong Decoction on the treatment of acute respiratory distress syndrome (ARDS) caused by severe acute pancreatitis (SAP).Methods:From February 2021 to April 2022, 120 patients with ARDS caused by SAP who were admitted to the department of critical care medicine of Tianjin Nankai Hospital and whose syndrome differentiation belonged to the syndrome of knot chest were selected. They were randomly divided into pure traditional Chinese medicine group and acupuncture medicine group, with 60 cases in each group. The pure traditional Chinese medicine group was received Qingyi Xianxiong Decoction on the basis of conventional western medicine treatment, and the acupuncture medicine group was received electric acupuncture treatment on the basis of the pure traditional Chinese medicine group. The two groups continued to be treated for 7 days. The primary outcome was the ventilator-free days within 28 days after admission to the intensive care unit (ICU), and the secondary outcome measures were mechanical ventilation time, the length of ICU stay, total lenth of hospital stay, time of intra-abdominal pressure recovery, scores of organ function, oxygenation index (PaO 2/FiO 2), serum inflammatory factors, blood amylase, urine amylase, etc. Results:Compared with the pure traditional Chinese medicine group, the ventilator-free days in the acupuncture medicine group within 28 days after admission to the ICU were significantly longer [day: 22.10±2.29 vs. 20.97±2.31, P < 0.05, odds ratio ( OR) = 1.24, 95% confidence interval (95% CI) was 1.053-1.460, P < 0.05]. The time of mechanical ventilation, the length of ICU stay, total length of hospital stay, and recovery time of intra-abdominal pressure were significantly shortened [mechanical ventilation time (days): 5.90±2.29 vs. 7.03±2.31, the length of ICU stay (days): 8.07±1.89 vs. 12.08±2.23, total length of hospital stay (days): 19.55±6.82 vs. 22.28±5.19, recovery time of intra-abdominal pressure (days): 6.05±1.81 vs. 8.45±1.76, all P < 0.05]. The Murray score and bedside index for severity in acute pancreatitis (BISAP) score of the two groups after 7 days of treatment were significantly lower than those before treatment, while PaO 2/FiO 2 was significantly higher than those before treatment, and the Murray score of the acupuncture medicine group after 7 days of treatment was significantly lower than that of the pure traditional Chinese medicine group [score: 0.50 (0.33, 0.75) vs. 1.00 (1.00, 1.33), P < 0.05], PaO 2/FiO 2 was significantly higher than that in the pure traditional Chinese medicine group [mmHg (1 mmHg ≈ 0.133 kPa): 390.75±27.73 vs. 330.02±42.34, P < 0.05]. With the prolongation of treatment time, the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), serum amylase and urine amylase in both groups after treatment continued to decrease, and the levels of the inflammatory factors in the acupuncture medicine group after 7 days of treatment were significantly lower than those in the pure traditional Chinese medicine group [TNF-α (ng/L): 38.20±10.00 vs. 45.35±5.09, IL-6 (ng/L): 0.95±0.44 vs. 7.42±1.39, CRP (mg/L): 8.55±2.79 vs. 36.20±13.97, all P < 0.05]. Subgroup analysis showed that biliary system disease was a risk factor for the duration of mechanical ventilation ≥ 7 days in the treatment of ARDS with acupuncture and medicine ( OR = 2.728, 95% CI was 1.293-5.754). Conclusion:Compared with the pure traditional Chinese medicine, acupuncture combined can better reduce the clinical symptoms of patients with ARDS caused by SAP, promote the recovery of patients, and reduce systemic inflammatory reaction, which is worthy of clinical promotion.

Analysis of the incidence trend of thyroid cancer in Qingpu District of Shanghai from 2007 to 2016 / 上海预防医学

ObjectiveTo understand the incidence and change trend of thyroid cancer in Qingpu District， Shanghai from 2007 to 2016， and to provide a reference for formulating relevant prevention and treatment strategies. MethodsThe incidence data of thyroid cancer among residents in Qingpu District from 2007 to 2016 were collected using the Shanghai Malignant Tumor Registration System， and the crude incidence rate was calculated for different gender and age groups. The age-standardized incidence rate was calculated using the world standard population， and the annual percentage change （APC） was calculated using Joinpoint software to analyze the time trend of the incidence of thyroid cancer. ResultsThe incidence of thyroid cancer changed from 8.97/105 in 2007 to 52.02/105 in 2016， with an increase of 479.93% （APC=23.60， P<0.05）. The standardized incidence rate of thyroid cancer in men and women was 11.21/105 and 32.11/105， respectively， Male to female incidence ratio was 1∶3. Thyroid cancer in Qingpu District was mainly concentrated in the 25‒64 age group， accounting for 88.03% of the total incidence. ConclusionFrom 2007 to 2016， the incidence of thyroid cancer in Qingpu District， Shanghai has a significant upward trend. The age of high incidence tends to be younger and the incidence of women is significantly higher than that of men. Corresponding prevention and treatment measures should be formulated in consideration of the discovered incidence characteristics.

Effects of transcutaneous electrical acupoint stimulation on mitochondrial quality control during endotoxin-induced acute lung injury in mice / 中华麻醉学杂志

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on mitochondrial quality control during endotoxin-induced acute lung injury (ALI) in mice.Methods:Twenty-four clean-grade healthy male C57BL/6J mice, aged 4-6 weeks, weighing 15-20 g, were divided into 4 groups ( n=6 each) according to the random number table method: control group (group C), endotoxin-induced ALI group (group L-ALI), endotoxin-induced ALI plus acupoint electroacupuncture group (group L-ALI+ EA), and endotoxin-induced ALI plus non-acupoint electroacupuncture group (group L-ALI+ SEA). Lipopolysaccharide (LPS) 15 mg/kg was injected via the caudal vein to develop the model of endotoxin-induced ALI in anesthetized mice.In group L-ALI+ EA, at 5 days before LPS injection, bilateral Zusanli and Feishu acupoints were stimulated with an electric stimulator for 30 min each time at a voltage of 1-2 mA and a frequency of 2/15 Hz until the end of the experiment.In group L-ALI+ SEA, stimulation was performed at the points 0.5 cm lateral to the acupoints of bilateral Zusanli and Feishu non-meridian and non-acupoint sites using the shallow puncture method, and the other treatment methods were the same as those previously described in group EA.Group C received no treatment.The mice were sacrificed by euthanasia at 12 h after LPS administration, and lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope) and structure and morphology of mitochondria (with a transmission electron microscope) and for determination of the levels of reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) and contents of glutathione (GSH) and glutathione oxidized (GSSG). The GSH/GSSG ratio was calculated.The expression of mitochondrial fusion proteins mitofusin 1 (Mfn1), Mfn2, optic atrophy1 (OPA1), dynamin-related protein 1 (Drp1), fission protein 1 (Fis1), peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor-1 (NRF1), NRF2, PTEN-induced putative protein kinase 1 (PINK1) and the E3 ubiquitin ligase (Parkin) was determined by Western blot. Results:Compared with group C, the level of ROS and contents of GSSG and mtDNA were significantly increased, GSH content and GSH/GSSG ratio were decreased, the expression of Mfn1, Mfn2, OPA1, NRF1, NRF2 and PGC-1α was down-regulated, and the expression of Drp1, Fis1, PINK1 and Parkin was up-regulated in L-ALI, L-ALI+ EA and L-ALI+ SEA groups ( P<0.05). Compared with group L-ALI, the level of ROS and contents of GSSG and mtDNA were significantly decreased, GSH content and GSH/GSSG ratio were increased, the expression of Mfn1, Mfn2, OPA1, NRF1, NRF2 and PGC-1α was up-regulated, and the expression of Drp1, Fis1, PINK1 and Parkin was down-regulated in group L-ALI+ EA ( P<0.05). Compared with group L-ALI+ EA, the level of ROS and contents of GSSG and mtDNA were significantly increased, GSH content and GSH/GSSG ratio were decreased, the expression of Mfn1, Mfn2, OPA1, NRF1, NRF2 and PGC-1α was down-regulated, and the expression of Drp1, Fis1, PINK1 and Parkin was up-regulated in group L-ALI+ SEA ( P<0.05). Conclusions:TEAS can reduce endotoxin-induced ALI probably through regulating mitochondrial quality control in mice.

Role of HO-1 in endotoxin-induced acute lung injury in mice: relationship with regulation of mitochondrial quality control / 中华麻醉学杂志

Objective:To evaluate the role of heme oxygenase-1 (HO-1) in endotoxin-induced acute lung injury (ALI) and the relationship with the regulation of mitochondrial quality control in mice.Methods:Clean-grade healthy male adult C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were selected.HO-1 inducible gene knockout mice (HO-1 -/-) were prepared based on CRISPER/Cas9-mediated EGE system, and HO-1 gene overexpression mice (HO-1 + /+ ) were prepared by transfection of HO-1 overexpressed adenovirus vector.The mice were divided into 2 groups ( n=6 each) using a random number table method: control group (group WT, group HO-1 -/-, group HO-1 + /+ ) and endotoxin-induced ALI group (group ALI, group HO-1 -/-+ ALI, group HO-1 + /+ + ALI). Lipopolysaccharide 15 mg/kg was injected through the tail vein to develop the model of endotoxin-induced ALI, and the equal volume of normal saline was given instead in each control group.The mice were sacrificed by bloodletting at 12 h after lipopolysaccharide or normal saline administration.The lung tissues were harvested for microscopic examination of the pathological changes which were scored, for determination of GSH and GSSG contents, for observation of the ultrastructure of mitochondria (with a transmission electron microscope) and survival within 12 h, for measurement of mitochondrial membrane potential (MMP) levels, and for determination of the expression of mitochondrial quality control-related proteins mitochondrial fusion protein 2 (Mfn2) and dynamin-related protein 1 (Drp1), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitophagy marker protein PTEN-induced kinase 1 (PINK1) and E3 ubiquitin-protein ligase Parkin.The ratio of GSH/GSSG was calculated. Results:Compared with control group (group WT, group HO-1 + /+ and group HO-1 -/-), the 12-h survival rate and MMP were significantly decreased, the lung injury score was increased, GSH content and GSH/GSSG ratio were decreased, and the content of GSSG was increased in endotoxin-induced ALI groups (group ALI, group HO-1 + /+ + ALI and group HO-1 -/-+ ALI) ( P<0.05). Compared with group ALI, the 12-h survival rate and MMP were significantly decreased, the lung injury score was increased, the GSH content and GSH/GSSG ratio were decreased, the GSSG content was increased, and the expression of HO-1, Mfn2, PGC-1α, NRF1, PINK1 and Parkin was down-regulated, and Drp1 expression was up-regulated in group HO-1 -/-+ ALI, and 12-h survival rate and MMP were significantly increased, lung injury score was decreased, GSH content and GSH/GSSG ratio were increased, GSSG content was decreased, the expression of HO-1, Mfn2, PGC-1α, NRF1, PINK1 and Parkin was up-regulated, and the expression of Drp1 was down-regulated in group HO-1 + /+ + ALI ( P<0.05). Conclusions:HO-1 is involved in the process of endotoxin-induced ALI in mice, which is related to the regulation of mitochondrial quality control.

Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Effect of anticoagulation combined with average volumeassuredpressuresupporton acute exacerbation of chronic obstructive pulmonary disease patients with type Ⅱrespiratory failure / 中国医师进修杂志

Objective:to investigate the therapeutic effect of low molecular weight heparin combined with average volumeassuredpressuresupport (AVAPS) on patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with type Ⅱ respiratory failure.Methods:A total of 82 patients with AECOPD combined with type Ⅱ respiratory failure in the Second People′s Hospital of Xindu District of Chengdu from February 2018 to April 2020 were selected as the research objects, and they were randomly divided into two groups with 41 cases in each group. The control group was given AVAPS mode, and the observation group was given low molecular weight heparin combined with AVAPS mode. The arterial partial pressure of oxygen (PaO 2), arterial carbon dioxide (PaCO 2), and forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), maximum peak expiratory flow rate (PEF), interleukin (IL)-6, IL-8, tumor necrosis factor-(TNF-α), 16 kDa Clara cell protein (CC16), surfactant protein D(SP-D), adiponectin (APN), superoxide dismutase (SOD), D-dimer, fibrinogen before and after treatment were compared between the two groups and the incidence of adverse reactions were observed. Results:After treatment, the levels of FEV 1, FVC, PEF, PaO 2 in the observation group were higher than those in the control group: (1.78 ± 0.29) L vs. (1.47 ± 0.25) L, (2.47 ± 0.29) L vs.(2.20 ± 0.25) L, (5.14 ± 0.37) ml/s vs. (4.69 ± 0.35) ml/s, (88.37 ± 10.52) mmHg (1 mmHg = 0.133 kPa) vs. (80.16 ± 9.87) mmHg; and the level of PaCO 2 was lower than that in the control group: (65.07 ± 6.71) mmHg vs. (70.84 ± 6.50) mmHg; and the differences were statistically significant ( P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in the observation group were lower than those in the control group: (0.47 ± 0.09) ng/L vs. (0.58 ± 0.10) ng/L, (64.37 ± 7.25) ng/L vs. (88.24 ± 8.34) ng/L, (45.37 ± 4.63) ng/L vs. (66.31 ± 4.92) ng/L; and the levels of SOD and APN were higher than those in the control group: (92.37 ± 10.85) U/mg vs. (76.13 ± 9.84) U/mg, (13.94 ± 0.76) mg/L vs. (11.58 ± 1.21) mg/L; and the differences were statistically significant ( P<0.05). After treatment, the level of CC16 in the observation group was higher than that in the control group: (114.78 ± 12.15) μg/L vs. (107.41 ± 11.06) μg/L; while the levels of SP-D, D-dimer and FIB were lower than those in the control group: (93.24 ± 9.85) μg/L vs. (103.25 ± 10.78) μg/L, (0.58 ± 0.07) mg/L vs. (0.79 ± 0.11) mg/L, (1.98 ± 0.29) g/L vs. (2.56 ± 0.34) g/L; and the differences were statistically significant ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Low-molecular-weight heparin combined with AVAPS mode in the treatment of AECOPD complicated with type Ⅱ respiratory failure can significantly improve the lung inflammation and coagulation function in patients, adjust blood gas analysis and CC16, SP-D levels, and promote the recovery of patients′ lung function.

Analysis of the epidemiological characteristics and survival rate of cancer in Qingpu District， Shanghai from 2012 to 2016 / 上海预防医学

Objective:To analyze the incidence and death characteristics of cancer and survival rate of residents in Qingpu District， Shanghai from 2012 to 2016， and to provide a scientific basis for subsequent cancer prevention and treatment. Methods:The malignant tumor incidence and death data were collected by the Shanghai Malignant Tumor Case Registration System. Based on these data， the crude incidence and mortality rate of cancer， the standardized rate， the order of incidence and death of the top 10 cancers， and the overall survival rate were calculated using the life table method. The relative survival rate for 1 to 5 years was calculated using the Ederer II method according to survival probability in the abbreviated life table for the same period. The annual percentage change （APC） was calculated by Joinpoint software， and the trend of morbidity and mortality was analyzed. Results:A total of 10 893 new malignant tumor cases were diagnosed in the region from 2012 to 2016. The crude incidence rate of cancer in the whole region was 464.68/100 000 （502.06/100 000 for men and 428.57/100 000 for women）， and the standardized incidence rate was 224.61/100 000 （235.52/100 000 for men， and 217.98/100 000 for women）. A total of 5 820 people died of cancer， the crude mortality rate of cancer in the whole region was 248.28/100 000 （321.92/100 000 for men and 177.13/100 000 for women）， and the standardized mortality rate was 97.08/100 000 （133.14/100 000 for men and 66.38/100 000 for women）. Patients with malignant tumors diagnosed in Qingpu District in 2012 showed higher 5-year relative survival for breast cancer （87.03%）， malignant tumors of brain and central nervous system （73.62%）， and colorectal cancer （58.22%）. A relative low 5-year survival rate was observed in patients with pancreatic cancer （3.76%）， esophageal cancer （10.55%）， and liver cancer （15.79）. Conclusion:Lung cancer and malignant tumors of the digestive system （including gastric cancer and colorectal cancer） are the main types of cancer threatening the health of residents in Qingpu District. The survival rates of breast cancer， malignant tumors of brain and central nervous system， and colorectal cancer have reached or approached the level of developed countries. However， the overall survival rate of malignant tumors in Qingpu District is lower than that in the city， and needs to be further improved.

Research advances in the pathogenesis of alcoholic liver disease / 临床肝胆病杂志

Alcoholic liver disease (ALD) is a common cause of liver dysfunction and death due to liver-related diseases, which brings great harm to human health and social development. Many factors are involved in the development and progression of ALD, such as oxidative stress, change in gut microbiota, genetic variation, autophagy inhibition, and microRNAs. This article summarizes the mechanism of action of these factors in ALD, in order to provide a basis for the treatment of ALD and the discovery of new drug targets.

Elective Splenectomy Combined with Modified Hassab's or Sugiura Procedure for Portal Hypertension in Decompensated Cirrhosis.

Objective: Portal hypertension is a major complication of decompensated cirrhosis. In China, modified Hassab's and Sugiura procedure are the two major methods of nonshunting surgery. This study aims to compare the efficacy and safety of the two procedures for portal hypertension. Method: Between January 1994 and December 2009, 172 elective patients diagnosed with decompensated cirrhosis with significant hypersplenism adopted elective splenectomy for hypersplenism, and also modified Hassab's (n = 91) or Sugiura (n = 81) procedure was additionally performed to reduce the risk of variceal bleeding. Postoperative mortality and morbidity data were collected, and a retrospectively comparative analysis was conducted. Results: All of the patients were treated successfully without death during operation, and no variceal bleeding occurred during hospitalization. There were 4 (4.4%) deaths in Hassab's group and 3 (3.7%) deaths in Sugiura group postoperatively (P > 0.05). During follow-up, the survival rate was 90.2%, 82.42%, and 71.43% in Hassab's group and 96.29%, 81.48%, and 75.31% in Sugiura group in 1, 3, and 5 years (P > 0.05). There were 22/71 and 12/63 patients in each groups who suffered no deadly variceal bleeding (P = 0.11). Bleeding related death and no bleeding related death occurred in 7/23 and 3/13 patients in each group (P = 0.26 and 0.14, respectively). Conclusion: Elective splenectomy combined with modified Sugiura procedure seemed to be associated with a reduced trend of no deadly variceal bleeding compared with Hassab's procedure. As statistical significance was not found, further large scale and prospective study was warranted.

Application of Mini-Clinical Evaluation Exercise in the training of patient-doctor communication ability of interns in department of neurology / 中华医学教育探索杂志

Objective@#To investigate the application effect of Mini-Clinical Evaluation Exercise (Mini-CEX) in the training of patient-doctor communication ability of interns in department of neurology.@*Methods@#A total of 60 clinical interns who received practice teaching in Department of Neurology in The Third Affiliated Hospital of Army Medical University from January 2016 to June 2017 were selected, and a questionnaire survey on the communication barriers between patients and doctors was performed on admission to analyze the main causes of these barriers. The Mini-CEX was used for communication ability training of interns, and its application effect was evaluated.@*Results@#At the end of training (one month later), the number of patient-doctor communication, completeness of medical history collection, physical examination kills and the median and pass rate of patient satisfaction of interns were significantly improved, as compared with before (P<0.05), and the degree of satisfaction with Mini-CEX reached above 95% among the teachers and clinical interns.@*Conclusion@#Mini-CEX for communication ability training can improve the patient-doctor communication ability of interns in department of neurology. Mini-CEX also has a certain teaching effect and thus holds promise for application in practice teaching.

Association between elective cesarean delivery and duration of breastfeeding in Ma′anshan City from 2013 to 2014 / 中华预防医学杂志

Objective@#To analyze the correlation between elective cesarean delivery and duration of breastfeeding in Ma′anshan city from 2013 to 2014.@*Methods@#From May 2013 to September 2014, a total of 3 474 pregnant women with the first prenatal checkup were recruited from Ma′anshan maternal and child health care hospital. Finally, 3 109 pregnant women were included after exclusion of those with terminated pregnancies, adverse birth outcomes, twin or multiple pregnancies, breech traction, breech midwifery and loss of delivery information. Demographic data of pregnant women, mode of delivery and breast feeding of children were collected through questionnaires and hospital records. Logistic regression model was used to analyze the relationship between elective cesarean delivery and duration of breastfeeding in children, with the mode of delivery as independent variable and the duration of breastfeeding as dependent variable.@*Results@#The age of 3 109 subjects was (26.6±3.6) years old, the rate of vaginal delivery was 51.1% (1 589), and the rate of elective cesarean delivery was 46.4% (1 443), among which the rate of non-indicative elective cesarean delivery was 26.4% (820), the rate of indicative elective cesarean delivery was 20.0% (623), and the rate of emergency cesarean delivery was 2.5% (77). The proportion of breastfeeding lasting until 4, 12 and 18 months was 45.0% (1 348/2 998), 23.7% (702/2 962) and 5.2% (154/2 944), respectively. After adjusting the confounding factors, compared with vaginal delivery, the OR (95%CI) values of breastfeeding for 4 months in indicative elective cesarean delivery and non-indicative elective cesarean delivery women were 0.870(0.714-1.059), 0.795(0.665-0.949), and the OR (95%CI) values of breastfeeding for 12 months were 0.772(0.611-0.975), 0.755(0.610-0.934), respectively.@*Conclusion@#Elective cesarean delivery may result in shorter duration of breastfeeding in children.

Diagnostic value of pyruvate kinase M2 gene for papillary thyroid carcinoma in fine-needle aspiration specimens / 中华内分泌代谢杂志

Objective To investigate the diagnostic value of pyruvate kinase M2 ( PKM2) gene expression in papillary thyroid carcinoma ( PTC). Methods Quantitative real-time PCR ( RT-qPCR) was used to detect the expression of PKM2 mRNA in benign thyroid nodules, PTC, and normal thyroid cells around nodules of fine-needle aspiration (FNA) specimens. Immunohistochemistry ( IHC) was used to detect the expression of PKM2 protein in thyroid tissue after thyroidectomy. The receiver operating characteristic curve was constructed to evaluate the diagnostic value of PKM2 in PTC. Results The expression of PKM2 mRNA was detectable in FNA specimens of thyroid nodules,higher in PTC than those in normal thyroid tissue and benign thyroid nodules (P<0.01). PKM2 expression level was correlated with diameter of PTC ( P<0.05) , but had no correlation with lymph node metastasis, BRAFV600E mutation, and American Joint Committe on Cancer( AJCC) stage ( P>0.05) . The expression level of PKM2 mRNA in FNA specimens of thyroid nodules was paralleled with the expression level of PKM2 protein in postoperation pathological tissues. The accuracy, sensitivity, specificity of PKM2 gene in the diagnosis of PTC were 62.8％, 46.9％, and 95.7％, respectively. The accuracy and sensitivity of PKM2 combined with BRAFV600E were increased to 87.6％and 83.7％. Conclusion Detection of PKM2 gene in FNA specimens is highly specific in the diagnosis of PTC, making it a valuable molecular marker for preoperative diagnosis. The combination of PKM2 and BRAFV600E detection shows a higher diagnosis efficiency.

Application of Mini-Clinical Evaluation Exercise in the training of patient-doctor communication ability of interns in department of neurology / 中华医学教育探索杂志

Objective To investigate the application effect of Mini-Clinical Evaluation Exercise(Mini-CEX)in the training of patient-doctor communication ability of interns in department of neurology.Methods A total of 60 clinical interns who received practice teaching in Department of Neurology in The Third Affiliated Hospital of Army Medical University from January 2016 to June 2017 were selected,and a questionnaire survey on the communication barriers between patients and doctors was performed on admission to analyze the main causes of these barriers.The Mini-CEX was used for communication ability training of interns,and its application effect was evaluated.Results At the end of training(one month later),the number of patient-doctor communication,completeness of medical history collection,physical examination kills and the median and pass rate of patient satisfaction of interns were significantly improved,as compared with before(P＜0.05),and the degree of satisfaction with Mini-CEX reached above 95％among the teachers and clinical interns.Conclusion Mini-CEX for communication ability training can improve the patient-doctor communication ability of interns in department of neurology.Mini-CEX also has a certain teaching effect and thus holds promise for application in practice teaching.

PRISMA-efficacy and safety of lixisenatide for type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to systematically evaluate the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus. METHODS: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Google, Web of Science and the Chinese Science Citation Database were searched up to March 2018. Randomized controlled trials determining the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus were eligible for inclusion. Two authors independently extracted the data in a prespecified Microsoft Excel spreadsheet. A meta-analysis was performed using Review Manager 5.3 software. Weighted mean difference (WMD) and relative risk (RR) together with their corresponding 95% confidence intervals (CIs) were estimated, and only the random effects model was used in order to achieve a more conservative estimate of the efficacy and safety. RESULTS: Fourteen multicenter randomized controlled trials involving 11,947 patients were eligible for inclusion. Compared to placebo, lixisenatide could more significantly reduce the level of HbA1c (WMD=-0.44; 95% confidence interval [CI] [-0.55,-0.33]), and a higher proportion of lixisenatide-treated patients achieved the HbA1c level of < 7.0% (RR = 1.89, 95% CI [1.75-2.03]) and < 6.5% (RR = 3.03, 95% CI [2.54-3.63]) than the placebo-treated patients. Lixisenatide was also associated with a significant reduction in fasting plasma glucose and 2-hour postprandial plasma glucose levels. The risks for any adverse events, gastrointestinal adverse events, and symptomatic hypoglycemia significantly increased in the lixisenatide-treatedment group compared to those in the placebo group. However, lixisenatideit did not increase the risks of serious adverse events, death, or severe hypoglycemia. CONCLUSIONS: Lixisenatide was more effective than placebo in patients with type 2 diabetes mellitus, and the mild-to-moderate adverse events were found to be tolerated during the follow-up.

Efficacy and Safety of Endoscopic Intralesional Triamcinolone Injection for Benign Esophageal Strictures.

OBJECTIVES: To evaluate the efficacy and safety of endoscopic intralesional triamcinolone injection (ITI) for benign esophageal strictures combined with endoscopic dilation (ED). METHODS: Online databases including MEDLINE, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for prospective randomized control trials (RCTs) between 1966 and March 2018. A meta-analysis was conducted according to the methods recommended by the Cochrane Collaboration. RESULTS: Six RCTs consisting of 176 patients were selected. Meta-analysis results showed that additional ITI had a significant advantage in terms of stricture rate and required ED sessions. Surgery-related and non-surgery-related strictures showed similar results. Additional ITI was not associated with significantly increased risk of complications. CONCLUSIONS: Our meta-analysis showed that additional ITI therapy was supposed to be effective and safe for benign esophageal strictures as it reduced the stricture rate and required ED sessions. However, more RCTs are necessary to support these findings.