Reconstruction of foot and ankle defects using the vaccum sealing drainage versus the induced-membrane the elderly: A retrospective comparative study.

The purpose of this study was to compare the reconstructive outcomes of soft-tissue defects around foot and ankle with vaccum sealing drainage (VSD) or induction membrane (IM) of cement formation and attempt to provide an optimal strategy for elderly patients. A retrospective review of all continuous patients with foot and ankle reconstruction using different flaps from October of 2016 and October of 2020 was performed. Based on the different way, the patients were divided into two groups: VSD group (n = 26) and IM group (n = 27). Outcomes were assessed according to the size of the defect, frequency of debridement procedures, hospitalization time, duration of healing, the healing rate, major amputation rate, functional outcomes and complications. Immunohistochemistry (IHC) detection of vascular endothelial growth factor (VEGF) was also be completed. We found that there was no difference in demographic characteristics, size of the defect, debridement times and functional outcomes between the two groups (p > 0.05); however, a significant difference in the wound healing time, hospitalization time and complications were noted between them(p < 0.05). The fresh granulation tissue of both groups showed abundant positive expression of VEGF. Thus, the VSD and IM are both available for foot and ankle reconstruction in elderly patients. However, the IM group offers short hospitalization time, duration of healing and lower frequency of postoperative complications. Thus, we advocate the IM for reconstruction of defects of the foot and ankle region in the elderly patients.

MicroRNA-1297 participates in the repair of intestinal barrier injury in patients with HIV/AIDS via negative regulation of PLCß1.

To explore the role of the miRNA-1297/phospholipase Cß1 (PLCß1) axis in intestinal barrier injury. Abnormally expressed miR-1297 and its target gene PLCß1 as well as their transcriptome sequencing were confirmed by bioinformatics analysis. Next, the intestinal barrier injury was induced by lipopolysaccharide (LPS) in the CCCHIE-2 cells. Subsequently, the impacts of miR-1297 and PLCß1 on the transcriptome were estimated. QRT-PCR and Western blotting were conducted to detect the relative mRNA and protein expressions, respectively. The cell viability and permeability were analyzed by MTT assay and fluorescent yellow detection. miR-1297 was significantly upregulated in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and targeted PLCß1. Moreover, overexpressed PLCß1 was mainly enriched in the transforming growth factor-beta signaling pathway, while the knockdown of miR-1297 was focused on the arginine biosynthesis pathway. The overexpression of miR-1297 could reduce the PLCß1 expression and inhibit the viability of CCCHIE-2 cells injured by LPS, while the effect of the downregulation of miR-1297 was on the opposite. Western blotting and cell fluorescence localization experiments revealed that the inhibition of miR-1297 increased the expressions of PLCß1 and ZO-1. In addition, the upregulation of miR-1297 strengthened the permeability in cells injured by LPS, as did the knockdown of PLCß1. miR-1297 could restrain the repair of intestinal barrier injury via negatively regulating PLCß1 and its tight junction downstream protein ZO-1 in CCC-HIE-2 cells injured by LPS, which indicated that PLCß1 and miR-1297 might be important targets for the repair of intestinal barrier injury.

Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice.

BACKGROUND: Metformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) in rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformin's participation in the pathophysiology of withdrawal symptoms via modulation of gut microbiota. METHODS: In order to define the functional impacts of gut microbiota and metformin to the behavioural deficits during METH withdrawal, we utilized a combination of fecal microbiota transplantation (FMT), high-throughput sequencing, and untargeted metabolomics technologies. RESULTS: First, METH addicts exhibited higher α diversity and distinct microbial structures compared to healthy controls. In particular, the relative abundance of Rikenellaceae was positively correlated with the severity of anxiety and depression. Second, both human-to-mouse and mouse-to-mouse FMTs confirmed that METH-altered-microbiota transplantation is sufficient to promote anxiety and depression-like behaviours in recipient germ-free mice, and these behavioural disturbances could be ameliorated by metformin. In-depth analysis revealed that METH significantly altered the bacterial composition and structure as well as relative abundance of several bacterial taxa and metabolites, including Rikenellaceae and inosine, respectively, whereas add-on metformin could remodel these alterations. Finally, the inosine complementation successfully restored METH-induced anxiety and depression-like behaviours in mice. CONCLUSION: This study demonstrates that METH withdrawal-induced anxiety and depression-like behaviours are reversible and transmissible via gut microbiota in a mouse model. The therapeutic effects of metformin on psychiatric manifestations are associated with microbiota-derived metabolites, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

Plasma metabolites changes in male heroin addicts during acute and protracted withdrawal.

BACKGROUND: Heroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown. METHODS: A total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. We performed metabolic profiling of plasma samples based on ultraperformance liquid chromatography coupled to tandem mass spectrometry to explore the potential biomarkers and mechanisms of heroin withdrawal. RESULTS: Among the metabolites analyzed, omega-6 polyunsaturated fatty acids (linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, n-6 docosapentaenoic acid), omega-3 polyunsaturated fatty acids (docosahexaenoic acid, docosapentaenoic acid), aromatic amino acids (phenylalanine, tyrosine, tryptophan), and intermediates of the tricarboxylic acid cycle (oxoglutaric acid, isocitric acid) were significantly reduced during acute heroin withdrawal. Although majority of the metabolite changes could recover after months of withdrawal, the levels of alpha-aminobutyric acid, alloisoleucine, ketoleucine, and oxalic acid do not recover. CONCLUSIONS: In conclusion, the plasma metabolites undergo tremendous changes during heroin withdrawal. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and withdrawal stages in heroin addicts.

miR-125b-5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS-induced intestinal mucosa cell injury model.

Intestinal barrier injury is an important cause of death in patients with acquired immune deficiency syndrome (AIDS). Therefore, it is of great significance to identify a therapeutic target for intestinal barrier injury to delay the progression of AIDS. microRNA (miRNA/miR)-125b-5p has an extensive role in cancer and controlling intestinal epithelial barrier function, but its role in human immunodeficiency virus-related intestinal mucosal damage remains unknown. The present study was designed to explore the effects of miR-125b-5p on lipopolysaccharide (LPS)-induced intestinal mucosal injury and the underlying mechanism. The expression of miR-125b-5p and ASCT2 mRNA was detected in colon biopsy samples of 10 patients with AIDS and 10 control healthy subjects. Human intestinal embryonic mucosa cells (CCC-HIE-2) were used to establish an LPS-induced intestinal mucosa cell injury model in vitro. Cell proliferation and apoptosis were determined by MTT assays and flow cytometry, respectively. miR-125b-5p levels and ASCT2 mRNA and protein expression levels in the LPS-induced intestinal mucosa cell injury model were detected by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The interaction between miR-125b-5p and ASCT2 was analyzed using a dual luciferase reporter assay. The results demonstrated that miR-125b-5p levels were increased and ASCT2 mRNA expression levels were decreased in colon samples from patients with AIDS and in LPS-induced intestinal mucosa cells. In the LPS-induced intestinal mucosa cell injury model, transfection with miR-125b-5p mimic inhibited cell proliferation and promoted cell apoptosis, while transfection with a miR-125b-5p inhibitor increased cell proliferation and attenuated cell apoptosis. Furthermore, miR-125b-5p mimic transfection resulted in a decrease of ASCT2 mRNA and protein expression, whereas the inhibitor increased ASCT2 mRNA and protein expression. Dual luciferase reporter assays suggested that ASCT2 was a direct target of miR-125b-5p, and its restoration weakened the effect of miR-125b-5p on LPS-induced intestinal mucosa cell injury. Transfection with the miR-125b-5p mimic also exhibited a suppressive effect on the PI3K/AKT/mTOR pathway in the LPS-induced intestinal mucosal cell injury model. Overall, the present study indicated that miR-125b-5p accelerated LPS-induced intestinal mucosa cell injury by targeting ASCT2 and upregulating the PI3K/AKT/mTOR pathway. The current findings may provide novel targets for the treatment of intestinal barrier injury in patients with AIDS.

Berberine-Albumin Nanoparticles: Preparation, Thermodynamic Study and Evaluation Their Protective Effects Against Oxidative Stress in Primary Neuronal Cells as a Model of Alzheimer's Disease.

Berberine has shown an outstanding antioxidant activity, however the low bioavailability limits its applications in pharmaceutical platforms. Therefore, in this paper, after fabrication of the berberine-HSA nanoparticles by desolvation method, they were well characterized by TEM, SEM, DLS, and FTIR techniques. Afterwards the interaction of HSA and the berberine was evaluated by molecular docking analysis. Finally, the antioxidant activity of the berberine-HSA nanoparticles against H2O2-induced oxidative stress in cultured neurons as a model of AD was evaluated by cellular assays. The results showed that the prepared berberine-HSA nanoparticles have a spherical-shaped morphology with a size of around 100 nm and zeta potential value of -31.84 mV. The solubility value of nanoparticles was calculated to be 40.27%, with a berberine loading of 19.37%, berberine entrapment efficiency of 70.34%, and nanoparticles yield of 88.91%. Also, it was shown that the berberine is not significantly released from HSA nanoparticles within 24 hours. Afterwards, molecular docking investigation revealed that berberine spontaneously interacts with HSA through electrostatic interaction. Finally, cellular assays disclosed that the pretreatment of neuronal cultures with berberine-HSA nanoparticles decreased the H2O2-stimulated cytotoxicity and relevant morphological changes and enhanced the CAT activity. In conclusion, it can be indicated that the nanoformulation of the berberine can be used as a promising platform for inhibition of oxidative damage-induced Alzheimer's disease (AD).

Development of L-carnosine functionalized iron oxide nanoparticles loaded with dexamethasone for simultaneous therapeutic potential of blood brain barrier crossing and ischemic stroke treatment.

The development of suitable drug delivery carriers is significant in biomedical applications to improve the therapeutic efficiency. Recent progress in nanotechnological fields, paved the way for the formulation of variety of drug carriers. The brain disorders such as ischemic stroke, brain cancer, and CNS disorders were poorly treated due to the presence of blood brain barrier that hinders the passage of drugs to the brain. Hence, the formulated drugs should have the ability to cross the blood-brain barrier (BBB) for ischemic stroke treatment. In the present work, we have synthesized PLGA functionalized magnetic Fe3O4 nanoparticle (MNP) with L-carnosine peptide (LMNP) composite loaded with dexamethasone (dm@LMNP) and demonstrated as efficient drug delivery platform for simultaneous BBB crossing and treatment of ischemic stroke. The surface morphology, particles size and zeta potential of the prepared material was studied from SEM, PSD, PDI and TEM analyses. The drug loading of dexamethasone in LMNP (dm@LMNP) vesicles was found to be 95.6 ± 0.2%. The in vitro drug release kinetics displayed that prepared composited LMNP material provides controlled and sustainable releasing efficiency at pH 7.4 and 5.8 when compared to the PLGA NPs and free dexamethasone drug molecules. The cytotoxicity and the biocompatibility test results were found to be satisfactory. The L-carnosine loaded nano-formulation has been greatly leads to effective BBB crossing to access the brain tissues. These results showed that the Fe3O4 nanoparticles/PLGA polymer can be used as an effective drug carrier for the treatment of stroke and simultaneous blood brain barrier crossing.

The Protective Effects of Melatonin Against LPS-Induced Septic Myocardial Injury: A Potential Role of AMPK-Mediated Autophagy.

Aim: Melatonin is an indolamine secreted by the pineal gland, as well as most of the organs and tissues. In addition to regulating circadian biology, studies have confirmed the multiple pharmacological effects of melatonin. Melatonin provides a strong defense against septic myocardial injury. However, the underlying mechanism has not been fully described. In this study, we investigated the protective effects of melatonin against lipopolysaccharide (LPS)-induced myocardial injury as well as the mechanisms involved. Methods: Mice were intraperitoneally injected with LPS to induce a septic myocardial injury model or an LPS shock model, depending on the dose of LPS. Melatonin was given (20 mg/kg/day, via intraperitoneal injection) for a week prior to LPS insult. 6 h after LPS injection, echocardiographic analysis, TUNEL staining, transmission electron microscopy (TEM), western blot, quantitative real-time PCR and ELISA were used to investigate the protective effects of melatonin against LPS induced myocardial injury. AMPK inhibitor, autophagy activator and inhibitor, siRNAs were used for further validation. Results: Survival test showed that melatonin significantly increased the survival rate after LPS-induced shock. In the sepsis model, melatonin markedly ameliorated myocardial dysfunction, decreased the release of inflammatory cytokines, activated AMP-activated protein kinase (AMPK), improved mitochondrial function, and activated autophagy. To confirm whether the protection of melatonin was mediated by AMPK and autophagy, Compound C, an AMPK inhibitor; 3-MA, an autophagy inhibitor; and Rapamycin (Rapa), an autophagy activator, were used in this study. AMPK inhibition down-regulated autophagy, abolished protection of melatonin, as indicated by significantly decreased cardiac function, increased inflammation and damaged mitochondrial function. Furthermore, autophagy inhibition by 3-MA significantly impaired the protective effects of melatonin, whereas autophagy activation by Rapa reversed LPS + Compound C induced myocardial injury. In addition, in vitro studies further confirmed the protection of melatonin against LPS-induced myocardial injury and the mechanisms involving AMPK-mediated autophagy signaling. Conclusions: In summary, our results demonstrated that melatonin protects against LPS-induced septic myocardial injury by activating AMPK mediated autophagy pathway.

Role of common ERCC1 polymorphisms in cisplatin-resistant epithelial ovarian cancer patients: A study in Chinese cohort.

Epithelial ovarian cancer (EOC) contributes the majority of death cases among various ovarian malignancies. Although a standard method of treatment is the surgical removal of malignant tissue followed by platinum-based chemotherapy, a group of patients does not respond appropriately to cisplatin. An appropriate response to cisplatin has been linked with the nucleotide excision repair mechanism. The present study aims to investigate the role of polymorphisms in DNA repair genes, excision repair cross-complementation group 1 (ERCC1) with susceptibility to EOC development and tumour response to platinum-based chemotherapy in Chinese EOC patients. Patients (n = 559) reporting to the Department of Oncology and general surgery, the First Affiliated Hospital of Kunming Medical University, were enrolled in the study. Three hundred twenty-three healthy controls hailing from similar geographical areas without a history of cancer enrolled as healthy controls. Excision repair cross-complementation group 1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were genotyped by appropriate methods. Distribution of genotypes and allele for ERCC1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were comparable among healthy controls and EOC patients. Interestingly, homozygous mutant and the minor allele for rs11615 and rs3212986 polymorphisms were significantly higher in nonresponder EOC patients when compared to those with a proper response to cisplatin treatment. The prevalence of other SNPs was comparable among the two treated clinical categories. Furthermore, combined genotype revealed significant association of rs11615: TT/ rs3212986: AA genotype combination with cisplatin nonresponder. Variants of rs11615, rs3212986 polymorphisms are associated with cisplatin resistance in Chinese EOC patients. Combined rs11615 and rs3212986 genotypes can be used as a predictive biomarker for platinum-based chemotherapy outcomes.

Draft genome sequence analysis of a high carbapenem-resistant Klebsiella quasipneumoniae subsp. quasipneumoniae strain isolated from an HIV-positive patient with pneumonia.

OBJECTIVES: The rapid spread of Klebsiella spp. is recognised as a major threat to public health owing to a rise in the number both of healthcare- and community-acquired infections. Here we report the draft genome sequence of a high carbapenem-resistant Klebsiella quasipneumoniae subsp. quasipneumoniae strain (Cln185) isolated from a human immunodeficiency virus (HIV)-positive patient with pneumonia. METHODS: Classical microbiological methods were applied to isolate and identify the strain. Genomic DNA was sequenced using an Illumina HiSeq platform and the reads were de novo assembled into contigs using CLC Genomics Workbench. The assembled contigs was annotated and whole-genome sequencing (WGS) was performed. RESULTS: WGS analysis revealed that the genome comprised a circular chromosome of 5 406 774bp with a GC content of 57.73%. Three important antimicrobial resistance genes (blaIMP-38, blaOKP-B-6 and blaDHA-1) were detected. In addition, genes conferring resistance to aminoglycosides, ß-lactams, fluoroquinolones and tetracycline were also identified. CONCLUSION: The draft genome sequence reported here will lay the foundation for future research on antimicrobial resistance and pathogenic mechanisms in K. quasipneumoniae subsp. quasipneumoniae and also will promote comparative analysis with genomic features among different sources of clinically important multidrug-resistant strains.

Acute Massive Gastrointestinal Bleeding in the Elderly.

An 82-year patient presented with nausea, coffee-ground emesis, melena and hematochezia on July 10, 2011. The patient received blood transfusion on July 11, and continued to bleed from July 12 to 17. The patient underwent upper gastrointestinal endoscopy on July 16. There were no abnormalities in the esophagus, stomach and duodenum. Then the patient presented with shortness of breath, extreme fear, fatigue, hypotension, sweating, and cold limbs. Dopamine, as well as pressurised infusion of packed red blood cells and fresh frozen plasma were given to the patient to maintain blood pressure. CT angiography (CTA) revealed no aortic fistula, and enteroscopy revealed active bleeding in the vicinity of the ligament of Treitz. The retrograde exploration of gastroscopy revealed a 5×4 cm diverticulum on the posterior wall of the duodenum under the ligament of Treitz. Active bleeding of the small artery in the diverticulum was observed via incision of the duodenal wall, and the diverticulum was isolated. Hemostasis was achieved after ligation of blood vessels, and diverticulectomy was performed. Enteroscopy is important for the diagnosis of duodenal and upper small intestinal diseases. Repeated endoscopic exploration of multiple sites in the small intestine revealed the cause of the bleeding. The multidisciplinary team finally found the cause of the bleeding and its proper management.

Molecular insights of Gas6/TAM in cancer development and therapy.

Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML. Interestingly, Gas6 also has a role in establishing tumour dormancy in the bone marrow microenvironment and in suppressing intestinal tumorigenesis. Numerous studies regarding cancer therapy have targeted Gas6 and TAM receptors with good results. However, some findings have suggested that Gas6 is associated with the development of resistance to cancer therapies. Concerning these significant effects of Gas6 in numerous cancers, we discuss the roles of Gas6 in cancer development in this review. First, we introduce basic knowledge on Gas6 and TAM receptors. Next, we describe and discuss the involvement of Gas6 and TAM receptors in cancers from different organ systems. Finally, we highlight the progress in therapies targeting Gas6 and TAM receptors. This review presents the significant roles of Gas6 in cancers from different systems and may contribute to the continued promotion of Gas6 as a therapeutic target.

Clinical and pathological significance of N-Myc downstream-regulated gene 2 (NDRG2) in diverse human cancers.

Human N-Myc downstream-regulated gene 2 (NDRG2), located at chromosome 14q11.2, has been reported to be down-regulated and associated with the progression and prognosis of diverse cancers. Collectively, previous studies suggest that NDRG2 functions as a candidate tumor-suppressor gene; thus, up-regulation of NDRG2 protein might act as a promising therapeutic strategy for malignant tumors. The aim of this review was to comprehensively present the clinical and pathological significance of NDRG2 in human cancers.

Cardiac-specific overexpression of metallothionein attenuates myocardial remodeling and contractile dysfunction in l-NAME-induced experimental hypertension: Role of autophagy regulation.

Hypertension is an independent risk factor for heart disease and is responsible for the increased cardiac morbidity and mortality. Oxidative stress plays a key role in hypertensive heart diseases although the precise mechanism remains unclear. This study was designed to examine the effect of cardiac-specific overexpression of metallothionein, a cysteine-rich antioxidant, on myocardial contractile and intracellular Ca(2+) anomalies in N(G)-nitro-l-arginine methyl ester (l-NAME)-induced experimental hypertension and the mechanism involved with a focus on autophagy. Our results revealed that l-NAME treatment (14 days) led to hypertension and myocardial anomalies evidenced by interstitial fibrosis, cardiomyocyte hypertrophy, increased LV end systolic and diastolic diameters (LVESD and LVEDD) along with suppressed fractional shortening. l-NAME compromised cardiomyocyte contractile and intracellular Ca(2+) properties manifested as depressed peak shortening, maximal velocity of shortening/relengthening, electrically-stimulated rise in intracellular Ca(2+), elevated baseline and peak intracellular Ca(2+). These l-NAME-induced histological and mechanical changes were attenuated or reconciled by metallothionein. Protein levels of autophagy markers LC3B and p62 were decreased and increased, respectively. Autophagy signaling molecules AMPK, TSC2 and ULK1 were inactivated while those of mTOR and p70s6K were activated by l-NAME, the effects of which were ablated by metallothionein. Autophagy induction mimicked whereas autophagy inhibition nullified the beneficial effect of metallothionein against l-NAME. These findings suggested that metallothionein protects against l-NAME-induced myocardial anomalies possibly through restoration of autophagy.

Epithelial ovarian cancer: A case report.

An 82-year-old female was diagnosed with ovarian cancer in May 2004. Following gynecological surgery, pathological evaluation showed stage IIIC epithelial ovarian cancer. From June 2004 to January 2005, the patient received six cycles of conventional treatment combined with intravenous paclitaxel (Taxol®) and cisplatin. The patient developed abdominal distension and experienced a gradual deterioration in health during 2007, with admission to The First Affiliated Hospital in May 2007. The patient presented with severe abdominal distension and breathing difficulty on May 15 and appeared to be in critical condition. Ultrasound examination revealed massive ascites and left-side pleural effusion. Thoracentesis and abdominocentesis were performed, and 300 mg carboplatin was administered intraperitoneally on May 19, followed by a second abdominocentesis on May 21. However, these treatments did not alleviate the symptoms, and 200 mg bevacizumab was administered by intravenous infusion on May 27. The condition of the patient gradually improved and 400 mg bevacizumab was administered by intravenous infusion every two weeks from June 9. From December, the dosage of bevacizumab was reduced to 200 mg every two weeks. In addition, 300 mg carboplatin was administered intraperitoneally on November 4 and intraperitoneal carboplatin chemotherapy was repeated thereafter. The patient exhibited disease-free survival until July 2009, at which time disease progression was observed and the cancer recurred in August 2009. The patient died of multiple organ failure in September 2009. Bevacizumab rapidly eliminated the patient's massive ascites and pleural effusion, and achieved an effect that was not possible with other treatments. Therefore, bevacizumab is an effective therapy for late-stage relapse and refractory ovarian cancer.

[Value of color Doppler ultrasound in the examination of prethrombotic state].

OBJECTIVE: To explore the clinical value of color Doppler ultrasound in patients with prethrombotic state (PTS). METHODS: From October 2011 to November 2012, a total of 201 patients were diagnosed with PTS. There were 95 males and 106 females with an average age of 52 years (range: 15-78). They were divided into intervention and observation groups on the basis of drug intervention. And the relevant literatures were reviewed and the images of color Doppler ultrasound before and after treatment compared. RESULTS: Before treatment, blood flow peak rates of common femoral, popliteal and calf intermuscular veins were (0.16 ± 0.03), (0.14 ± 0.03) and (0.13 ± 0.02) m/s; after treatment, (0.19 ± 0.03), (0.17 ± 0.03) and (0.15 ± 0.01) m/s respectively. The peak flow increased and sluggish flow decreased or disappeared in 152 PS patients. It indicated a relief or an obvious resolution of hypercoagulable state. And the symptom of lower extremity soreness was greatly relieved. Among 49 patients without drug intervention, severe full-lumen storm floating occurred in 12 cases. And 8 of them suffered deep vein thrombosis within 2 weeks. The incidence of thrombus was 66.7%. CONCLUSION: Color Doppler ultrasound may detect and assess PTS effectively so as to guide effective interventions.

Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction and apoptosis.

Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6weeks. Following 2weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)Ca(2+) exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH(2)-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na(+)Ca(2+) exchanger, cardiac contractile and intracellular Ca(2+) defects, cardiac fibrosis, overt O(2)(-) production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling.