Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China.

OBJECTIVE: Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. METHODS: Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. RESULTS: The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). CONCLUSIONS: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.

Hemocoagulase agkistrodon-induced anaphylactic shock: A case report and literature review.

Hemocoagulase agkistrodon for injection is the national first-class new drug of China with good hemostatic function and safety for capillary hemorrhage in abdominal incision of surgical patients. Adverse drug reactions (ADRs) to hemocoagulase agkistrodon are rarely reported. In this paper, we describe a case of a 41-year-old woman who developed anaphylactic shock attributed to hemocoagulase agkistrodon before colon cancer surgery. Based on the Naranjo ADR probability score, a "probable" cause and effect relationship existed for this case. Although the cause of anaphylactic reaction (hemocoagulase or excipient) and exact mechanism of hemocoagulase agkistrodon-induced anaphylactic reaction are unknown, attention should be drawn to potential ADRs in clinical use.

Efficacy and safety of the all-oral bedaquiline-containing regimen as treatment for pediatric multidrug/rifampicin-resistant tuberculosis: a multicenter, retrospective, cohort study.

OBJECTIVE: The study aimed to observe the efficacy and safety of an all-oral bedaquiline (BDQ)-containing regimen for pediatric multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) through a multicenter, retrospective study in China. METHODS: In the study, pediatric patients receiving all-oral BDQ-containing regimen (BDQ group) with clinical matched control group were included, the control group received an injection-containing regimen. The treatment outcomes and the incidence of adverse events (AEs) were compared and analyzed. RESULTS: 79 pediatric patients were enrolled, including 37 cases in BDQ group and 42 cases in the control group, the median age was 12 {8-16} and 11 {9-15} in both groups respectively. Favorable treatment outcome and cure rate in BDQ group were significantly higher than those in control group (100%vs 83.3%, p 0.03; 94.6%vs 63.3%, p 0.00). Median time of sputum culture conversion in BDQ group was significantly shorter than that in the control group (4 weeks vs 8 weeks, p 0.00). The incidence of AEs in the BDQ group was significantly less than that in the control group (48.6% vs 71.4%, p 0.03). No AEs leading to treatment discontinuation of BDQ occurred. CONCLUSIONS: The all-oral BDQ-containing regimens may be effective and safe in the Chinese pediatric population.

Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Thermal ablation versus repeated hepatic resection for recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Repeated hepatic resection (HR) and thermal ablation therapy (TAT) are increasingly being used to treat recurrent intrahepatic cholangiocarcinoma (RICC). This study compared the efficacy and safety of these procedures for RICC treatment. METHODS: Patients were studied retrospectively after curative resection of RICCs by repeated HR (n = 32) or TAT (n = 77). Treatment effectiveness and prognosis were compared between the two treatment groups. RESULTS: The repeated HR and TAT groups did not differ in their overall survival (OS; p = 0.996) or disease-free survival (DFS; p = 0.692) rates. However, among patients with recurrent tumors >3 cm in diameter, patients in the repeated HR group had a higher OS rate than patients in the TAT group (p = 0.037). The number of recurrent tumors and the recurrence interval were significant prognostic factors for OS. The major complications incidence rate was greater in the repeated HR group than in the TAT group (p < 0.001). CONCLUSIONS: Repeated HR and TAT are both effective treatments for RICC with similar overall efficacies. TAT should be preferred in any cases when the RICC is ≤3 cm in diameter and technically feasible. However, for large tumors (>3 cm), repeated HR may be a better choice.

Profile of hepatitis B virus resistance mutations against nucleoside/nucleotide analogue treatment in Chinese patients with chronic hepatitis B.

AIM: Antiviral drug-resistant HBV mutants are complex and currently partly understood. This study was performed to analyze the profile of hepatitis B virus (HBV) resistance mutations against nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). METHODS: This was a population-based cross-sectional study. Serum samples of 179 patients with virological breakthrough undergoing different NAs treatment were obtained between January 2008 and December 2012. The HBV reverse transcriptase region was sequenced and the following NAs-resistant changes including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236 and rtM250 were analyzed. RESULTS: In this cohort, 21.2% (38/179) were genotypes B and 78.8% (141/179) were genotypes C; and 89.4% (160/179) of them detected NAs-resistant mutations. The prevalence of HBV mutations at rtM204 was 93.0% (106/114) in patients with lamivudine (LAM) or telbivudine (LdT)-based therapies, and that of rtN236 mutations was 76.1% (35/46) in patients with adefovir dipivoxil (ADV)-based therapies. Among LAM/LdT based therapies, HBV rtM204I was significantly associated with HBV rtL80I/V mutations [rtM204I+rtL80I/V (50.0%, 32/64) vs. rtM204V+rtL80I/V (27.3%,9/33), P=0.032]; while the HBV rtM204V mutations was significantly associated with HBV rtL180M mutations [rtM204V+rtL180M (100%, 33/33) vs. rtM204I+rtL180M (60.9%, 39/64), P<0.001]. Additionally, HBV rtA181 mutations were observed in 19.3% (22/114) of patients with LAM/LdT-based therapy and 23.9% (11/46) of patients with ADV-based therapy. CONCLUSIONS: Majority of virological breakthrough is associated with NAs-resistant HBV, and the mutation patterns of NAs-resistant HBV are complicated in real clinical practice.

The Correlations of Minimal Inhibitory Concentration Values of Anti-TB Drugs with Treatment Outcomes and Clinical Profiles in Patients with Multidrug-Resistant Tuberculosis (MDR-TB) in China.

Objective: It is a challenge to obtain satisfactory treatment outcomes for patients with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB); the study aims to correlate the Minimum Inhibitory Concentration (MIC) value of drugs with the outcome of patients with MDR/RR-TB to obtain an understanding for better regimens and optimal outcomes. Methods: The patients diagnosed with MDR/RR-TB were retrospectively enrolled from January 1, 2018 to December 31, 2019, recorded clinical characteristics, MIC DST (Drug Susceptibility Test) results, and followed the treatment outcome. The data were analyzed on the correlations of MIC DST values with outcomes and clinical characteristics. Results: A total of 276 patients with MDR/RR-TB were included, containing 98 cases (35.5%) with newly treated patients and 178 cases (64.5%) with re-treated patients. A total of 220 cases recorded treatment success (79.7%) and 49 cases recorded treatment failure or died. MIC values of isoniazid (H), moxifloxacin (Mfx), and ethionamide (Eto) in newly treated patients were lower than those in retreated patients, and resistance levels of Mfx and H were closely associated with the treatment outcome (P < 0.05) while those of other drugs had no close association with treatment outcome. Conclusions: MIC values of some anti-TB drugs, such as fluoroquinolones (FQs) and H, can reflect the treatment outcome for patients with MDR/RR-TB, which can contribute to making regimens for better treatment outcomes.

[Changes and significance of peripheral blood T cell subsets, soluble interleukin-2 receptor and interferon-gamma in patients with retreatment pulmonary tuberculosis and initial treatment tuberculosis].

OBJECTIVE: The aim of this study was to compare the expression of peripheral blood T cell subsets, soluble interleukin-2 receptor (sIL-2R) and interferon-gamma (IFN-γ) in patients with retreatment pulmonary tuberculosis, initial treatment pulmonary and extra-pulmonary tuberculosis, and therefore to explore the cellular immune changes and the significance among different types and severity of tuberculosis. METHODS: A total of 170 patients with tuberculosis in Pulmonary Hospital of Shanghai from December 2009 to January 2011, including 98 males and 72 females, aged from 16 to 70 years (average 40 years), were included in this study. The patients were divided into retreatment pulmonary tuberculosis group (47 cases), initial treatment pulmonary tuberculosis group (62 cases) and initial treatment extra-pulmonary tuberculosis group (61 cases). Furthermore, the 109 patients with pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (52 cases) vs those with lung cavity (57 cases), patients with involvement of 1 - 2 lung fields (48 cases), vs 3 - 4 lung fields (26 cases) and 5 - 6 lung fields (35 cases). Peripheral blood T cell subsets (by flow cytometry doubled-labeled antibody), sIL-2R and IFN-γ (by ELISA) were determined in 170 patients. Differences between means of 2 groups were tested by t test, differences among multiple groups were tested by analysis of variance (ANOVA), and multiple comparisons among multiple groups were tested by LSD-t test or χ² test. Linear regression equation was used to analyze the correlations. RESULTS: The levels of peripheral blood CD4/CD8 in patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis patients were significantly lower than that in initial treatment pulmonary tuberculosis patients, [(1.7 ± 0.7), (1.6 ± 0.7) and (2.0 ± 0.7) respectively (F = 4.380, P < 0.05)]. The levels of serum sIL-2R in patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis were significantly higher than that in initial treatment pulmonary tuberculosis patients [(224 ± 89) pmol/L, (209 ± 98) pmol/L, (167 ± 73) pmol/L, (F = 6.402, P < 0.01)]. The levels of serum IFN-γ in patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis were significantly higher than that in initial treatment pulmonary tuberculosis patients [(37 ± 23) ng/L, (37 ± 24) ng/L, (29 ± 16) ng/L, (F = 2.799, P < 0.05)]. The levels of peripheral blood CD4/CD8 in initial treatment and retreatment cavity pulmonary tuberculosis patients were lower than that in pulmonary tuberculosis patients without cavity, but the results of sIL-2R and IFN-γ were the opposite [(1.7 ± 0.6) vs (2.0 ± 0.8), (214 ± 93) pmol/L vs (167 ± 68) pmol/L and (38 ± 22) ng/L vs (27 ± 14) ng/L, t = -2.813 to 3.076, P < 0.05 or P < 0.01]. The level of serum sIL-2R was negatively correlated with peripheral blood CD4/CD8 level in all the patients (r = -0.380, P < 0.01). CONCLUSIONS: Patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis had lower cellular immune function as compared to those with initial treatment pulmonary tuberculosis, and the cellular immune function was significantly correlated with the extent and cavity formation of pulmonary lesions.

Risk factors and predictive model of adrenocortical insufficiency in patients with traumatic brain injury.

BACKGROUND: Neuroendocrine dysfunction after traumatic brain injury (TBI) has received increased attention due to its impact on the recovery of neural function. The purpose of this study is to investigate the incidence and risk factors of adrenocortical insufficiency (AI) after TBI to reveal independent predictors and build a prediction model of AI after TBI. METHODS: Enrolled patients were grouped into the AI and non-AI groups. Fourteen preset impact factors were recorded. Patients were regrouped according to each impact factor as a categorical variable. Univariate and multiple logistic regression analyses were performed to screen the related independent risk factors of AI after TBI and develop the predictive model. RESULTS: A total of 108 patients were recruited, of whom 34 (31.5%) patients had AI. Nine factors (age, Glasgow Coma Scale [GCS] score on admission, mean arterial pressure [MAP], urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, diffuse axonal injury [DAI], and skull base fracture) were probably related to AI after TBI. Three factors (urinary volume [X 4], serum sodium level [X 5], and DAI [X 8]) were independent variables, based on which a prediction model was developed (logit P= -3.552+2.583X 4+2.235X 5+2.269X 8). CONCLUSIONS: The incidence of AI after TBI is high. Factors such as age, GCS score, MAP, urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, DAI, and skull base fracture are probably related to AI after TBI. Urinary volume, serum sodium level, and DAI are the independent predictors of AI after TBI.

[Construction of Zinc-alpha2-glycoprotein expression plasmid and its expression in 3t3-l1 preadipocytes].

OBJECTIVE: To construct mouse Zinc-alpha2-glycoprotein (mZAG) eucaryotic expression plasmid and identify its expression in 3T3-L1 preadipocytes. METHODS: The total RNA from mouse liver tissue was extracted. The reverse-transcript(RT)-PCR method was used to amplify the complete domain sequence of mZAG, and the confirmed PCR products was inserted into expression plasmid by DNA ligation. The mZAG expression plasmids with various concentrations (0, 0.4, 0.8, and 1.6 microg) were transfected into 3T3-L1 preadipocytes, and ZAG expression in mRNA and protein level was determined by real-time fluorescence quantitative PCR and Western blot, respectively. RESULTS: DNA sequencing confirmed the right sequence of mZAG expression plasmid pcDNA3.1(-)-mZAG. After the mZAG expression plasmid with different concentrations were transfected into 3T3-L1 preadipocytes, mZAG mRNA level significantly increased and reached 2.58 folds (P=0.002), 3.67 folds (P=0.000 and 5.19 folds (P=0.001) of that in the control group (no mZAG transfection). mZAG protein level also significantly increased and reached 2.75 folds of that in the control group (P=0.017). Treating 3T3-L1 cells with small interfering RNA (siRNA) sequence siRNA 1 and siRNA 4 resulted in a decrease of mZAG mRNA to 49% and 41% of those in the control group(no siRNA sequence transfection) (P=0.002P=0.000)and a decrease of mZAG protein to 55% and 62% of that in the control group (P=0.004,P=0.025). CONCLUSIONS: mZAG expression plasmid pcDNA3.1(-)-mZAG was successfully established in this study. This plasmid can be well expressed in 3T3-L1 preadipocytes. siRNA 1 and siRNA 4 can effectively inhibit the expression of mZAG in these cells.

A pair of new diastereoisomeric phenylpropanoid-substituted flavan from the leaves of Ilex centrochinensis.

A pair of new diastereoisomeric flavan, containing an additional phenylpropanoid (C6-C3) unit in the molecule, has been isolated from the leaves of Ilex centrochinensis. Their structures were identified by extensive spectral analysis and comparison with the data of known analogues.

miR-574-3p inhibits proliferation and invasion in esophageal cancer by targeting FAM3C and MAPK1.

Esophageal cancer is considered as one of the leading malignancies. MicroRNA-574-3p (miR-574-3p) was used as a postoperative prognostic indicator in patients with esophageal squamous cell carcinoma. However, the underlying mechanism miR-574-3p involvement in esophageal cancer remains unclear. In this study, the expression of miR-574-3p was reduced in esophageal cancer tissues and cells. In vitro, miR-574-3p mimics and inhibitor were transfected into esophageal cancer cells (TE-1 and TE-8 cells) to up- or downregulating of miR-574-3p. miR-574-3p inhibited proliferation, migration and invasion, and promoted apoptosis in esophageal cancer cells. In addition, miR-574-3p was confirmed to target family with sequence similarity 3 member C (FAM3C) and mitogen-activated protein kinase 1 (MAPK1). miR-574-3p suppressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling via regulating FAM3C and MAPK1. In vivo, overexpression of miR-574-3p suppressed tumor growth in mice. Our findings indicated that miR-574-3p repressed proliferation and invasion of esophageal cancer via regulation of FAM3C and MAPK1, which provides a new biomarker for esophageal cancer treatment.

BODIPY-Decorated Nanoscale Covalent Organic Frameworks for Photodynamic Therapy.

Covalent organic frameworks (COFs), an emerging class of organic porous materials, have attracted intense attention due to their versatile applications. However, the deliberate fabrication of COF-based nanomaterials for nanomedical application remains challenging due to difficulty in their size- and structure-controlled synthesis and poor aqueous dispersibility. Herein, we report two boron-dipyrromethene (BODIPY)-decorated nanoscale COFs (NCOFs), which were prepared by the Schiff-base condensation of the free end -CHO (bonding defects in COFs) on the established imine-based NCOFs with the amino-substituted organic photosensitizer BODIPY via "bonding defects functionalization" approach. Thus BODIPY has been successfully nanocrystallized via the NCOF platform, and can be used for photodynamic therapy (PDT) to treat tumors. These NCOF-based PDT agents featured nanometer size (∼110 nm), low dark toxicity, and high phototoxicity as evidenced by in vitro and in vivo experiments. Moreover, the "bonding defects functionalization" approach might open up new avenues for the fabrication of additional COF-based platforms for biomedical treatment.

Corilagin Interferes With Toll-Like Receptor 3-Mediated Immune Response in Herpes Simplex Encephalitis.

Herpes simplex encephalitis (HSE) is the most common infectious disease of the central nervous system worldwide. However, the pathogenesis of HSE is not clear. Research has shown that the immune response mediated by the toll-like receptor 3 (TLR3) signaling pathway is essential to protect the central nervous system against herpes simplex virus (HSV) infection. However, an excessive immune response may cause tissue damage accompanied by pathological changes. The aim of this study was to explore the molecular mechanism via which corilagin controls HSE through the TLR3 signaling pathway in vitro and in vivo. Cells and mice were pre-treated with polyriboinosinic polyribocytidylic acid [poly(I:C)] or HSV type 1, and then treated with corilagin. After treatment, the mRNA and protein levels of TLR3, TLR-like receptor-associated interferon factor (TRIF), tumor necrosis factor (TNF) receptor type 1-associated DEATH domain protein (TRADD), TNF receptor-associated factor (TRAF) 3 and 6, nuclear factor-kappa-B (NF-κB) essential modulator (NEMO), P38, and interferon regulatory factor 3 (IRF3) were decreased. Interleukin-6 (IL-6), TNF-α, and type 1 interferon-ß were also decreased. When TLR3 expression was silenced or increased, corilagin still inhibited the expression of TLR3 and its downstream mediators. Hematoxylin-eosin (HE) staining and immunohistochemical examinations of mouse brain tissues revealed that corilagin lessened the degree of brain inflammation. Altogether, these results suggest that corilagin may regulate the immune response in HSE and relieve inflammatory injury by interfering with the TLR3 signaling pathway.

Role of coxsackievirus and adenovirus receptor in the pathogenesis of dilated cardiomyopathy and its influencing factor.

BACKGROUND: Although clinical treatment for heart failure and sudden death has been improved over the last few decades, the morbidity and mortality of dilated cardiomyopathy (DCM) have increased. So a better understanding of the underlying molecular events leading to DCM is urgent. Persistent viral infection (especially coxsackievirus group B3) of the myocardium in viral myocarditis and DCM has never been neglected by experts. Recent data indicate that the up-regulation of coxsackievirus and adenovirus receptor (CAR) in viral cardiomyopathy contributes to viral infection as a key factor in the pathogenesis of this disease. This study aimed to investigate the role and regulatory mechanism of CAR in DCM by the bioinformatic method. METHODS: We identified the clusters of genes co-expressed with CAR by clustering algorithm based on the public available microarray dataset of DCM (Kittleson, et al. 2005), and mapped these genes into the protein-protein interaction networks to investigate the interaction relationship to each other at the protein level after confirming that the samples are characterized by the cluster of genes in correctly partitioning. RESULTS: The gene cluster GENESET 11 containing 33 genes including CAR with similar expression pattern was identified by cluster algorithm, of which 19 genes were found to have interaction information of the protein encoded by them in the current human protein interaction database. Especially, 12 genes present as critical nodes (called HUB node) at the protein level are involved in energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis, cell proliferation, tissue repair, etc. CONCLUSIONS: The genes in GENESET 11 together with CAR may play a pathogenic role in the development of DCM, mainly involved in the mechanism of energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis and tissue repair.

[The initial approach of two sides hypogastric artery ligation and isolation with laparoscope before excision of presacral tumor].

OBJECTIVE: To observe the significance of excision of presacral tumor after two sides hypogastric artery ligation and tissue dissociation with laparoscope. METHODS: Twenty-one patients with sacral tumor were performed excision of presacral tumor after two sides hypogastric artery ligation and tissue dissociation with laparoscope. RESULTS: All sacral tumor were removed successfully, the mean volume of operative blood was 800 ml (range 500-1900 ml), and all the patients were followed up 3-25 months, averaged time 11 months. One patient was recurred after 2 months of operation (the patient was Ewing's sarcoma, and refused to accept radiotherapy and chemotherapy after operation), 1 patents died of brain metastases after 9 months of operations. There were no recurrence in the others patients. CONCLUSIONS: The excision of presacral tumor after two sides hypogastric artery ligation and tissue dissociation with laparoscope is an effective operation method, with the advantages of decreasing the operative blood and difficulty of sacral tumor excision, and diminishing the operation wound.

Aberrant DNA Methylation Involved in Obese Women with Systemic Insulin Resistance.

BACKGROUND: Epigenetics has been recognized as a significant regulator in many diseases. White adipose tissue (WAT) epigenetic dysregulation is associated with systemic insulin resistance (IR). The aim of this study was to survey the differential methylation of genes in obese women with systemic insulin resistance by DNA methylation microarray. METHODS: The genome-wide methylation profile of systemic insulin resistant obese women was obtained from Gene Expression Omnibus database. After data preprocessing, differing methylation patterns between insulin resistant and sensitive obese women were identified by Student's t-test and methylation value differences. Network analysis was then performed to reveal co-regulated genes of differentially methylated genes. Functional analysis was also implemented to reveal the underlying biological processes related to systemic insulin resistance in obese women. RESULTS: Relative to insulin sensitive obese women, we initially screened 10,874 differentially methylated CpGs, including 7402 hyper-methylated sites and 6073 hypo-methylated CpGs. Our analysis identified 4 significantly differentially methylated genes, including SMYD3, UST, BCL11A, and BAI3. Network and functional analyses found that these differentially methylated genes were mainly involved in chondroitin and dermatan sulfate biosynthetic processes. CONCLUSION: Based on our study, we propose several epigenetic biomarkers that may be related to obesity-associated insulin resistance. Our results provide new insights into the epigenetic regulation of disease etiology and also identify novel targets for insulin resistance treatment in obese women.

[Well-to-Wheels Fossil Energy Consumption and CO2 Emissions of Hydrogen Fuel Cell Vehicles in China].

Hydrogen fuel cell vehicles (FCVs) have the advantage of high energy efficiency and zero tailpipe emissions. They have been progressively commercialized in recent years. Hydrogen production has diversified technological pathways, which vary greatly in terms of energy and environmental impacts. In this study, the life cycle assessment (LCA) method was applied to evaluate well-to-wheels (WTW) fossil energy consumption and carbon dioxide (CO2) emissions of FCVs using various hydrogen production pathways. The greenhouse gases, regulated emissions, and energy use in transportation (GREET) model, developed by the Argonne National Laboratory, was applied as the assessment tool, and a China-specific database was investigated and developed to evaluate typical hydrogen production pathways. Then, we compared the WTW fossil energy consumption and CO2 emissions of FCVs with those of gasoline vehicles (GVs), hybrid electric vehicles (HEVs), and battery electric vehicles (BEVs). The results indicated that renewable-energy-based electrolysis of water and biomass gasification are two prospective hydrogen production pathways with significant WTW energy and climate benefits which can help FCVs reduce fossil energy consumption and CO2 emissions by approximately 90% more than GVs. Among the current pathways with mass adoption, hydrogen production from coke oven gas (COG) has substantial energy and CO2 mitigation benefits, which enables FCVs to achieve a lower WTW fossil energy consumption than HEVs and lower WTW CO2 emissions than HEVs and BEVs. Considering the resource reserves and technological maturity in China, hydrogen production from COG and other industrial by-products is recommended for hydrogen energy and FCV development in the short term. In the medium and long terms, utilization of renewable energy to produce hydrogen should be promoted.

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo.

Aims: Emodin is an anthraquinone with potential anti-inflammatory properties. However, the possible molecular mechanisms and protective effects of emodin are not clear. The objective of this study was to investigate the possible molecular mechanisms and protective effects of emodin on lipopolysaccharide (LPS)-induced acute liver injury (ALI) via the Toll-like receptor 4 (TLR4) signaling pathway in the Raw264.7 cell line and in Balb/c mice. Methods: This study established an inflammatory cellular model and induced an ALI animal model. TLR4 was overexpressed by lentivirus and downregulated by small interfering RNA (siRNA) technology. The mRNA and protein levels of TLR4 and downstream molecules were detected in cells and liver tissue. The tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels in supernatant and serum were determined by ELISA. The distribution and expression of mannose receptor C type 1 (CD206) and arginase 1 (ARG1) in the liver were tested by immunofluorescence. Mouse liver function and histopathological observations were assessed. Results: Administration of emodin reduced the protein and/or mRNA levels of TLR4 and its downstream molecules following LPS challenge in Raw264.7 cells and in an animal model. Additionally, emodin suppressed the expression of TNF-α and IL-6 in cell culture supernatant and serum. The inhibitory effect of emodin was also confirmed in RAW264.7 cells, in which TLR4 was overexpressed or knocked down. Additionally, ARG1 and CD206 were elevated in the emodin groups. Emodin also decreased serum ALT and AST levels and alleviated the liver histopathological damage induced by LPS. Conclusion: Emodin showed excellent hepatoprotective effects against LPS-induced ALI, possibly by inhibiting TLR4 signaling pathways.

Anterior transversalis fascia approach versus preperitoneal space approach for inguinal hernia repair in residents in northern China: study protocol for a prospective, multicentre, randomised, controlled trial.

INTRODUCTION: Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as 'tension' repair or 'tension-free' repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. METHODS AND ANALYSIS: This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). ETHICS AND DISSEMINATION: This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015-027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. TRIAL REGISTRATION NUMBER: NCT02984917; preresults.