Association of weight-adjusted-waist index with non-alcoholic fatty liver disease and liver fibrosis: a cross-sectional study based on NHANES.

AIM: The purpose of this study was to explore the association of weight-adjusted-waist index (WWI) with non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS: A cross-sectional study including 6587 participants was conducted in the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression was used to validate the association of WWI with NAFLD and liver fibrosis, and smoothed curve fitting and threshold effect models were used to validate non-linear relationships. Subgroup analyses were used to verify the stability of the relationship between the independent and dependent variables in different populations. RESULTS: There was a positive association of WWI with NAFLD and liver fibrosis. In the model adjusted for all covariates, the effect values of WWI with NAFLD and liver fibrosis were (OR = 3.44, 95% CI: 3.09-3.82) and (OR = 2.40, 95% CI: 2.05-2.79), respectively. This positive correlation became more significant as WWI increased when WWI was presented in quartiles (P for trend < 0.01). Smoothed curve fitting and threshold effects analysis suggested a non-linear correlation between WWI and NAFLD (LLR < 0.01), with the positive correlation between WWI and NAFLD becoming more significant when WWI was less than 11.44 [5.93 (95% CI: 5.04-6.98)]. However, there was a linear correlation between WWI and liver fibrosis (LLR = 0.291). When subgroup analyses were performed by indicators such as age, race and gender, we found that the positive association between WWI and the dependent variables (NAFLD and liver fibrosis) was more pronounced in white male participants aged < 40 years. CONCLUSIONS: Among adults in the United States, WWI was positively associated with the prevalence of NAFLD and liver fibrosis. Participants with a WWI less than 11.44 should be cautious about the possibility of an increased risk of NAFLD development due to a higher WWI. Meanwhile, white males younger than 40 years of age should be more cautious about the higher risk of NAFLD and liver fibrosis that might be associated with an increased WWI.

MiR-183-5p-PNPT1 Axis Enhances Cisplatin-induced Apoptosis in Bladder Cancer Cells.

OBJECTIVE: It has been reported that intrinsic apoptosis is associated with the progression of bladder cancer (BC). Recent evidence suggests that polyribonucleotide nucleotidyltransferase 1 (PNPT1) is a pivotal mediator involved in RNA decay and cell apoptosis. However, the regulation and roles of PNPT1 in bladder cancer remain largely unclear. METHODS: The upstream miRNA regulators were predicted by in silico analysis. The expression levels of PNPT1 were evaluated by real-time PCR, Western blotting, and immunohistochemistry (IHC), while miR-183-5p levels were evaluated by qPCR in BC cell lines and tissues. In vitro and in vivo assays were performed to investigate the function of miR-183-5p and PNPT1 in apoptotic RNA decay and the tumorigenic capability of bladder cancer cells. RESULTS: PNPT1 expression was decreased in BC tissues and cell lines. Overexpression of PNPT1 significantly promoted cisplatin-induced intrinsic apoptosis of BC cells, whereas depletion of PNPT1 potently alleviated these effects. Moreover, oncogenic miR-183-5p directly targeted the 3' UTR of PNPT1 and reversed the tumor suppressive role of PNPT1. Intriguingly, miR-183-5p modulated not only PNPT1 but also Bcl2 modifying factor (BMF) to inhibit the mitochondrial outer membrane permeabilization (MOMP) in BC cells. CONCLUSION: Our results provide new insight into the mechanisms underlying intrinsic apoptosis in BC, suggesting that the miR-183-5p-PNPT1 regulatory axis regulates the apoptosis of BC cells and might represent a potential therapeutic avenue for the treatment of BC.

Clinical study of GeneXpert combined with T-SPOT and TB-Ab on bacterial-negative pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To investigate the diagnostic efficacy of rifampin-resistant real-time fluorescent quantitative nucleic acid amplification detection technology (GeneXpert MTB/RIF) in bronchoalveolar lavage fluid (BALF) combined with peripheral blood tuberculosis infection T cell spot test (T-SPOT) and tuberculosis antibody (TB-Ab) in smear-negative pulmonary tuberculosis. Methods　The clinical data of 114 cases of clinically diagnosed smear-negative pulmonary tuberculosis, 80 cases of non-tuberculous pulmonary diseases and 22 cases of smear-positive pulmonary tuberculosis in our hospital from January 2019 to January 2021 were retrospectively analyzed. The detection results of peripheral blood T-SPOT, TB-Ab and BALF GeneXpert in the three groups were analyzed. The sensitivity, specificity, negative predictive value, positive predictive value, false negative rate, false positive rate and Youden index of the three detection methods were compared. The differences in the positive detection rate of smear-negative pulmonary tuberculosis between the separate detection and the combined detection of the three methods were compared. The receiver operating characteristic curve (ROC) was performed to calculate the area under the curve (AUC). Results　The sensitivity of BALF GeneXpert and peripheral blood T-SPOT and TB-Ab was 66.91%, 80.88% and 90.44%, respectively. The specificity was 98.75%, 73.75% and 41.25%, respectively; the diagnostic coincidence rates were 78.70%, 78.24% and 72.22%, respectively, which were higher than 70.00%. In the smear-negative pulmonary tuberculosis group, the positive detection rates of these three methods in the smear-negative pulmonary tuberculosis group were 63.15%, 79.82% and 90.35%, respectively, and the differences were statistically significant compared with those in the non-tuberculosis pulmonary disease group (all P<0.01). The positive detection rate of the three combined methods in the smear-negative pulmonary tuberculosis group was 96.49 %, which was significantly higher than that of TB-GeneXpert method and T-SPOT, and the differences were statistically significant (χ2=37.283, P<0.01; χ2=13.612, P<0.01); the Youden index of combined detection was significantly higher than that of single detection, and the AUC of combined detection was 0.977, which was significantly higher than that of single detection. Conclusion　BALF GeneXpert combined with peripheral blood T-SPOT and TB-Ab can significantly improve the diagnostic rate of bacterial-negative pulmonary tuberculosis, providing a strong basis for guiding clinical treatment.

Clinical Features of COVID-19 Patients with Diabetes and Secondary Hyperglycemia.

People with diabetes have higher risks of various infections. Therefore, these diabetic patients might be at increased risk of COVID-19 and have a poorer prognosis. Up until now, little is known about critical role in the pathogenesis. This study aims to investigate the clinical characteristics of COVID-19 patients with diabetes and secondary hyperglycemia, as well as to explore the purported mechanisms. 80 confirmed COVID-19 subjects were classified into the euglycemia group, secondary hyperglycemia group, and diabetes group. Severity of COVID-19 was defined based on the diagnostic and treatment guideline for SARS-CoV-2 issued by Chinese National Health Committee. According to the severity of the disease, patients of the mild type and common type were registered as mild cases (patients with minimal symptoms and negative CT findings), while patients of the severe type and critical type were enrolled as severe cases (patients with positive CT findings and different extent of clinical manifestations). Patients in the diabetes group were older than those in the euglycemia group, and most of them were male. In the diabetes group, the proportion of severe cases was 57.14%, which was significantly higher than those in the other two groups, and 32% of the COVID-19 patients diagnosed as severe cases were with diabetes. The CD4+ cell counts in the diabetes group were lower than those in the other two groups, while the levels of LDH and hs-CRP were higher. Compared with the euglycemia group, the CD3+ cell counts and the CD4+/CD8+ ratio were decreased, whereas the levels of IL-6 were increased in the secondary hyperglycemia group and diabetes group, with the diversities in the diabetes group being especially more significant. The Spearman correlation analysis revealed that the presence of diabetes was positively correlated with age, hs-CRP, LDH, IL-6, CD8+ cells, and severity of COVID-19 and negatively correlated with CD3+ cell counts, CD4+ cell counts, and CD4+/CD8+ ratio. Compared with the other two groups, the diabetes group exhibited more diverse and multifocal features in CT imagings. Diabetes is a risk factor for influence of the progression and prognosis of COVID-19 due to ongoing inflammation and impaired immune response.

Dexmedetomidine Attenuates Glutamate-Induced Cytotoxicity by Inhibiting the Mitochondrial-Mediated Apoptotic Pathway.

BACKGROUND Glutamate (GLU) is the most excitatory amino acid in the central nervous system and plays an important role in maintaining the normal function of the nervous system. During cerebral ischemia, massive release of GLU leads to neuronal necrosis and apoptosis. It has been reported that dexmedetomidine (DEX) possesses anti-oxidant and anti-apoptotic properties. The objective of this study was to investigate the effects of DEX on GLU-induced neurotoxicity in PC12 cells. MATERIAL AND METHODS PC12 cells were treated with 20 mM GLU to establish an ischemia-induced injury model. Cell viability was accessed by MTT assay. MDA content and SOD activity were analyzed by assay kits. Apoptosis rate, ROS production, intracellular Ca²âº concentration, and MMP were evaluated by flow cytometry. Western blot analysis was performed to analyze expressions of caspase-3, caspase-9, cyt-c, bax, and bcl-2. RESULTS PC12 cells treated with GLU exhibited reduced cell viability and increased apoptosis rates, which were ameliorated by pretreatment with DEX. DEX significantly increased SOD activity, reduced content of MDA, and decreased production of ROS in PC12 cells. In addition, DEX clearly reduced the level of intracellular Ca²âº and attenuated the decline of MMP. Moreover, DEX notably reduced expressions of caspase-3, caspase-9, cyt-c, and bax and increased expression of bcl-2. CONCLUSIONS Our findings suggest that DEX can protect PC12 cells against GLU-induced cytotoxicity, which may be attributed to its anti-oxidative property and reduction of intracellular calcium overload, as well as its ability to inhibit the mitochondria-mediated apoptotic pathway.

Safety and effective of laparoscopic microwave ablation for giant hepatic hemangioma: A retrospective cohort study.

INTRODUCTION: The purpose of this study was to evaluate the advantages and disadvantages of laparoscopic microwave ablation (LMWA) as compared with conventional open resection (ORES) for the treatment of giant hepatic hemangioma. METHODS: and analysis: A retrospective chart review was conduct on patients with hepatic hemangioma underwent LMWA or ORES between 2014 and 2016. RESULTS: Of 131 patients, 37 patients underwent ORES and 94 patients underwent LMWA. Blood loss, operative time, postoperative hospital stay, hospital cost (RMB) were significantly different between two groups. Patients after LMWA experienced significantly less pain than those patients undergoing ORES. At a mean follow-up period of 12.8 ±â€¯3.6 months in ORES group and 13.5 ±â€¯2.5 months in LMWA group, no long-term complication was observed. CONCLUSION: Compared with ORES, LMWA is a safe and effective minimally invasive for treating giant hepatic hemangioma.

Detection of early-stage extrahepatic cholangiocarcinoma in patients with biliary strictures by soluble B7-H4 in the bile.

Increasing evidence has demonstrated that serum soluble B7-H4 (sB7-H4) is a useful tumour marker for cancer diagnosis and prognosis evaluation. Whether sB7-H4 is expressed in the bile of cholangiocarcinoma (CC) and is related to the progression of CC need to be explored. Bile sB7-H4 was obtained through endoscopic retrograde cholangiopancreatography (ERCP) from 213 patients with biliary strictures and detected was detected by a B7-H4 ELISA kit. Diagnostic value was compared among bile sB7-H4, CA19-9, CA12-5, CEA and ERCP-based cytological/tissue examination. Additionally, the correlations between the bile sB7-H4 concentration and the clinical characteristics of early-stage cholangiocarcinoma (ESCC) were studied. The bile sB7-H4 levels of patients with ESCC were significantly higher than in patients with benign biliary strictures (BBS) (P<0.001). The receiver operating characteristic (ROC) curves of CA19-9, CA12-5 and CEA were 0.713, 0.554 and 0.451, respectively, were significantly lower than the ROC curves of bile sB7-H4 (0.837), the sensitivity of ERCP-based cytological/tissue examination was 57.5% and 68.4%, which was lower than that of bile sB7-H4 (81.7%) at cut-off value. A high level of bile sB7-H4 in patients with ESCC was found to be correlated with vascular invasion (P<0.001), lymph node metastasis (P<0.001) and TNM stage (P=0.018), respectively. The overall survival rate (OS) of ESCC patients in the high sB7-H4 group was significantly lower than the OS of patients in the low sB7-H4 group (P=0.009). Bile sB7-H4 could serve as a valuable biomarker for patients with ESCC and high levels of bile sB7-H4 correlate with poor clinical outcomes.

Look into hepatic progenitor cell associated trait: Histological heterogeneity of hepatitis B-related combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (CHC) is a mixed tumor containing elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell (HPC) origin. However, detailed histological or phenotypic description is rarely documented. In the present study, we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining, focusing on HPC associated phenotypic observation of intermediate area of the tumor. It was found that tumor cells showed remarkable heterogeneity in intermediate area. Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei, arranging in solid nests mostly. By Keratin 7 (K7) staining, it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the "transitional" cells. Then, these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization. In conclusion, the HPC associated trait in CHC can be interpreted by HPC origin or gain of "stemness" by dedifferentiation. It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.

Intraoperative Parathyroid Localization with Near-Infrared Fluorescence Imaging Using Indocyanine Green during Total Parathyroidectomy for Secondary Hyperparathyroidism.

The detection of all glands during total parathyroidectomy (TPTX) in secondary hyperparathyroidism (SHPT) patients is often difficult due to their variability in number and location. The objective of this study was to evaluate the feasibility of near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) for intraoperative parathyroid gland (PTG) localization in SHPT patients. Twenty-nine patients with SHPT were divided into two groups with or without intraoperative NIRF imaging. ICG was administered in patients undergoing intraoperative imaging, and the fluorescence of PTGs was assessed. Clinical and histopathologic variables were analyzed to determine factors associated with ICG uptake. Comparisons between NIRF and preoperative imaging, as well as differences between groups with or without NIRF imaging, were carried out to evaluate the efficacy of this technique. Most PTGs could be clearly identified, including one ectopic gland. The sensitivity of NIRF imaging is 91.1% in contrast to 81.82% for ultrasonography (US), 62.34% for 99mTc-MIBI and 85.71% for computed tomography (CT). In addition, intraoperative NIRF imaging can reduce the operation time and improve the complete resection rate compared with the group not using it. Intraoperative NIRF imaging using ICG during TPTX is technically feasible and reliable for assisting surgeons in detecting and confirming PTGs.

Mesh fixation with glue versus suture for chronic pain and recurrence in Lichtenstein inguinal hernioplasty.

BACKGROUND: Chronic pain following mesh-based inguinal hernia repair is frequently reported, and has a significant impact on quality of life. Whether mesh fixation with glue can reduce chronic pain without increasing the recurrence rate is still controversial. OBJECTIVES: To determine whether tissue adhesives can reduce postoperative complications, especially chronic pain, with no increase in recurrence rate, compared with sutures for mesh fixation in Lichtenstein hernia repair. SEARCH METHODS: We searched the following electronic databases with no language restrictions: the Cochrane Central Register of Controlled Trials (CENTRAL; issue 4, 2016) in the Cochrane Library (searched 11 May 2016), MEDLINE Ovid (1986 to 11 May 2016), Embase Ovid (1986 to 11 May 2016), Science Citation Index (Web of Science) (1986 to 11 May 2016), CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), VIP (a full-text database in China), Wanfang databases. We also checked reference lists of identified papers (included studies and relevant reviews). SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials comparing glue versus sutures for mesh fixation in Lichtenstein hernia repair. Cluster-RCTs were also eligible. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and assessed the risk of bias independently. Dichotomous outcomes were expressed as odds ratio (OR) with 95% confidence intervals (CI). Continuous outcomes were expressed as mean differences (MD) with 95% CIs. MAIN RESULTS: Twelve trials with a total of 1932 participants were included in this review. The overall postoperative chronic pain in the glue group was reduced by 37% (OR 0.63, 95% CI 0.44 to 0.91; 10 studies, 1418 participants, low-quality evidence) compared with the suture group. However, the results changed when we conducted subgroup analysis with regard to the type of mesh. Subgroup analysis of included studies using lightweight mesh showed the reduction of chronic pain was less profound and insignificant (OR 0.77, 95% CI 0.50 to 1.17). Subgroup analysis of included studies using heavyweight mesh resulted in a significant benefit from the fixation with glue (OR 0.38, 95% CI 0.17 to 0.82).Hernia recurrence was similar between the two groups (OR 1.44, 95% CI 0.63 to 3.28; 12 studies, 1932 participants, low-quality evidence). Fixation with glue was superior to suture regarding duration of the operation (MD -3.13, 95% CI -4.48 to -1.78; 9 studies, 1790 participants, low-quality evidence); haematoma (OR 0.52, 95% CI 0.31 to 0.86; 10 studies, 1384 participants, moderate-quality evidence); and recovery time to daily activities (MD -1.26, 95% CI -1.89 to -0.63; 3 studies, 403 participants, low-quality evidence).We also investigated adverse events. There were no significant differences between the two groups. For superficial wound infection pooled analyses showed OR 1.23, 95% CI 0.37 to 4.11; 7 studies, 763 participants (low-quality evidence); for mesh/deep infection OR 0.67, 95% CI 0.16 to 2.83; 8 studies, 1393 participants (low-quality evidence). Furthermore, we investigated seroma (a postoperative swelling caused by fluid) (OR 0.83, 95% CI 0.51 to 1.33); and persisting numbness (OR 0.81, 95% CI 0.57 to 1.14).Finally, six trials involving 1009 participants reported postoperative length of stay, resulting in non-significant difference between the two groups (MD -0.12, 95% CI: -0.35 to 0.10)Due to the lack of data, it was impossible to draw any distinction between synthetic glue and biological glue.Eight out of 12 trials showed high risk of bias in at least one of the investigated domains. Two studies were quasi-randomised controlled trials and the allocation sequence of one trial was not concealed. Nearly half of the included trials either did not provide adequate information or had high risk of bias regarding blinding processes. The risk of bias for incomplete outcome data of all the included studies varied from low to high risk of bias. Two trials did not report on some important outcomes. One study was funded by the manufacturer producing the fibrin sealant. Therefore, according to the 'Summary of findings' tables, the quality of the evidence (GRADE) for the outcomes is moderate to low. AUTHORS' CONCLUSIONS: Based on the short-term results, glue may reduce postoperative chronic pain and not simultaneously increase the recurrence rate, compared with sutures for mesh fixation in Lichtenstein hernia repair. Glue may therefore be a sensible alternative to suture for mesh fixation in Lichtenstein repair. Larger trials with longer follow-up and high quality are warranted. The difference between synthetic glue and biological glue should also be assessed in the future.

Look into Hepatic Progenitor Cell Associated Trait: Histological Heterogeneity of Hepatitis B-Related Combined Hepatocellular-Cholangiocarcinoma / 华中科技大学学报（医学）（英德文版）

Combined hepatocellular-cholangiocarcinoma (CHC) is a mixed tumor containing elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC).Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell (HPC) origin.However,detailed histological or phenotypic description is rarely documented.In the present study,we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining,focusing on HPC associated phenotypic observation of intermediate area of the tumor.It was found that tumor cells showed remarkable heterogeneity in intermediate area.Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei,arranging in solid nests mostly.By Keratin 7 (K7) staining,it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the "transitional" cells.Then,these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization.In conclusion,the HPC associated trait in CHC can be interpreted by HPC origin or gain of"stemness" by dedifferentiation.It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.

CCL2-CCR2 signaling promotes hepatic ischemia/reperfusion injury.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is a type of uncontrolled inflammatory cascade in which neutrophils, an early infiltrating immune cell population, elicit significant tissue damage. However, the precise mechanism for neutrophil recruitment and infiltration remains to be fully characterized. METHODS: A hepatic partial I/R model was reproduced in wild-type, CCL2(-/-) and CCR2(-/-) mice. Tissue damage was evaluated by serum enzyme analysis, hematoxylin-eosin staining, and cytokine production measurement. Mobilization of neutrophils from the bone marrow and subsequent infiltration into the liver were measured by flow cytometry. C-C motif chemokine receptor 2 (CCR2) expression on neutrophils and C-C motif chemokine ligand 2 (CCL2) chemotaxis were measured using flow cytometry. The cellular source of CCL2 in the liver was determined by deleting specific cell groups and performing intracellular staining. RESULTS: Liver damage was ameliorated, and neutrophil recruitment and accumulation were decreased in both CCL2(-/-) and CCR2(-/-) mice compared with wild-type mice. Neutrophils displayed upregulated expression of CCR2 during I/R, and these cells were required for CCL2-induced chemotaxis. Depletion of Kupffer cells protected the liver from I/R injury. Furthermore, genetic ablation of CCL2 reduced liver injury, as demonstrated by decreases in the levels of alanine aminotransferase and aspartate aminotransferase and subsequent reductions in neutrophil recruitment and accumulation. CONCLUSIONS: Kupffer cells secrete CCL2 to promote CCR2-expressing neutrophil recruitment from the bone marrow and subsequent infiltration into the liver during I/R. These findings reveal a novel pro-inflammatory role of cell-mediated CCL2-CCR2 interactions during this sterile insult.

Insulin down-regulates the expression of ubiquitin E3 ligases partially by inhibiting the activity and expression of AMP-activated protein kinase in L6 myotubes.

While insulin is an anabolic hormone, AMP-activated protein kinase (AMPK) is not only a key energy regulator, but it can also control substrate metabolism directly by inducing skeletal muscle protein degradation. The hypothesis of the present study was that insulin inhibits AMPK and thus down-regulates the expression of the ubiquitin E3 ligases, muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in skeletal muscle cells. Differentiated L6 myotubes were treated with 5-aminoimidazole-4-carboxamide-1-ß-4-ribofuranoside (AICAR) and/or compound C to stimulate and/or block AMPK respectively. These treatments were also conducted in the presence or absence of insulin and the cells were analysed by western blot and quantitative real-time PCR. In addition, nucleotide levels were determined using HPLC. The activation of AMPK with AICAR enhanced the mRNA levels of MAFbx and MuRF1. Insulin reduced the phosphorylation and activity AMPK, which was accompanied by reduced MAFbx and MuRF1 mRNA levels. Using a protein kinase B (PKB/Akt) inhibitor, we found that insulin regulates AMPK through the activation of Akt. Furthermore, insulin down-regulated AMPK α2 mRNA. We conclude that insulin inhibits AMPK through Akt phosphorylation in L6 myotubes, which may serve as a possible signalling pathway for the down-regulation of protein degradation. In addition, decreased expression of AMPK α2 may partially participate in inhibiting the activity of AMPK.

Effects of oxygen concentration and pressure on Drosophila melanogaster: oxidative stress, mitochondrial activity, and survivorship.

Organisms are known to be equipped with an adaptive plasticity as the phenotype of traits in response to the imposed environmental challenges as they grow and develop. In this study, the effects of extreme changes in oxygen availability and atmospheric pressure on physiological phenotypes of Drosophila melanogaster were investigated to explore adaptation mechanisms. The changes in citrate synthase activity (CSA), lifespan, and behavioral function in different atmospheric conditions were evaluated. In the CAS test, hyperoxia significantly increased CSA; both hypoxia and hyperbaric conditions caused a significant decrease in CSA. In the survivorship test, all changed atmospheric conditions caused a significant reduction in lifespan. The lifespan reduced more after hypoxia exposure than after hyperbaria exposure. In behavioral function test, when mechanical agitation was conducted, bang-sensitive flies showed a stereotypical sequence of initial muscle spasm, paralysis, and recovery. The percentage of individuals that displayed paralysis or seizure was measured on the following day and after 2 weeks from each exposure. The majority of flies showed seizure behavior 15 days after exposure, especially after 3 h of exposure. The percentage of individuals that did not undergo paralysis or seizure and was able to move in the vial, was also tested. The number of flies that moved and raised the higher level of the vial decreased after exposure. Animal's speed decreased significantly 15 days after exposure to extreme environmental conditions. In summary, the alteration of oxygen availability and atmospheric pressure may lead to significant changes in mitochondria mass, lifespan, and behavioral function in D. melanogaster.

Nucleot(s)ide analogues for hepatitis B virus-related hepatocellular carcinoma after curative treatment: a systematic review and meta-analysis.

AIM: The benefit of nucleot(s)ide analogues (NA) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment has been widely debated due to the relatively weak evidence. The objective of this systematic review was to evaluate the effect of NA on recurrence and survival after curative treatment of HBV-HCC. METHODS: A systematic electronic search was performed. All controlled trials comparing NA versus placebo or no treatment were considered for inclusion. Results were expressed as Hazard Ratio for recurrence and survival with 95% confidence intervals using RevMan 5.2. RESULTS: We included 13 trials with 6350 patients. There were significant improvements for recurrence-free survival (HR 0.66, 95% CI 0.54-0.80; p<0.0001) and overall survival (HR 0.56, 95% CI 0.43-0.73; p<0.0001) in the adjuvant NA group compared with the control group. Sensitivity analyses confirmed the robustness of the results. There were no serious adverse effects being reported. Lamivudine resistance was from 28.6% to 37.5% but could be rescued by other types of NA or combination therapy. CONCLUSION: Our study suggested benefits of adjuvant NA therapy following curative treatment of HBV-HCC. Since the great proven efficacy of NA in improving clinical and viral parameters besides HCC, further studies should be focused on broadening the indications for NA therapy after curative treatment of HBV-HCC.

Transarterial (chemo)embolization for curative resection of hepatocellular carcinoma: a systematic review and meta-analyses.

PURPOSE: To assess the beneficial and harmful effects of transarterial embolization (TAE) or transarterial chemoembolization (TACE) for curative resection of hepatocellular carcinoma (HCC). METHODS: The authors conducted an extensive search of studies on this strategy. All randomized controlled trials comparing TACE or TAE plus operation versus operation only were considered for inclusion, regardless of blinding, language, or publication status. Results were performed with disease-free survival (DFS) and overall survival (OS) as the primary endpoint. Tumor response and adverse events were secondary endpoints. RESULTS: A total of 10 studies involving 909 HCC participants finally fulfilled the predefined inclusion criteria. Four trials assessed preoperative TACE versus control and six trials assessed postoperative TACE versus control. There were significant improvements for DFS [HR 0.62 (95 % CI 0.49-0.79)] and OS [HR 0.60 (0.46-0.79)] in the postoperative TACE compared with the control when the mean tumor size was bigger than 5 cm. However, preoperative TACE did not improve DFS [HR 0.92 (0.71-1.20)] and OS [HR 1.07 (0.78-1.46)] for curative resection of HCC. Substantial differences in criteria for assessing tumor response did not allow quantitative analyses. Fever (26.7-85.9 %), abdominal pain (19.3-71.2 %), and nausea/vomiting (27.4-66.3 %) were common adverse events. Relatively rare but more serious complications were also reported. CONCLUSIONS: Postoperative TACE offers potential benefits for curative resection of HCC when the mean tumor size is bigger than 5 cm.

Antiviral therapy after curative treatment of hepatitis B/C virus-related hepatocellular carcinoma: A systematic review of randomized trials.

AIM: Available published work on the benefit of adjuvant antiviral therapy after curative treatment of hepatocellular carcinoma (HCC) reports controversial results. The objective of this systematic review was to evaluate the effect of adjuvant antiviral therapy on recurrence and survival after curative treatment of HCC. METHODS: We conducted an extensive search strategy. All randomized controlled trials comparing adjuvant antiviral therapy versus placebo or no treatment were considered for this review. Results were expressed as hazard ratio for time-to-event outcomes with 95% confidence intervals using RevMan 5. RESULTS: We included nine trials (three of low risk of bias and six of unclear risk of bias) with 954 patients. All the included studies used conventional interferon (IFN) as adjuvant antiviral therapy; none of them used pegylated IFN or nucleoside analogs. There were significant improvements for recurrence-free survival and overall survival in the adjuvant IFN group compared with the control group. Subgroup analysis also showed a significant difference favoring IFN therapy in hepatitis C virus (HCV)-related HCC patients, but for hepatitis B virus (HBV)-related patients, the difference failed to reach statistical significance. A dose reduction was needed in 28.3% of patients and discontinuation of IFN therapy happened in 8.2% of patients due to moderate to severe side-effects. CONCLUSION: Our study suggested potential benefits of adjuvant IFN therapy following curative treatment of HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more effective adjuvant antiviral regimens, either used alone or in combination, for virus-related HCC, especially HBV-related HCC, are needed.

A novel model of burn-blast combined injury and its phasic changes of blood coagulation in rats.

Burn-blast combined injury has a complex pathological process that may cause adverse complications and difficulties in treatment. This study aims to establish a standard animal model of severe burn-blast combined injury in rats and also to investigate early phasic changes of blood coagulation. By using 54 Wistar rats, distance from explosion source (Hexogen) and size of burned body surface area were determined to induce severe burn-blast combined injury. Thereafter, 256 rats were randomly divided into four groups (n = 64): blast injury group, burn injury group, burn-blast combined injury group, and sham injury group. Gross anatomy and pathological changes in lungs were investigated at 3, 24, 72, and 168 h, respectively. Blood was also collected for analyzing coagulation parameters as prothrombin time, activated partial thromboplastin time, and plasma levels of fibrinogen, D-dimer, antithrombin III, and α2-antiplasmin from 0 to 168 h after injury. Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury when placing rats 75 cm away from explosion source and a full-thickness burn injury of 25% total body surface area. The rats with burn-blast combined injury had more severe lung injuries when compared with the other three groups. Pathological examination in the BBL group showed diffused alveolar hemorrhage, fluid filling, alveolar atelectasis, rupture and hyperplasia of partial alveolar septum, emphysema-like change, reduced capillary bed, and infiltration of extensive polymorphonuclear cells after injury. The blood of combined injured rats was in a hypercoagulable state within 24 h, shortly restored from 24 to 48 h, and rehypercoagulated from 48 to 72 h after injury. A secondary excessively fibrinolytic function was also found thereafter. The rat model of burn-blast combined injury was successfully established by simulating real explosion characteristics. Rats with burn-blast combined injuries suffered from more severe lung injuries and abnormal coagulation and fibrinolytic function than those induced by a burn injury or a blast injury component. Hence, a time-dependent treatment strategy on coagulation function should be emphasized in clinical therapy of burn-blast combined injury.

In vitro cytotoxicity of fluorescent silica nanoparticles hybridized with aggregation-induced emission luminogens for living cell imaging.

Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and uniform in size, with an average diameter of approximately 100 nm, and emitted strong fluorescence at the peak of 490 nm. The FSNP-SD selectively stained the cytoplasmic regions and were distributed in the cytoplasm. Moreover, they can stay inside cells, enabling the tacking of cells over a long period of time. The intracellular vesicles and multinucleated cells were increase gradually with the rise of FSNP-SD concentration. Both cell viability and survival only lost less than 20% when the cells were exposed to the high concentration of 100 µg/mL FSNP-SD. Additionally, the cell apoptosis and intracellular ROS assay indicated that FSNP-SD had no significant toxic effects at the maximum working concentration of 80 µg/mL. This study demonstrated that the FSNP-SD are promising biocompatible fluorescent probes for living cell imaging.

Role of neutrophil elastase in lung injury induced by burn-blast combined injury in rats.

OBJECTIVE: Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn-blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn-blast combined injury in rats. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn-blast combined injury (BB) group, burn-blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury. RESULTS: In BB group, PaO2 decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes. CONCLUSION: Sivelestat, exerts a protective effect in lung injury after burn-blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8.