Assembly of Copper Alkynyl Clusters into Dimensionally Diverse Coordinated Polymers Mediated by Pyridine Ligands.

Surface ligands play crucial roles in modifying the properties of metal nanoclusters and stabilizing atomically precise structures, and also serve as vital linkers for constructing cluster-based coordination polymers. In this study, we present the results of the solvothermal synthesis of eight novel copper alkynyl clusters incorporating pyridine ligands using a one-pot method. The resulting compounds underwent characterization through elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Our observations revealed that distinct pyridine ligands with varying lengths and coordination sites exert significant influence on the structure and dimensionality of the clusters. The structural diversity of these clusters led to the formation of one-dimensional (1D), two-dimensional (2D), or dimer arrangements linked by seven pyridine bridging ligands. Remarkably, these complexes exhibited unique UV-vis absorption and photoluminescence properties, which were influenced by the specific bridging ligand and structural framework. Furthermore, density functional theory (DFT) calculations demonstrated the capability of the conjugated system in the pyridine ligand to impact the band gap of clusters. This study not only unveils the inherent structural diversity in coordination polymers based on copper alkynyl clusters but also offers valuable insights into harnessing ligand engineering for structural and property modulation.

Chiral Canoe-Like Pd0 or Pt0 Alloyed Copper Alkynyl Nanoclusters Display Near-Infrared Luminescence.

Alloying nanoclusters (NCs) has emerged as a widely explored and versatile strategy for tailoring tunable properties, facilitating in-depth atomic-level investigations of structure-property correlations. In this study, we have successfully synthesized six atomically precise copper NCs alloyed with Group 10 metals (Pd or Pt). Notably, the Pd0 or Pt0 atom situated at the center of the distorted hexagonal antiprism Pd0/Pt0@Cu12 cage, coordinated with twelve Cu+ and two tBuC≡C- ligands. Moreover, ligand exchange strategies demonstrated the potential for Cl- and Br- to replace one or two alkynyl ligands positioned at the top or side of the NCs. The chirality exhibited by these racemic NCs is primarily attributed to the involvement of halogens and a chiral (Pd/Pt)@Cu18 skeleton. Furthermore, all the NCs exhibit near-infrared (NIR) luminescence, characterized by emission peaks at 705-755 nm, lifetimes ranging from 6.630 to 9.662 µs, and absolute photoluminescence quantum yields (PLQYs) of 1.75 %-2.52 % in their crystalline state. The experimental optical properties of these NCs are found to be in excellent agreement with the results of theoretical calculations. These alloy NCs not only offer valuable insights into the synthesis of Pd0/Pt0-Cu alloy NCs, but also bridge the gap in understanding the structure-luminescence relationships of Pd0/Pt0-Cu molecules.

'Food can help numb the pain': A mixed methods exploration of disordered eating, shame and self-compassion in an international community sample of men and women.

Background: Research into disordered eating (DE), shame and self-compassion (SC) has poorly represented men, general populations and non-Western communities. Aim: To explore associations between these variables in an international community sample of men and women. Methods: An online exploratory sequential mixed methods cross-sectional survey assessed levels of (quantitative Phase 1) and perceptions of (qualitative Phase 2) eating behaviours, external shame and body image shame (BIS) and SC. Results: Phase 1: Nearly 60% of our 142 survey participants were male (82/142) and about one-third were from India (43/142). About one-third of people (41/142) had a high-level concern regarding dieting, body weight, or eating (based on Eating Attitudes Test scores), and they had significantly higher levels of external shame, BIS and (SC-related) self-judgement and overidentification - compared to the 101/142 participants with low concern. Men had healthier levels of study outcomes than women. Phase 2: Four key themes were identified using inductive thematic analysis of the responses of 55 survey participants: (T1) DE as a Psychological Issue, (T2) DE as a Social Issue, (T3) The Vicious Cycle of Shame and (T4) Seeking Help. Conclusion: In participants in Phase 1 of our study - who were mostly male - DE behaviours were related to more external shame and body image-specific shame, and to less SC. Men had healthier levels of study variables than women. In Phase 2, participants talked about a vicious cycle of pathological eating and shame.

Epigenetic network of EZH2/SFRP1/Wnt in the epithelial-mesenchymal transition of laryngeal carcinoma cells.

Enhancer of Zeste Homologue 2 (EZH2) as a histone methyltransferase epigenetically regulates laryngeal carcinoma (LGC) progression. The present study sought to explore the role and mechanism of EZH2 in the epithelial-mesenchymal transition (EMT) of LGC cells. Expressions of EZH2, secreted frizzled-related protein 1 (SFRP1), and trimethylation of lysine 27 on histone H3 (H3K27me3) in LGC tissues or cells were detected via reverse transcription quantitative polymerase chain reaction (qRT-PCR) and western blotting. Upon transfection of si-EZH2, si-SFRP1, oe-SFRP1, or H3K27me3 upregulation, cell viability was assessed via cell counting kit-8, protein levels of E-cadherin, N-cadherin, ß-catenin, c-Myc, and Cyclin D1 were determined via western blotting, and Vimentin expression was determined via immunofluorescence. The enrichment level of H3K27me3 in the SFRP1 promoter was measured via chromatin immunoprecipitation-PCR. EZH2 was highly expressed in LGC tissues and cells. Silencing EZH2 repelled the EMT of LGC cells. Mechanically, EZH2 upregulated H3K27me3 in the SFRP1 promotor to inhibit SFRP1 expression, and SFRP1 overexpression inactivated the Wnt pathway. H3K27me3 upregulation or SFRP1 downregulation reversed the inhibition of silencing EZH2 in the EMT of LGC cells. Overall, EZH2 upregulated H3K27me3 in the SFRP1 promoter to inhibit SFRP1 expression and activate the Wnt pathway, thereby facilitating the EMT of LGC cells.

TWIST1 transcriptionally regulates glycolytic genes to promote the Warburg metabolism in pancreatic cancer.

Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC.

GSTM1 null polymorphisms is associated with laryngeal cancer risk: a meta-analysis.

Many studies have examined the association between the GSTM1 (null or non-null genotype) polymorphism and laryngeal cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed was searched for case-control studies published up to December 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 23 studies, comprising 2,562 laryngeal cancer cases and 4,091 controls, were included. Overall, for null versus present, the pooled OR was 1.22 (95 % CI = 1.10-1.36), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR = 1.71; 95 % CI = 1.34-2.19; P = 0.011 for heterogeneity) and in Caucasians (OR = 1.13, 95 % CI = 1.00-1.27; P = 0.036 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism is an increased risk of laryngeal cancer in Asians and Caucasians.

Bmo-miR-3351 modulates glutathione content and inhibits BmNPV proliferation by targeting BmGSTe6 in Bombyx mori.

MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in the host response to invading pathogens. Among these pathogens, Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of substantial economic losses in sericulture, and there are relatively few studies on the specific functions of miRNAs in the B. mori-BmNPV interaction. Therefore, we conducted transcriptome sequencing to identify differentially expressed (DE) messenger RNAs (mRNAs) and miRNAs in the midgut of 2 B. mori strains (BmNPV-susceptible strain P50 and BmNPV-resistant strain A35) after BmNPV infection. Through correlation analysis of the miRNA and mRNA data, we identified a comprehensive set of 21 miRNAs and 37 predicted target mRNAs. Notably, miR-3351, which has high expression in A35, exhibited remarkable efficacy in suppressing BmNPV proliferation. Additionally, we confirmed that miR-3351 binds to the 3' untranslated region (3' UTR) of B. mori glutathione S-transferase epsilon 6 (BmGSTe6), resulting in its downregulation. Conversely, BmGSTe6 displayed an opposite expression pattern to miR-3351, effectively promoting BmNPV proliferation. Notably, BmGSTe6 levels were positively correlated with glutathione S-transferase activity, consequently influencing intracellular glutathione content in the infected samples. Furthermore, our investigation revealed the protective role of glutathione against BmNPV infection in BmN cells. In summary, miR-3351 modulates glutathione content by downregulating BmGSTe6 to inhibit BmNPV proliferation in B. mori. Our findings enriched the research on the role of B. mori miRNAs in the defense against BmNPV infection, and suggests that the antiviral molecule, glutathione, offers a novel perspective on preventing viral infection in sericulture.

Photocatalytic Tandem Radical Cyclization Enables Expeditious Total Synthesis of Epoxyhinokiol Analogues for Anticancer Activity Evaluation.

A photocatalytic radical cascade with an unusual endo-trig cyclization was developed, which enables the efficient assembly of divergent tricyclic diterpenoid frameworks. The first total synthesis of abietane 10-epi-epoxyhinoliol was thus achieved in six steps by a subsequent reductive coupling of i-PrBr under photoredox/nickel dual catalysis. Inhibitory tests of chiral 10-epi-epoxyhinoliol and its analogues in 4T1 cancer cells demonstrated the critical role of the C12 hydroxyl group, leading to a discovery of the simplified analogue with better activity.

Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

[Investigation of entecavir treatment in patients with LAM-refractory chronic hepatitis B].

OBJECTIVE: To evaluate the efficacy and safety of entecavir (ETV) as a long-term treatment in patients with lamivudine (LAM)-refractory chronic hepatitis B (CHB). METHODS: In this phase II study of ETV-056, 32 CHB patients with resistance to LAM monotherapy were administered ETV at 1.0 mg/day and monitored over a period of 8 years. The virologic, serologic and biochemical responses were measured throughout the treatment course. Outcomes analysis was conducted according to intention-to-treat principles. RESULTS: At baseline and treatment weeks 8, 12, 24, 48, 96, 144, 192, 240, and 420, the proportion of patients with HBV DNA less than 300 copies/ml was 0, 6.3% (2/32), 9.4% (3/32), 18.8% (6/32), 18.8%(6/32), 46.9% (15/32), 43.8% (14/32), 50.0% (16/32), 50.0% (16/32), and 62.5% (20/32). At treatment weeks 48, 96, 168, 192, 240, and 420, the proportion of patients experiencing virological breakthrough was 6.1% (2/32), 9.4% (3/32), 12.5% (4/32), 18.8%(6/32), 25.0%(8/32), and 28.1% (9/32). In the 8 year study period, 32.3% (10/31) of patients achieved HBs seroconversion and four patients achieved HBe seroconversion. CONCLUSION: While treatment with 1.0 mg/day ETV for up to 8 years resulted in mild HBV DNA suppression and increase of HBeAg seroconversion, the safety profile of this therapy was good but the economic cost was high and virological breakthrough rates were high.

Potential for NPY receptor-related therapies for polycystic ovary syndrome: an updated review.

Polycystic ovary syndrome (PCOS) is a complex endocrine disease that can cause female infertility and bring economic burden to families and to society. The clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, and polycystic ovarian changes, often accompanied by insulin resistance and obesity. Although its pathogenesis is unclear, PCOS involves the abnormal regulation of the hypothalamic-pituitary-ovarian axis and the abnormal activation of GnRH neurons. Neuropeptide Y (NPY) is widely distributed in the arcuate nucleus of the hypothalamus and functions as the physiological integrator of two neuroendocrine systems, one governing feeding and the other controlling reproduction. In recent years, an increasing number of studies have focused on the improvement of the reproductive and metabolic status of PCOS through the therapeutic application of NPY and its receptors. In this review, we summarize the central and peripheral regulation of NPY and its receptors in the development of PCOS and discuss the potential for NPY receptor-related therapies for PCOS.

Protective effects of the notoginsenoside R1 on acute lung injury by regulating the miR-128-2-5p/Tollip signaling pathway in rats with severe acute pancreatitis.

Notoginsenoside R1 (NG-R1), the extract and the main ingredient of Panax notoginseng, has anti-inflammatory effects and can be used in treating acute lung injury (ALI). In this study, we explored the pulmonary protective effect and the underlying mechanism of the NG-R1 on rats with ALI induced by severe acute pancreatitis (SAP). MiR-128-2-5p, ERK1, Tollip, HMGB1, TLR4, IκB, and NF-κB mRNA expression levels were measured using real-time qPCR, and TLR4, Tollip, HMGB1, IRAK1, MyD88, ERK1, NF-κB65, and P-IκB-α protein expression levels using Western blot. The NF-κB and the TLR4 activities were determined using immunohistochemistry, and TNF-α, IL-6, IL-1ß, and ICAM-1 levels in the bronchoalveolar lavage fluid (BALF) using ELISA. Lung histopathological changes were observed in each group. NG-R1 treatment reduced miR-128-2-5p expression in the lung tissue, increased Tollip expression, inhibited HMGB1, TLR4, TRAF6, IRAK1, MyD88, NF-κB65, and p-IκB-α expression levels, suppressed NF-κB65 and the TLR4 expression levels, reduced MPO activity, reduced TNF-α, IL-1ß, IL-6, and ICAM-1 levels in BALF, and alleviated SAP-induced ALI. NG-R1 can attenuate SAP-induced ALI. The mechanism of action may be due to a decreased expression of miR-128-2-5p, increased activity of the Tollip signaling pathway, decreased activity of HMGB1/TLR4 and ERK1 signaling pathways, and decreased inflammatory response to SAP-induced ALI. Tollip was the regulatory target of miR-128-2-5p.

Vacuoles in Bryophytes: Properties, Biogenesis, and Evolution.

Vacuoles are the most conspicuous organelles in plants for their indispensable functions in cell expansion, solute storage, water balance, etc. Extensive studies on angiosperms have revealed that a set of conserved core molecular machineries orchestrate the formation of vacuoles from multiple pathways. Usually, vacuoles in seed plants are classified into protein storage vacuoles and lytic vacuoles for their distinctive morphology and physiology function. Bryophytes represent early diverged non-vascular land plants, and are of great value for a better understanding of plant science. However, knowledge about vacuole morphology and biogenesis is far less characterized in bryophytes. In this review, first we summarize known knowledge about the morphological and metabolic constitution properties of bryophytes' vacuoles. Then based on known genome information of representative bryophytes, we compared the conserved molecular machinery for vacuole biogenesis among different species including yeast, mammals, Arabidopsis and bryophytes and listed out significant changes in terms of the presence/absence of key machinery genes which participate in vacuole biogenesis. Finally, we propose the possible conserved and diverged mechanism for the biogenesis of vacuoles in bryophytes compared with seed plants.

Effects of Visual Feedback During Balance Training on Knee Function and Balance Ability in Postoperative Patients After Knee Fracture: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of visual feedback training on knee function and balance ability in postoperative patients with knee fracture. METHODS: A clinical randomized controlled trial with 104 participants, randomly assigned (1:1) to a visual feedback training group or a  control group. Eligible participants were evaluated using Lysholm scores, the Tinetti scale, and the evaluation module of TecnoBody® to demonstrate dynamic balance function in a standing position before treatment and after 4 and 8 weeks of treatment. RESULTS: Both visual feedback training and control groups improved significantly in the Lysholm and Tinetti scores after 8 weeks. Compared with the control group, the TecnoBody® tests included centre of pressure path length, and the area over centre of pressure movement, both of which significantly improved in the visual feedback training group at 8 weeks after treatment. There was no difference between the 2 groups in terms of their Lysholm scores and Tinetti gait before the intervention and 4 weeks after treatment. CONCLUSION: Applying visual feedback training in conjunction with traditional rehabilitation strategies may improve knee function and motor control in postoperative patients with knee fracture. Although visual feedback training does not have a short-term effect on knee function and gait, this method could be a useful addition for rehabilitation of knee fracture patients.

Therapeutic potential of exosomes/miRNAs in polycystic ovary syndrome induced by the alteration of circadian rhythms.

Polycystic ovary syndrome (PCOS) is a reproductive dysfunction associated with endocrine disorders and is most common in women of reproductive age. Clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, polycystic ovary, insulin resistance, and obesity. Presently, the aetiology and pathogenesis of PCOS remain unclear. In recent years, the role of circadian rhythm changes in PCOS has garnered considerable attention. Changes in circadian rhythm can trigger PCOS through mechanisms such as oxidative stress and inflammation; however, the specific mechanisms are unclear. Exosomes are vesicles with sizes ranging from 30-120nm that mediate intercellular communication by transporting microRNAs (miRNAs), proteins, mRNAs, DNA, or lipids to target cells and are widely involved in the regulation of various physiological and pathological processes. Circadian rhythm can alter circulating exosomes, leading to a series of related changes and physiological dysfunctions. Therefore, we speculate that circadian rhythm-induced changes in circulating exosomes may be involved in PCOS pathogenesis. In this review, we summarize the possible roles of exosomes and their derived microRNAs in the occurrence and development of PCOS and discuss their possible mechanisms, providing insights into the potential role of exosomes for PCOS treatment.

[Effects of puerarin on proliferation, apoptosis and Kv1.5 gene expression of pulmonary artery smooth muscle cells induced by hypoxia].

OBJECTIVE: To study the effects of puerarin on proliferation, apoptosis and Kv1.5 gene expression of rat pulmonary artery smooth muscle cells (PASMCs) induced by hypoxia. METHODS: The rat PASMCs were divided into 5 groups: control group, hypoxia group, hypoxia plus puerarin (1 × 10(-5) mol/L) group, hypoxia plus puerarin (1 × 10(-4) mol/L) group and hypoxia plus puerarin (1 × 10(-3) mol/L) group, and cultured at 37°C for 24 h. The proliferation of rat PASMCs was detected by CCK-8 assay and flow cytometry, the activity of caspase-3 was measured with spectrophotometric method, Kv1.5 protein was detected by western blot, Kv1.5 mRNA was detected by real-time PCR. RESULTS: The cell viability and proportion of synthesis phase in control group were 0.940 ± 0.045 and 9.67% ± 1.28%, which were significantly lower than those (1.296 ± 0.034 and 18.19% ± 1.19%) in hypoxia group (P < 0.05). The Caspase-3 activity, Kv 1.5 protein and Kv 1.5 mRNA in control group were 0.1073 ± 0.0113, 0.886 ± 0.038 and 0.0377 ± 0.0031, which were significantly higher than those (0.0664 ± 0.0049, 0.602 ± 0.064 and 0.0108 ± 0.0014) in hypoxia group (P < 0.05). As compared with hypoxia group, the cell viability and proportion of synthesis phase in 3 hypoxia plus puerarin groups significantly decreased, and the Caspase-3 activity, Kv 1.5 protein and Kv 1.5 mRNA in 3 hypoxia plus puerarin groups significantly enhanced (P < 0.05). CONCLUSION: Puerarin could decrease the proliferation and increase the apoptosis induced by hypoxia in rat PASMCs, and the up-regulated expression of Kv1.5 gene may be the mechanism of puerarin effects.

[Comparison of the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients].

OBJECTIVE: To compare the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients. METHODS: In this open-label study we randomly assigned 125 CHB patients to receive 0.5 mg of entecavir (n = 56) or 10mg of adefovir (n = 69) once daily for 48 weeks. RESULTS: HBV DNA, ALT and HBeAg were quantified at baseline and at 0, 24, 48 weeks. At week 24 and 48, more patients in entecavir group than in adefovir group achieved undetectable serum HBV DNA level (68% vs 35%, 84% vs 49%, P < 0.05). The percentage of patients with normal ALT level in the two groups at week 48 was similar (100% vs 94%, P > 0.05). Among the HBeAg positive patients, more patients in entecavir group than in adefovir group had HBeAg loss at week 24 and 48 (23% vs 7%, 44% vs 15%, P < 0.05). The ratio of HBeAg seroconversion was similar in the two groups at week 24 (18% vs 7%, P > 0.05), but more patients in entecavir group than in adefovir group achieved HBeAg seroconversion at week 48 (33% vs 12%, P < 0.05). The retreated patients in the entecavir group had a higher chance to achieve undetectable serum HBV DNA level (79% vs 34%, P < 0.05), HBeAg loss (42% vs 17%, P > 0.05), and seroconversion (26% vs 17%, P > 0.05), than these in the adefovir group. The safety profiles and adverse event profiles were similar in the two groups. CONCLUSIONS: Compared to adefovir, entecavir is more potent to suppress HBV replication.

Small molecule proteomics quantifies differences between normal and fibrotic pulmonary extracellular matrices.

BACKGROUND: Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown. METHODS: Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 µL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 µL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed. RESULTS: Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin ß1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9). CONCLUSIONS: Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

[Five years trial of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area].

OBJECTIVE: To evaluate the efficacy and safety of five-year trail of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area. METHODS: 32 patients failed with lamivudine therapy were enrolled in this study. In the double-blind phase, patients were randomly divided into entecavir 1.0 mg/d group (n = 28) and placebo group(n = 4) for 12 weeks. In the open-lable phase, patients received ETV 1.0 mg/d for 240 weeks. HBV DNA level, liver function, HBV serology were observed. RESULTS: The mean reduction in HBV DNA level at week 12 was 4.05 log10 copies/ml in ETV group, and 0.08 log10 copies/ml in placebo group (P less than 0.05). The mean of HBV DNA level after 240 weeks of ETV treatment was decreased to 2.58 log10 copies/ml. The proportion of patients with HBV DNA less than 3 log10 copies/ml was 0, 6.25%, 15.6% , 50%, and 57.14% at 0, 8, 24, 96 and 240 weeks respectivfely. There were 2 patients with HBsAg seroconversion and 4 patients with HBeAg seroconversion at the end of the study. The ALT level returned to normal at week 12 and remained normal throughout the following 240 weeks. One patient had a severe adverse event during the trail. CONCLUSION: Entecavir is effective and safe for the chronic hepatitis B patients failed with lamivudine therapy.

[Nucleos(t)ides as prophylaxis for the reactivation of hepatitis B virus in immunosuppressed patients].

OBJECTIVE: To investigate the incidence of HBV reactivation and its clinical characteristics in the non-active HBsAg carriers receiving chemotherapy or immunosuppressant treatment, and to evaluate the role of nucleos(t)ide analogues against HBV reactivation. METHODS: Non-active HBsAg carriers suffering from cancer, autoimmune diseases recieving immunosuppression therapy or cytotoxic chemotherapy were enrolled in the study. The in-patients from June 2002 to April 2007 in the Second Affiliated Hospital of Chongqing Medical University were assigned in the control group. The outpatients or in-patients with the similar disease condition from April 2007 to July 2008 were enrolled in the preventive group. The characteristics of HBV replication, liver damage, clinical symptoms and effectiveness of nucleos(t)ide analogues as prophylaxis for HBV reactivation were observed. The nucleos(t)ide analogues were used before chemotheraphy or immunosuppressive agents. The characheristics and clinical manifestations about HBV reactivation were investigated. RESULTS: Of the 32 patients in preventive group, the amount of HBV DNA was detected in the 1rst, 3rd, 6th and 12th month after nucleos(t)ide analogues treatment. After chemotherapy or immunosuppressant treatment, only 9.4% (3/32) of them suffered from HBV reactivation, as indicated by positive HBV DNA in the serum and abnormal liver function. Ot the 77 patients in control group without nucleos(t)ide analogues treatment before chemotherapy or immunosuppression therapy, 58.4% (45/77) shown HBV reactivation, 4 patients in the control group died of liver failure, and one liver failure patient recieved liver transplantation. CONCLUSION: HBV can be activated in immunosuppressed patients, nucleos(t)ide analogues should be used in early phase to prevent HBV reactivation.