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Wei Yan,1 Xue Luo,1 Qing-Jun Gao,1 Bing-Feng Chen,2 Hui Ye1 1Department of Thyroid Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, People’s Republic of China; 2Guizhou Medical University, Guiyang, 550001, People’s Republic of ChinaCorrespondence: Hui Ye, Department of Thyroid Surgery, Affiliated Hospital of Guizhou Medical University, No. 28 of Guiyi Street, Yunyan District, Guiyang, 550001, People’s Republic of China, Tel +86-85186772361, Fax +86-85186773426, Email 1710681307@qq.comObjective: To analyze the correlation between body mass index (BMI) and clinicopathological factors of papillary thyroid cancer (PTC).Methods: The clinical data of patients with PCT who were hospitalized in the Department of Thyroid Surgery of the Affiliated Hospital of Guizhou Medical University from March 2023 to September 2023 were retrospectively collected, including age, gender, height, weight, BMI, v-raf murine sarcoma viral oncogene homolog B (BRAF) gene mutation, tumor size, multifocus, Hashimoto’s thyroiditis, lymph node metastasis and other clinicopathological factors. According to the World Health Organization (WHO) definition for Asian population, BMI≥ 25kg/m2 was obese group, 23≤BMI≤ 24.9kg/m2 was overweight group, 18.5≤BMI≤ 22.9kg/m2 was normal weight group, and BMI≤ 18.5kg/m2 was low weight group. The clinicopathological factors of overweight and obese patients with PTC were analyzed.Results: A total of 164 PTC patients were included, with an average BMI of (24.44± 3.57) kg/m2. Age of overweight and obese PTC patients (Z=1.978, p=0.083); Gender of overweight and obese PTC patients (χ2 value: 11.570, p=0.004); Tumor size in overweight and obese PTC patients (Z=0.894, p=0.411); BRAF gene mutation in overweight and obese PTC patients (χ2 value: 1.452, p =0.623); Multifocal lesions were found in overweight and obese patients (χ2 value: 1.653, p =0.201). Hashimoto’s thyroiditis was found in overweight and obese PTC patients (χ2 value: 1.147, p=0.298). Overweight and obese patients with PTC had lymph node metastasis (χ2 value: 1.690, p =0.251).Conclusion: Overweight and obesity in PTC patients are correlated with male, but not with age, tumor size, BRAF mutation, multifocality, Hashimoto’s thyroiditis and lymph node metastasis.Keywords: papillary thyroid carcinoma, body mass index, clinicopathological factors, correlation analysis

Alpha-actin-1 (ACTN1) is a cytoskeletal protein, and new evidence suggests that it is associated with tumor progression and prognosis. However, the expression of ACTN1 in thyroid carcinoma (THCA) and its biological functions are not fully understood. This study aimed to explore the expression and biological function of ACTN1 in THCA. Bioinformatics analysis revealed that ACTN1 was significantly upregulated in THCA and was associated with tumor size, extraglandular invasion, lymph node and distant metastasis, patient prognosis, and immune cell infiltration. qRT-PCR, immunohistochemistry, and western blotting verified the high expression of ACTN1 in the PTC samples. In vitro and in vivo experiments showed that overexpression of ACTN1 promoted THCA cell proliferation, cell cycle, migration, and invasion, and induced epithelial-mesenchymal transition (EMT); knockdown of ACTN1 inhibited these malignant behaviors. Mechanistically, ACTN1 knockdown reduced the phosphorylation levels of PI3K, AKT, and mTOR, whereas its overexpression increased these levels. After treating ACTN1 knockdown cells with the PI3K activator 740Y-P, the invasion and migration ability of the tumor was restored, suggesting that ACTN1 may promote the invasion and migration of THCA by activating the PI3K/AKT/mTOR pathway. In conclusion, ACTN1 is an important regulator of THCA progression and may serve as a potential molecular marker for predicting THCA invasion and metastasis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: The Ethics Committee of the Affiliated Hospital of Guizhou Medical University approved all the experiments. All the patients had signed informed consents. We confirm that all methods were performed in accordance with the relevant guidelines and regulations. Animal studies were reported according to the ARRIVE guidelines., (© 2024. The Author(s).)

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated. Results: 666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion: CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t -test, or Log-Rank test according to the data. Results: 593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores. Conclusion: After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Purpose: Eukaryotic translation elongation factor 1α2 (eEF1A2) promotes tumour progression in various cancers. We performed a pan-cancer analysis of eEF1A2 and explored its role in thyroid carcinoma (THCA)., Methods: Databases from The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and the Human Protein Atlas (HPA) were used to investigate the differential expression of eEF1A2 in pan-cancer. The pathological stage, prognostic characteristics, tumour microenvironment (TME), tumour mutational burden (TMB), and microsatellite instability (MSI) were analysed in diverse tumours with different expression levels of eEF1A2. The expression levels in papillary thyroid carcinoma (PTC) and its specific role in cell proliferation, migration, invasion, and cell glycolysis in PTC cells were verified by quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry, cell counting kit-8, colony formation, wound healing, Transwell assay, and lactate acid and glucose assays. Results: eEF1A2 was differentially expressed in various malignant tumour tissues compared to control tissues and was associated with poor pathological stage and prognosis in most types of tumours. Moreover, eEF1A2 expression closely correlated with the infiltration of immunosuppressive cells, TMB, and MSI in some tumour types. Expression of eEF1A2 in PTC is higher than the para-carcinoma, and eEF1A2 downregulation suppressed TPC-1 and BCPAP cell proliferation, migration, invasion, and glycolysis., Conclusion: Our study suggests that the expression of eEF1A2 is related to the prognosis and immune infiltration of some tumours and may be a predictor of prognosis and immunotherapy. eEF1A2 could promote malignant behaviour of PTC cells ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: In recent decades, thyroid cancer (TC) has exhibited a rising incidence pattern. Elevated levels of the transcription factor FOXP4 have been strongly linked to the progression of diverse tumors; nevertheless, its specific role in thyroid cancer remains underexplored. The primary objective of this study was to elucidate the functions of FOXP4 and its associated target gene, FBXW7, in the context of thyroid cancer., Methods: FOXP4 and FBXW7 expression levels in TC tissues and cell lines were assessed through immunohistochemistry and RT-qPCR analyses. The functional aspects of FOXP4, including its effects on cell proliferation, migration capabilities, cell cycle regulation, and epithelial-mesenchymal transition (EMT), were investigated. Furthermore, the interaction between FOXP4 and FBXW7 was confirmed using chromatin immunoprecipitation (ChIP) assays. The impact of FBXW7 on FOXP4-mediated cellular phenotypes was subsequently examined. Additionally, the in vivo role of FOXP4 and FBXW7 in tumor growth was elucidated through the establishment of a murine tumor model., Results: Elevated levels of FOXP4 were observed in papillary carcinoma tissues, and patients exhibiting high FBXW7 levels showed a more favorable prognosis. KTC-1 cells displayed a concomitant increase in FOXP4 expression and decrease in FBXW7 expression. FOXP4 overexpression in these cells enhanced cell proliferation, migration capabilities, and EMT. The interaction between the FOXP4 protein and the FBXW7 promoter was confirmed, and the effects of FOXP4 were mitigated upon overexpression of FBXW7. Furthermore, knockdown of FOXP4 led to decelerated growth of transplanted tumors and increased FBXW7 levels within the tumors., Conclusion: The findings of the current study underscore the regulatory role of FOXP4 in the transcription of FBXW7 and establish a clear link between aberrations in FBXW7 expression and the manifestation of malignant phenotypes in highly aggressive TC cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Thyroid cancer (THCA) is the most common endocrine cancer in the world. Although most patients with THCA have a good prognosis, the prognosis of those with THCA who have an extra-glandular invasion, vascular invasion, and distant metastasis is poor. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of highly aggressive THCAs. It has been identified that forkhead box P4 (FOXP4) may be a new biomarker for the proliferation and prognosis for tumor diagnosis. However, the expression and function of FOXP4 in THCA remain to be determined., Methods: In the present study, the function of FOXP4 in cells was investigated through the comprehensive analysis of data in The Cancer Genome Atlas and combined with experiments including immunohistochemistry (IHC), colony formation, Cell Counting Kit-8 assay, wound scratch healing, and transwell invasion assay., Results: In the present study, relevant bioinformatic data showed that FOXP4 was highly expressed in THCA, which was consistent with the results of the IHC and cell experiments. Meanwhile, 10 FOXP4-related hub genes were identified as potential diagnostic genes for THCA. It was found in further experiments that FOXP4 was located in the nucleus of THCA cells, and the expression of FOXP4 in the nucleus was higher than that in the cytoplasm. FOXP4 knockdown inhibited in vitro proliferation of the THCA cells, whereas overexpression promoted the proliferation and migration of THCA cells. Furthermore, deficiency of FOXP4 induced cell-cycle arrest., Conclusion: FOXP4 might be a potential target for diagnosing and treating THCA.

Objective: This experiment was designed to observe the effects of aerobic exercise on depressive behavior in rats induced by chronic unpredictable mild stress (CUMS), and to explore the possible mechanism by detecting the proteins related to mitochondrial autophagy. Methods: SD rats were randomly divided into three groups: blank control group (C, n =12), depression model group (D, n =12) and post-depression exercise group (D+E, n =12). Group D and D+E were modeled with CUMS for 28 days, and group D+E underwent aerobic exercise intervention for 4 weeks after model establishment. Then the behavior of rats was evaluated. The concentrations of whole brain dopamine and norepinephrine were determined by ELISA kits. The morphology and structure of mitochondria in the frontal lobe were observed with the transmission electron microscope (TEM). Mitochondrial autophagy lysosomes were localized by immunofluorescence colocalization. The expressions of LC3 and P62 proteins in the frontal lobe were measured with Western Blotting. The relative content of mitochondrial DNA was detected using Real-time PCR. Results: ①Compared with group C, the sucrose preference ratio in group D was decreased significantly( P ＜0.01); Compared with group D, the sucrose preference ratio in group D+E was increased significantly ( P ＜0.01). ②In the open field experiment, compared with group C, group D had a significant decrease in activity, average speed and total distance ( P ＜0.05); Compared with group D, the average rate of activity in group D+E was significantly higher ( P ＜0.05). ③ELISA results showed that the levels of whole brain dopamine and norepinephrine were significantly lower in group D rats than those in group C ( P ＜0.05). ④Under transmission electron microscopy, compared with group C, group D had different degrees of mitochondrial swelling, decreased crest density, and intermembrane space dilation.; Compared with group D, a significant increase in mitochondrial autophagosomes and autophagic lysosomes was observed in neurons in group D+E. Increased co-localization of mitochondria with lysosomes in the D+E group could be observed under fluorescence microscopy. ⑤Compared with group C, the expression of P62 was increased significantly( P ＜0.05), and LC3II/LC3I ratio was decreased significantly ( P ＜0.05) in group D; Compared with group D, LC3II/LC3I ratio was significantly higher in group D+E than that in group D ( P ＜0.05). ⑥Compared with group C, the relative number of mitochondrial DNA in the frontal lobe of group D was increased significantly ( P ＜0.05). Conclusion: Aerobic exercise has a significant improvement effect on depression induced by CUMS in rats, and its mechanism may be related to the upregulation of the level of linear autophagy.

A Gram-positive, rod-shaped, motile, spore-forming bacterium, designated strain IB182496 T , was isolated from coastal sand of the South China Sea. The strain grew optimally at pH 7.0-9.0, 20-30 °C, and with NaCl 3.0-5.0 %. The predominant menaquinone was MK-7 and the major cellular fatty acids were anteiso-C 15 : 0 , iso-C 16 : 0 and C 16 : 0 . The polar lipids in the cell wall included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified phospholipids and one unidentified lipid. The comparison of 16S rRNA gene sequences indicated that strain IB182496 T was most closely related to ' Paenibacillus sambharensis ' SMB1 and Paenibacillus tarimensis SA-7-6 T with similarities of 95.7 and 95.5 %, respectively. The whole-genome average nucleotide identity values between strain IB182496 T and the two reference strains were 70.8 and 70.5%, and the digital DNA-DNA hybridization values were 18.7 and 18.0 %, respectively. Genomic analyses showed that strain IB182496 T presented a genome of 6.22 Mbp with chromosomal G+C content of 60.3 %, and a total of 5261 genes were predicted. The combined phylogenetic relatedness, phenotypic and genotypic features supported the conclusion that strain IB182496 T should be considered as representing a novel species of the genus Paenibacillus , for which we propose the name Paenibacillus sabuli sp. nov. with the type strain IB182496 T (=MCCC 1K04627 T =JCM 34216 T ).

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM., (© 2022. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Background: The sigma receptors are a relatively novel receptor group with respect to knowledge of their effect on health. Although the sigma-1 receptor agonist PRE-084 exhibits a cardioprotective effect in some studies, the benefits in cases of myocardial ischemia/reperfusion (I/R) are not clear. The aim of this study was to explore the mechanism of action and assess the effect of PRE-084 on myocardial I/R injury in rats., Methods: In this study, rats were assigned randomly to three groups with computer (n = 14 for each group): a sham group, an I/R group, and a PRE-084 group. In the PRE-084 group, rats were administered PRE-084 1 h before operation. In the myocardial I/R model, the left anterior descending branch of rats was ligated and opened half an hour later. Cardiac function was assessed, and the apoptosis index was evaluated. The mechanisms of the cardioprotective effects of PRE-084 were explored., Results: PRE-084 pretreatment preserved cardiac function and reduced myocardial apoptosis (F = 86.0, P < 0.01) with Western blotting analysis, showing significantly reduced expression of Bax (F = 75.7, P < 0.01) and cleaved-caspase 3 (F = 44.7, P < 0.01), along with increased expression of the Bcl-2 protein (P < 0.01) and phosphorylated protein kinase B (p-Akt) (P < 0.01) and phosphorylated-endothelial nitric oxide synthase (p-eNOS; P < 0.01)., Conclusion: PRE-084 preserved cardiac function and reduced myocardial apoptosis through the activation of Akt and eNOS., Competing Interests: There are no conflicts of interest.

Background: The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood., Objectives: To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes., Methods: 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes ( rs2069762/-330 G/T of IL-2 , rs2430561/+874A>T of IFN-γ, rs1800896/-1082G>A  and rs1800872/-592C>A of IL-10 and rs2243250/ -589 C>T of IL-4 ) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene-gene interactions were assessed using the multifactor-dimensionality reduction method., Results: Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874  AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874  AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05)., Conclusions: Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10--592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection., Competing Interests: Competing interests: None., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO 2 ), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO 2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass.

Hepatocellular carcinoma (HCC) is one of the most common malignancies with high fatality rate in China. To investigate the related risk factors and therapeutic targets, and actively carry out the prevention and early treatment is of great public health value. Signal transducer and activators of transcription 3 (STAT3) is the key molecule of multiple inflammation-associated signaling pathways. Recent studies have found that HCC patients have high expressing levels of STAT3 in tumor tissues, and aberrant activation of STAT3 is closely associated with the occurrence, development, invasion, metastasis, and prognosis of HCC. In this paper, we reviewed the researches on the associations of STAT3 with the occurrence and prognosis of HCC and prospected on the issues of causal prophylaxis and targeted therapy for HCC which could offer reference for the protection strategy of HCC.

A novel 1,2-cis stereoselective synthesis of protected α-D-Gal-(1→2)-D-Glc fragments was developed. Methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranoside (13), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-α-D-glucopyranoside (15), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-β-D-glucopyranoside (17), and methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-β-D-glucopyranoside (19) were favorably obtained by coupling a new donor, isopropyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-1-thio-β-D-galactopyranoside (2), with acceptors, methyl 3-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranoside (4), methyl 3,4,6-tri-O-benzoyl-α-D-glucopyranoside (5), methyl 3-O-benzoyl-4,6-O-benzylidene-β-D-glucopyranoside (8), and methyl 3,4,6-tri-O-benzoyl-β-D-glucopyranoside (12), respectively. By virtue of the concerted 1,2-cis α-directing action induced by the 3-O-allyl and 4,6-O-benzylidene groups in donor 2 with a C-2 acetyl group capable of neighboring-group participation, the couplings were achieved with a high degree of α selectivity. In particular, higher α/β stereoselective galactosylation (5.0:1.0) was noted in the case of the coupling of donor 2 with acceptor 12 having a β-CH(3) at C-1 and benzoyl groups at C-4 and C-6., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To study the relationship between polymorphisms in interleukin-2 gene at position -330 (IL-2-330) and the clinical outcome of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection., Methods: 277 subjects were recruited including 79 chronic HCV co-HBV infection, 55 chronic HCV infection, 69 chronic HBV infection and 74 controls. Single nucleotide polymorphisms of IL-2-330 was investigated by restricted fragment long polymorphism-PCR (RFLP-PCR). Hepatocellular injury, as revealed by alanine aminotransferase (ALT) was detected by Beckman LX-20 analyzer. The presence of hepatitis C viral particles in serum was determined by RT-nPCR., Results: (1) IL-2-330 polymorphisms showed close association with persistent HBV and/or HCV infection. IL-2-330 TT was associated with an increased risk, but IL-2-330 GG with a reduced risk of persistent HBV and/or HCV infection (χ(2) = 14.24, P = 0.03) with ORs (95%CI) as 7.14 (2.13 - 23.81), 3.46 (1.17 - 10.02) and 2.93 (1.15 - 7.46) respectively. However, IL-2-330 TT/GG did not significantly differ between patients with HBV and/or HCV infection (χ(2) = 2.09, P = 0.72). IL-2-330 T allele was associated with an increased risk, but the -330G allele was associated with a reduced risk of chronic HBV/HCV infection (χ(2) = 12.33, P = 0.01), with ORs (95%CI) as 2.26 (1.39 - 3.69), 1.82(1.09 - 3.03) and 1.73 (1.10-2.73) respectively. (2) IL-2-330 polymorphisms showed significant association with the outcome of HBV and HCV infection (χ(2) = 13.52, P = 0.04). IL-2-330 TT was associated with an increased risk, but -330 GG with a reduced risk of mild CH, moderate/severe CH, and cirrhosis. The ORs (95%CI) appeared to be 3.33 (1.75 - 6.32), 3.31 (1.75 - 6.26), 11.23 (3.09 - 40.76) respectively. IL-2-330 T allele was associated with an increased risk, but the -330 G allele was associated with a reduced risk of mild CH, moderate/severe CH and cirrhosis (χ(2) = 12.32, P = 0.01), with ORs as 1.86 (1.32 - 2.63), 1.71 (1.27 - 2.31) and 2.77 (1.57 - 4.89) respectively. (3) The polymorphisms of IL-2-330 showed no association with HCV RNA replication (χ(2) = 0.83, P = 0.66; χ(2) = 0.20, P = 0.66). The polymorphisms of IL-2-330 were not significantly associated with abnormal ALT (χ(2) = 1.10, P = 0.58; χ(2) = 0.08, P = 0.78)., Conclusion: These results suggested that IL-2-330 TT/T was associated with an increased risk, but IL-2-330 GG/G was associated with reduced risk of persistent HBV and/or HCV infection, and with the development of mild CH, moderated/severe CH, and cirrhosis.

Objective: To explore the association between polymorphisms of interferon-gamma gene intron 1 at position +874 (IFN-gamma+874) gene and the susceptibility of HBV and/or HCV infection with different clinical outcomes., Methods: IFN-gamma+874 gene SNP were detected in 277 subjects including 79 chronic HBV/HCV coinfections, 69 individuals only with HBV infection, 55 individuals only with HCV infection and 74 controls, by sequence specific primers-PCR (SSP-PCR). Hepatocellular injury as suggested by alanine aminotransferase (ALT) was detected by Beckman LX-20. The status of viral particles in serum was determined by RT-nPCR. The possible association of the polymorphism of IFN-gamma+874 with the susceptibility of HBV and/or HCV infection and the outcome of these infections were analyzed., Results: (1) IFN-gamma+874 AA frequency in individuals with chronic HBV, HCV, HBV/HCV coinfections were significant higher than that in controls (chi(2) = 16.15, P = 0.01);OR (95%CI) of IFN-gamma+874 AA in chronic infection with HBV, HCV, HBV/HCV coinfections appeared to be 2.70 (1.24 - 5.92), 3.22 (1.43 - 7.25) and 4.02 (1.88 - 8.55) compared with +874 TA. No significant differences were found among HBV, HCV, HBV/HCV coinfections (chi(2) = 1.97, P = 0.73). There were no significant association of IFN-gamma+874 A/T allele frequency with HBV and/or with HCV infection (chi(2) = 4.87, P = 0.18). (2) The clinical outcomes of mild chronic hepatitis (CH), moderate/severe CH and cirrhosis with HBV and/or HCV infection were associated with IFN-gamma+874 AA [chi(2) = 14.17, P = 0.03; OR = 3.09 (1.51 - 6.33), 3.85 (1.70 - 8.70), 3.14 (1.08 - 9.17)]. No significant relationships were found between IFN-gamma+874 A/T allele frequency and the clinical outcome of HBV/HCV infection (chi(2) = 6.07, P = 0.11). (3) There were no significant associations of IFN-gamma+874 genotype/allele frequency with HCV duplication (chi(2) = 2.36, P = 0.31). (4) There were no significant associations of IFN-gamma+874 genotype/allele frequency with abnormal ALT (chi(2) = 0.15, P = 0.93)., Conclusion: These results suggested that polymorphisms in the IFN-gamma+874 had some influence on chronic HCV and/or HBV infection, and on the outcome of HCV and/or HBV infections. IFN-gamma+874 AA genotype and T allele were possible risk to chronic HBV and/or HCV infections and to the outcomes of HBV and/or HCV infection. However, IFN-gamma+874 TA genotype might serve as possible protective factors to them.

Aim: To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection., Methods: Samples were obtained from 203 patients infected with HBV and/or HCV while donating plasma in 1987, and 74 controls were obtained from a rural area of North China. Antibodies to HBV or HCV antigens were detected by enzyme-linked immunoassay. The presence of viral particles in the serum was determined by nested reverse-transcriptase polymerase chain reaction (PCR). Hepatocellular injury, as revealed by alanine aminotransferase (ALT) and aspartate aminotransferase level, was detected by a Beckman LX-20 analyzer. DNA was extracted from blood cells. Then, the single nucleotide polymorphisms of IL-2-330, IFN-gamma+874, IL-10-1082/-592 and IL-4-589 were investigated by restriction fragment length polymorphism-PCR or sequence specific primer-PCR., Results: Persistent infection with HBV, HCV, and HBV/HCV coinfection was associated with IL-2-330 TT genotype and T allele, IFN-gamma+874 AA genotype, and IL-10-1082 AA genotype. The clinical outcome of HBV and/or HCV infection was associated with IL-2-330 TT genotype and T allele, IFN-gamma+874 AA genotype, and IL-10-1082 AA genotype. IL-2-330 GG genotype frequency showed a negative correlation with clinical progression, IL-10-1082 AA genotype frequency showed a positive correlation and IL-10-1082 AG genotype frequency showed a negative correlation with clinical progression. HCV RNA positive expression was associated with IL-10-1082 AA genotype and the A allele frequency. Abnormal serum ALT level was associated with IL-10-592 AC genotype frequency and IL-4-589 CC genotype, CT genotype, and the C allele., Conclusion: These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage.

As compared with the ordinary landfill cover material, clay soil, the effect of methane stress on oxidation rate and microbial community structure was investigated in waste soil (material from biologically treated municipal solid waste). The results showed that the moisture content of the clay soil was low, due to the low water retaining capacity. As environmental temperature and rainfall changed, the clay soil caked and inhibited methanotrophs growth. However, with a high organic matter, water-holding capacity and porosity, the waste soil provided a favor condition for methanotrophs growth and propagation. After exposure to methane flow for 120 days, methane oxidation potential in the middle and bottom layers of the waste soil column increased to 11.25-13.48 micromol/(g x h), which was 10.4-24.5 times higher than that in clay soil column. The topsoils were both found to be dried and inhibit methane oxidation. Methane oxidation (removal) efficiency by the waste soil column reached 48.3% at the end of the experiment, which was 5-6 times higher than that by the clay soil column. The amounts of the phospholipid fatty acid (PLFA) biomarks 16:1 omega 8c and 18:1 omega 8c for Type I and II methanotrophs, respectively, showed that a strong linear relationship was observed between methane oxidation potential and PLFA 18:1 omega 8c content in soil samples.

Objective: To study the clinical classification and characteristics as well as prognosis of mushroom poisoning., Methods: We retrospectively analyzed 191 papers published domestically for 3466 cases of mushroom poisoning from 1995 to 2004 and studied the Xinqiao Hospital data of 172 cases of mushroom poisoning treated from 1980 through 2004. We made a retrospective investigation and clinical classification of all the 3638 cases of mushroom poisoning., Results: Among the 3638 patients, clinical manifestations as gastroenteritis were found in 571, all of them were cured. The most common symptoms were those of acute renal failure being found in 1450 cases; 1414 were cases (97.5%) and 36 died (2.5%). Symptoms of toxic hepatitis were found in 1010 cases, 841 were cases (83.3%) and 169 died (16.7%). Psychoneurological disorder was manifested in 214 cases; 197 were cases (92.1%) and 17 died (7.9%). Erythrolysis was found in 73 cases; 71 were cases (97.3%) and 2 died (2.7%). The therapeutic effect and prognosis of mushroom poisoning with different clinical manifestation varied very significantly (P < 0.001). Of the 320 cases clinically unclassified, multiple organ dysfunction syndrome was found in 222 cases; 98 were cases (44.1%) and 124 died (55.9%). Definite classification could not be made in 98 cases; 90 were cases (91.8%) and 8 died (8.2%)., Conclusions: The clinical classification of mushroom poisoning was usually of four types as described in the textbooks or special articles, but it should be of five types according to the analysis of the data of the present study, i.e. gastroenteritis type, acute renal failure type, toxic hepatitis type, psychoneurological disorder type and erythrolysis type. It is not clear whether there is a mixed type or not. Further investigation is needed in this respect.

Streptomyces hygroscopicus 17997 produces the antiviral and antitumor ansamycin antibiotic, geldanamycin. Studies on geldanamycin biosynthetic pathway will provide good tools for genetic manipulation of the antibiotic-producing strain to improve the productivity or to facilitate making novel geldanamycin analogs. The structural similarities between geldanamycin and ansamycins such as rifamycin or ansatrienin suggest that both geldanamycin and ansamycins has a closely related pathways of biosynthesis and that biosynthetic system for geldanamycin is similar to the one of type I polyketide synthase (PKS) enzyme system. To explore the possible PKS genes involved in geldanamycin biosynthesis, the degenerate primers were designed according to the conserved sequence of KS-AT region from erythromycin and oleandomycin type I PKS genes. Cosmids containing multiple PKS genes (pCGBK2,4,6,10,11,18) were obtained by hybridization with the PCR products, which were amplified from S. hygroscopisus 17997 genomic DNA. The designed primers above were used for PCR. Development of a Streptomyces temperate phage phiC31-derivative KC515( tsrR) transduction system was carried out for identification of cosmids containing the PKS gene related to biosynthesis of geldanamycin. Several factors, mainly the Ca2+ and Mg + concentrations in different culture media affecting the frequency of gene transfection, were optimized .Transfection efficiency could reach up to 10(3) /microg DNA on YMG medium supplemented with 10mmol/L MgSO4. Reversely, the transfection efficiency decreased when YMG medium was supplemented with 30mmol/L MgSO4. Gene transfection system based on the integration-defective phage KC515 had been established for S. hygroscopicus17997. Recombinant phages (ph111, 258, 287, 116, 105) were constructed by insertion of the homologous to PKS gene fragments into the KC515 phage vector. Gene disruption experiments were performed by transduction of recombinant phages into S. hygroscopicus 17997 genome, and disruption of geldanamycin production was observed as a result of homologous recombination between the cloned insert in recombinant phage and the S. hygroscopicus 17997 genome by integration. Thiostrepton resistant transductants were selected and integration event was analyzed by Southern hybridization. The fermentation broth extracts from five resistant transductants were analyzed by TLC and HPLC. The results showed that only G16 mutant failed to produce geldanamycin. This result showed that the integration of the insert DNA fragment in recombinant phage phl6 into the chromosome of S. hygroscopicus disrupted the expression of the geldanamycin biosynthetic genes. The original cosmid pCGBK10 containing this cloned insert was predicted to encode PKS genes in the geldanamycin biosynthesis. This study laid the foundation for cloning the PKS genes involved in geldanamycin biosynthetic gene cluster from S. hygroscopicus 17997.