[Current status and prospects of genetic research on IgA nephropathy].

IgA nephropathy is the most common primary glomerulonephritis worldwide, and genetic factors may play an important role in its pathogenesis. Following candidate gene association analysis and genome-wide linkage study, genome-wide association studies (GWAS) have found multiple susceptibility genes related to the pathogenesis and clinical phenotype of IgA nephropathy. Meanwhile, structural variation and epigenetic changes are also closely related to IgA nephropathy. Genetic variants have been found to explain about 11% of its heritability. In the current era of genomic medicine, how to find more susceptible genes/loci, whole genome sequencing studies (WGS) provide clues to further understand the genetic variation of IgA nephropathy. How to find the cell type-specific susceptibility genes associated with IgA nephropathy, multi-omics studies will conduct comprehensive analysis via single-cell sequencing, expression quantitative trait locus (eQTL) and genomics to find the pathogenic genes and offer insights into the development of targeted drugs, which will be the trend and direction of future research.

Evidence for Band Renormalizations in Strong-Coupling Superconducting Alkali-Fulleride Films.

There has been a long-standing debate about the mechanism of the unusual superconductivity in alkali-intercalated fullerides. In this Letter, using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structures of superconducting K_{3}C_{60} thin films. We observe a dispersive energy band crossing the Fermi level with the occupied bandwidth of about 130 meV. The measured band structure shows prominent quasiparticle kinks and a replica band involving the Jahn-Teller active phonon modes, which reflects strong electron-phonon coupling in the system. The electron-phonon coupling constant is estimated to be about 1.2, which dominates the quasiparticle mass renormalization. Moreover, we observe an isotropic nodeless superconducting gap beyond the mean-field estimation (2Δ/k_{B}T_{c}≈5). Both the large electron-phonon coupling constant and large reduced superconducting gap suggest a strong-coupling superconductivity in K_{3}C_{60}, while the electronic correlation effect is suggested by the observation of a waterfall-like band dispersion and the small bandwidth compared with the effective Coulomb interaction. Our results not only directly visualize the crucial band structure but also provide important insights into the mechanism of the unusual superconductivity of fulleride compounds.

[Concerns about COVID-19-associated liver injury].

Patients infected with 2019-nCoV/SARS-CoV-2 are usually accompanied with liver injury, which may correlates with the severe forms of the disease. The pathogenesis of COVID-19-associated liver injury is not only related to the underlying liver diseases, viral cholangitis, systemic inflammatory response, and hypoxic liver injury, but also to multiple factors that lead to liver injury in patients. Therefore, during the course of treatment, the patient's liver function should be closely monitored, and attention should be paid to the occurrence of drug-induced liver injury.

[Current status of hyperkalemia in dialysis patients in China].

Objective: To investigate the prevalence and associated factors of hyperkalemia in dialysis patients. Methods: Patients underwent hemodialysis (HD) and peritoneal dialysis (PD) from multi-center databases were recruited from January 2017 to December 2019, and those aged ≥18 years and with dialysis duration ≥3 months were included to analyze the prevalence and related factors of hyperkalemia. Results: A total of 12 364 patients were enrolled in the study, and 6 836 cases were men. The average age of the patients was (51±15) years. Among these patients, 4 230 cases underwent HD while 8 134 received PD. Hyperkalemia was detected in 20.7% (2 554/12 364) of the patients while hypokalemia was found in 17.0%(2 102/12 364) of the patients. Multivariate logistic regression showed that HD (OR=2.25, 95%CI: 1.54-3.30), diabetes mellitus (DM) (OR=1.65, 95%CI: 1.17-2.32), high body mass index (BMI) (OR=1.06, 95%CI: 1.03-1.09), high levels of serum albumin (OR=1.04, 95%CI: 1.01-1.07) and phosphorus (OR=3.12, 95%CI: 2.44-4.00), low levels of serum bicarbonate (OR=0.89, 95%CI: 0.87-0.92), triglycerides (OR=0.76, 95%CI: 0.68-0.85) and creatinine (OR=0.95, 95%CI: 0.90-0.99), usage of angiotensin converting enzyme inhibitor/Angiotensin Ⅱ receptor antagonist (ACEI/ARB, OR=1.38, 95%CI: 1.11-1.72) and beta-blocker (OR=1.32, 95%CI: 1.07-1.64) were associated with hyperkalemia. Conclusions: Hyperkalemia occurred in 20.7% of the dialysis patients. HD, DM, high BMI, high levels of serum albumin and phosphorus, low levels of serum bicarbonate, triglycerides and creatinine, use of ACEI/ARB were associated with hyperkalemia.

Ocnus is essential for male germ cell development in Drosophila melanogaster.

The ocnus (ocn) gene encodes a protein abundant in the testes, implying its role in testis development. When Drosophila melanogaster is infected with the endosymbiont wMel Wolbachia, which affects the spermatogenesis of its hosts, ocn is downregulated in the third-instar larval testes, suggesting a role of ocn in spermatogenesis. In this study, we knocked down ocn in the testes and found that the hatch rates of embryos derived from ocn-knockdown males were significantly decreased, and 84.38% of the testes were much smaller in comparison to controls. Analysis of the smaller testes showed no germ cells but they had an extended hub. Using RNA-sequencing (RNA-Seq), we identified 69 genes with at least a twofold change (q-value < 5%) in their expression after ocn knockdown; of these, eight testes-specific and three reproduction-related genes were verified to be significantly downregulated using quantitative reverse transcription-PCR. Three genes (orientation disruptor, p24-2 and CG13541) were also significantly downregulated in the presence of Wolbachia. Furthermore, 98 genes were not expressed when ocn was knocked down in testes. These results suggest that ocn plays a crucial role in male germ cell development in Drosophila, possibly by regulating the expression of multiple spermatogenesis-related genes. Our data provide important information to help understand the molecular regulatory mechanisms underlying spermatogenesis.

Carcass traits, meat quality, antioxidant status and antioxidant gene expression in muscle and liver of Hu lambs fed perilla seed.

The effects of perilla (Perilla frutescens L.) seed on carcass traits, meat quality, antioxidant status and antioxidant gene expression in the liver and muscle of Hu lambs were investigated in this study. Sixty Hu lambs (23.02 ± 1.36 kg) were randomly divided into four experimental groups receiving diets containing 0%, 5%, 10% or 15% perilla seed (CD, 5%PFSD, 10%PFSD and 15%PFSD, respectively). The addition of perilla seed had no significant impacts on carcass traits (p > .05). There were no differences in pH, meat colour, drip loss, cooking loss or shear force among the four treatments (p > .05). Addition of perilla seed increased (p < .05) deposition of intramuscular lipids but had no effect on other chemical components in the longissimus dorsi (LD) (p > .05). The 15%PFSD diet decreased the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content in the liver (p < .05 for both) but increased the activity of these antioxidant enzymes in LD (p < .05 for both). Compared to CD, addition of perilla seed increased superoxide dismutase (SOD) and glutathione peroxidase (GPX) expression in the liver and LD (p < .05 for all). These results indicate that perilla seed supplementation in lambs' diets can increase deposition of intramuscular lipids and improve muscular oxidative status and meat quality.

Optimal expression and purification of sapelovirus A structural protein VP1, and its immunogenicity in mice.

Sapelovirus A (SV-A) is a positive-sense single-stranded RNA virus which is associated with acute diarrhea, pneumonia and reproductive disorders. The virus capsid is composed of four proteins, and the functions of the structural proteins are unclear. In this study, we expressed SV-A structural protein VP1 and studied its antigenicity and immunogenicity. SDS-PAGE analysis revealed that the target gene was expressed at high levels at 0.6 mM concentration of IPTG for 24 h. The mouse polyclonal antibody against SV-A VP1 protein was produced and reached a high antiserum titer (1: 2,048,000). Immunized mice sera with the recombinant SV-A VP1 protein showed specific recognition of purified VP1 protein by western blot assay and could recognize native SV-A VP1 protein in PK-15 cells infected with SV-A by indirect immunofluorescence assay. The successfully purified recombinant protein was able to preserve its antigenic determinants and the generated mouse anti-SV-A VP1 antibodies could recognize native SV-A, which may have the potential to be used to detect SV-A infection in pigs.

Cancer deaths and cases attributable to lifestyle factors and infections in China, 2013.

BACKGROUND: The burden of cancer in China is high, and it is expected to further increase. Information on cancers attributable to potentially modifiable risk factors is essential in planning preventive measures against cancer. We estimated the number and proportion of cancer deaths and cases attributable to ever-smoking, second-hand smoking, alcohol drinking, low fruit/vegetable intake, excess body weight, physical inactivity, and infections in China, using contemporary data from nationally representative surveys and cancer registries. METHODS: The number of cancer deaths and cases in 2013 were obtained from the National Central Cancer Registry of China and data on most exposures were obtained from the China National Nutrition and Health Survey 2002 or 2006 and Global Adult Tobacco Smoking 2010. We used a bootstrap simulation method to calculate the number and proportion of cancer deaths and cases attributable to risk factors and their corresponding 95% confidence intervals (CIs), allowing for uncertainty in data. RESULTS: Approximately 718 000 (95% CI 702 100-732 200) cancer deaths in men and 283 100 (278 800-288 800) cancer deaths in women were attributable to the studied risk factors, accounting for 52% of all cancer deaths in men and 35% in women. The numbers for incident cancer cases were 952 500 (95% CI 934 200-971 400) in men and 442 700 (437 200-447 900) in women, accounting for 47% of all incident cases in men and 28% in women. The greatest proportions of cancer deaths attributable to risk factors were for smoking (26%), HBV infection (12%), and low fruit/vegetable intake (7%) in men and HBV infection (7%), low fruit/vegetable intake (6%), and second-hand smoking (5%) in women. CONCLUSIONS: Effective public health interventions to eliminate or reduce exposure from these risk factors, notably tobacco control and vaccinations against carcinogenic infections, can have considerable impact on reducing the cancer burden in China.

Molecular cloning and characterization of a short peptidoglycan recognition protein from silkworm Bombyx mori.

Peptidoglycan is the major bacterial component recognized by the insect immune system. Peptidoglycan recognition proteins (PGRPs) are a family of pattern-recognition receptors that recognize peptidoglycans and modulate innate immune responses. Some PGRPs retain N-acetylmuramoyl-L-alanine amidase (Enzyme Commission number: 3.5.1.28) activity to hydrolyse bacterial peptidoglycans. Others have lost the enzymatic activity and work only as immune receptors. They are all important modulators for innate immunity. Here, we report the cloning and functional analysis of PGRP-S4, a short-form PGRP from the domesticated silkworm, Bombyx mori. The PGRP-S4 gene encodes a protein of 199 amino acids with a signal peptide and a PGRP domain. PGRP-S4 was expressed in the fat body, haemocytes and midgut. Its expression level was significantly induced by bacterial challenges in the midgut. The recombinant PGRP-S4 bound bacteria and different peptidoglycans. In addition, it inhibited bacterial growth and hydrolysed an Escherichia coli peptidoglycan in the presence of Zn2+ . Scanning electron microscopy showed that PGRP-S4 disrupted the bacterial cell surface. PGRP-S4 further increased prophenoloxidase activation caused by peptidoglycans. Taken together, our data suggest that B. mori PGRP-S4 has multiple functions in immunity.

Cloning and functional identification of moricins from the diamondback moth, Plutella xylostella (L.).

Antimicrobial peptides (AMPs) are small-molecule peptides that play crucial roles in insect innate immune responses. To better understand the function of AMPs in Plutella xylostella, one of the main pests of cruciferous vegetables, three full-length cDNAs encoding moricins were cloned from Pl. xylostella. Two variants of the moricin named PxMor2 and PxMor3 were heterologously expressed and purified. A secondary structure analysis using circular dichroism demonstrated that the two peptides adopted an α-helical structure in the membrane-like environment, but in aqueous solution, they were present in random coiled conformation. Antimicrobial activity assays demonstrated that PxMor2 exhibited high activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli; however, PxMor3 only demonstrated high activity against E. coli. Scanning electron microscopy and confocal laser-scanning microscopy analyses suggest that PxMors can lead to the disruption of bacterial membrane, which might be the mechanism by which PxMors inhibit bacterial growth. This study contributes to the understanding of Pl. xylostella AMPs and immune responses, and also enriches the knowledge of insect moricin.

Combination of LINE-1 hypomethylation and RASSF1A promoter hypermethylation in serum DNA is a non-invasion prognostic biomarker for early recurrence of hepatocellular carcinoma after curative resection.

Hepatocarcinogenesis, a multistep process, involves not only genetic mutations but also epigenetic alterations. Widespread of global DNA hypomethylation is accompanied with specific regional hypermethylation especially at tumor suppressor genes' promoters. The aim of this study is to determine the efficacy of combined DNA methylation analysis of a global DNA methylation marker - LINE-1 and a tumor suppressor gene highly associated with the malignancy of HCC- RASSF1A in serum as a novel prognostic marker for diagnosis of early recurrence after curative resection.LINE-1 was hypomethylated in 66.7% (70/105) and RASSF1A promoter was hypermethylated in 73.3% (77/105) of HCC serum DNA samples by methylation specific PCR, but in none of the healthy controls: LINE-1 hypometylation (0/50) and RASSF1A hypermethylation (0/50). A significant association was found between LINE-1 hypomethylation and clinical pathologic features including HBsAg positivity (p=0.009), tumor size (p=0.001) and AFP levels (p<0.001). Besides, significant correlation was detected between RASSF1A promoter hypermethylation and lymph nodes metastasis (p=0.045).The results of Kaplan-Meier estimates of survival suggested that LINE-1 hypomethylation was highly associated with poor survival of patients (disease-free survival p=0.002, overall survival p=0.0123). More importantly, co-evaluation of LINE-1 hypomethylation and RASSF1A promoter hypermethylation was found to be significantly correlated to early recurrence and poor prognosis (disease-free survival p=0.0001, overall survival p=0.05) in patients after curative resection.In conclusion, our study showed that the combined examination of LINE-1 hypomethylation and RASSF1A promoter hypermethylation was effective in predicting early recurrence of HCC after curative resection. Patients with dual positivity of LINE-1 hypomethylation and RASSF1A promoter hypermethylation should be supplied with more intensive care and close follow-up after they undergo tumor resection.

[Effect of molar ligation and local Porphyromonas gingivalis inoculation on alveolar bone loss in the mouse].

OBJECTIVE: To compare the extent and time course of alveolar bone loss and osteoclast activation in two murine models of periodontal disease: molar ligation and Porphyromonas gingivalis (P. gingivalis) oral inoculation. METHODS: A split-mouth design was applied to two groups of mice (C57BL6, 6-8 weeks old, n=24 in both groups), resulting in four treatment groups: (1) Control group: unligated upper right 2nd molars receiving CMC only, (2)Ligature group: ligation of a 9-0 suture around the upper left 2nd molar, (3) P. gingivalis group: unligated upper right 2nd molar receiving P. gingivalis challenge only, (4)Ligature+P.gingivalis group: ligation of the upper left 2nd molar in combination with oral inoculation with 109 colony-forming units(CFU) P. gingivalis. Alveolar bone loss was measured as the cementoenamel junction and alveolar bone crest (CEJ-ABC) distance. In the study, 48 C57BL6 mice were designed and treated as described above, and osteoclasts were counted on histological sections following tartrate-resistant acid phosphatase (TRAP) staining and counts were normalized to alveolar bone surface distance. Then 36 C57BL6 mice were investigated, of which 30 were ligated a 9-0 silk ligature around the 2nd molar in the left maxillary quadrant and 6 were not ligated. After ligation for 1 week, the ligatures in 12 mice were taken off for either 1 week or 2 weeks. The CEJ-ABC distance of the 6 mice without ligation was baseline. The CEJ-ABC distances were measured and analyzed. The data were analyzed with one-way ANOVA. RESULTS: Molar ligation induced marked alveolar bone loss after 3, 6, 9 and 12 weeks [(0.16±0.04) mm, (0.16±0.02) mm, (0.18±0.03) mm, (0.17±0.02) mm], vs. corresponding controls [(0.09±0.03)mm,(0.10±0.01)mm,(0.12±0.04)mm,(0.12±0.01)mm] and P. gingivalis group [(0.09±0.03)mm, (0.12±0.01)mm,(0.12±0.02)mm,(0.10±0.01)mm], P<0.05. Combined treatment with molar ligation and P. gingivalis did not further increase the CEJ-ABC distance. Evidence for osteoclast activation was found one day after molar ligation, and TRAP-positive cell numbers peaked on day 3 (12±4 vs. control 2±2, P<0.01). After taking off ligature following ligation for 2 weeks, it showed significantly regrowth of alveolar bone compared with that before removal of the ligature on day 7 [(0.07±0.02)mm vs. (0.13±0.01)mm, P<0.01]. CONCLUSION: Molar ligation is a rapid and effective way to induce periodontal bone loss in mice. Osteoclast activation occurs within 24 hours of ligature placement, and the extent of bone loss well exceeds that of the P.gingivalis-induced bone loss. Removing ligature after periodontal disease might help bone regeneration by regrowth of the alveolar bone.

Occidiofungin is an important component responsible for the antifungal activity of Burkholderia pyrrocinia strain Lyc2.

AIMS: To identify the taxonomy of tobacco rhizosphere-isolated strain Lyc2 and investigate the mechanisms of the antifungal activities, focusing on antimicrobials gene clusters identification and function analysis. METHODS AND RESULTS: Multilocus sequence typing and 16S rRNA analyses indicated that strain Lyc2 belongs to Burkholderia pyrrocinia. Bioassay results indicated strain Lyc2 showed significant antifungal activities against a broad range of plant and animal fungal pathogens and control efficacy on seedling damping off disease of cotton. A 55·2-kb gene cluster which was homologous to ocf gene clusters in Burkholderia contaminans MS14 was confirmed to be responsible for antifungal activities by random mutagenesis; HPLC was used to verify the production of antifungal compounds. Multiple antibiotic and secondary metabolized biosynthesis gene clusters predicated by antiSMASH revealed the broad spectrum of antimicrobials activities of the strain. CONCLUSIONS: Our results revealed the mechanisms of antifungal activities of strain Lyc2 and expand our knowledge about production of occidiofungin in the bacteria Burkholderia. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the mechanisms of antifungal activities of strain Lyc2 has contributed to discovery of new antibiotics and expand our knowledge of production of occidiofungin in the bacteria Burkholderia.

Serum uric acid predicts cardiovascular mortality in male peritoneal dialysis patients with diabetes.

BACKGROUND AND AIMS: Serum uric acid may predict mortality in diabetic patients and dialysis patients. However, the relationship between serum uric acid and prognosis in diabetic peritoneal dialysis (PD) patients is unclear. METHODS AND RESULTS: We conducted a cohort study of 1278 incident PD patients, (mean age 47.6 years), of which 328 (25.7%) had diabetes and 289 (22.6%) had diabetic nephropathy. During a median follow-up period of 30.7 months, 231 deaths occurred, of which 126 were ascribed to cardiovascular events. Mean serum uric acid was lower for diabetic patients than non-diabetic patients (6.8 ± 1.3 vs. 7.4 ± 1.4 mg/dL, respectively; P < 0.001). Cox regression models were adjusted for glycated hemoglobin, dialysis-related factors, traditional risk factors, and treatments. After adjustments, the highest sex-specific tertile of uric acid was associated with an increased risk of cardiovascular mortality (HR, 2.26; 95% CI, 1.14-4.48) compared to the lowest tertile in diabetic patients. Adjusted HRs per 1 mg/dL higher uric acid for all-cause and cardiovascular mortality were 1.09 (95% CI, 0.91-1.32) and 1.42 (95% CI, 1.13-1.79) for diabetic men and 1.06 (95% CI, 0.83-1.35) and 1.12 (95% CI, 0.78-1.61) for diabetic women, respectively. Elevated serum uric acid predicted a higher risk of all-cause and cardiovascular mortality in non-diabetic men but not in non-diabetic women. CONCLUSIONS: Elevated serum uric acid is an independent predictor of cardiovascular mortality in diabetic male PD patients.

Genetic background of Escherichia coli isolates from peritoneal dialysis patients with peritonitis and uninfected control subjects.

Escherichia coli is the most common cause of Gram-negative peritonitis resulting in peritoneal function deterioration as well as poor clinical outcome in continuous ambulatory peritoneal dialysis (PD) patients. In this study, we analyzed the phylogenetic background and genetic profile of the E. coli isolates and sought to determine the characteristics of specific bacteria associated with peritonitis. E. coli isolates from 56 episodes of peritonitis in 46 PD patient cases and rectal isolates from 57 matched PD control patient cases were compared for both phylogenetic groups and the presence of virulence factors (VFs). There were no significant differences in terms of demographic data between the peritonitis and control groups. Peritonitis isolates exhibited a significantly greater prevalence of 8 VFs. In multivariate logistic regression analysis, kpsMT II (group 2 capsule synthesis) was the strongest VF predictor of peritonitis (OR = 8.02; 95%CI = 3.18-20.25; P < 0.001), followed by traT (serum-resistance-associated outer membrane protein) (OR = 3.83; 95%CI = 1.33-11.03; P = 0.013). The pathogenic groups of E. coli contained a higher concentration of individual VFs compared to the commensal groups. The prevalence of pathogenic E. coli was much higher in peritoneal isolates than rectal isolates (64.3 vs 31.6%, P = 0.001). Our results indicate that the E. coli peritonitis and rectal isolates are different in PD patients. The specific VFs associated with peritonitis isolates may directly contribute to the pathogenesis of peritonitis.

[Application and effect observation of hybrid aortic stent grafts for endovascular repair in the treatment of complicated infrarenal abdominal aortic aneurysm].

OBJECTIVE: To evaluate the effectiveness of the hybrid graft technique for complicated infrarenal abdominal aortic aneurysms (AAAs). METHODS: The clinical data of 183 patients who underwent endovascular aneurysm repair (EVAR) for AAA with challenging anatomy at Zhongshan Hospital Affiliated to Shanghai Fudan University from 2010 to 2015 were retrospectively analyzed. Endografts were divided into two groups: Hybrid Group (28 cases) used more than one type of stent graft, and Standard Group (110 cases) used only one stent graft type. Patients were recommended to undergo CT angiography at 1, 3, 6, 12 month after the procedure. Clinical data were analyzed with a focus on postoperative hospital stay, endoleak, limb occlusion, complications of approach, complications of system, converted to open operation and secondary intervention. RESULTS: Technical success was achieved in all patients in both groups. Compared with hybrid group and standard group, there was no difference in postoperative hospital stay ((5.35±2.99) and (5.92±3.70) days, t=0.753, P>0.05). During the follow up, there was no difference in endoleak (10.7% and 18.2%), limb graft occlusion (3.6% and 10.9%), complications of approach (0 and 1.8%), complications of system (7.1% and 0.9%), converted to open operation (0 and 0.9%) between two groups (χ(2)=0.896, 1.408, 0.517, 4.078, 0.256, all P>0.05). However, there was statistically significant difference in secondary intervention between two groups (3.6% and 19.1%, 2=4.011, P<0.05). CONCLUSION: The use of hybrid stent graft in patients with unfavorable neck and iliac artery anatomy AAA is feasible, and it could improve the postoperative outcomes such as secondary intervention rate.

[Effect of hypoxia-inducible factor-2α/stearoyl-CoA desaturase-1 pathway on biological behaviors of hepatoma cells induced by hypoxia].

Objective: To investigate whether hypoxia-inducible factor-2α (HIF-2α) affects the biological behaviors of hepatoma cells through regulating stearoyl-CoA desaturase-1 (SCD1) in a hypoxic environment. Methods: HepG2 and SMMC-7721 cells were exposed to 1% O2 to establish the hypoxic models. After hepatoma cells were stimulated by hypoxia for 0, 3, 6, 12, and 24 hours, fluorescent quantitative PCR and Western blot were used to measure the mRNA and protein expression of HIF-2α and SCD1 over time. HIF-2α interfering plasmids and SCD1 inhibitor CAY10566 were used to divide the cells into blank group (nomoxia), hypoxic group (1% O2 for 12 h), hypoxic negative control group (negative HIF-2α plasmid+1% O2 for 12 h), hypoxic interference group (HIF-2α interfering plasmid+1% O2 for 12 h), hypoxic CAY group (CAY10566 10 µmol+1% O2 for 12 h), and hypoxic interference+CAY group (HIF-2α interfering plasmid+CAY10566 10 µmol+1% O2 for 12 h). Western blot was used to measure the protein expression of HIF-2α and SCD1 in hepatoma cells, CCK8 assay was used to measure the proliferative capacity of hepatoma cells, Annexin-V/PE flow cytometry was used to measure the apoptosis of hepatoma cells, and transwell invasion assay was used to measure the invasion of hepatoma cells. A one-way analysis of variance was used to compare the means of multiple samples. Results: Both HepG2 and SMMC-7721 cells showed increasing mRNA and protein expression of HIF-2α and SCD1 over the time of hypoxic induction. After the expression of HIF-2α was downregulated in a hypoxic environment, hepatoma cells showed a significant reduction in the protein expression of SCD1; inhibition of SCD1 expression had no significant effect on the protein expression of HIF-2α in hepatoma cells. After HIF-2α was interfered with and SCD1 expression was inhibited, HepG2 and SMMC-7721 cells showed significantly greater reduction in the protein expression of SCD1 than those with HIF-2α or SCD1 inhibition alone (0.53±0.04 vs 1.12±0.04 or 1.12±0.04; 0.44±0.10 vs 0.90±0.10 or 0.99±0.13) (HIF-2α: FhepG2 = 1026.89, PhepG2 = 0.00, FSMMC-7721 = 2186.22, PSMMC-7721 = 0.00; SCD1: FhepG2 = 1347.93, PhepG2 = 0.00, FSMMC-7721 = 46.43, PSMMC-7721 = 0.00). Inhibition of the expression of HIF-2α or SCD1 reduced the proliferation and invasion of HepG2 and SMMC-7721 cells and promoted apoptosis (P < 0.05); interference and downregulation of HIF-2α combined with inhibition of SCD1 expression by CAY10566 achieved significantly greater reductions in proliferation and invasion and a significantly greater increase in apoptosis rate of hepatoma cells, compared with inhibition of HIF-2α or SCD1 alone (P <0.05). Conclusion: HIF-2α/SCD1 pathway may be one of the important mechanisms for hypoxia to regulate the energy metabolism of hepatoma cells and affect their biological behaviors.

Analysis of polymorphisms in the FUT1 and TAP1 genes and their influence on immune performance in Pudong White pigs.

FUT1 and TAP1 have been identified as candidate genes that offer resistance against Escherichia coli F18 infection, with the AA genotype in FUT1 and the GG genotype in TAP1 conferring resistance. In order to confirm polymorphisms at FUT1 M307 and TAP1 G729, and evaluate their influence on immunity performance in Pudong White pigs, we performed polymerase chain reaction-restriction fragment length polymorphism analysis, measured immune indices, and compared the results with those observed in Large White pigs. The AA genotype of FUT1 was first discovered in Pudong White pigs and has not been found in other Chinese domestic pig breeds. The frequency of the AA genotype in Pudong White and Large White pigs was 0.018 and 0.052, respectively. The GG genotype of TAP1 was also detected in the two breeds, with a frequency of 0.708 and 0.695, respectively. Chi-square fitness analysis of both genes showed that these loci deviated from Hardy-Weinberg equilibrium in the two breeds (P < 0.05). No significant differences were observed in interleukin-6 (IL-6) and IL-10 levels among the three genotypes at FUT1 and TAP1 in the two breeds (P > 0.05). Individuals for all genotypes of TAP1 in both pig breeds had similar TNF-α levels (P > 0.05), implying that Pudong White pigs may have the same ability for hepatocyte inflammatory response and B cell differentiation as Large White pigs. These differences have a degree of influence on Pudong White pig's immune ability to resist F18 or other infections.

Diabetic retinopathy in predicting diabetic nephropathy in patients with type 2 diabetes and renal disease: a meta-analysis.

AIMS/HYPOTHESIS: The aim of this meta-analysis is to determine the predictive value of diabetic retinopathy in differentiating diabetic nephropathy from non-diabetic renal diseases in patients with type 2 diabetes and renal disease. METHODS: Medline and Embase databases were searched from inception to February 2012. Renal biopsy studies of participants with type 2 diabetes were included if they contained data with measurements of diabetic retinopathy. Pooled sensitivity, specificity, positive predictive value, negative predictive value and other diagnostic indices were evaluated using a random-effects model. RESULTS: The meta-analysis investigated 26 papers with 2012 patients. The pooled sensitivity and specificity of diabetic retinopathy to predict diabetic nephropathy were 0.65 (95% CI 0.62, 0.68) and 0.75 (95% CI 0.73, 0.78), respectively. The pooled positive and negative predictive value of diabetic retinopathy to predict diabetic nephropathy were 0.72 (95% CI 0.68, 0.75) and 0.69 (95% CI 0.67, 0.72), respectively. The area under the summary receiver operating characteristic curve was 0.75, and the diagnostic odds ratio was 5.67 (95% CI 3.45, 9.34). For proliferative diabetic retinopathy, the pooled sensitivity was 0.25 (95% CI 0.16, 0.35), while the specificity was 0.98 (95% CI 0.92, 1.00). There was heterogeneity among studies (p < 0.001), and no publishing bias was identified. CONCLUSIONS/INTERPRETATION: Diabetic retinopathy is useful in diagnosing or screening for diabetic nephropathy in patients with type 2 diabetes and renal disease. Proliferative diabetic retinopathy may be a highly specific indicator for diabetic nephropathy.

Ligation of the intersphincteric fistula tract plus a bioprosthetic anal fistula plug (LIFT-Plug): a new technique for fistula-in-ano.

AIM: Ligation of the intersphincteric fistula tract and reinforcement with a bioprosthetic graft are two recently reported procedures that have shown promise in the treatment of anal fistula. This study was undertaken to validate combining ligation of the intersphincteric fistula tract plus bioprosthetic anal fistula plug and report our preliminary results and experience. METHOD: Twenty-one patients with transsphincteric anal fistula were treated with ligation of the intersphincteric fistula tract plus concurrent bioprosthetic plug of the anal fistula. We evaluated healing time, fistula closure rate and postoperative anal function according to the Wexner continence score. RESULTS: No mortality or major complications were observed. Median operative time was 20 (range 15-40) min. After a median follow-up of 14 (range 12-15) months, the overall success rate was 95% (20/21), with a median healing time of 2 (range 2-3) weeks for external anal fistula opening and 4 (range 3-7) weeks for intersphincteric groove incision. Only 1 (5%) patient reported rare incontinence for gas postoperatively (Wexner score 1). CONCLUSIONS: Ligation of the intersphincteric fistula tract plus a bioprosthetic anal fistula plug is an easy, safe, effective and useful alternative in the management of anal fistula. Further randomized controlled studies are necessary to better evaluate long-term results.