Preliminary study of low-pressure ionization chamber for online dose monitoring in FLASH carbon ion radiotherapy.

The FLASH effect of carbon ion therapy has recently attracted significant attention from the scientific community. However, the radiobiological mechanism of the effect and the exact therapeutic conditions are still under investigation. Therefore, the dosimetry accuracy is critical for testing hypotheses about the effect and quantifying FLASH Radiotherapy. In this paper, the FLASH ionization chamber at low-pressure was designed, and its dose rate dependence was verified with the Faraday cup. In addition, the dose response was tested under the air pressure of the ionization chamber of 10 mbar, 80 mbar and 845 mbar, respectively. The results showed that when the pressure was 10 mbar, the dose linearity was verified and calibrated at the dose rate of ∼50 Gy s-1, and the residuals were less than 2%. In conclusion, the FLASH ionization chamber is a promising instrument for online dose monitoring.

ANTXR1 as a potential prognostic biomarker for hepatitis B virus-related hepatocellular carcinoma identified by a weighted gene correlation network analysis.

BACKGROUND: With high incidence and mortality rates, hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Chronic hepatitis B virus (HBV) infection is a leading cause of HCC, especially for Asians and blacks. However, the molecular mechanisms underlying HBV-related HCC are unclear. This study sought to identify novel prognostic biomarkers and explore the potential pathogenesis of HBV-related HCC. METHODS: The gene expression profiles and corresponding clinical information of HCC from The Cancer Genome Atlas Liver Hepatocellular Carcinoma data set were analyzed by a weighted gene co-expression network analysis. Correlations between the co-expression modules and clinical traits were calculated. Next, key modules associated with HBV infection were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted for the genes in the key modules. The hub genes were identified based on the protein-protein interaction (PPI) network via the Cytoscape. Finally, an overall survival (OS) analysis was performed. RESULTS: The two modules (i.e., the brown and yellow modules) most relevant to HBV infection were constructed. A functional enrichment analysis revealed that the genes in the two modules were mainly enriched in HCC-related pathways, such as the phosphatidylinositol-3-kinase and protein kinase B signaling pathway, focal adhesion, human papillomavirus infection, the Rap1 signaling pathway, and the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. Ten hub genes [i.e., COL3A1, ANTXR1, COL14A1, THBS2, ADAMTS2, AEBP1, PRELP, EMILIN1, DCN and PODN] in the brown module, and 10 hub genes [i.e., USP34, SEC24C, ZNF770, STAG1, TSTD2, PKD1P6, CCNK, GFT2I, NT5C2 and SMG6] in the yellow module were identified. Among the hub genes, ANTXR1 (Anthrax-toxin receptor 1) was significantly correlated with HBV-related HCC patients' OS. CONCLUSIONS: ANTXR1 represents a potential therapeutic target for HBV-related HCC. This study offers novel insights into the molecular mechanisms of HBV-induced tumorigenesis, which needs to be further validated by basic experiments and large-scale cohort studies.

microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4.

Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential role of miR-9-5p in the progression of HCC. Expression of pyruvate dehydrogenase kinase 4 (PDK4) and miR-9-5p was examined in HCC tissues collected from HCC patients and cell lines. The proliferation, migration, invasion, and apoptosis of HCC cells, and levels of oxygen consumption rate, extracellular acidification rate and reactive oxygen species (ROS) as well as the tumorigenicity of transfected cells in vivo were measured after gain- and loss-of-function experiments in HCC cells. It was revealed that miR-9-5p was upregulated, while PDK4 was poorly expressed in HCC tissues and cells, associating with a poor prognosis of HCC patients. miR-9-5p directly targeted PDK4 and could downregulate its expression, thus leading to promoted cell proliferation, invasion and migration, enhanced mitochondrial activity and energy metabolism, and suppressed apoptosis in HCC cells, along with increased tumorigenicity in mouse xenograft models. Altogether, miR-9-5p facilitated mitochondrial energy metabolism of HCC cells by downregulating PDK4, promoting the development of HCC. miR-9-5p and PDK4 may serve as potential therapeutic targets for preventing recurrence and metastasis of HCC.

Comparison of 6-year Follow-up Result of Hybrid Surgery and Anterior Cervical Discectomy and Fusion for the Treatment of Contiguous Two-segment Cervical Degenerative Disc Diseases.

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the mid-term outcomes of hybrid surgery (HS) and anterior cervical discectomy and fusion (ACDF) for the treatment of contiguous two-segment cervical degenerative disc diseases. SUMMARY OF BACKGROUND DATA: HS has become one of the most controversial subjects in spine communities, and the comparative studies of HS and ACDF in the mid- and long-term follow-up are rarely reported. METHODS: From 2009 to 2012, 42 patients who underwent HS (n = 20) or ACDF (n = 22) surgery for symptomatic contiguous two-level cervical degenerative disc diseases were included. Clinical and radiological records, including Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), Visual Analogue Scale (VAS), local cervical lordosis, and range of motion (ROM), were reviewed retrospectively. Complications were recorded and evaluated. RESULTS: Mean follow-up was 77.25 and 79.68 months in HS group and ACDF group, respectively (P > 0.05). Both in HS group and ACDF group, significant improvement for the mean JOA, NDI, and VAS scores was found at 2-week postoperation and at the last follow-up (P < 0.05). However, there were no significant differences between the two groups (P > 0.05). At the last follow-up, the range of motion (ROM) of superior adjacent segments in ACDF group was significantly larger than HS group (P < 0.05), while the ROM of C2-C7 was significantly smaller (P < 0.05). In the HS group, two (10%) sagittal wedge deformities, one (5%) heterotopic ossification, and one (5%) anterior migration of the Byran disc prosthesis were found. No symptomatic adjacent segment degeneration occurred in two groups. CONCLUSION: HS appears to be an acceptable option in the management of contiguous two-segment cervical degenerative disc diseases. It yielded similar mid-term clinical improvement to ACDF, and demonstrated better preservation of cervical ROM. The incidence of postoperative sagittal wedge deformity was low; however, it can significantly reduce the cervical lordosis. LEVEL OF EVIDENCE: 4.

APPL1 acts as a protective factor against podocytes injury in high glucose environment.

APPL1, an intracellular adaptor protein, takes part in numerous metabolic reactions. Although APPL1 plays a key role in glucose metabolism via adiponectin pathway and has been proved associated with type 2 diabetes, little is known about its role in diabetic nephropathy. To explore the role of APPL1 in diabetic nephropathy, we upregulated the expression of APPL1 in cultured mouse podocytes by adenovirus infection and tested the effects of APPL1 overexpression in podocytes treated with high glucose. Here, a mouse podocyte cell line (generated from H-2Kb-tsA58 immortmouse) was cultured and divided into four groups: Group 1 (normal glucose, NG), Group 2 (high glucose, HG), Group 3 (HG and infected with control adenovirus) and Group 4 (HG and infected with Ad-APPL1). Cell vitality of Group 4 is significantly higher than Group 2, but notably lower than Group 1 (P<0.01). The apoptosis rate of Group 4 was much lower (P<0.01) than Group 2 and Group 3. A decrease in phase G0/G1 and an increase in phase S was observed in Group 4 compared with Group 2 (P<0.01). These data suggested the protective role of APPL1 overexpression in high glucose condition. Moreover, the levels of Nephrin, AMPK and p-AMPK were decreased by high-glucose treatment, but increased by APPL1 overexpression. In conclusion, in the experimental high glucose condition, APPL1 acts as a protective factor against podocytes injury through regulating AMPK signaling, and may be a new therapy target for diabetic nephropathy.

Prevalence of nonalcoholic fatty liver disease and its metabolic risk factors in women of different ages and body mass index.

OBJECTIVE: This study aims to investigate the prevalence of nonalcoholic fatty liver disease (NAFLD), to determine the metabolic risk factors of this disease, and to predict nonalcoholic steatohepatitis (NASH) with liver fibrosis in women of different ages and body mass index (BMI). METHODS: In 2010-2011, a cross-sectional survey was conducted among 9,360 women at the health checkup center of Zhongnan Hospital (Wuhan, China). The probability of NASH with liver fibrosis was predicted using BAAT (BMI, age, alanine aminotransferase, and triglycerides) score. RESULTS: The prevalence of NAFLD increased from 5.3% to 18.8% in women younger than 45 years versus women aged 45 to 55 years and rose to 27.8% in women older than 55 years. In obese women, the prevalence of NAFLD was 48.4%. Women older than 45 years and obese women with NAFLD had more unfavorable metabolic risk factors. Multiple regression analyses showed that increased BMI and low aspartate aminotransferase-to-alanine aminotransferase ratio were closely related to NAFLD in women of different ages, whereas increasing BMI, BAAT score, age, high triglycerides, alanine aminotransferase, and low aspartate aminotransferase-to-alanine aminotransferase ratio were all closely related to NAFLD in obese women. The prevalence of NASH with a BAAT index of 3 or higher was 13.2% and 14.9% in women older than 55 years and obese women with NAFLD, respectively. CONCLUSIONS: Obese and postmenopausal women have a high prevalence of NAFLD and severe metabolic disorders. The prevalence of NASH seems to be considerably higher in obese and postmenopausal women with NAFLD.

Sex-specific prevalence of fatty liver disease and associated metabolic factors in Wuhan, south central China.

BACKGROUND: This study aimed to investigate the sex-specific prevalence and metabolic risk factors of fatty liver disease (FLD), and to predict the prevalence of steatohepatitis with liver fibrosis in Wuhan, south central China. METHODS: A cross-sectional study was conducted among 25,032 participants who underwent health checkups from 2010 to 2011 in Zhongnan hospital. RESULTS: The prevalence of FLD was higher among men than among women (31.8 vs. 12.9%, P<0.0001). However, it increased markedly with age among women, and in the age-groups above 60 years, the prevalence was similar between men and women (26.4 vs. 27.6%, P>0.05). FLD was associated with obesity, increased levels of total cholesterol, triglycerides (TG), low-density lipoproteins, serum uric acid, aspartate aminotransferase, alanine aminotransferase, and fasting blood sugar, an aspartate aminotransferase/alanine aminotransferase ratio of less than 1, and a decreased level of high-density lipoprotein in both sexes. Multiple regression analyses showed that obesity, elevated levels of fasting blood sugar, TG, total cholesterol, and alanine aminotransferase, an aspartate aminotransferase/alanine aminotransferase ratio of less than 1, serum uric acid levels, and decreased high-density lipoprotein levels were related to FLD in men, whereas age played a more prominent role in women. The prevalence of steatohepatitis with advanced fibrosis, estimated using the BMI, age, ALT, and TG index (BAAT index), was 2.5% in men and 1.4% in women; more women with FLD had a BAAT score of 3 or higher compared with men (9.0 vs. 6.6%). CONCLUSION: The prevalence of FLD in China is high among men and elderly women and is mainly related to various metabolic parameters. The prevalence of steatohepatitis with advanced fibrosis is considerably high among individuals with FLD.

Prevalence and associated metabolic factors of fatty liver disease in the elderly.

OBJECTIVE: The aim of this study was to investigate the metabolic risk factors for fatty liver disease in the elderly, and determine the prevalence of fatty liver disease in the elderly in Wuhan, central China. METHODS: The study was a case-control study based on all 4226 adults above 60 years of age from a cohort investigated in 2010-11 at the medical examination center of Zhongnan hospital, using 3145 randomly selected adults under 60 years of age from the same cohort as controls. Fatty liver disease (FLD) was identified with ultrasound imaging. The risk factors measured were body mass index (BMI), and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low density lipoprotein (LDL) and serum uric acid (SUA). The probability of steatohepatitis with advanced fibrosis was predicted using a score based on BMI, age, ALT, and TG (BAAT),and using AST/ALT ratio (AAR). RESULTS: FLD was higher in the elderly (26.7%) than in the non-elderly (22.8%) and similar in the elderly between men and women (26.6% vs 27.0%, p>0.05). BMI, TC, TG, LDL, SUA, AST and ALT were all significantly higher in FLD, whereas the level of HDL was markedly lower. Multiple regression analyses showed that obesity, high TC, TG, SUA, low HDL, and elevated ALT, AAR<1 were closely related to the elderly FLD, while male sex, obesity, high TC, TG, low HDL, elevated ALT, AST and AAR<1 were closely related to the non-elderly FLD. The prevalence of steatohepatitis with advanced fibrosis estimated as BAAT index≥3 was 2.4% in all subjects, and was higher in the elderly FLD patients than in the non-elderly FLD patients. CONCLUSION: The prevalence of FLD is higher in the elderly, and is broadly related to the same metabolic risk factors as in the non-elderly. However, female-sex is no longer protective with increasing age, and the prevalence of steatohepatitis with advanced fibrosis is estimated to be considerably higher in the elderly FLD patients than in the non-elderly FLD controls.

Prevalence and risk factors of fatty liver disease in the Shuiguohu district of Wuhan city, central China.

BACKGROUND: Fatty liver disease (FLD) is highly prevalent in Western countries, but recent data have shown that FLD is also emerging in China. AIM: To investigate the prevalence and risk factors of FLD in the Shuiguohu district of Wuhan city, central China, during 1995-2004. METHODS: 12247 individuals (7179 men and 5068 women) over 18 years of age who were living in the area were investigated for FLD in the Zhongnan Hospital of Wuhan University from 1995 to 2004. FLD was determined by the ultrasonographic method. Height, weight, blood pressure, fasting blood sugar, alanine aminotransferase, total cholesterol and triglyceride were determined by routine laboratory methods. RESULTS: The prevalence of FLD was 12.5% in 1995, and rose gradually to 24.5% by 2003-4. The prevalence was twice as high in men (28.1%) as in women (13.8%), and increased with age in females, and males <60 years of age. Multivariate analysis showed that several risk factors were profoundly associated with the prevalence of FLD, including male sex, old age, obesity, hyperlipidaemia (cholesterol or triglyceride), fasting hyperglycemia and hypertension. CONCLUSION: The prevalence of FLD in the Shuiguohu district of Wuhan city, central China, was shown to have increased during the 10-year period, 1995 to 2004. The FLD was found to be closely associated with sex, age, obesity and other metabolic syndrome features.

N-acetyltransferase 2 slow acetylator genotype associated with adverse effects of sulphasalazine in the treatment of inflammatory bowel disease.

AIM: N-acetyltransferase 2 (NAT2) is an important enzyme catalyzing N-acetylation of sulfasalazine (SASP). The aim of the present study was to investigate associations of the genotypes of NAT2 with inflammatory bowel disease (IBD), and with adverse effects of SASP, which is used as the first-line treatment of IBD. PATIENTS AND METHODS: The wildtype allele (NAT2*4) and three variant alleles (NAT2*5B, NAT2*6A and NAT*7B) of the NAT2 gene were determined in 101 patients with IBD (84 patients with ulcerative colitis and 17 patients with Crohn's disease) and 109 healthy controls by the polymerase chain reaction-restriction fragment length polymorphism method. Sixty-eight patients with IBD treated with SASP were followed, and their adverse reactions were recorded. RESULTS: Eleven patients (16%) experienced adverse effects from SASP, including nine cases of sulfapyridine (SP) dose-related adverse effects and two cases of hypersensitivity (skin rash). Patients with the slow acetylator genotypes without the NAT2*4 allele experienced adverse effects more frequently (36%) than those with the fast acetylator genotypes with at least one NAT2*4 allele (11%), but the results were not significantly different (OR of 0.26, 95% CI 0.065 to 1.004; P=0.051). However, those with the slow acetylator genotypes experienced more SP dose-related adverse effects than those with the fast acetylator genotypes (36% versus 8%, OR of 0.17, 95% CI 0.039 to 0.749; P=0.019). CONCLUSIONS: The NAT2 gene polymorphism was not associated with susceptibility to IBD in Chinese populations, but the NAT2 slow acetylator genotypes were significantly associated with SP dose-related adverse effects of SASP in the treatment of IBD.

Association between interleukin-1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population.

BACKGROUND AND AIM: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients. METHODS: Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test. RESULTS: The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases. CONCLUSION: IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.

Distribution of signal transducer and activator of transcription 6 gene G2964A polymorphism in Chinese patients with ulcerative colitis.

BACKGROUND AND AIMS: The signal transducer and activator of transcription 6 (STAT6) gene is located on chromosome 12q13.3-14.1 just within the IBD2 region and is a key transcription factor involved in interleukin (IL)-4 and IL-13-mediated Th2 response. The aim of the present study was to determine distribution of the STAT6 gene polymorphism in Chinese patients with ulcerative colitis. METHODS: The G2964A polymorphism in the 3' untranslated region of the STAT6 gene was studied in 84 unrelated Chinese patients with ulcerative colitis and 176 healthy controls by PCR and the amplification created restriction site method. The results were then compared with those from a Dutch study published previously. RESULT: Significant differences in genotype and allele frequencies of the STAT6 G2964A polymorphism were not found between patients with ulcerative colitis and healthy controls. Subgroups of the patients with ulcerative colitis classified according to the age at onset, sex and location of disease did not differ significantly in the distribution of this polymorphism. However, the genotypes (P < 0.0001, chi-squared = 75.332) and allele frequencies (P < 0.0001, odds ratio = 4.298, 95% confidence interval = 3.070-6.018) were significantly different between the Chinese and Dutch populations. CONCLUSION: The STAT6 G2964A polymorphism is not involved in the genetic susceptibility to ulcerative colitis in Chinese patients.

Matrine improves 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice.

Matrine is an alkaloid found in kinds of Sophora plants mainly including Sophora flavescens, Sophora alopecuroides and Sophora subprotrata. The aim of the present study was to evaluate therapeutic effects of matrine on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Two hours following colonic instillation of TNBS, matrine with several doses was given by gastric gavage once daily for 7 days. Comparing with the 0.9% NaCl-treated mice with TNBS-induced colitis, matrine (10 and 20 mg kg(-1))-treated mice with TNBS-induced colitis were shown improvements of weight loss, macroscopic score, histological score, and myeloperoxidase (MPO) activity. Moreover, treatments with matrine (10 and 20 mg kg(-1)) decreased the up-regulated mRNA and protein levels of tumour necrosis factor-alpha (TNF-alpha) caused by TNBS. Our findings suggest that matrine improves TNBS-induced colitis in mice and the therapeutic mechanism might be related to the reduction of up-regulated colonic TNF-alpha production caused by TNBS.