Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Review of Load Balancing Mechanisms in SDN-Based Data Centers

With the continuous expansion of the data center network scale, changing network requirements, and increasing pressure on network bandwidth, the traditional network architecture can no longer meet people’s needs. The development of software defined networks has brought new opportunities and challenges to future networks. The data and control separation characteristics of SDN improve the performance of the entire network. Researchers have integrated SDN architecture into data centers to improve network resource utilization and performance. This paper first introduces the basic concepts of SDN and data center networks. Then it discusses SDN-based load balancing mechanisms for data centers from different perspectives. Finally, it summarizes and looks forward to the study on SDN-based load balancing mechanisms and its development trend.

Efficacy and safety of low-dose tetracycline,amoxicillin quadruple therapy in Helicobacter pylori infection:A retrospective single center study

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have declined with the rise of antibiotic-resistant strains in recent years.Although highly effective with a low prevalence of resistance,standard dose tetracycline is associated with frequent adverse events.The efficacy and safety of low-dose tetracycline as part of tetra-cycline and amoxicillin-containing bismuth quadruple therapy are not well described.AIM To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients with H.pylori infection receiving tetracycline,amoxicillin,proton pump inhibitor,and bismuth for 14 days at Sir Run Run Shaw Hospital(1/2022-6/2023)were evaluated.The low-dose tetracycline group received tetracycline 500 mg twice daily(bid)while the standard dose group received 750 mg bid or 500 mg three times daily(tid).Primary endpoints were H.pylori eradication rate and treatment-related adverse events.

Association between inflammatory bowel disease and all-cause dementia:A two-sample Mendelian randomization study

BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Traditional Chinese medicine(TCM) has played a positive role in the management of hepatocarcinoma. Hepatocarcinoma patients may present Qi-stagnation, damp-heat, blood stasis, Qi-deficiency, Yin-deficiency and other TCM syndromes(Zheng). Modern treatments such as surgery, transarterial chemoembolization(TACE) and high intensity focus ultrasound treatment would influence the manifestation of TCM syndromes. Herbs with traditional efficacy of tonifying Qi, blood and Yin, soothing liver-Qi stagnation, clearing heat and detoxifying and dissolving stasis, have been demonstrated to be potent to prevent hepatocarcinogenesis. TCM has been widely used in all aspects of integrative therapy in hepatocarcinoma, including surgical resection, liver transplantation, TACE, local ablative therapies and even as monotherapy for middle-advanced stage hepatocarcinoma. Clinical practices have confirmed that TCM is effective to alleviate clinical symptoms, improve quality of life and immune function, prevent recurrence and metastasis, delay tumor progression, and prolong survival time in hepatocarcinoma patients. The effective mechanism of TCM against hepatocarcinoma is related to inducing apoptosis, autophagy, anoikis and cell senescence, arresting cell cycle, regulating immune function, inhibiting metastasis and angiogenesis, reversing drug resistance and enhancing effects of chemotherapy. Along with the progress of research in this field, TCM will contribute more to the prevention and treatment of hepatocarcinoma.

Outcomes of furazolidone-and amoxicillin-based quadruple therapy for Helicobacter pylori infection and predictors of failed eradication

AIM To evaluate the outcomes of furazolidone-and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori(H. pylori) infection and identify predictors of failed eradication.METHODS Patients with H. pylori infection treated with furazolidone, amoxicillin, bismuth, and proton pump inhibitor therapy(January 2015 to December 2015) who received the ^(13)C-urea breath test > 4 wk after treatment were evaluated. Demographic and clinical data including prior H. pylori treatment attempts, medication adherence, alcohol and cigarette consumption during therapy, and treatment-related adverse events were recorded by reviewing medical records and telephone surveys. H. pylori eradication rates for overall and subgroups were evaluated. Multivariate analysis was performed to identify independent predictors of failed H. pylori eradication.RESULTS Of the 992 patients treated and retested for H. pylori infection, the overall eradication rate was 94.5% [95% confidence interval(CI): 94.1%-95.9%]. H. pylori eradication rate of primary therapy was 95.0%(95%CI: 93.5%-96.5%), while that of rescue therapy was 91.3%(95%CI: 86.8%-95.8%). Among the 859 patients who completed the study protocol, 144(17%) reported treatment-related adverse events including 24(3%) leading to premature discontinuation. On multivariate analysis, poor medication adherence [adjusted odds ratio(AOR) = 6.7, 95%CI: 2.8-15.8], two or more previous H. pylori treatments(AOR = 7.4, 95%CI: 2.2-24.9), alcohol consumption during therapy(AOR = 4.4, 95%CI: 1.5-12.3), and possibly smoking during therapy(AOR = 1.9, 95%CI: 0.9-4.3) were associated with failed H. pylori eradication. CONCLUSION Furazolidone-and amoxicillin-based quadruple therapy for H. pylori infection in an area with a high prevalence of clarithromycin resistance demonstrated high eradication rates as primary and rescue therapies with a favorable safety profile. Patient education targeting abstinence from alcohol during therapy and strict medication adherence may further optimize H. pylori eradication.

Anticancer activity of genistein on implanted tumor of human SG7901 cells in nude mice

AIM： To investigate genistein-induced apoptosis of implanted tumors of SG7901 cells in nude mice, and the relationship between this apoptosis and expression of Bcl-2 and Bax. METHODS： Establishing a transplanted tumor model by injecting human SG7901 cells into subcutaneous tissue of nude mice. Genistein （0.5, 1 and 1.5 mg/kg） was directly injected adjacent to the tumor, six times at 2-d intervals. Then, changes in tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphological alterations by transmission electron microscopy （TEN）, measured the apoptotic rate by the TUNEL staining method, and detected the expression of apoptosisregulated gene Bcl-2 and bax by immunohistochemical staining and RT-PCR. RESULTS： Genistein 0.5, 1 and 1.5 mg/kg significantly inhibited carcinoma growth when it was injected near the tumor by 10.8%, 29.9% and 39.6%, respectively. Genistein induced implanted tumor cells to undergo apoptosis, with apoptotic characteristics seen by TEM. The apoptosis index was increased progressively with increasing genistein dose （28.9% ± 1.2%, 33.8% ±1.6% and 37.7% ±1.2%）. The positive rate of Bcl-2 protein was decreased progressively （11.9%± 0.9%, 5.9%± 0.7% and 4.2% ±0.6%）, and the positive rate of bax protein was increased progressively （0.9% ±1.7%, 24.9% ±0.8% and 29.6% ± 1.7%） by immunohistochemical staining, with increasing dose of genistein. The density of Bcl-2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time by RT-PCR. CONCLUSION： Genistein was able to induce apoptosisof transplanted tumor cells. This apoptosis may be mediated by down-regulation of the apoptosis-regulated gene Bcl-2 and up-regulation of apoptosis-regulated gene bax.

Association of GTF2IRD1–GTF2I polymorphisms with neuromyelitis optica spectrum disorders in Han Chinese patients

Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders(NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders(odds ratio(OR) = 1.364, 95% confidence interval(CI) 1.019–1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies(AQP4-IgG) positivity(OR = 1.397, 95% CI 1.021–1.912; P = 0.036) and stratification according to coexisting autoimmune diseases(OR = 1.446, 95% CI 1.072–1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients(OR = 3.15, 95% CI 1.183–8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China(approval number: 2016-31) on March 2, 2016.

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease:A multicenter cross-sectional study in China

Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Expert consensus on early childhood caries management

Early childhood caries(ECC)is a significant chronic disease of childhood and a rising public health burden worldwide.ECC may cause a higher risk of new caries lesions in both primary and permanent dentition,affecting lifelong oral health.The occurrence of ECC has been closely related to the core microbiome change in the oral cavity,which may be influenced by diet habits,oral health management,fluoride use,and dental manipulations.So,it is essential to improve parental oral health and awareness of health care,to establish a dental home at the early stage of childhood,and make an individualized caries management plan.Dental interventions according to the minimally invasive concept should be carried out to treat dental caries.This expert consensus mainly discusses the etiology of ECC,caries-risk assessment of children,prevention and treatment plan of ECC,aiming to achieve lifelong oral health.

Overt gastrointestinal bleeding because of hookworm infection

Hookworm infection is a relatively common cause of anemia in endemic areas.The most common hookworm species are Ancylostoma duodenale and Necator americanus.In this report we present a case of overt gastrointestinal bleeding Wause of hookworm infection.Capsule endoscopy revealed many hookworms in the lumen of proximal jejunum where active bleeding was seen. The patient was successfully treated with Albendazole.

Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori:A retrospective single center study

BACKGROUND Although highly effective as a component of Helicobacter pylori(H.pylori)treatment regimen,tetracycline is associated with a high incidence of medicationrelated adverse events.Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates.AIM To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients(10/2020-12/2021)who received tetracycline and furazolidone quadruple therapy for H.pylori infection at Sir Run Run Shaw Hospital were identified.All patients received tetracycline,furazolidone,proton pump inhibitor,and bismuth for 14 d as primary or rescue therapy.Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily.RESULTS Three hundred and ninety-four patients[mean age=46.3±13.9,male=137(34.8%),and 309(78.4%)primary therapy]completed tetracycline and furazolidone quadruple therapy for H.pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118(750 mg twice daily)and 119(500 mg three times daily).Eradication rates in the modified tetracycline dose group were 92.40%and in the standard groups,eradication rates were 93.20%for 750 mg twice daily group and 92.43%for 500 mg three times daily group,respectively,without statistical difference(P=0.959).The incidence of adverse events was lower in the modified tetracycline dose(15.3%vs 32.3%and 29.4%;P=0.002)compared to the standard dose group.CONCLUSION In a real-world experience,modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy,comparable to standard tetracycline dose regimens,with a favorable safety profile.

Acquired double pylorus:A case report

Double pylorus is one of the rare anomalies of the gastrointestinal tract,it can be congenital or acquired.In this case we report a case of double pylorus because of chronic peptic ulcer.Upper GI endoscopy revealed gastroduodenal fistula located on the lesser curve of the antrum,the patient’s symptoms were improved rapidly by intensive antiulcer treatment.

Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease

Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is associated with metabolic disorders.This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.Methods:A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers.We compared the severity of fibrosis in patients with different components of metabolic disorders.Based on standard noninvasive tests and metabolic disorders,we developed new algorithms to identify advanced fibrosis.Results:Metabolic syndrome(MetS)was frequent in NAFLD patients(133/246,54%).Patients with MetS had a higher proportion of significant fibrosis(p=0.014)and higher LSM values(9.2 kPa,vs.7.4 kPa,p=0.002)than those without MetS.Patients with more metabolic disorders had higher fibrosis stages(p=0.017).Reduced highdensity lipoprotein cholesterol(odds ratio[OR]:2.241,95%confidence interval[CI]:1.004–5.002,p=0.049)and raised fasting glucose(OR:4.500,95%CI:2.083–9.725,p<0.001)were significantly associated with advanced fibrosis.Using these two metabolic disorders as a screening tool,a sensitivity,specificity and accuracy of 92%,81%and 83%was achieved,respectively.With the new algorithms combining metabolic disorders with noninvasive measurements,the number of patients requiring liver biopsy was reduced,especially in combination with the Fibrosis-4 score and metabolic disorders(36%to 17%,p<0.001).In addition,this stepwise algorithm could achieve a high accuracy(85%)and high negative predictive value(93%).Conclusions:Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis.With further validation and investigation,new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.

Status and Trends of GAP Base Construction of Chinese Materia Medica in Guangdong Province

It is one of the key points for modernization and internationalization of traditional Chinese medicines to construct the Good Agricultural Practice (GAP) base of Chinese materia medica (CMM). GAP helps to minimize contamination and improve the quality of CMM during the plantation and the production of Chinese crude drugs. In this article, the status and development of CMM production bases of GAP in Guangdong Province, China, are presented. The suggestions upon the problems during the development of GAP for Chinese crude drugs are also provided.

Efficient electrical control of magnetization switching and ferromagnetic resonance in flexible La_(0.7)Sr_(0.3)MnO_(3) films

Efficient electrical control of magnetic property is critical for the development of various spintronics. However, traditional magnetoelectric devices require adoption of piezoelectric component, resulting in complicated device architecture and complex conditioning circuit. More importantly, traditional strain-mediated magnetoelectric structures could not be developed in flexible form due to the existence of magnetostrictive component, which could be easily affected by mechanical deformation in flexible devices. Here we have systematically investigated pure current control of the magnetic properties of La_(0.7)Sr_(0.3)MnO_(3) thin films. Ferromagnetic to paramagnetic phase transition has been realized with a small current density of 5.2 × 10^(3) A/cm^(2), which is three orders smaller than the working current density of spintronics based on spin-orbit torque and spin-transfer torque. The effective tuning of magnetic property has been attributed to the current induced Joule heating effect. For La_(0.7)Sr_(0.3)MnO_(3) film grown on flexible Mica with a smaller thermal conductivity, dramatic change of ferromagnetic resonance field of 1340 Oe and nonvolatile magnetization switching have been achieved with an ultra-small current density of 7.4 × 10^(2) A/cm^(2). These results represent a crucial step towards effective electrical control of both static and dynamic magnetic properties in flexible magnetic thin films and open a new avenue for exploring electrical controlled flexible spintronics.