A systematic review and meta-analysis of genotypic methods for detecting antibiotic resistance in Helicobacter pylori.

BACKGROUND: Antibiotic susceptibility testing is essential for tailored treatments to cure Helicobacter pylori (H. pylori) infection. However, phenotypic methods have some limitations. OBJECTIVES: To evaluate the feasibility of genotypic detection methods compared with phenotypic detection methods using samples taken from H. pylori-infected patients. METHODS: Literature searches were conducted in the following databases (from January 2000 to November 2016): PubMed, Embase, the Cochrane Library, and Web of Science. A meta-analysis and systematic review was performed for studies that compared genotypic methods with phenotypic methods for the detection of H. pylori antibiotic susceptibility. RESULTS: This meta-analysis showed that the pooled sensitivity, specificity, and diagnostic odds ratio (DOR) for the A2142G/C and/or A2143G combination for the detection of clarithromycin resistance in the strain samples were 0.97 (95% CI: 0.94-0.99), 1.00 (95% CI: 0.99-1.00), and 13 742 (95% CI: 1708-110 554), respectively. The pooled sensitivity, specificity, and DOR for the A2142G/C and/or A2143G combination for the detection of clarithromycin resistance in biopsy samples were 0.96 (95% CI: 0.90-0.99), 0.96 (95% CI: 0.91-0.99), and 722 (95% CI: 117-4443), respectively. The summarized sensitivity, specificity, and DOR value for the ability of the genotypic methods to detect quinolone resistance in biopsy specimens were 0.97 (95% CI: 0.87-0.99), 0.99 (95% CI: 0.92-1.00), and 6042 (95% CI: 486-75 143), respectively. CONCLUSION: The genotypic detection methods were reliable for the diagnosis of clarithromycin and quinolone resistance in the strain and biopsy specimens. The A2142G/C and/or A2143G combination had the best sensitivity and specificity for the detection of clarithromycin resistance.

The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication.

BACKGROUND: Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. AIM: To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. MATERIALS AND METHODS: Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. RESULTS: The internalization level in the eradication success group was 5.40±5.78 × 10-3  cfu/cell, and the median was 6.194 × 10-3  cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10-3  cfu/cell, and the median was 10.28 × 10-3  cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (P<.05). No significant difference was observed between the susceptible strains and the resistant strains when the internalization levels were compared (P>.05). CONCLUSIONS: The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure.

Review: efficacy and safety of hybrid therapy for Helicobacter pylori infection: a systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and safety of hybrid therapy compared to other pre-existing therapies and to new therapies. METHODS: Through a search of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Conference Proceedings Citation Index, two independent reviewers systemically identified randomized, controlled trials that compared hybrid therapy to other pre-existing and new therapies. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with 95% confidence intervals (CIs). RESULTS: We identified 6 studies, 5 of which compared hybrid therapy and sequential therapy, and 3 of which compared hybrid therapy and concomitant therapy. Pooled estimates of the 5 randomized controlled trials (RCTs) revealed no significant differences between hybrid therapy and sequential therapy and no evidence of heterogeneity (I(2)  = 0%; p = .803), the pooled RRs were 1.02 (95% CI: 0.93-1.12) (intention-to-treat (ITT)), and 1.03 (95% CI: 0.94-1.13) (per protocol (PP)). Pooled estimates of the 3 RCTs showed no significant differences between hybrid therapy and concomitant therapy with no evidence of heterogeneity (I(2)  = 0%; p = .967), the pooled RRs were 0.99 (95% CI: 0.89-1.10) (ITT) and 0.99 (95% CI: 0.89-1.10) (PP). No significant differences in adverse events were noted among hybrid therapy, sequential therapy, and concomitant therapy ((RR: 1.13; 95% CI: 0.87-1.48; I(2)  = 13.2%; p = .327), (RR: 0.89; 95% CI: 0.73-1.08; I(2)  = 0%; p = .978) (ITT), respectively). After consideration of all treatment arms, the ITT eradication rates with hybrid therapy, concomitant therapy, and sequential therapy were 88.6, 86.3, and 84.7%, respectively. And the PP eradication rates were 92.1, 92.5, and 87.5%. No significant differences were observed between the groups in terms of compliance. CONCLUSIONS: All three of these therapies yielded good eradication rates. Hybrid therapy could be an alternative to sequential therapy and concomitant therapy, but additional RCTs are needed to confirm this finding.

Aerobic interval training protects against myocardial infarction-induced oxidative injury by enhancing antioxidase system and mitochondrial biosynthesis.

1. Aerobic interval training (AIT) exerts beneficial effects on cardiovascular disease. However, its cardioprotective mechanisms are not fully understood. The aim of the present study was to evaluate AIT-mediated anti-oxidation by focusing on anti-oxidase and mitochondrial biogenesis in rats after myocardial infarction (MI). 2. Sprague-Dawley rats were divided into three groups: (i) a sham-operated control (CON); (ii) an MI group; and (iii) an MI + AIT group. Myocardial microstructure and function, markers of oxidative stress, mitochondrial anti-oxidase, Phase II enzymes and mitochondrial biogenesis were assessed. In addition, levels of nuclear factor-erythroid 2-related factor (Nrf2) and phosphorylated (p-) AMP-activated protein kinase (AMPK) were determined. The anti-oxidative gene sirtuin 3 (SIRT3) and the prosurvival phosphatidylinositol-3 kinase (PI3-K)-protein kinase B (Akt) signalling cascade were also evaluated. 3. Compared with CON, there was noticeable microstructure injury, cardiac dysfunction and oxidative damage in rats after MI. In addition, decreased mitochondrial anti-oxidase content, Phase II enzyme (except heme oxygenase-1) expression and mitochondrial biogenesis were observed in the post-MI rats as well as reduced protein levels of the regulators Nrf2 and p-AMPK and suppression of SIRT3 levels and PI3-K/Akt signalling. These detrimental modifications were considerably ameliorated by AIT, as evidenced by increases in anti-oxidase, mitochondrial biogenesis, Nrf2 and AMPK phosphorylation, as well as SIRT3 upregulation and PI3-K/Akt signalling activation. Moreover, PI3-K inhibitor-LY294002 (20 mg/kg) treatment partly attenuated AIT-elicited increases in Nrf2 levels and AMPK phosphorylation. 4. Based on these results, we conclude that AIT effectively alleviates MI-induced oxidative injury, which may be closely correlated with activation of the anti-oxidase system and mitochondrial biosynthesis. Increased SIRT3 expression and activation of PI3-K/Akt signalling may play key roles in AIT-mediated anti-oxidation. These results open up new avenues for exercise intervention therapies for MI patients.

Aerobic interval training attenuates mitochondrial dysfunction in rats post-myocardial infarction: roles of mitochondrial network dynamics.

Aerobic interval training (AIT) can favorably affect cardiovascular diseases. However, the effects of AIT on post-myocardial infarction (MI)-associated mitochondrial dysfunctions remain unclear. In this study, we investigated the protective effects of AIT on myocardial mitochondria in post-MI rats by focusing on mitochondrial dynamics (fusion and fission). Mitochondrial respiratory functions (as measured by the respiratory control ratio (RCR) and the ratio of ADP to oxygen consumption (P/O)); complex activities; dynamic proteins (mitofusin (mfn) 1/2, type 1 optic atrophy (OPA1) and dynamin-related protein1 (DRP1)); nuclear peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α); and the oxidative signaling of extracellular signal-regulated kinase (ERK) 1/2, c-Jun NH2-terminal protein kinase (JNK) and P53 were observed. Post-MI rats exhibited mitochondrial dysfunction and adverse mitochondrial network dynamics (reduced fusion and increased fission), which was associated with activated ERK1/2-JNK-P53 signaling and decreased nuclear PGC-1α. After AIT, MI-associated mitochondrial dysfunction was improved (elevated RCR and P/O and enhanced complex I, III and IV activities); in addition, increased fusion (mfn2 and OPA1), decreased fission (DRP1), elevated nuclear PGC-1α and inactivation of the ERK1/2-JNK-P53 signaling were observed. These data demonstrate that AIT may restore the post-MI mitochondrial function by inhibiting dynamics pathological remodeling, which may be associated with inactivation of ERK1/2-JNK-P53 signaling and increase in nuclear PGC-1α expression.

The impact of grandparenting on mental health among rural middle-aged and older adults in China: exploring the role of children's support.

Objectives: In the rural regions of China, characterized by a pronounced aging demographic and limited resources, a substantial proportion of middle-aged and older adults engage in grandparenting roles. Yet, the literature lacks consistent evidence regarding the effects of grandparenting on the mental health of this cohort. Accordingly, this study aimed to explore the impact of grandparenting on the mental health of rural middle-aged and older adults, as well as the underlying mechanisms. Methods: This analysis encompassed 10,881 middle-aged and older adults, utilizing data from the 2018 Harmonized China Health and Retirement Longitudinal Study (CHARLS). The mental health of participants was assessed using the Center for Epidemiological Studies Depression-10 (CESD-10) scale, while support from children was categorized into financial and emotional types. The study employed logistic and OLS regression models to identify the mediating role of child support and utilized the Karlson-Holm-Breen (KHB) method for decomposing this mediating effect. Results: The findings demonstrated that grandparenting had a significant negative impact on depression among rural middle-aged and older adults. Furthermore, children's support played a vital role in mediating this relationship, accounting for approximately one-third of the overall influence. Moreover, the decomposition analysis revealed that both emotional and economic support from adult children equally contributed to the declination of depression among rural middle-aged and older adults. Conclusion: Grandparenting significantly enhances mental well-being in rural middle-aged and older adults, with the support from adult children serving as a vital pathway for this positive impact. Both economic and emotional assistance from children hold equal importance in this dynamic. It underscores the necessity of fortifying the family support system to amplify the support provided by children, which in turn could significantly enhance the mental health of rural middle-aged and older adults.

Correlation analysis of hypertension, traditional Chinese medicine constitution, and LPL gene polymorphism in the elderly in communities in Shanghai.

BACKGROUND: Research on the genetic mechanisms of hypertension has been a hot topic in the cardiovascular field. OBJECTIVE: To study the correlation between senile hypertension and traditional Chinese medicine (TCM) constitution and lipoprotein lipase (LPL) gene polymorphism and to provide the theoretical basis for TCM prevention and treatment of hypertension. METHODS: The elderly population in communities in Shanghai (hypertensive: 264 cases; non-hypertensive: 159 cases) was taken as the research object. Essential data and information on TCM constitution were collected. The LPL gene mutation was detected using the second-generation sequencing method. Statistical analysis was performed to clarify the relationship between hypertension and senile hypertension. The correlation of TCM constitution with risk factors and LPL gene polymorphisms was studied. RESULTS: The primary TCM constitutions in the hypertension group were phlegm-dampness constitution (51.52%), yin-deficiency constitution (17.42%), balanced constitution (15.53%), and yin-deficiency (9.43%). Logistic regression analysis showed that the phlegm-dampness constitution (P< 0.05, OR = 2.587) and yin-deficiency constitution (P< 0.01, OR = 2.693) were the risk constitutions of hypertension in the elderly. A total of 37 LPL gene mutation loci (SNP: 22; new discovery: 15) were detected in the LPL gene, and the mutation rates of rs254, rs255, rs3208305, rs316, rs11570891, rs328, rs11570893, and rs13702 were relatively high, which were 26.24%, 26.24%, 16.08%, 14.66%, 13.24%, 12.06%, and 10.64%. In the phlegm-dampness group, the proportion of rs254 CC type, rs255 TT type, and rs13702 TT type in the hypertensive group (77.21%, 77.21%, and 93.38%) was higher than that in the non-hypertensive group (56.41%, 56.41%, and 82.05%), The difference was statistically significant (P< 0.05). CONCLUSION: The phlegm-dampness constitution and yin-deficiency constitution are the risk factors of hypertension in the elderly; in the phlegm-dampness population, rs254 CC type, rs255 TT type, and rs13702 TT type are the risk factors for elderly hypertension.

Internal fixation of intertrochanteric hip fractures: a clinical comparison of two implant designs.

OBJECTIVE: To compare two internal fixation devices clinically in stabilisation of intertrochanteric femur fractures. METHODS: Eighty-seven patients were randomised upon their admission to the hospital using a sealed envelope method. Forty-five were treated with proximal femur nail antirotation (PFNA) and 42 with reverse less invasive stabilisation system (LISS). The perioperative data were recorded and compared in relation to fracture type. RESULTS: In each type of fractures, no significant differences were found with respect to the blood loss, the quality of reduction, the time to bony healing, and the Harris hip score between the 2 groups. The mean duration of surgery was significantly longer in reverse LISS group than in PFNA group. CONCLUSION: Both the PFNA and the reversed LISS are effective in the treatment of different types of intertrochanteric femur fractures. PFNA is superior to reverse LISS in terms of surgical time, weight-bearing, and perhaps fluoroscopy time.

Macrophage migration inhibitory factor facilitates astrocytic production of the CCL2 chemokine following spinal cord injury.

Spinal cord injury causes accumulation of a large number of leukocytes at the lesion site where they contribute to excessive inflammation. Overproduced chemokines are responsible for the migratory process of the leukocytes, but the regulatory mechanism underlying the production of chemokines from resident cells of the spinal cord has not been fully elucidated. We examined the protein levels of macrophage migration inhibitory factor and chemokine C-C motif chemokine ligand 2 in a spinal cord contusion model at different time points following spinal cord injury. The elevation of macrophage migration inhibitory factor at the lesion site coincided with the increase of chemokine C-C motif chemokine ligand 2 abundance in astrocytes. Stimulation of primary cultured astrocytes with different concentrations of macrophage migration inhibitory factor recombinant protein induced chemokine C-C motif chemokine ligand 2 production from the cells, and the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine attenuated the stimulatory effect. Further investigation into the underlying mechanism on macrophage migration inhibitory factor-mediated astrocytic production of chemokine C-C motif chemokine ligand 2 revealed that macrophage migration inhibitory factor activated intracellular JNK signaling through binding with CD74 receptor. Administration of the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine following spinal cord injury resulted in the reduction of chemokine C-C motif chemokine ligand 2-recruited microglia/macrophages at the lesion site and remarkably improved the hindlimb locomotor function of rats. Our results have provided insights into the functions of astrocyte-activated chemokines in the recruitment of leukocytes and may be beneficial to develop interventions targeting chemokine C-C motif chemokine ligand 2 for neuroinflammation after spinal cord injury.

[Use of zebrafish models for the research of traditional Chinese medicine].

Traditional Chinese medicine (TCM) exhibits a broad range of effects on biological activity that is probably due to interactions of complex chemical constituents with multiple targets in the body. Understanding the active chemical constituents in TCM is very important in providing rationales for the clinical usage of TCM. The zebrafish (Danio rerio) has recently become a popular model in the field of drug screening, specifically emerging as an important vertebrate model for in vivo high-content drug screening of multiple efficacy parameters and whole-organism toxicity. The authors also discussed the advantages of the zebrafish model for evaluating drug metabolism. Zebrafish usage in TCM screening should be a viable approach that helps identify active chemical markers, biological pathways and mechanistic actions of TCM.

Acetylcholine prevents angiotensin II-induced oxidative stress and apoptosis in H9c2 cells.

Apoptosis of cardiomyocytes plays an important role in the development of cardiovascular diseases (CVD). Numerous studies have shown that generation of reactive oxygen species (ROS) induced by the renin-angiotensin system (RAS) is involved in this pathological process. Recent studies also suggested that acetylcholine (ACh) prevented the hypoxia-induced apoptosis of mouse ES cells by inhibiting the ROS production. However, whether ACh can inhibit the action of angiotensin II (Ang II) and subsequently prevent CVD development remains unclear. In this study, H9c2 cells were stimulated by 10(-6) M Ang II for 24 h with or without 10(-5) M ACh, 10(-5) M ACh + 10(-4) M atropine respectively. The results demonstrated that Ang II increased apoptosis index by fourfold (vs. the control group, P < 0.01), which were significantly diminished by ACh. However, the atropine (ACh receptor [AChR] inhibitor) treatment blocked the protective effect of ACh. Subsequently, Ang II significantly increases the expression and activity of NADPH oxidase so that ROS production is increased by sevenfold (vs. control group, P < 0.01). The activity and expression of caspase-3 along with the Bax/Bcl2 ratio and the levels of p38 mitogen activated protein kinase (MAPK) phosphorylation also appeared to follow a similar trend. Furthermore, we observed that ACh could reduce up-regulation of AT1 receptor expression induced by Ang II. However, all these effects of ACh were inhibited by atropine. In conclusion, ACh prevents Ang II-induced H9c2 cells apoptosis through down-regulation of the AT1 receptor and inhibition of ROS-mediated p38 MAPK activation as well as regulation of Bcl-2, Bax and caspase-3.

[Effects of different intensity exercise on morphology and structure of atrioventricular node and protein expressions of VEGF, VIP and Syn in rats].

Objective: To investigate the effects of different intensities of aerobic exercise on the morphology of the atrioventricular node and the expressions of vascular endothelial growth factor (VEGF), vasoactive intestinal peptide (VIP) and synaptophysin (Syn) in rats. Methods: Three-month-old SD rats were randomly divided into 3 groups: quiet control group (C), moderate-intensity aerobic exercise group (AE), and high-intensity aerobic exercise group (FE), each with 8 rats. The moderate-intensity aerobic exercise and high-intensity aerobic exercise rat models were rats established by using 8-week treadmill training ways. Results: Compared with the quiet control group, in the moderate-intensity aerobic exercise group, the atrioventricular nodule muscle fibers were evenly distributed, with smaller gaps, a sense of transparency, and collagen tightly wraps around the atrioventricular nodules. The intercalary disc had a clear structure and complete connection, and the capillary tube wall was relatively clear. Thick elastic fibers were more developed, the expression levels of VEGF and VIP in the atrioventricular node were increased significantly (P＜0.05), and there was no significant change in the expression of Syn. In the high-intensity aerobic exercise group, the atrioventricular nodule muscle fibers were unevenly distributed and arranged abnormally, connection between cells were disordered, and vacuolated. The intercalary disk was twisted, circling and overlapping, fuzzy, discontinuous, and extremely dilated. The wall was thick and the endothelial cells were arranged sparsely and disorderly. Moreover, high-intensity aerobic exercise significantly inhibited the expressions of VEGF, VIP, and Syn (P＜0.05). Conclusion: Aerobic exercise training of different intensities has obvious effects on the morphology and structure of the atrioventricular node and the expressions of VEGF, VIP and Syn. Moderate aerobic exercise can maintain and promote the normal morphology and structure of the atrioventricular node, while high-intensity aerobic exercise can damage the morphology and structure of the ventricular node, which is presumably closely related to the arrhythmia induced by high-intensity exercise.

Totally Extraperitoneal Herniorrhaphy (TEP): Lessons Learned from Anatomical Observations.

BACKGROUND: Totally extraperitoneal herniorrhaphy (TEP) is a therapeutic challenge because of its complex anatomical location in inguinal region. The aim of this study was to describe the related surgical anatomy through laparoscopic observation and share the lessons learned from a review of 250 primary inguinal hernia repair procedures performed at our hospital from January 2013 to November 2019. Patients and Methods. There were 245 men and 5 women (median age: 63.2 years). Right hernia (60.2%) was the most common site. Indirect hernia (60.5%) was the most common abnormality. The classification of type II (65.0%) was the most common form. Surgical techniques comprised retromuscular approach using cauterized dissection, management of variations of arcuate line, Retzius space and Bogros space dissection, hernia sac reduction, and mesh positioning. RESULTS: The incidence of peritoneum injury was in 27 (10.1%). No epigastric vessels were injured. There were 8 (3%) hematoma and 18 (6.8%) seroma. No mesh infection, chronic pain, and recurrence were found after follow-up of an average of 35 months. CONCLUSION: A good understanding of the anatomically complex nature in the inguinal region can make it easier and safer to learn the TEP approach. Early and midterm outcomes after TEP are satisfactory.

Characteristics of Helicobacter pylori Heteroresistance in Gastric Biopsies and Its Clinical Relevance.

BACKGROUND: Antimicrobial susceptibility testing (AST) plays a vital role in anti-Helicobacter pylori treatment, but the traditional AST method has difficulty detecting heteroresistance, which may cause an increased prevalence of resistant strains and eradication failure. AIMS: To investigate the characteristics of heteroresistance in H. pylori in gastric biopsies and investigate its clinical relevance. METHOD: A total of 704 gastric biopsies were selected for 23S rRNA and gyrA gene sequencing, 470 H. pylori isolates from these biopsies were selected for AST, and the clinical characteristics of the patients were reviewed. RESULT: For the 699 biopsies that were positive for 23S rRNA gene, 98 (14.0%) showed a heteroresistance genotype, and a wild type (WT) combined with A2143G (86.7%) genotype was found in most samples. For the 694 biopsies that were positive for gyrA gene, 99 (14.3%) showed a heteroresistance genotype, and a WT combined with 87K (26.3%) or WT combined with 91N (23.2%) genotype was predominant. According to the E-test results, the resistance rates of heteroresistance genotype samples for clarithromycin and levofloxacin were 36.2% and 68.1%, respectively. When dividing the heteroresistance samples into different groups according to the sequencing profile peaks of the mutation position, the resistance rates were higher along with mutation peaks at the mutation position. In addition, patients infected with mutated or heteroresistant strains showed lower peptic ulcer detection rates than those infected with the WT strain (p < 0.05). CONCLUSION: Heteroresistance genotypes for clarithromycin and levofloxacin were not rare in H. pylori. Most cases with a heteroresistance genotype showed a susceptible phenotype for clarithromycin and a resistance phenotype for levofloxacin. Patients infected with heteroresistance genotype strains showed a lower peptic ulcer detection rate than those infected with the WT strain.

Analysis of m6A-Related lncRNAs for Prognosis Value and Response to Immune Checkpoint Inhibitors Therapy in Hepatocellular Carcinoma.

INTRODUCTION: N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play pivotal roles in the progression of hepatocellular carcinoma (HCC). However, how their interaction is involved in the prognostic value of HCC and immune checkpoint inhibitors (ICIs) therapy remains unclear. METHODS: The RNA sequencing and clinical data of HCC patients were collected from TCGA database. The prognostic m6A-related lncRNAs were screened out with Pearson correlation test, univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. Patients with HCC were classified into 2 subtypes by consensus clustering. Survival analyses were performed to assess the prognostic value of different clusters and risk models. Potential tumor correlated biological pathways correlated with different clusters were explored through gene set enrichment analysis. We also identified the relationship of the risk model and clusters with response to immune checkpoint inhibitors (ICIs) therapy and tumor microenvironment (TME). Furthermore, the prognostic value of the 9 m6A-related lncRNAs was validated in the external cohort. Finally, the role of SNHG4 was explored by silencing and overexpression of SNHG4 through conducting proliferation, migration and invasion experiments. RESULTS: Patients from 2 clusters and different risk groups based on m6A-related lncRNAs had significantly different clinicopathological characteristics and overall survival outcomes. Tumor-correlated biological pathways were found to be correlated with Cluster 2 through GSEA. Moreover, we found that patients from different clusters and risk groups expressed higher levels of immune checkpoint genes and had distinct TME and different responses for ICIs therapy. Prognostic value of this risk model was further confirmed in the external cohort. Finally, consistent with the discovery, SNHG4 played an oncogenic role in vitro. CONCLUSION: Our study demonstrated that the 9 m6A-related lncRNA signature may serve as a novel predictor in the prognosis of HCC and optimize (ICIs) therapy. SNHG4 plays an oncogenic role in HCC.

Exercise benefits cardiovascular health in hyperlipidemia rats correlating with changes of the cardiac vagus nerve.

The role of exercise training on hemodynamic parameters, blood lipid profiles, inflammatory cytokines, cholinesterase-positive nerves and muscarinic cholinergic (M(2)) receptors expression in the heart was investigated in Sprague-Dawley male rats with hyperlipidemia (HL). The rats were subjected to a high-fat diet and exercise training for 8 weeks, and then the hemodynamic parameters, the profiles of blood lipid and inflammatory cytokines, and the expression of cholinesterase-positive nerves and M(2) receptors were measured. HL rats displayed cardiac dysfunction, dysregulation of inflammatory cytokines, and decreased cholinesterase-positive nerves and M(2) receptors expression. The combination of hyperlipidemia with exercise training (AT) restored the profiles of blood lipids and the levels of inflammatory cytokines. In addition, AT and HL + AT improved cardiac function with increasing cholinesterase-positive nerves and M(2) receptors expression. Overall, these data show that the increased expression of cholinesterase-positive nerves and M(2) receptors in the heart is partially responsible for the benefits of exercise training on cardiac function in hyperlipidemia rats.

Genotype profiles of Helicobacter pylori from gastric biopsies and strains with antimicrobial-induced resistance.

BACKGROUND AND AIMS: The genotypic method could significantly shorten the time needed to obtain antibiotic susceptibility data for Helicobacter pylori. The aim of this study was to explore the profile of H. pylori from gastric biopsies and strains with antibiotic-induced resistance. METHODS: A total of 124 gastric biopsies were used to perform gene sequencing and to perform bacterial culture and susceptibility testing. Seven susceptible strains were selected to develop resistance to clarithromycin, levofloxacin, and metronidazole. Four susceptible strains were selected to transfer candidate mutations. The genotype profiles of these groups were analyzed by sequencing analysis. The antibiotic susceptibility of these strains was detected using the E-test method. RESULTS: Phenotypic resistance to clarithromycin, levofloxacin, and metronidazole was observed in 35.5%, 40.0%, and 79.8% strains, respectively. Point mutations in 23 S rRNA, gyrA, and rdxA genes were observed in 39.5%, 38.7%, and 86.3% of gastric biopsies, respectively. The A2143G mutation in the 23S rRNA occurs in most clarithromycin-resistant samples. The A2142C point mutation showed a higher efficacy than A2142G and A2143G for inducing clarithromycin resistance. The D91N and N87K mutations in gyrA occurs in most levofloxacin-resistant samples, and double point mutations showed a higher efficacy than single mutations for inducing levofloxacin resistance. Phenotypic resistance and mutations in rdxA lacked consistency. CONCLUSION: Genotype-based gastric biopsy analysis was reliable for determining clarithromycin and levofloxacin resistance. A2143G in 23S rRNA and N87K/D91N in the gyrA gene occurred in most resistant strains. Mutations in the rdxA gene were not good indicators of metronidazole resistance.

[Treatment of type C intercondylar fractures of distal humerus using dual plating].

OBJECTIVE: To evaluate the clinical outcome of dual plating in the treatment of humeral intercondylar type-C fractures in adults. METHODS: From June 2004 to October 2007, 38 cases of type-C distal humeral fractures were stabilised with dual plating. There were 21 males and 17 females. The average age was 43 years with a range from 21 to 71 years. According to the AO classification, 9 cases were of type C1, 17 of C2 and 12 of C3. The posterior midline approach was selected. Twenty-one cases were exposed through the trans-olecranon osteotomy, 11 through the Campbell (Van Gorder) approach, 6 through triceps sparing approach. Autogenous bone graft was performed in 5 cases because of severe comminution. RESULTS: Thirty-five patients were followed-up for 14-30 months (mean 24.2 months). At the latest follow-up, the elbow flexion averaged 119 degrees (range 90 degrees - 135 degrees ), and the loss of extension averaged 16.2 degrees (range 5 degrees - 25 degrees ). All the patients got bony healing, the average healing period was 14 weeks. The patients were evaluated using the criteria of Aitken and Rorabeek and the scores were 13 excellent, 16 good, 6 fair. Twenty-nine patients (82.9%) had a good or excellent results. Complications included 4 cases of traumatic osteoarthritis, 2 heterotopic ossification, 1 ulnar neuropathy. Infection as well as loosening or breakage of the implant was not found. CONCLUSIONS: The dual plating is able to provide rigid fixation for the humeral intercondylar fractures. In addition, it can allow early functional exercise after operation, decrease the related complications significantly, and improve the functional results.

Characteristics of Helicobacter pylori antibiotic resistance: data from four different populations.

Aims: To describe the characteristics of Helicobacter pylori (H. pylori) antibiotic resistance in clinical isolates from four populations. Methods: In total, 1463 H. pylori strains were examined for antibiotic resistance. Among these strains, 804 were isolated from treatment-naïve adults, 133 from previously treated adults, 100 from treatment-naïve children and 426 from a population who participated in a health survey (age ≥ 40 years). The minimum inhibitory concentration was determined by the E-test method. Results: In the treatment-naïve adult group, the resistance rates for metronidazole, clarithromycin, levofloxacin, amoxicillin, rifampicin and tetracycline were 78.4, 19.0, 23.3, 1.2, 1.7 and 2.3%, respectively. Compared with this group, the previously treated adult group had significantly higher resistance rates for metronidazole (99.2%), clarithromycin (58.3%) and levofloxacin (52.3%). In addition, the treatment-naïve children had a lower metronidazole resistance rate (46.0%) than the treatment-naïve adults. The resistance rate for clarithromycin was low in treatment-naïve patients with ages ranging from 10 to 24 years. For the strains isolated from the general population group, the resistance rates for metronidazole, clarithromycin, levofloxacin, amoxicillin, rifampicin and tetracycline were 78.6, 10.1, 25.1, 0.5, 2.1 and 0.9%, respectively. Compared with the treatment-naïve adult group, the general population group showed significant differences in clarithromycin resistance. Conclusion: The resistance rates for metronidazole, clarithromycin and levofloxacin were high, especially in previously treated adults. Compared to those in treatment-naïve younger patients, the resistance rates for clarithromycin were significantly lower in treatment-naïve patients with ages ranging from 10 to 24 years and in the general population.

Fourth-generation quinolones in the treatment of Helicobacter pylori infection: A meta-analysis.

AIM: To assess the efficacy and safety of fourth-generation quinolones for Helicobacter pylori (H. pylori) eradication, we conducted this systematic review and meta-analysis of randomized clinical trials. METHODS: Major literature databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of H. pylori eradication therapies and included fourth-generation quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed. RESULTS: Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat (ITT) analysis [75.4% vs 81.8%; odds ratio (OR) = 0.661; 95% confidence interval (CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by per-protocol analysis (79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis (30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies (84.3% vs 71.9%) and in Asian vs European groups (76.7% vs 89.1%). CONCLUSION: Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of H. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.