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Summary Objective To explore the risk factors of cerebral neurological complications after surgery for Stanford type A aortic arch surgery. Methods One hundred sixteen patients who received Stanford type A aortic dissection from January 2012 to December 2019 were recruited. All patients received surgery under deep hypothermic circulatory arrest (DHCA) and general anesthesia. They were grouped by degree of postoperative cerebral neurological complication. The related factors of cerebral neurological complications were analyzed by single-factor analysis and multi-factor logistic regression. Results Postoperative neurological complications were observed in 31 cases (26.72 %). Two groups were identified: permanent neurological dysfunction (PND) was observed in seven cases, and temporary neurological dysfunction (TND) was observed in 24 cases. In-hospital mortality was 9.48 % (11/116), with six in the cerebral complication groups and five in the non-complication group. Single-factor analysis showed the associated factors were age, stroke history, carotid plaque or stenosis, emergency surgery, renal dysfunction, hypotension, aortic clamping time, deep hypothermic circulatory arrest time, postoperative hypoxemia, postoperative low cardiac output and plasma transfusion >800 ml, and erythrocyte suspension transfusion >6 U. Multi-factor logistic analysis showed the independent predictive factors were DHCA time >40 min, plasma transfusion >800 ml, erythrocyte suspension transfusion >6 U, history of stroke, and carotid plaque or stenosis. Conclusion The factors independently associated with neurological complications are DHCA time >40 min, plasma transfusion >800 ml, erythrocyte suspension transfusion >6 U, history of stroke, and carotid plaque or stenosis. Our findings suggest that patients with these risk factors should receive intervention during treatment to reduce cerebral neurological complications.

This experiment was conducted to evaluate the effects of different levels of tannic acid (TA) on growth performance, diarrhea rate, nutrient digestibility and intestinal health in weaned piglets. A total of 180 weaned piglets (Duroc × Landrace × Yorkshire, 24 d of age, initial average BW = 7.77 ± 0.17 kg) were allotted to 5 groups (6 pigs/pen and 6 replicates/group) in a randomized complete block design according to their gender and body weight. Piglets were fed a basal diet, or the basal diet supplemented with 0.05%, 0.1%, 0.2% or 0.4% TA for 28 d. The supplementary levels of TA in the diets were obtained by adding tannalbin containing 51% TA and 40.17% protein. The results showed that, compared with the CON group, dietary TA did not affect ADFI, ADG or F:G, and linearly reduced (P

A capture probe was constructed using a combination of magnetic Fe3O4 nanoparticles and an aptamer directed towardListeria monocytogenes. A signal probe was prepared by combining luminol-functionalized flowerlike gold nanoparticles, obtained by combining luminol with chitosan bearing a complementary sequence of the aptamer. The complex consisting of the capture probe and signal probe could be removed through magnetic separation. Where the target was present within a sample, it competed with the complementary sequence for binding to the aptamer, causing a change of the chemiluminescent signal. The results indicated that a good linear relationship existed over the concentration range 1.0 × 101–1.0 × 105 CFU·mL–1. It was established that it was feasible to use this approach to detect L. monocytogenes at levels as low as 6 CFU·mL–1 in milk samples.

IntroductionMultiple myeloma (MM) is a malignant hematologic tumor. Although many new drugs are currently found to significantly improve the median survival, MM is still not curable due partly to drug resistance recurrence. Epidemiological studies have shown that patients with type 2 diabetes have a high risk of malignancy, and patients’ treatment with metformin could reduce the risk of cancer as well as associated mortality.Material and methodsWe used chemotherapeutics – melphalan combined with metformin or the single drug – to treat RPMI8226 cells and used a series of tests to detect the drug sensitivity, apoptotic rate, DNA damage and the concentration of ATP. SPSS 17.0 was used to analyze the data.ResultsThe inhibitory effect of melphalan on RPMI8226 cells was significantly increased after metformin was added (p < 0.05), and the inhibitory effect was enhanced with the increasing concentration of melphalan. The comet assay showed that metformin increased melphalan-induced DNA damage and increased the apoptotic rate from 12.7 ±2.8% to 18.8 ±1.5% (p < 0.05). In the ATP concentration test, the concentration of ATP in the tumor cells was significantly decreased from 0.42 ±0.01 µmol/l to 0.08 ±0.02 µmol/l (p < 0.05).ConclusionsMetformin can promote DNA damage induced by melphalan and decrease the concentration of ATP in the process of repairing DNA damage to hinder the anti-apoptotic process of tumor cells, which showed the pesticide effect of the enhanced sensitivity of multiple myeloma cells to melphalan.

Background: Gallbladder lesions have become more common nowadays. But there is limited evidence-based guidance on surveillance of these patients for malignancy. Predicting malignancy could help clinicians better manage this condition and improve the prognosis. We evaluated the independent and joint effects of metabolic syndrome components on the risk of malignancy among patients with gallbladder lesions. Methods: Using a multicenter database, consecutive patients with pathologically confirmed gallbladder lesions between 2012 and 2019 were identified. Univariate and multivariate logistic regression analyses were used to evaluate the effects of metabolic syndrome components (diabetes, hypertension, dyslipidemia and obesity) as additive or combined indicators for the risk of malignancy. Unadjusted and adjusted odds ratios were calculated. Results: Of the 625 patients, 567 patients were identified with benign gallbladder lesions and 58 patients with gallbladder cancer (GBC). GBC group had less obesity but more dyslipidemia. Among all metabolic syndrome components, only dyslipidemia was significantly associated with GBC (odds ratio 2.674, 95% confidence interval 1.173-6.094). Dyslipidemia was an independent risk factor for malignancy (adjusted odds ratio 2.164, 95% confidence interval 1.165-4.021), regardless of whether the other risk factors and metabolic syndrome components were combined. Patients with decreased high-density lipoprotein had 3.035-fold higher risk of malignancy (adjusted odds ratio 3.035, 95% confidence interval 1.645-5.600). Conclusions: Dyslipidemia is associated with a 2.674-fold increase in the risk of malignancy in patients with gallbladder lesions. Dyslipidemia is an independent risk factor for malignancy, regardless of the presence of the other risk factors and metabolic syndrome components.

Background Tannic acid (TA) is potential to reduce diarrhea in weaning pigs, but knowledge about the influence of TA on intestinal barrier integrity and function is still scarce. This experiment was conducted to investigate the effects of dietary TA supplementation on growth performance, diarrhea rate, intestinal barrier integrity and function of weaned pigs. Methods A total of 108 crossbred (Duroc × Landrace × Yorkshire) piglets, with an initial average body weight of 6.60 ± 0.27 kg, were allotted to 3 groups (6 pigs/pen and 6 replicates/group) in a randomized complete block design according to their gender and body weight. Piglets were fed the basal diet with 0 (control, CON), 0.2% and 1.0% TA, respectively. The trial lasted for 28 d. Results Compared with the CON group, dietary 0.2% and 1.0% TA supplementation didn’t affect ADFI, ADG and F:G (P > 0.05), but reduced diarrhea rate, diarrhea index and diarrhea score of piglets (P P P P P P P OCLN) mRNA and 0.2% TA group had higher zonula occludens-2 (ZO-2) level (P OCLN mRNA levels in the jejunum (P ZO-1) mRNA levels in the ileum (P Conclusion In conclusion, dietary supplementation of 0.2% or 1.0% TA could effectively alleviate post-weaning diarrhea without altering growth performance in weaned piglets, which might be achieved by improving intestinal barrier integrity and function.

To establish a practical and simplified Chinese thyroid imaging reporting and data system (C-TIRADS) based on the Chinese patient database. A total of 2141 thyroid nodules that were neither cystic nor spongy were used in the current study. These specimens were derived from 2141 patients in 131 alliance hospitals of the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound. The ultrasound features, including location, orientation, margin, halo, composition, echogenicity, echotexture, echogenic foci and posterior features were assessed. Univariate and multivariate analyses were performed to investigate the association between ultrasound features and malignancy. The regression equation, the weighting, and the counting methods were used to determine the malignant risk of the thyroid nodules. The areas under the receiver operating characteristic curve (Az values) were calculated. Of the 2141 thyroid nodules, 1572 were benign, 565 were malignant, and 4 were borderline. Vertical orientation, ill-defined, or irregular margin (including extrathyroidal extension), microcalcifications, solid, and markedly hypoechoic were positively associated with malignancy, while comet-tail artifacts were negatively associated with malignancy. The logistic regression equation yielded the highest Az value of 0.913, which was significantly higher than that obtained using the weighting method (0.893) and the counting method (0.890); however, no significant difference was found between the latter two. The C-TIRADS, based on the counting method, was designed following the principle of balancing the diagnostic performance and sensitivity of the risk stratification with the ease of use. A relatively simple C-TIRADS was established using the counting value of positive and negative ultrasound features.

Thyroid nodules are very common all over the world, and China is no exception. Ultrasound plays an important role in determining the risk stratification of thyroid nodules, which is critical for clinical management of thyroid nodules. For the past few years, many versions of TIRADS (Thyroid Imaging Reporting and Data System) have been put forward by several institutions with the aim to identify whether nodules require fine-needle biopsy or ultrasound follow-up. However, no version of TIRADS has been widely adopted worldwide till date. In China, as many as ten versions of TIRADS have been used in different hospitals nationwide, causing a lot of confusion. With the support of the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association, the Chinese-TIRADS that is in line with China's national conditions and medical status was established based on literature review, expert consensus, and multicenter data provided by the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound.

Background: Accessible, equitable, and efficient pediatric service is critical to achieve optimal child health. This study aimed to evaluate the effectiveness of a multi-component intervention on the pediatric health system over two different periods in Guangzhou.Methods: Based on the World Health Organization (WHO) “six building blocks” model and Donabedian's “Structure-Process-Outcomes” framework, an intervention package was developed to increase financial and human resouce investment to strengthen basic health care and strive for a better quality of pediatric care. This multi-component intervention package was conducted in Guangzhou to improve the pediatric service delivery during two stages (2011–2014 and 2016–2019). The main outcome indicators were the changes in the allocation of pediatricians and pediatric beds, pediatric service efficiency, and the impact of pediatricians on child mortality.Results: We found that pediatricians per 1,000 children (PPTC) and pediatric beds per 1,000 children (PBPTC) increased from 1.07 and 2.37 in 2010 to 1.37 and 2.39 in 2014, then to 1.47 and 2.93 in 2019, respectively. Infant mortality rate (IMR) and under-5 mortality rate (U5MR) dropped from 5.46‰ and 4.04‰ in 2010 to 4.35‰ and 3.30‰ in 2014 then to 3.26‰ and 2.37‰ in 2019. The Gini coefficients of PPTC and PBPTC decreased from 0.48 and 0.38 in 2010, to 0.35 and 0.28 in 2014, then to 0.35 and 0.22 in 2019, respectively, representing the improvement of pediatric resources distribution according to service population. However, equalities in the spatial distribution were not improved much. The average efficiency of pediatric service fluctuated from 2010 to 2019. A unit increase in PPTC was associated with an 11% reduction in IMR and a 16% reduction in U5MR.Conclusions: Findings suggest this multi-component intervention strategy is effective, particularly on the reduction of child mortality. In future, more rigorous and multi-faceted indicators should be integrated in a comprehensive evaluation of the intervention.

Objective: Risk factors for the development of pneumonia among patients with diabetes mellitus are unclear. The aim of our study was to elucidate the potential risk factors and attempt to predict the probability of pneumonia based on the history of diabetes. Methods: We performed a population-based, prospective multicenter cohort study of 1,043 adult patients with diabetes in China during 2017–2019. Demographic information, comorbidities, or laboratory examinations were collected. Results: The study included 417 diabetic patients with pneumonia and 626 no-pneumonia-onset diabetic patients. The predictive risk factors were chosen on the basis of a multivariate logistic regression model to predict pneumonia among patients with diabetes including: male sex (odds ratio [OR]=1.72, 95% confidence interval [CI]: 1.27–2.33, p

Objectives: Left ventricular (LV) involvement has been associated with unfavorable prognosis in arrhythmogenic cardiomyopathy (ACM). We aim to evaluate LV mechanics by cardiovascular magnetic resonance-feature tracking (CMR-FT) in ACM patients with right ventricular (RV) dysfunction.Methods: We retrospectively recruited ACM patients diagnosed according to the revised Task Force Criteria (rTFC) from January 2015 to July 2017. All patients underwent CMR examinations and collections of clinical, electrocardiographic data. The strain and dyssynchrony parameters of LV and RV were analyzed. These patients were followed, and primary study outcome was defined as a composite of cardiovascular events (arrhythmic events and heart transplantation), secondary study outcome included arrhythmic events.Results: Eighty-nine ACM patients (40.40 ± 13.98 years, 67.42% male) were included. LV and RV ejection fractions were 49.12 ± 12.02% and 22.28 ± 10.11%, respectively. During a median (IQR) follow-up for 18.20 (11.60-30.04) months, 30 patients experienced cardiovascular events which included 22 patients who experienced arrhythmic events. Patients with cardiovascular events had impaired LV global longitudinal strain (−10.82 ± 2.77 vs. −12.61 ± 3.18%, p = 0.010), impaired LV global circumferential strain (−11.81 ± 2.40 vs. −13.04 ± 2.83%, p = 0.044), and greater LV longitudinal dyssynchrony (LVLD) (80.98 ± 30.98 vs. 64.23 ± 25.51 ms, p = 0.012) than those without. After adjusting for age, sex, and other confounding factors, LVLD ≥89.15 ms was an independent risk factor for cardiovascular events (HR: 4.50, 95% CI: 1.94 to 10.42; p = 0.001) and for arrhythmic events (HR: 4.79, 95% CI: 1.74 to 13.20; p = 0.003).Conclusions: LVLD by CMR-FT was an independent risk factor for cardiovascular and arrhythmic events in ACM patients in advanced stage, which could provide prognostic value for this subtype.

OBJECTIVE This study aimed to investigate the clinical effects and perioperative treatment experience of elderly patients with valvular heart disease combined with coronary heart disease undergoing cardiac valve surgery (CVS) and coronary artery bypass grafting (CABG) concurrently. METHODS Seventy-eight patients with heart valve disease and coronary heart disease, aged over 65 and who underwent CVS and CABG concurrently between January 2016 and December 2020, were enrolled in this study. The clinical indexes related to cardiac function before and after surgery, early postoperative complications, and prognosis were analyzed retrospectively to explore the clinical effects and perioperative treatment experience of elderly patients undergoing these two procedures concurrently. RESULTS All patients were reexamined by echocardiography one month after surgery. The results showed that the left ventricular end-diastolic dimension, N-terminal pro-B-type natriuretic peptide levels, cardiothoracic ratio, and troponin-I levels were significantly lower than before surgery, and the differences were statistically significant (P < 0.05). The echocardiography revealed that the left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening were larger than before surgery, and these differences were statistically significant (P < 0.05). CONCLUSION It is feasible and effective for elderly patients to undergo CVS and CABG concurrently. Perioperative management can reduce mortality, achieving good clinical effects.

S100B, a member of the multigene family of Ca 2+ -binding proteins, is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. Recently, we demonstrated that low concentrations of S100B attenuated microglia activation through the induction of STAT3. Furthermore, S100B downregulation in a murine glioma model inhibited macrophage trafficking and tumor growth. Based on these observations, we hypothesized that S100B inhibitors may have antiglioma properties through modulation of tumor microenvironment. To discover novel S100B inhibitors, we developed a high-throughput screening cell-based S100B promoter-driven luciferase reporter assay. Initial screening of 768 compounds in the NIH library identified 36 hits with >85% S100B inhibitory activity. Duloxetine (Dul, an SNRI) was selected for the initial proof-of-concept studies. At low concentrations (1–5 μM) Dul inhibited S100B and CCL2 production in mouse GL261 glioma cells, but had minimal cytotoxic activity in vitro . In vivo , however, Dul (30 mg/kg/14 days) inhibited S100B production, altered the polarization and trafficking of tumor-associated myeloid-derived cells, and inhibited the growth of intracranial GL261 gliomas. Dul therapeutic efficacy, however, was not observed in the K-Luc glioma model that expresses low levels of S100B. These findings affirm the role of S100B in gliomagenesis and justify the development of more potent S100B inhibitors for glioma therapy.

This study explored the magnitude and clinical correlates of anxiety in three groups of patients with major depressive disorder (MDD): those with comorbid anxiety disorders (the COM group), those with subthreshold core anxiety disorder symptoms that are the screening items for anxiety disorders on the MINI (the SUB group), and those with neither anxiety disorders nor subthreshold core anxiety disorder symptoms (the NON group). Anxiety symptomatology of 1052 patients from 8 psychiatric settings in mainland China, who met DSM-IV TR criteria for MDD, was assessed using the MINI. The presence of core anxiety symptoms was determined by patient endorsement of any screening item of panic disorder, agoraphobia, social anxiety disorder, or generalized anxiety disorder. The prevalences of comorbid subthreshold core anxiety symptoms and anxiety disorders were 13% and 28.7%, respectively. The SUB and COM cases showed similar patterns of clinical presentation. Both were more likely than the NON cases to be characterized by younger age, concurrent dysthymia and OCD, suicidal ideation and attempted suicides. These findings highlight the importance of assessing both anxiety symptoms and anxiety disorders in the presence of MDD, and suggest the need for novel assessments capable of addressing different levels of anxiety in depressed patients.

PURPOSE Hypertension (HTN) patients suffer from increased risk of left ventricular (LV) diastolic dysfunction and LV hypertrophy (LVH). Evaluation of early LV diastolic function requires accurate noninvasive diagnostic tools. The aim of this study was to evaluate whether cardiovascular magnetic resonance feature-tracking (CMR-FT) could detect early LV dysfunction and evaluate LV-left atrium (LA) correlation in HTN patients. MATERIALS AND METHODS In all, 89 HTN patients and 38 age-matched and sex-matched controls were retrospectively enrolled and underwent CMR examination. HTN patients were divided into LVH (n=38) and non-LVH (n=51) groups. All LV deformation parameters were analyzed in radial, circumferential, and longitudinal directions, including peak strain, peak systolic strain rate and peak diastolic strain rate (PDSR), LA strain and strain rate (SR), including LA reservoir function (es, SRs), conduit function (ee, SRe), and booster pump function (ea, SRa). RESULTS Compared with controls, the LV PDSR in radial, circumferential, and longitudinal directions and the LA reservoir and conduit function were significantly impaired in HTN patients regardless of LVH (all P

Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. Interactions between high pesticide levels and polymorphisms in rs11931074 and rs16940758 (α-HCH or β-HCH interacted with TT genotype in rs11931074 and δ-HCH interacted with TT genotype in rs16940758) were associated with the risk of PD. In cell model, α-HCH and propanil increased the level of reactive oxygen species and decreased the mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

Background Collagen cross‐linking is covalent bonds among collagen fibers from catalysis of lysyl oxidase (LOX) and advanced glycation end products (AGEs). We aimed to evaluate the formation of enzymatic and nonenzymatic collagen cross‐linking and its clinical significance in patients with hypertrophic obstructive cardiomyopathy. Methods and Results Forty‐four patients with hypertrophic obstructive cardiomyopathy who underwent surgical myectomy were consecutively enrolled. Cardiovascular magnetic resonance parameters of left atrial/left ventricular function were measured, including peak filling rate (PFR) and early peak emptying rate (PER‐E). Total collagen was the sum of soluble and insoluble collagen, which were assessed by collagen assay. The myocardial LOX and AGEs expression were measured by molecular and biochemical methods. Compared with patients without atrial fibrillation, insoluble collagen ( P =0.018), insoluble collagen fraction ( P =0.017), and AGEs ( P =0.039) were higher in patients with atrial fibrillation, whereas LOX expression was similar ( P =0.494). The insoluble collagen fraction was correlated with PFR index (PFR normalized by left ventricular filling volume) (r=−0.44, P =0.005), left atrial diameters (r=0.36, P =0.021) and PER‐E index (PER‐E normalized by left ventricular filling volume) (r=−0.49, P =0.001).Myocardial LOX was positively correlated with total collagen (r=0.37, P =0.025) and insoluble collagen fraction (r=0.53, P P =0.006) and PER‐E index (r=−0.35, P =0.027). In multiple regression analysis, myocardial LOX was independently associated with PFR, while insoluble collagen fraction showed independent correlation with PER‐E after adjustment for clinical confounders. Conclusions Collagen cross‐linking plays an important role on heart remodeling in hypertrophic obstructive cardiomyopathy. Myocardial LOX expression is independently correlated with left ventricular stiffness, while accumulation of AGEs cross‐links might be associated with the occurrence of atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy.

Background Arrhythmogenic cardiomyopathy (ACM) is characterized by a high incidence of ventricular tachyarrhythmia and sudden death. Implantable cardioverter-defibrillator (ICD) implantation is the cornerstone of management. Objective This study aims to reveal the prognostic value of the contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) amount in predicting varying lethal outcomes among ACM patients with ICDs. Methods The 88 patients with definite ACM who were all referred for contrast-enhanced CMR received an ICD and were followed up for a median of 4.0 years. Results Fifty-four patients had no left ventricular (LV) involvement and sixteen had an LV LGE amount > 15%. During the follow-up time, appropriate ICD therapy was seen in 57, electrical storm (ES) in 19, and cardiac death in 9 patients. Compared with those without LV involvement, patients with LV LGE amount > 15% had a higher risk of cardiac death (log-rank P = 0.021). LV LGE amount was associated with an increased risk of ICD therapy [adjusted hazard ratio (HR) 1.035, 95% confidence interval (CI) 1.008–1.062, P = 0.010], and cardiac death (adjusted HR 1.082, 95% 1.006–1.164, P = 0.034), independently of LV ejection fraction. LV LGE mass of >15% demonstrated an over 2-fold increase in ICD therapy (adjusted HR 2.180, 95%CI 1.058–4.488, P = 0.035) and an over 7-fold increase in cardiac death (unadjusted HR 7.198, 95%CI 1.399–37.043, P = 0.018) than those without LV involvement, respectively. Conclusions The LV LGE-CMR in ACM shows a dose-dependent association with ICD therapy and cardiac death. And LV LGE amount of >15% is a strong predictor.

Background Huntington’s disease (HD) is a hereditary disease which could have a large impact on patients’ quality of life. As the neurodegenerative disorders progress, HD patients are expected to regularly take follow-up medical visits for proper treatment. This study aimed to analyze the general situation of health services utilization of Chinese HD patients and factors associated with their adherence to follow-up medical visits. Methods We collected data from a questionnaire-based investigation conducted by the Chinese Huntington’s Disease Association. Data from 232 respondents were included to investigate whether they adhered to regular follow-up medical visits and the influencing factors. Based on Andersen’s behavioral model, the independent variables were categorized into predisposing, enabling and need factors. The variables were analyzed by chi-square test and stepwise logistic regression analysis. Results Thirty-one point nine percent of the respondents had regular follow-up medical visits over the past year. Univariate analysis showed that there were significant differences with 6 factors (P Conclusions Poor adherence to medical visits among Chinese HD patients is derived from multiple factors, including reimbursement of health insurance, perceived stage of disease and effectiveness of drugs, need for accompanying family members and self-care ability. To promote HD patients’ health services utilization, the improvement of the health insurance system, the enhancement of social support and the development of therapeutic approaches still have a long way to go.

Objective To understand the genetic diversity and molecular epidemiology characteristics of group A Rotavirus (RVA) in domestic sewage through next generation sequencing (NGS), and to explore the feasibility and necessity of NGS method for RVA environmental surveillance. Methods In this study, two sewage samples from Jinan each quarter in 2019 were selected for concentration, RNA extraction, and then RT-PCR reaction. The amplified positive products were subjected to NGS. Finally, the results were analyzed for diversity and phylogeny. Results A total of 9 G-genotypes and 13 P-genotypes were detected. The Simpson diversity indices in autumn and winter were relatively high. Phylogenetic analysis showed that the dominant types G9 and P[8] were closely related to human-derived sequences. Conclusions This study proves that environmental surveillance as a means to understand the prevalence of RVA in the population is not only feasible but necessary. NGS based environmental surveillance greatly improves our understanding on RVA genetic diversity, and should be encouraged as a sensitive surveillance tool.

IntroductionDespite the increase in the survival rate of high-risk infants (HRIs) worldwide, the prevalence of motor and neurodevelopmental sequelae in such newborns has not shown concomitant improvement. Meanwhile, there are few cohorts that explore factors related to the development of HRIs in China. Therefore, the Guangzhou High-Risk Infant Cohort (GHRIC) has been designed to examine the complex relationships among a myriad of factors influencing growth and development in such children.Methods and analysisThe GHRIC study is a prospective cohort study that by the year 2023 will enrol an estimated total of 3000 HRIs from Guangzhou Women and Children’s Medical Center (GWCMC) in Guangzhou, China. This study is designed to assess the growth and cognitive characteristics of HRIs and the risk factors affecting their development and prognoses. Data on risk factors, neurodevelopmental and cognitive-function evaluations, laboratory results, and specimens will be collected and analysed. Information on perinatal and clinical interventions for these infants will also be recorded during regular follow-up visits until age 6.Ethics and disseminationThe protocol for this study has been approved by the Research Ethics Committee of GWCMC, which accepted responsibility for supervising all of the aspects of the study (No. 2017102712). Study outcomes will be disseminated through conference presentations, peer-reviewed publications, the Internet and social media.Trial registration numberChiCTR-EOC-17013236

Single-cell and in situ cell-based operation with nanopipette approach offers a possibility to elucidate the intracellular processes and may aid the improvement of therapy efficiency and precision. We present here a photo-responsive hydrogel-nanopipette hybrid system that can achieve single-cell operation with high spatial/temporal resolution and negligible cell damage. This strategy overcomes long-time obstacles in nanopipette single-cell studies as high electric potential (ca. 1000 mV) or organic solvent is always used during operations, which would inevitably impose disturbance and damage to targeted cells. The light-triggered system promotes a potential-free, non-invasive single-cell injection, resulting in a well-retained cell viability (90 % survival rate). Moreover, the photo-driven injection enables a precisely dose-controllable single-cell drug delivery. Significantly reduced lethal doses of doxorubicin (163-217 fg cell-1 ) are demonstrated in corresponding cell lines.

Psoriasis is a chronic, recurrent skin disease requiring long‐term management. Agents that repair the skin's barrier function are invaluable additives in topical treatments of psoriasis. This multicenter, randomized, controlled trial evaluated the efficacy and safety of a linoleic acid‐ceramide‐containing moisturizer (LA‐Cer) for mild‐to‐moderate psoriasis vulgaris. We randomized 178 patients from both northern and southern regions of China into two groups: 81 patients in the control group received mometasone furoate (MF, 0.1%) cream, while MF in combination with LA‐Cer was administered to 86 patients in the treatment group for 4 weeks. The LA‐Cer‐MF group maintained the use of moisturizer after topical glucocorticoid administration. The primary endpoint, Psoriasis Area and Severity Index 50 (PASI 50) response, revealed the superiority of LA‐Cer‐MF with lower relapse rates at week 8. The use of the LA‐Cer‐containing moisturizer as maintenance therapy resulted in a continuous improvement in the clinical state in terms of body surface area, PASI, investigators' assessment of skin dryness and desquamation, and Physician Global Assessment of Psoriasis score, and in the patients' quality of life. Thus, the LA‐Cer‐containing moisturizer is a promising agent to prevent and treat psoriasis as it enhances the therapeutic effect induced by topical glucocorticoids and delays relapse.

Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. The interaction between rs11931074 in α-synuclein (SNCA) and α-HCH or β-HCH, respectively, as well as rs16940758 in the microtubule-associated protein tau (MAPT) gene and δ-HCH were related to increased risk of PD. In addition, α-HCH and propanil enhanced the production of reactive oxygen species and decreased of mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

Saikosaponin a (SSa), a triterpene saponin extracted from Bupleurumfalcatum L., has been reported to have anti-inflammatory activity. In the present study, we investigated the effects of SSa on lead-induced kidney injury in common carp. Kidney histological changes were detected by H&E staining. The levels of TNF-α, IL-1β, MPO, MDA, GSH, and SOD activity were also measured. Furthermore, the NF-κB and Nrf2 signaling pathways were tested by western blot analysis. The results showed that lead-induced kidney histological change was attenuated by SSa. Lead-induced TNF-α, IL-1β, MPO, and MDA production were also suppressed by SSa. Meanwhile, lead could decrease GSH level and SOD activity and the decreases were inhibited by SSa. Furthermore, we found SSa significantly inhibited lead-induced NF-κB translocation. In addition, the expression of Nrf2 and HO-1 were increased by the treatment of SSa and Keap1 expression was decreased by SSa. In conclusion, this study indicated that SSa inhibited lead-induced kidney injury in carp through suppressing inflammatory and oxidative responses, and the mechanism may be involved in the inhibition of NF-κB and activation of Nrf2 signaling pathway.

Summary Background & aims Previous studies linking the gut microbiome with childhood obesity largely used the body mass index to measure obesity and reached inconsistent findings. Little evidence has linked the gut microbiome to regional body fat deposition. We investigated whether the abundance of specific taxa in the gut microbiota and the concentrations of short-chain fatty acids (SCFAs) were associated with the content and regional deposition of body fat in children. Methods This cross-sectional study involved 236 children aged 6–9 years. The fat mass contents/percentages in the total body and the android, gynoid, and limb regions were determined by dual-energy X-ray absorptiometry, and the android-to-gynoid fat mass ratio and fat-to-lean mass ratios were calculated. Fecal samples were subjected to16S rRNA amplicon sequencing, and the fecal SCFA concentrations were quantified via high-performance liquid chromatography. Results A weighted gene co-expression network analysis identified seven modules of co-expressed operational taxonomic units (OTUs). A total of 57 OTUs from 4 key modules were selected for further analysis. After adjustment of covariates and controlling for the false discovery rate (FDR), a multiple linear regression analysis revealed significant correlations of the abundances of some OTUs with obesity and body fat measures. For instance, the OTUs classified to the species Ruminococcus gnavus and Flavonifractor plautii showed significant negative correlations with the total and regional body fat (β: −0.250 to −0.180, PFDR: 0.041–0.049), whereas OTUs belonging to the genera Blautia and Romboutsia exhibited positive correlations with body fat measures (β: 0.184–0.222, PFDR: 0.041–0.049). The fecal concentrations of acetic, propionic, and butyric acids and total SCFAs were significantly positively correlated with various parameters of body fat distribution (β: 0.160–0.275, PFDR: Conclusion The gut microbiome and SCFAs are significantly associated with obesity and body fat distribution in pediatric population.

Background. To eliminate mother-to-child transmission of syphilis, the Chinese government recommends a treatment regimen that slightly differs from the World Health Organization- (WHO-) recommended treatment. However, little is known about their difference in efficacy. This study is aimed at comparing the effect of China-recommended and WHO-recommend treatment regimens on adverse pregnancy outcomes (APOs) and at examining associated risk factors of APOs among syphilis-seropositive women. Methods. Using the syphilis registry data, we retrospectively collected data from 4488 syphilis-infected pregnant women in Guangzhou during 2011-2018. Multivariate analyses were used to investigate the association between treatment regimens and APOs (ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth or low birth weight, newborn smaller than gestational age, congenital syphilis, and infant death) and the association between risk factors and APOs. Results. Of 3474 participants, 27.3% had at least one APO. Compared to those receiving WHO-recommended treatment, women who received China-recommended treatment were less likely to have APOs (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.38-0.57), whereas those who received no treatment had 1.6 times higher odds of experiencing APOs. One common risk factor across different APOs was high levels of log2-transformed toluidine red unheated serum test (TRUST) titers before treatment (OR 1.14, 95% CI 1.10-1.19). China-recommended treatment was effective in reducing APOs for those with TRUST≥1:8 (OR 0.21, 95% CI 0.14-0.29) and those with TRUST<1:8 (OR 0.62, 95% CI 0.50-0.77). Conclusions. Syphilis-seropositive women receiving China-recommended treatment had lower odds of APOs, especially when TRUST titers before treatment were high. Findings can be used to guide health professionals to reduce APOs among syphilis-infected mothers and promote nationwide use of China-recommended treatment.

Background Great growth inequalities between urban and rural areas have been reported in China over the past years. By examining urban/rural inequalities in physical growth among children Methods The height, body weight and nutrition status of children under 7 years old were obtained from two successive cross-sectional surveys and one health surveillance system. Student’s t-test, Spearman’s rank-order correlation and polynomial regression were used to assess the difference in physical growth between children in urban and rural areas and the association between socioeconomic index and secular growth changes. Results A height and weight difference was found between urban and rural children aged 0–6 years during the first two decades of our research (1985–2005), which gradually narrowed in both sex groups over time. By the end of 2015, elder boys (age group ≥5 year) and girls (age group ≥4 year) in rural areas were taller than their counterparts in urban areas (p P = 0.03) for boys, and a − 0.05 difference (P = 0.82) for girls. When GDP increased, the gap in boys’ weight-for-age z-score (WAZ from 0.25 to 0.01) and height-for-age z-score (HAZ from 0.55 to 0.03) between urban and rural areas diminished, and disappeared when the GDP per capita (USD) approached 25,000. In either urban or rural areas, the urbanization rate and GDP were positively associated with the prevalence of obesity (all R > 0.90 with P R P Conclusion Growth inequalities gradually decreased with economic development and urbanization, while new challenges such as obesity emerged. To eliminate health problems due to catch-up growth among rural children, comprehensive intervention programs for early child growth should be promoted in rural areas.

Although obesity is considered osteoprotective, the effects of body fat and fat distribution on bone tissue after adjusting for the effects of body weight remain uncertain. This study evaluated the relationships between fat mass, fat distribution, and bone mineral status beyond its weight-bearing effect. We recruited 466 children aged 6&ndash, 10 years in China. Dual-energy X-ray absorptiometry was used to determine the bone mineral density (BMD) and bone mineral content (BMC) in the total body and total body less head (TBLH), as well as the fat mass (FM) and percentage fat mass (%FM) of the total and segmental body. Weight-adjusted measures of FM and %FM were derived using the residual method. After adjusting for the effects of covariates, we observed statistically significant, dose-dependent negative relationships between the TBLH&middot, BMD/BMC and various weight-adjusted measures of body fat (p for trend: &lt, 0.001&ndash, 0.038). For each standard deviation increment in the weight-adjusted total body, TBLH, trunk and limbs, the size-adjusted BMC decreased approximately 9.44, 9.28, 8.13, and 6.65 g in boys, respectively, and by approximately 13.74, 13.71, 7.84, and 12.95 g in girls, respectively. Significant inverse associations between FM accumulation in the total body and most body parts with the BMD/BMC were observed in both boys and girls after adjusting for weight and potential confounders.

Renal interstitial fibrosis is considered to be the typical manifestation of diabetic nephropathy (DN). Mangiferin has shown positive effect on the prevention or treatment of diabetes and its complications. The aim of this study was to explore the inhibitive effect and mechanism of mangiferin on renal interstitial fibrosis in diabetic mice. Streptozotocin- (STZ-) induced diabetic mice were treated with mangiferin (15, 30, and 60 mg/kg/d) for 4 weeks. The morphology of kidneys was observed by Masson’s trichrome staining, and the biochemical parameters (fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), serum creatinine (SCr), and urine protein) were determined by kits. In addition, the levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and IL-1β), antioxidant enzymes (SOD, CAT, and GSH-Px), MDA, and ROS were assessed. Furthermore, the expressions of fibronectin (FN), collagen I (Col I), and α-SMA were measured by immunohistochemistry. Regulations of TGF-β1 and the PTEN/PI3K/Akt pathway were detected by Western blotting. Treatment with mangiferin significantly ameliorated renal dysfunction in diabetic mice, as evidenced by the increase in body weight and decreases in FBG, TG, TC, BUN, SCr, urine protein, and the kidney to body weight ratio (KW/BW). Furthermore, mangiferin treatment prevented renal interstitial fibrosis evidenced by decreases in the positive expression of FN, Col I, and α-SMA, in comparison with morphological changes in the renal tissue. Meanwhile, mangiferin increased antioxidant enzymes, reduced the TNF-α, IL-6, and IL-1β, as well as MDA and ROS. Additionally, mangiferin administration also downregulated TGF-β1, upregulated PTEN, and decreased the phosphorylation of both PI3K and Akt. These findings demonstrate that mangiferin may reduce inflammation and oxidative stress in DN, thereby inhibiting the renal interstitial fibrosis by reducing the TGF-β1-mediated elevation of Col I, FN, and α-SMA through the PTEN/PI3K/Akt pathway.

Biothiols are crucial reactive sulfur species in living cells, playing an essential role in maintaining the normal function of organisms. Effective detection of biothiols promotes the exploration of metabolic pathways and physiological functions of organisms. In this paper, a cyanine-based, mitochondria-targetable fluorescent probe, Cy-DNBS, was designed and synthesized. This probe uses a lipophilic cation unit as mitochondrial targeting site and DNBS group as the fluorescence quencher as well as the recognition site. The probe shows a distinct fluorescence emission at 604 nm upon rapid interaction with intracellular biothiols, owing to the removal of the 2,4-dinitrobenzene-sulfonyl (DNBS) group and the blockage of PET process. Moreover, the probe can not only image endogenous thiols, but also efficiently target mitochondria and evaluate thiol fluctuations under mitochondrial oxidative stress induced by H2O2. Collectively, the new low cytotoxic probe can serve as a promising tool for monitoring cellular thiols and further exploring elevant disease processes.

// Hang Gao 1 , Yanyan Song 2 , Dongsong Li 1 , Wei Feng 1 and Jianguo Liu 1 1 Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, Jilin Province, China 2 Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin Province, China Correspondence to: Jianguo Liu, email: jgliu.2005@aliyun.com Keywords: osteoarthritis chondrocyte, IL-1β, NF-κB, LXRα Received: May 04, 2017 Accepted: August 26, 2017 Published: September 30, 2017 ABSTRACT Saikosaponin a (SSa), one of the main active components of Bupleurum falcatum , has been reported to have anti-inflammatory effect. In the present study, we investigated the anti-inflammatory effect of SSa on IL-1β-stimulated human osteoarthritis chondrocytes. The cells were pretreated with SSa 12 h before IL-1β treatment. The production of PGE2 and NO were detected by ELISA and Griess method. The levels of MMP1, MMP3, and MMP13 were measured by ELISA and qRT-PCR. The expression of NF-κB and LXRα were tested by western blot analysis. The results showed that SSa inhibited IL-1β-induced PGE2 and NO production in a concentration-dependent manner. SSa also suppressed IL-1β-induced MMP1, MMP3, and MMP13 production. Furthermore, SSa significantly attenuated IL-1β-induced phosphorylation levels of NF-κB p65 and IκBα. SSa also up-regulated the expression of LXRα. The inhibition of SSa on PGE2, NO, MMP1, MMP3, and MMP13 production were reversed by LXRα siRNA or GGPP, the inhibitor of LXRα. In conclusion, our results demonstrated that SSa inhibited inflammatory responses in human chondrocytes in vitro . SSa might be a potential therapeutic drug for osteoarthritis.

// Weiwei Gai 1, 2, * , Wenwen Zheng 1, * , Chong Wang 3, * , Gary Wong 4 , Yanyan Song 1 and Xuexing Zheng 2 1 College of Veterinary Medicine, Jilin University, Changchun, China 2 School of Public Health, Shandong University, Jinan, China 3 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China 4 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China * These authors have contributed equally to this work Correspondence to: Xuexing Zheng, email: zhengxx2513@hotmail.com Keywords: rabies virus, IL-18, immune responses, vaccine, antibody titer Received: March 03, 2017 Accepted: July 18, 2017 Published: September 16, 2017 ABSTRACT Several studies have shown that interleukin-18 (IL-18) plays an important role in both innate and adaptive immune responses. In this study, we investigated the pathogenicity and immunogenicity of recombinant rabies virus expressing IL-18 (rHEP-IL18). Experimental results showed that Institute of Cancer Research (ICR) mice that received a single intramuscular immunization with rHEP-IL18 elicited the highest titers of serum neutralizing antibodies and the strongest cell-mediated immune responses to prevent the development of rabies disease, compared with immunization with the parent virus HEP-Flury. Mice inoculated with rHEP-IL18 developed significantly higher IFN-γ responses, increased percentages of CD4 + and CD8 + T-lymphocytes compared to HEP-Flury. Flow cytometry results show that rHEP-IL18 recruited more activated T- and B-cells in lymph nodes or peripheral blood, which is beneficial for virus clearance in the early stages of infection. A higher percentage of mice immunized with rHEP-IL18 survived wild-type rabies virus (RABV) challenge, compared to HEP-Flury mice. Our results show that rHEP-IL18 is promising as a novel vaccine for RABV prevention and control.

Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found to ameliorate diabetic testicular damage (DTD) in rodents. However, it was unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on multiple diabetic complications. However, the effect of EGCG has not been studied in DTD. The present study aims to explore the role of NRF2 in both self and EGCG protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced loss in testicular weight and spermatozoa count, and increase in testicular apoptotic cell death, as compared with the WT mice. EGCG activated NRF2 expression and function, preserved testicular weight and spermatozoa count, and attenuated testicular apoptotic cell death, endoplasmic reticulum stress, inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO diabetic mice. The present study demonstrated for the first time that NRF2 plays a critical role in both self and EGCG protection against DTD.

The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling. This review summarizes the evasion strategies of host cGAS DNA sensing pathway by Kaposi’s Sarcoma-associated Herpesvirus (KSHV) and their contributions to KSHV life cycles. [Image: see text]

Environmental surveillance has been used successfully in monitoring enterovirus (EV) circulation; however cell culture method may introduce a selective bias in those EV strains that are recovered from the environment. In this study, urban sewage samples were collected monthly in Jinan, China in 2018 and concentrated via membrane adsorption/elution method. A P1 seminested RT-PCR (RT-snPCR) and NGS method was developed, by which amplicons of 4000 nucleotide in length covering the entire P1 region of EVs were obtained from sewage concentrates and were further analyzed by next generation sequencing (NGS). In addition, for each sewage concentrate, two other assays - cell culture and NGS based partial VP1 amplicon sequencing - were conducted in parallel and compared. The results showed that the P1 RT-snPCR and NGS method generated the most data, with 32 serotypes identified belonging to species EV-A (n = 11), EV-B (n = 14), and EV-C (n = 7). These serotypes covered all those detected from the methods of cell culture (n = 10) and partial VP1 amplicon sequencing (n = 16). EV serotypes from acute flaccid paralysis surveillance correlated with those from sewage. Phylogenetic analysis on coxsackievirus B5, a common pathogen of meningitis, revealed close genetic relationship between environmental and clinical sequences. These results demonstrate sewage contains different EVs related to a variety of diseases. Traditional cell culture method underestimates the existence of some serotypes. NGS based environmental surveillance provides data which are consistent with those from clinical diseases, greatly improves our understanding on the actual circulation in the population, and should be encouraged for public health surveillance.

Background Left ventricular ( LV ) involvement is common in arrhythmogenic right ventricular cardiomyopathy ( ARVC ). We aim to evaluate LV involvement in ARVC patients by cardiovascular magnetic resonance feature tracking. Methods and Results Sixty‐eight patients with ARVC and 30 controls were prospectively enrolled. ARVC patients were divided into 2 subgroups: the preserved LV ejection fraction (LVEF) group ( LVEF ≥55%, n=27) and the reduced LVEF group ( LVEF LGE ) and cardiovascular magnetic resonance feature tracking were performed in all subjects. LV global and regional (basal, mid, apical) peak strain ( PS ) in radial, circumferential and longitudinal directions were assessed, respectively. Right ventricular global PS in three directions were also analyzed. Compared with the controls, LV global and regional PS were all significantly impaired in the reduced LVEF group (all P LV global longitudinal PS as well as mid and apical longitudinal PS were impaired in the preserved LVEF group (all P PS ( r =−0.47, −0.47, and −0.49, respectively, all P LVEF group showed significantly higher prevalence of LGE (95.10% versus 63.00%, P =0.002) than the preserved LVEF group. Moreover, LV radial PS was significantly reduced in LV segments with LGE (33.15±20.42%, n=46) than those without LGE (41.25±15.98%, n=386) in the preserved LVEF group ( P =0.016). Conclusions In patients with ARVC , cardiovascular magnetic resonance feature tracking could detect early LV dysfunction, which was associated with LV myocardial LGE and right ventricular dysfunction.

Background Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness. Aim To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line H pylori treatment in a region with high antimicrobial resistance. Methods We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s. Primary outcome was H pylori eradication. Results Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4% (82/96, P = 0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI -3.1% to 3.2%) and 6.2% intent-to-treat (-0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates. Conclusions Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy.

In the present study, our bioinformatics analysis first reveals the existence of a conserved guanine-rich sequence within the Zaire ebolavirus L gene. Using various methods, we show that this sequence tends to fold into G-quadruplex RNA. TMPyP4 treatment evidently inhibits L gene expression at the RNA level. Moreover, the mini-replicon assay demonstrates that TMPyP4 effectively inhibits the artificial Zaire ebolavirus mini-genome and is a more potent inhibitor than ribavirin. Although TMPyP4 treatment reduced the replication of the mutant mini-genome when G-quadruplex formation was abolished in the L gene, its inhibitory effect was significantly alleviated compared with wild-type. Our findings thus provide the first evidence that G-quadruplex RNA is present in a negative-sense RNA virus. Finally, G-quadruplex RNA stabilization may represent a new therapeutic strategy against Ebola virus disease.