Search

Developmental sevoflurane exposure leads to widespread neuronal cell death known as sevoflurane-induced neurotoxicity (SIN). Receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL)-driven necroptosis plays an important role in cell fate. Previous research has shown that inhibition of RIPK1 activity alone did not attenuate SIN. Since RIPK3/MLKL signaling could also be activated by Z-DNA/RNA binding protein 1 (ZBP1), the present study was designed to investigate whether ZBP1-mediated and RIPK3/MLKL-driven necroptosis is involved in SIN through in vitro and in vivo experiments. We found that sevoflurane priming triggers neuronal cell death and LDH release in a time-dependent manner. The expression levels of RIPK1, RIPK3, ZBP1 and membrane phosphorylated MLKL were also dramatically enhanced in SIN. Intriguingly, knockdown of RIPK3, but not RIPK1, abolished MLKL-mediated neuronal necroptosis in SIN. Additionally, inhibition of RIPK3-mediated necroptosis with GSK'872, rather than inhibition of apoptosis with zVAD, significantly ameliorated SIN. Further investigation showed that sevoflurane treatment causes mitochondrial DNA (mtDNA) release into the cytosol. Accordingly, ZBP1 senses cytosolic mtDNA and consequently activates RIPK3/MLKL signaling. This conclusion was reinforced by the evidence that knockdown of ZBP1 or depleting mtDNA with ethidium bromide remarkably improved SIN. Finally, the administration of the RIPK3 inhibitor GSK'872 relieved sevoflurane-induced spatial and emotional disorders without influence on locomotor activity. Altogether, these results illustrate that ZBP1 senses cytosolic mtDNA to induce RIPK3/MLKL-driven necroptosis in SIN. Elucidating the role of necroptosis in SIN will provide new insights into understanding the mechanism of anesthetic exposure in the developing brain.

Accurate identification of diabetic foot ulcer infection (IDFU) through inflammatory markers is still a challenge in clinical practice.This meta-analysis aims to investigates whether there is a significant indigenous association between CRP level and diabetic foot ulcer infection.The studies on the diagnosis of IDFU by inflammatory marker C-reactive protein published before November 2021 in PubMed, Web of Science, Embase, and Cochrane Library were searched. Since the included seven studies were cohort studies and cross-sectional studies, the quality evaluation was founded on the standard of Newcastle-Ottawa Scale (NOS), which was convenient and straightforward. The stata 15.0 software (Cambridge, UK) was used for statistical analysis of data collected for analysis.Finally, we included seven articles and investigated 592 patients, including 362 patients with IDFU and 230 patients without diabetic foot ulcer infection (NIDFU). Seven studies assessed the results of CRP, with significant heterogeneity among included studies (χMeta-analysis showed a clear association between C-reactive protein and IDFU. Understanding the pathophysiology of IDFU and rapid identification of risk factors for reducing patient burdens, amputation, and mortality are essential.

The present study was designed to determine the association between Acute Physiology and Chronic Health Evaluation (APACHE) scale and elevated pressure injure (PI) risk in intensive care units (ICU) and also evaluate the predictive value of APACHE score in PI patients. Comprehensive strategies were used to search studies from PubMed, Web of Science, and Ovid Embase electronic databases for observational studies that provided data about APACHE scores related to PI in ICU. Eligible studies were selected based on inclusion and exclusion criteria. The pooled SMD with 95% confidence intervals were calculated. A summary ROC curve was plotted to calculate area under curve (AUC) for APACHE-II (15-20). Twenty-one studies involving 11,102 patients who met selection criteria were included. The 11.0% of patients (1229/11102) in ICU developed PIs. Overall, the PI group had a higher score compared with the non-PI group in the APACHE II (22.1 ± 8.0 vs. 14.5 ± 7.4, mean ± SD). The APACHE-III of PI patients was significantly more than that in the non-PI group (79.9 ± 25.6 vs. 59.9 ± 30.4, mean ± SD). The pooled SMD was 0.82 (95% CI: 0.58-1.06, I

Aim: This study aims to provide reliable prognostic factors for patients with cryptococcal meningitis (CM). Patients & methods: Clinical characteristics and laboratory findings of CM patients were retrospectively reviewed. Results: Sixty-three patients with CM were enrolled and 38/63 were confirmed to be HIV serology positive. Among clinical characteristics, headache, nausea and/or vomiting, and fever were the most common symptoms. Among cerebrospinal fluid (CSF) parameters, changes in leukocyte count, lactate dehydrogenase and chloride were significantly associated with the outcome. An increased CSF/serum albumin quotient (QAlb) was indicative of an unfavorable outcome in HIV-negative patients. Conclusion: CSF lactate dehydrogenase and QAlb may improve the prediction of outcomes in patients with CM.

Background Numerous studies have examined catastrophic health expenditures (CHE) worldwide, mostly focusing on general or common chronic populations, rather than particularly vulnerable groups. This study assessed the medical expenditure and compensation of lung cancer, and explored the extent and influencing factors of CHE among households with lung cancer patients in China. Methods During 2018–2019, a hospital-based multicenter retrospective survey was conducted in seven provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. CHE was measured according to the proportion of out-of-pocket (OOP) health payments of households on non-food expenditures. Chi-square tests and logistic regression analysis was adjusted to determine the factors that significantly influenced the likelihood of a household with lung cancer patient to incur in CHE. Results In total, 470 households with lung cancer patients were included in the analysis. Health insurance was shown to protect some households from the impact of CHE. Nonetheless, CHE incidence (78.1%) and intensity (14.02% for average distance and 22.56% for relative distance) were still relatively high among households with lung cancer patients. The incidence was lower in households covered by the Urban Employee Basic Medical Insurance (UEMBI) insurance, with higher income level and shorter disease course. Conclusion More attention is needed for CHE incidence among vulnerable populations in China. Households with lung cancer patients were shown to be more likely to develop CHE. Therefore, policy makers should focus on improving the financial protection and reducing the economic burden of this disease.

Purpose To explore the high-risk period of the occupation of suicide after diagnosis; and clarify the risk factors of suicidal behaviors (suicidal ideation, suicide attempt, and suicidal death) behind the lung cancer patients during the cancer cure process. Methods This scoping review was conducted through the whole month of April 2021. We extracted data of the suicide mortality after diagnosis and latent risk factors of suicidal behaviors among lung cancer patients where we used to study from the two online databases which are PubMed and Web of Science. Two online databases were searched and written in English without age restriction. To note that the standardized mortality ratio (SMR), person-years, and odds ratio (OR) associated with lung cancer were documented. Results Out of 570 records, 23 studies mentioned suicidal behaviors and lung cancer met the included criteria. Eleven (n = 47.8%) of the selected publications reported changes in suicide mortality. None of them reported suicidal ideation or suicide attempt after diagnosis. The individuals with lung cancer have significantly higher rates of suicidal death (SMR, 2.04-13.4) during the first years after diagnosis and decrease over subsequent years (SMR, 0.66-3.17). The median time from cancer diagnosis to suicide death was around 7 months. Across all studies with the 22 studies that examined factors, we extracted the data of the suicidal ideation (n = 3), suicide attempt (n = 1), and suicidal death (n = 18) in individuals. For patients with suicidal ideation, there was a significantly higher incidence in males than in females. Among patients who attempted suicide, the incidence of mental illness is greater than the incidence of physical illness. Factors for suicidal death, including gender (male, 56.3-100%), prognosis tumors (poor, 25.8-66.3%), marital status (widowhood or unmarried, 19-75.7%), and age of patients (> 70 years, 24.5-47%) with lung cancer, play a vital role. Treatment of lung cancer is expected to affect a patient in his/her mental state. Conclusion Overall, our finding indicates that lung cancer patients have been presented with a higher incidence of suicide death in a specific period, especially the early years after diagnosis. Discovering risk factors for suicide helps prevent potential suicide. It is essential to screen lung cancer patients for suicidal ideation, especially those with high-risk factors. Future prospective studies are necessary to confirm these findings to support care.

Background and Purpose: Aceruloplasminemia (ACP) is a rare disorder of iron overload resulting from ceruloplasmin (CP) variants. Because of its rarity and heterogeneity, the diagnosis of ACP is often missed or misdiagnosed. Here, we aim to present a clinical spectrum of ACP and raise more attention to the early diagnosis. Methods: Whole exome sequencing (WES) was performed in a Chinese female patient suspected with ACP and her clinical data were collected in detail. The PubMed databases was searched for published ACP patients within the last decade, and we present a systematic review of their clinical features with data extracted from these researches. Results: A novel pathogenic variant (c.2689delC) and a known pathogenic variant (c.606dupA) within ceruloplasmin gene were identified in our patient and confirmed the diagnosis of ACP. Then we reviewed 50 ACP patients including the case we reported here. A possible timeline of symptoms was discovered, anemia appears first (29.7 years old on average), followed by diabetes (37.3 years old) and finally neurological symptoms (52.2 years old). The delay in diagnosis was significantly shortened in patients without neurological symptoms. Biochemical triad including anemia, low to undetectable serum ceruloplasmin, low serum iron and/or hyperferritinemia, showed better sensitivity in diagnosis than clinical triad including diabetes, neurological symptoms and retinal degeneration. Conclusions: Due to the variable symptom spectrum, patients with ACP often visit different departments, which can lead to misdiagnosis. Clinical attention needs to be paid to symptoms and tests that have a warning effect. Prompt diagnosis in the early stage of the disease can be beneficial.

Background:. Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC. Methods:. Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI). Results:. A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219–0.599, P

Summary Background & aims Maternal depression has been reported to be harmful to maternal and child health, and nutrition-mental health interactions may play a key role, but evidence from longitudinal studies throughout pregnancy remains insufficient. This study aimed to investigate the association of maternal dietary patterns with depressive symptoms throughout pregnancy. Methods This study was based in the Born in Guangzhou Cohort Study. Dietary patterns were defined by cluster analysis based on validated food frequency questionnaires in mid-pregnancy. A healthy diet score was also developed based on predefined criteria of existing dietary guidelines. Depressive symptoms were measured by Self-rating Depression Scale (SDS) in both early and late pregnancy, with SDS scores ≥53 defined as having depressive symptoms. Associations of dietary patterns with SDS scores were examined by linear-mixed models; associations of dietary patterns with the odds of having depressive symptoms were examined by mixed-effects logistic models. The associations of the healthy diet score with both dietary patterns and depressive symptoms were also explored. Results Six dietary patterns were identified in 17,430 pregnant women, namely ‘Varied’ (n = 3902, 22.4%), ‘Vegetables’ (n = 3269, 18.8%), ‘Meats’ (n = 2951, 16.9%), ‘Cereals’ (n = 2719, 15.6%), ‘Milk’ (n = 2377, 13.6%), and ‘Fruits’ (n = 2212, 12.7%). There were 19.3% and 15.7% of participants with depressive symptoms in early and late pregnancy, respectively. Compared with the ‘Varied’ pattern, all other patterns were associated with lower SDS scores during pregnancy except for ‘Cereals’ (‘Vegetables’: adjusted β [aβ] −0.78, 95% CI −1.16, −0.40; ‘Meats’: aβ −0.48, 95% CI −0.87, −0.09; ‘Milk’: aβ −0.52, 95% CI −0.94, −0.10; ‘Fruits’: aβ −0.85, 95% CI −1.27, −0.42). The ‘Vegetables’ (adjusted OR [aOR] 0.79, 95% CI 0.67, 0.93), ‘Milk’ (aOR 0.76, 95% CI 0.63, 0.91), and ‘Fruits’ (aOR 0.77, 95% CI 0.64, 0.93) patterns were associated with lower odds of having depressive symptoms during pregnancy than the ‘Varied’ pattern. Results for the healthy diet score revealed the healthiness of the ‘Vegetables’, ‘Fruits’, and ‘Milk’ patterns and supported an inverse association between healthy dietary patterns and depressive symptoms throughout pregnancy. Conclusions Diets rich in vegetables, fruits, nuts, and dairy products had an inverse association with depressive symptoms throughout pregnancy. Our findings add support to the existing dietary guidelines that healthy diets might also have potential benefits to maternal mental health.

Objective To examine the longitudinal associations of fetal growth with adverse child growth outcomes and to assess whether maternal metabolic factors modify the associations. Design Prospective cohort study. Setting Born in Guangzhou Cohort Study, China. Population A total of 4818 mother–child pairs. Methods Fetal growth was assessed according to estimated fetal weight (EFW) from 22 weeks of gestation until birth and the measurement of the birthweight. Fetal growth Z‐scores were computed from random effects in the multilevel linear spline models to represent fetal size in early pregnancy (22 weeks of gestation) and growth in mid‐pregnancy (22–27 weeks of gestation), early third trimester (28–36 weeks of gestation) and late third trimester (≥37 weeks of gestation). Main outcome measures Z‐scores for childhood stunting, low weight, overweight or obesity, length/height for age (LAZ/HAZ), weight for age (WAZ) and body mass index for age (BMIZ) at the age of 3 years. Adjusted associations were examined using multiple Poisson or linear regression models. Results Increased Z‐scores of fetal size in early pregnancy and growth in mid‐pregnancy and early third trimester were associated with a higher risk of childhood overweight or obesity (risk ratios 1.25–1.45). Fetal growth in each period was negatively associated with stunting and low weight, with the strongest associations observed for fetal size in early pregnancy and growth in mid‐pregnancy. The results for continuous outcomes (LAZ/HAZ, WAZ and BMIZ) were similar. The associations of fetal growth with overweight or obesity in childhood were stronger among mothers who were underweight and who were overweight or obese than among mothers of normal weight. Conclusions Accelerated fetal growth before 37 weeks of gestation is associated with children who are overweight or obese, whereas the critical period for stunting and low weight occurs before 28 weeks of gestation. Tweetable abstract Fetal growth during different periods is differentially associated with childhood stunting, underweight and overweight or obesity.

Background:. Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions. Methods:. We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths. Results:. Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes. Conclusions:. The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.

Wilson disease (WD) is a hereditary disorder of copper metabolism, resulting from mutations within ATP7B. Early diagnosis is essential for affected individuals. However, there are still patients with clinically suspected WD who do not have detectable pathogenic variants, which makes diagnosis difficult and delays treatment. This study included such patients from the authors' center and screened for the full-length sequence of ATP7B by next-generation sequencing. Newly identified synonymous and intronic variants were then analyzed with in silico tools. A minigene system was constructed to determine the pathogenicity of these variants in terms of splicing and blood RNA extraction, and RT-PCR experiments were performed on several patients to verify the splicing alterations. The phenotypes of the patients were also analyzed. Fourteen suspected pathogenic variants, including nine synonymous and five intronic variants, were detected in 12 patients with clinically suspected WD. Among them, four synonymous variants (c.1050GA, c.1122CG, c.3243GA, and c.4014TA) and four intronic variants (c.1543 +40GA, c.1707+6_1707+16del, c.1870-49AG, and c.2731-67AG) resulted in splicing changes in ATP7B. After the above analysis, the diagnosis of WD could be confirmed in eight clinically suspected patients with WD who showed a late age of onset.

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

OBJECTIVE: To analyze the current status of clinical trial registration of Traditional Chinese Medicine (TCM) for the treatment of neurological diseases. METHODS: Interventional clinical trials of TCM treatment for ischemic stroke, hemorrhagic stroke, vascular cognitive impairment, tension-type headache before September 22, 2020 on the platform of Chinese Clinical Trial Registry (ChiCTR), and ClinicalTrials.gov were searched. Two researchers independently selected the literature and extracted data. RESULTS: A total of 180 interventional clinical trials were included for analysis. Out of 180 trials, 127 were from ChiCTR and 53 from ClinicalTrials.gov. The countries primary sponsoring the included trials were China (176, 97.8%), and the common categories of primary sponsors were hospital (131, 72.8%). Among the study design, the largest proportion of allocation was randomized (172, 95.6%), interventional model assignment was parallel (163, 90.6%), masking was double blind 49 (27.2%), and the sample size was ≤ 400 (144, 80.0%). The trials were most carried out at a single center (102, 56.7%). Among the included studies, 112 (62.2%) registered on ChiCTR attached the ethical approval documents. In terms of trial stages, 50 (27.7%) studies were in phase Ⅳ. The mostly used intervention was Chinese herbal medicines (99, 55%), acupuncture (68, 37.8%) was the second. By searching the registration number on China National Knowledge Infrastructure Database and PubMed, 38 (21.1%) registered trials were published, including 25 protocol studies and 14 research results with one (NCT02275949) published both the protocol and the results. CONCLUSIONS: Irregular and inadequate reporting, untimely update and publication, insufficient information on traditional medicine unique characteristics, and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases. More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.

Wilson's disease (WD) currently lacks a promising indicator that could reflect neurological impairment and monitor treatment outcome. We aimed to investigate whether serum neurofilament light chain (sNfL) functions as a candidate for disease assessment and treatment monitoring of WD.We assessed preclinical and manifested WD patients' sNfL levels compared to controls and analyzed the differences between patients with various clinical symptoms. We then explored the correlation between clinical scales and sNfL levels. And repeated measurements were performed in 34 patients before and after treatment.WD patients with neurological involvement had significantly higher sNfL levels than both hepatic patients and controls. Positive correlations were found between Unified Wilson's Disease Rating Scale scores and sNfL and between semiquantitative magnetic resonance imaging scales and sNfL levels in WD patients. However, in the treatment follow-up analysis, the trend of sNfL before and after treatment disaccorded with clinical response.These findings suggest that sNfL levels can be an ideal indicator for the severity of neurological involvement but fail to evaluate change in disease condition after treatment. © 2022 International Parkinson and Movement Disorder Society.

Background Infection is a common problem and a major cause of morbidity and mortality for patients in intensive care units (ICUs). According to published meta-analyses, oral care has been found to reduce the risk of nosocomial pneumonia, and has been recommended to improve the oral environment for patients in ICUs. However, relatively little information is available about the effects of oral care in patients without ventilatory support in ICUs. Therefore, this review proposes to evaluate the effectiveness of oral care in preventing pneumonia in non-ventilated ICU patients. Methods Eight databases will be searched for relevant literature, including four Chinese and four English online databases, from their inception to the protocol publication date. Records obtained will be managed and screened via Endnote X7. All literature will be selected following pre-established inclusion criteria by two independent review authors to obtain quality trials. The quality of the included records will be evaluated according to the “risk of bias table”, recommended by the Cochrane Handbook for Systematic Reviews of Interventions. All the data will be extracted by one author and checked by another. If there is any disagreement, a final agreement will be reached with a third reviewer via consultation. If there are missing data, the original authors will be emailed to ask for it. If enough data were collected, the data synthesis will be performed using Review Manager (RevMan5.3). Both a random effect model and a fixed effect model will be undertaken. A Bayesian meta-analysis will also be performed to estimate the magnitude of the heterogeneity variance and comparing it with the distribution using the WinBUGS software. Otherwise, the results will be reported narratively. The sources of heterogeneity will be determined using meta-regression and subgroup analysis if there is significant heterogeneity. A funnel plot will be used to assess publication bias if there are enough records included. The Cochrane Handbook for Systematic Reviews of Interventions will be followed throughout the system evaluation process. Conclusion This review will provide evidence of oral care for intensive care unit patients without mechanical ventilation to prevent nosocomial pneumonia. Trial registration PROSPERO Research registration identifying number: CRD42020146932

Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 µM. Of note, 2,2'-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2'-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2'-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 µM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.

Antibiotics are designed to treat bacterial infections in humans and animals; however, the overuse of various antibiotics and consequent contamination in the environment can have adverse effects on aquatic, soil, and saprophytic organisms. The house fly, an important decomposer in ecosystems, has been used for bioconversion of human and animal waste. Vermireactors have been used to remove antibiotics from waste for pollution control, but the effects of antibiotics on fly larvae are unclear. In the present work, we aimed to reveal the mechanism underlying the effects of antibiotics on larval growth in house flies at the transcriptome and microbiome levels and the relationships between genes and the microbiota. Observation of house flies after antibiotic exposure showed that gentamicin sulfate and levofloxacin hydrochloride inhibited larval development to a greater extent than amoxicillin. Transcriptome analysis revealed that biological pathways related to protein synthesis and the metabolism of fatty acids, pentose, and glucuronate were significantly enriched in flies exposed to gentamicin sulfate and levofloxacin hydrochloride. Crucial genes in these pathways were identified as candidates for future study. Microbiome analysis revealed three key bacteria that were closely correlated with gentamicin sulfate and levofloxacin hydrochloride exposure. The correlation network between the differentially expressed genes and bacteria identified an important microbic effector, Pseudomonas and its associated genes. This work will improve the knowledge about the mechanism underlying the effects of antibiotics on the larval development of house flies in the environment and provide guidance for improving the application of house fly bioconversion.

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

Key Points Question Is the modified newborn genetic and hearing screening feasible in China? Findings In this population-based cohort study including 32 512 infants, incorporating the limited and expanded genetic screening into physiological screening was associated with identifying 31 newborns with hearing loss missed by the conventional hearing screening, providing etiologic information to 1299 participants, and targeting 517 children at risk of late-onset hearing loss to improve prevention. Meaning Large observational studies are needed to evaluate the cost-effectiveness and long-term benefits of integrated genetic and hearing screening programs., This cohort study investigates the feasibility and utility of a modified genetic and hearing screening program among newborn infants in Nantong, China., Importance Early identification and intervention for newborns with hearing loss (HL) may lead to improved physiological and social-emotional outcomes. The current newborn hearing screening is generally beneficial but improvements can be made. Objective To assess feasibility and evaluate utility of a modified genetic and hearing screening program for newborn infants. Design, Setting, and Participants This population-based cohort study used a 4-stage genetic and hearing screening program at 6 local hospitals in Nantong city, China. Participants were newborn infants born between January 2016 and June 2020 from the Han population. Statistical analysis was performed from April 1 to May 1, 2021. Exposures Limited genetic screening for 15 variants in 4 common HL-associated genes and newborn hearing screening (NHS) were offered concurrently to all newborns. Hearing rescreening and/or diagnostic tests were provided for infants with evidence of HL on NHS or genetic variants on screening. Expanded genetic tests for a broader range of genes were targeted to infants with HL with negative results of limited genetic tests. Main Outcomes and Measures The detection capability for infants with hearing impairment who passed conventional hearing screening, as well as infants with normal hearing at risk of late-onset HL due to genetic susceptibility. Results Among a total of 35 930 infants, 32 512 infants completed the follow-up and were included for analysis. Among the infants included in the analysis, all were from the Han population in China and 52.3% (16 988) were male. The modified genetic and hearing screening program revealed 142 cases of HL and 1299 cases of genetic variation. The limited genetic screening helped identify 31 infants who passed newborn hearing screening, reducing time for diagnosis and intervention; 425 infants with normal hearing with pathogenic SLC26A4 variation and 92 infants with MT-RNR1 variation were at risk for enlarged vestibular aqueduct and aminoglycoside-induced ototoxicity respectively, indicating early aversive or preventive management. Conclusions and Relevance This study found that performing modified genetic and hearing screening in newborns was feasible and provides evidence that the program could identify additional subgroups of infants who need early intervention. These findings suggest an advantage for universal adoption of such a practice.

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. Thequot;Cochrane bias risk assessmentquot; tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],Plt;0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],Plt;0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],Plt;0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],Plt;0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],Plt;0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.

Background Wnt/β-catenin signaling pathway is closely related to osteoarthritis. In our preliminary study, β-catenin conditional activation (cAct) mice that specifically over-express β-catenin gene in cartilage chondrocyte exhibits osteoarthritis-like phenotype in the lumbar disc and knee joint. Therefore, we used the mice to model FJ-OA and test the potential curative effect of Velvet Antler Polypeptide (VAP) on this mice model. Methods We tested the effect of VAP on β-catenin conditional activation mice, and used Cre negative littermates as controls. Micro-CT, histology and histomorphometry analysis were performed to evaluate the curative effect of VAP on mice facet joint-like phenotype. Expression of β-catenin and collagen II was detected by immunohistochemistry (IHC) and western-blot., MMP13, ADAMTS4 and ADAMTS5 was detected by immunofluorescence (IF). RT-PCR analysis was preformed to detect mRNA expression of cartilage degrading enzymes, such as MMP13, ADAMTS4 and ADAMTS5. Results Results of micro-CT (μCT) analysis showed that VAP could partially reverse lumbar disc osteophyte formation observed in β-catenin(ex3) Col2ER mice. Histology data revealed VAP partially improved facet joint cartilage tissue invades. Histomorphometry analysis showed an increase in total cartilage area after VAP treatment. IHC show that VAP reduced β-catenin protein levels and moderately up-regulated collagen II protein levels. RT-PCR and IF data showed that VAP down-regulated the expression of extracellular matrix synthesis (ECM) degradation enzymes MMP13, ADAMTS4 and ADAMTS5. Conclusion Taken together, VAP may modulate ECM by inhibits MMP13, ADAMTS4 and ADAMTS5 via Wnt /β-catenin signaling pathway. Velvet Antler Polypeptide may be a potential medicine for FJ-OA.

Background Most lung cancer patients are diagnosed after the onset of symptoms. However, whether the symptoms of lung cancer were independently associated with the diagnosis of lung cancer is unknown, especially in the Chinese population. Methods We conducted a 10 years (2005‐2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. As such, this study focused on nonsmall cell lung cancer (NSCLC). We calculated the odds ratios (ORs) for variables associated with the symptoms and physical signs using multivariate unconditional logistic regressions. Results A total of 7184 lung cancer patients were surveyed; finally, 6398 NSCLC patients with available information about their symptoms and physical signs were included in this analysis. The most common initial symptom and physical sign was chronic cough (4156, 65.0%), followed by sputum with blood (2110, 33.0%), chest pain (1146, 17.9%), shortness of breath (1090, 17.0%), neck and supraclavicular lymphadenectasis (629, 9.8%), weight loss (529, 8.3%), metastases pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients with squamous carcinoma and stage III disease were more likely to present with chronic cough (P

Background Prevalence of neonatal microcephaly in populations without Zika-epidemics is sparse. The study aimed to report baseline prevalence of congenital microcephaly and its relationship with prenatal factors in an area at risk of Zika outbreak. Methods This study included singletons born after 24 gestational weeks in 2017–2018 at four hospitals in Guangzhou, China. Microcephaly was defined as a head circumference at birth >3SD below the mean for sex and gestational age. Prevalence of microcephaly was estimated by binomial exact method. Multivariable logistic regression was used to examine the associations of microcephaly with prenatal factors. The population attributable fraction (PAF) for associated risk factors was calculated. Results Of 46,610 live births included, 154 (3.3, 95% CI 2.8–3.9 per 1000 live births) microcephalies were identified. Maternal hepatitis B virus carriers (HBV, OR 1.80, 95% CI 1.05–3.10) and primipara (OR 2.68, 95% CI 1.89–3.81) had higher risk of having a microcephalic baby. Higher prevalence of microcephaly was observed in women who had premature labor (OR 1.98, 95% CI 1.17–3.34) and had a baby with fetal growth restriction (OR 16.38, 95% CI 11.81–22.71). Four identified factors (HBV, primiparity, preterm labor, and fetal growth restriction) contributed to 66.4% of the risk of microcephaly. Conclusions The prevalence of microcephaly in Guangzhou was higher than expected. This study identified four prenatal risk factors that, together, contributed to two-thirds of the increased risk of microcephaly. This is the first reported association between maternal HBV carrier status and microcephaly.

In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.

Objective Generalized epilepsy is rarely reported in patients with Wilson disease (WD) and lacks experience in clinical practice. We aim to provide better experience for the diagnosis and treatment for WD patients with epilepsy in the future. Methods A retrospective study was performed in 13 Chinese WD patients with generalized epilepsy. Each patient was diagnosed with WD by clinical evaluation and genetic screening. Patients were given small doses of antiepileptic drugs (AEDs), followed by copper‐chelation therapy when the seizures stabilized. Clinical manifestations, brain imaging changes, and treatment and outcome after a long‐term follow‐up were analyzed. Results Four out of 13 (30.8%) patients stopped taking copper‐chelation drugs for more than 1 year before they were admitted for epilepsy. The incidence of epilepsy of WD patients in our cohort is 1.43% (13/910), lower than those (4.5%‐5.9%) in other populations. After the attack of epilepsy, frontal lobes were the most common abnormalities (13/13, 100%) in patients, followed by brain stem (8/13, 61.5%) and thalamus (7/13, 53.8%). After a long‐term follow‐up, brain imaging and clinical manifestations of 8 (8/9, 88.9%) WD patients were significantly improved. Conclusions We firstly described WD patients with generalized epilepsy in the Chinese population. WD patients with aggravation of neuropsychiatric symptoms are prone to occur epilepsy; thus, brain MRI should be performed regularly in those patients. Cortical abnormality in brain MRI is a warning sign of epilepsy. Irregular use of copper‐chelation drugs and excessive copper deposition in the brain may be the cause of seizures. Long‐term standardized treatment for WD can effectively prevent the extensive brain damage and reduce the incidence of epilepsy in WD patients.

Objective To assess potential risk factors in identifying women at risk for gestational diabetes mellitus (GDM). Methods The present study included data collected as part of a prospective cohort study, and included women with singleton pregnancies who underwent initial prenatal examination at a tertiary women and children's hospital in Guangzhou, China between February 1, 2012, and December 31, 2015. Maternal characteristics and medical history were investigated to evaluate associations with GDM. A risk factor scoring system for the prediction of GDM was generated using logistic regression. Results Overall, 1129 (13.5%) of 8381 women were diagnosed with GDM. Women older than 35 years had a 3.95‐fold increased risk of GDM (95% confidence interval 2.80–5.58) compared with women aged 16–25 years; obese women had a 6.54‐fold higher risk (95% confidence interval 3.50–12.23) compared with underweight women. A risk scoring system was established based on age, body mass index, family history of diabetes, weight gain, and history of GDM. Screening for women with a score of 12 or more would have reduced the number undergoing oral glucose tolerance testing by 2131 (25.4%) patients with a sensitivity of 87% for GDM detection. Conclusion The assessment of risk factors for GDM could provide a foundation for improving risk‐based screening strategies in this and similar populations.

Choline acetyltransferase (ChAT) expressing retinal amacrine cells are present across vertebrates. These interneurons play important roles in the development of retinal projections to the brain and in motion detection, specifically in generating direction-selective responses to moving stimuli. ChAT amacrine cells typically comprise two spatially segregated populations that form circuits in the 'ON' or 'OFF' synaptic layers of the inner retina. This stereotypic arrangement is also found across the adult human retina, with the notable exception that ChAT expression is evident in the ON but not OFF layer of the fovea, a region specialized for high-acuity vision. We thus investigated whether the human fovea exhibits a developmental path for ON and OFF ChAT cells that is retinal location-specific. Our analysis shows that at each retinal location, human ON and OFF ChAT cells differentiate, form their separate synaptic layers, and establish non-random mosaics at about the same time. However, unlike in the adult fovea, ChAT immunostaining is initially robust in both ON and OFF populations, up until at least mid-gestation. ChAT expression in the OFF layer in the fovea is therefore significantly reduced after mid-gestation. OFF ChAT cells in the human fovea and in the retinal periphery thus follow distinct maturational paths.

The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21–29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM.

Objective: To examine the association between progesterone concentration in early pregnancy and duration of pregnancy and risk of preterm delivery. Methods: Women enrolled in the Born in Guangzhou Cohort Study from 2013–2014, with a singleton pregnancy, who had serum progesterone measured at least one time between 4 and 10 weeks of gestation were included. The association between progesterone concentration both continuous and as categorical variable (quartile) and the risk of preterm delivery was assessed with Cox proportional hazards regression. Differences of length of gestation in four progesterone concentration quartiles were assessed using the Log-rank test. Results: We studied 1860 mother-newborn pairs. The mean overall progesterone concentration was 65.7 ± 21.3 nmol/L, with mean progesterone concentrations in the four quartiles of 42.4 ± 6.2 nmol/L (n = 463), 56.2 ± 3.3 nmol/L (n = 462), 68.9 ± 4.5 nmol/L (n = 470), and 95.1 ± 15.3 nmol/L (n = 465). There was no significantly difference in duration of gestation in four progesterone concentration groups (p=.511). There was no relation between progesterone level and preterm delivery (adjusted hazard ratio (HR) per 10 nmol/l progesterone level 1.00 (95% confidence interval (CI) 0.90, 1.11)). After adjusting for potential confounders, the HR of any preterm delivery for quartiles 1, 2 and 3 versus the highest quartile of progesterone level (> 77.3 nmol/L) was 1.04 (95% CI 0.52, 2.07), 1.17 (95% CI 0.60, 2.28), and 1.46 (95% CI 0.76, 2.78), respectively. When analysis was done for spontaneous preterm delivery only, also no association with first trimester progesterone was found. Conclusion: Lower first trimester serum progesterone concentration is not associated with reduction of length of gestation or increased risk of preterm delivery.

Background & Aims Wilson disease is an autosomal recessive disorder that impairs copper homeostasis and is caused by homozygous or compound heterozygous mutations in ATP7B, which encodes a copper-transporting P-type ATPase. Patients have variable clinical manifestations and laboratory test results, resulting in diagnostic dilemmas. We aimed to identify factors associated with symptoms and features of Wilson disease from a large cohort, over 15 years. Methods We collected data from 715 patients (529 with symptoms, 146 without symptoms, and 40 uncategorized) and a genetic confirmation of Wilson’s disease (mean age of diagnosis, 18.84 years), recruited from 3 hospitals in China from 2004 through 2019. We analyzed clinical data along with serum levels of ceruloplasmin (available from 636 patients), 24-hr urinary copper excretion (collected from 131 patients), Kayser-Fleisher rings (copper accumulation in eyes, with neurologic data from 355 patients), and magnetic resonance imaging (MRI) abnormalities. Differences among the groups were analyzed using 1-way analysis of variance followed by Tukey multiple comparison test. Results Of the 529 patients with symptoms, 121 had hepatic features, 355 had neurologic features, 28 had osteomuscular features (premature osteoarthritis, skeletal deformities, and pathological bone fractures), and 25 had psychiatric symptoms. Age of onset was significantly younger in patients with hepatic (16.94 ± 1.03 years; P = .0105) or osteomuscular features (13 ± 1.33 years; P = .0001) than patients with neurological features (19.48 ± 0.46 years). Serum levels of ceruloplasmin differed among asymptomatic patients and patients with osteomuscular or neurologic symptoms of Wilson disease. Serum levels of ceruloplasmin ranged from 18.93 mg/L to approximately 120.00 mg/L (quantiles of 0.025 to approximately 0.975). Fifty-one of 131 patients (39%) had urinary copper excretion levels below 100 μg/24 hr; there was significant variation in levels of urinary copper excretion between patients older than 14 years vs 14 years or younger. Of the 355 patients with neurologic features, 244 patients (69%) had abnormal findings from MRI and Kayser-Fleisher rings; only 1 patient with abnormal findings from brain MRI was negative for Kayser-Fleisher rings. Conclusions Serum level of ceruloplasmin, 24-hour urinary copper excretion, and Kayser-Fleisher rings can be used to identify patients who might have Wilson disease. Patients with serum levels of ceruloplasmin below 120 mg/L and children with urinary copper excretion above 40 μg should undergo genetic testing for Wilson’s disease. Patients with movement disorders and brain MRI abnormalities without Kayser-Fleisher rings are not likely to have Wilson disease.

The link between depression and anxiety status and cancer outcomes has been well-documented but remains unclear. We comprehensively quantified the association between depression and anxiety defined by symptom scales or clinical diagnosis and the risk of cancer incidence, cancer-specific mortality, and all-cause mortality in cancer patients. Pooled estimates of the relative risks (RRs) for cancer incidence and mortality were performed in a meta-analysis by random effects or fixed effects models as appropriate. Associations were tested in subgroups stratified by different study and participant characteristics. Fifty-one eligible cohort studies involving 2,611,907 participants with a mean follow-up period of 10.3 years were identified. Overall, depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted RR: 1.13, 95% CI: 1.06-1.19), cancer-specific mortality (1.21, 1.16-1.26), and all-cause mortality in cancer patients (1.24, 1.13-1.35). The estimated absolute risk increases (ARIs) associated with depression and anxiety were 34.3 events/100,000 person years (15.8-50.2) for cancer incidence and 28.2 events/100,000 person years (21.5-34.9) for cancer-specific mortality. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety were related to higher cancer incidence, poorer cancer survival, and higher cancer-specific mortality. Psychological distress (symptoms of depression and anxiety) was related to higher cancer-specific mortality and poorer cancer survival but not to increased cancer incidence. Site-specific analyses indicated that overall, depression and anxiety were associated with an increased incidence risks for cancers of the lung, oral cavity, prostate and skin, a higher cancer-specific mortality risk for cancers of the lung, bladder, breast, colorectum, hematopoietic system, kidney and prostate, and an increased all-cause mortality risk in lung cancer patients. These analyses suggest that depression and anxiety may have an etiologic role and prognostic impact on cancer, although there is potential reverse causality; Furthermore, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. Early detection and effective intervention of depression and anxiety in cancer patients and the general population have public health and clinical importance.

Background Previous studies proposed that there were racial or ethnic disparities in fetal growth, challenging the use of international standards in specific populations. This study was to evaluate the validity of applying the INTERGROWTH-21st standard to a Chinese population for identifying abnormal head circumference (HC), in comparison with a newly generated local reference. Methods There were 24,257 singletons delivered by low-risk mothers in four perinatal health-care centers in Southern China. New HC reference was constructed and comparison in distribution of HC categories was performed between the INTERGROWTH-21st standard and new reference after applying these two tools in study population. Logistic regression was used to examine the association between abnormal HC and adverse neonatal outcomes. Results There were 4.40% of the newborns identified with microcephaly (HC > 2 standard deviation below the mean) using the INTERGROWTH-21st standard, comparing to the proportion of 2.83% using new reference. The newborns identified with microcephaly only by the INTERGROWTH-21st standard were not at a higher risk of adverse neonatal outcome, compared with those identified as non-microcephaly by both tools (OR 0.73, 95% CI 0.47-1.13). Conclusion The new HC reference may be more appropriate for newborn assessment in Chinese populations than the INTERGROWTH-21st standard.

Eser, Sultan (Balikesir Author), Background In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. Methods CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights.Findings For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). Interpretation The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer., American Cancer Society Centers for Disease Control and Prevention Swiss Re Swiss Cancer Research foundation Swiss Cancer League Institut National du Cancer La Ligue Contre le Cancer Rossy Family Foundation US National Cancer Institute Susan G Komen Foundation

Purpose. To investigate the evidence of minimally invasive (MI) versus open (OP) posterior lumbar fusion in treatment of lumbar spondylolisthesis from current prospective literatures.Methods. The electronic literature database of Pubmed, Embase, and Cochrane library was searched at April 2016. The data of operative time, estimated blood loss and length of hospital stay, visual analog scale (VAS) of both lower back pain and leg pain, Oswestry disability index (ODI), SF-36 PCS (physical component scores) and SF-36 MCS (mental component scores), complications, fusion rate, and secondary surgery were extracted and analyzed by STATA 12.0 software.Results. Five nonrandom prospective comparative studies were included in this meta-analysis. The meta-analysis showed that the MI group had a significantly longer operative time than OP group, less blood loss, and shorter hospital stay. No significant difference was found in back pain, leg pain, ODI, SF-36 PCS, SF-36 MCS, complications, fusion rate, and secondary surgery between MI and OP groups.Conclusion. The prospective evidence suggested that MI posterior fusion for spondylolisthesis had less EBL and hospital stay than OP fusion; however it took more operative time. Both MI and OP fusion had similar results in pain and functional outcomes, complication, fusion rate, and secondary surgery.

Aims To evaluate the difference in maternal circulating leptin profile between pregnant women with and without gestational diabetes mellitus (GDM). Methods This is a nested case-control study embedded in the Born in Guangzhou Cohort Study in Guangzhou Women and Children’s Medical Center, with 198 GDM cases and 192 controls included. Maternal plasma leptin profile was defined as leptin concentrations measured at early (baseline) and late pregnancy, as well as a ratio of concentration at late to that at early pregnancy (R L 1 L 0 ) . General linear regression was used to assess the associations between GDM and log-transformed leptin measurements. Results Women with GDM had a higher baseline leptin concentration and lower R L 1 L 0 compared to those without GDM. The log leptin concentration at baseline (β: 0.19, 95%CI: 0.04, 0.34) and the log R L 1 L 0 (β: −0.22, 95%CI: −0.41, −0.03) were associated with GDM status. The R L 1 L 0 decreased significantly along with the increase of 1-hour glucose and the difference between 1-hour and fasting glucose levels in both GDM and non-GDM women. Conclusions Women with GDM had a certain profile of circulating leptin, with higher baseline concentration but less increase during pregnancy, suggesting an impaired compensatory response to increasing insulin resistance along with the progress of pregnancy.

Background The study was conducted to examine changes in diagnostic and staging imaging methods for lung cancer in China over a 10-year period and to determine the relationships between such changes and socioeconomic development. Methods This was a hospital-based, nationwide, multicenter retrospective study of primary lung cancer cases. The data were extracted from the 10-year primary lung cancer databases at eight tertiary hospitals from various geographic areas in China. The chi-squared test was used to assess the differences and the Cochran-Armitage trend test was used to estimate the trends of changes. Results A total of 7184 lung cancer cases were analyzed. Over the 10-year period, the utilization ratio of diagnostic imaging methods, such as chest computed tomography (CT) and chest magnetic resonance imaging (MRI), increased from 65.79% to 81.42% and from 0.73% to 1.96%, respectively, while the utilization ratio of chest X-ray declined from 50.15% to 30.93%. Staging imaging methods, such as positron emission tomography-CT, neck ultrasound, brain MRI, bone scintigraphy, and bone MRI increased from 0.73% to 9.29%, 22.95% to 47.92%, 8.77% to 40.71%, 42.40% to 62.22%, and 0.88% to 4.65%, respectively; abdominal ultrasound declined from 83.33% to 59.9%. These trends were more notable in less developed areas than in areas with substantial economic development. Conclusion Overall, chest CT was the most common radiological diagnostic method for lung cancer in China. Imaging methods for lung cancer tend to be used in a diverse, rational, and regionally balanced manner.

Background Vitamin D deficiency has been linked to an increased risk of asthma. This study aimed to quantify the effect of early life vitamin D status on asthma and wheeze later in life. Methods PubMed, Embase, CINAHL, and CNKI databases, the Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to July 2017. We included randomized controlled trials (RCTs) and cohort studies with vitamin D level in blood (maternal or cord or infant) or intake (maternal intake during pregnancy or infant intake) and asthma and/or wheeze. Two reviewers independently extracted data. Fixed- and random-effects models were used to summarize the risk estimates of comparisons between highest vs. lowest vitamin D categories. Results Of the 1485 studies identified, three RCTs and 33 cohort studies were included. We did not include the RCTs (1619 participants) in the meta-analysis as the comparators and outcome definitions were heterogenous. Three RCTs reported a non-statistically significant effect of vitamin D supplementation during pregnancy on offspring wheeze/asthma at 3 years of age. Pooled estimates of cohort studies suggest no association between antenatal blood vitamin D levels or vitamin D intake and offspring asthma assessed either > 5 years or ≤ 5 years. The estimate for blood vitamin D remained unchanged when two studies assessing asthma in adulthood were excluded, but a significant inverse association emerged between vitamin D intake and childhood asthma. We found no association between antenatal vitamin D level and wheeze. On the other hand, vitamin D intake during pregnancy may have a protective effect against wheeze. Conclusions The pooled estimates from cohort studies show no association between antenatal blood vitamin D level and asthma/wheeze in later life. Whereas, the pooled estimates from cohort studies suggest that antenatal vitamin D intake may have an effect on childhood asthma > 5 years or childhood wheeze. The inconsistent results from studies assessing vitamin D either in blood or intake may be explained by previously reported non-linear association between blood vitamin D3 and childhood asthma. Further trials with enough power and longer follow-up time should be conducted to confirm the results. Electronic supplementary material The online version of this article (10.1186/s12890-018-0679-4) contains supplementary material, which is available to authorized users.

Few studies have explored the relationship between dietary patterns and the risk of gestational diabetes mellitus (GDM). Evidence from non-Western areas is particularly lacking. In the present study, we aimed to examine the associations between dietary patterns and the risk of GDM in a Chinese population. A total of 3063 pregnant Chinese women from an ongoing prospective cohort study were included. Data on dietary intake were collected using a FFQ at 24–27 weeks of gestation. GDM was diagnosed using a 75 g, 2 h oral glucose tolerance test. Dietary patterns were determined by principal components factor analysis. A log-binomial regression model was used to examine the associations between dietary pattern and the risk of GDM. The analysis identified four dietary patterns: vegetable pattern; protein-rich pattern; prudent pattern; sweets and seafood pattern. Multivariate analysis showed that the highest tertile of the vegetable pattern was associated with a decreased risk of GDM (relative risk (RR) 0·79, 95 % CI 0·64, 0·97), compared with the lowest tertile, whereas the highest tertile of the sweets and seafood pattern was associated with an increased risk of GDM (RR 1·23, 95 % CI 1·02, 1·49). No significant association was found for either the protein-rich or the prudent pattern. The protective effect of a high vegetable pattern score was more evident among women who had a family history of diabetes (P for interaction = 0·022). These findings suggest that the vegetable pattern was associated with a decreased risk of GDM, while the sweets and seafood pattern was associated with an increased risk of GDM. These findings may be useful in dietary counselling during pregnancy.

Purpose: To analyze the incidence and mortality of laryngeal cancer in cancer registration areas of China in 2010. Materials and Methods: Until June 1, 2013, 219 population-based cancer registries submitted data of 2010 to the National Central Cancer Registry of China covering about 207,229,403 population, and 120 cancer registries were selected after quality evaluation for this analysis. Laryngeal cancer cases were selected from the database according to International Classification of Diseases 10th Revision coded as "C32." We calculated the crude incidence and mortality rates of laryngeal cancer by sex, age, and location (urban/rural). The China population in 2000 and Segi's population were used as standardized populations for the calculation of age-standardized rates. Results: In 2010, it was estimated that there were 20,272 new cases diagnosed as laryngeal cancer in China, including 17,703 males and 2569 females. The crude incidence rate of laryngeal cancer was 1.54/100,000 in 2010, accounting for 0.66% of overall new cancer cases. The age-standardized by China population (ASRcn) and by world population (ASRwld) were 1.18/100,000 and 1.20/100,000, respectively. Cumulative rate (0–74 years old) and truncated age-standardized rate (35–64 years old) were 0.15% and 1.98/100,000, respectively. Moreover, it was estimated that there were 11 914 cases died in laryngeal cancer in China, including 10,038 males and 1876 females. The crude mortality rate was 0.91/100,000, accounting for 0.61% of overall cancer deaths. The ASRcn and ASRwld were 0.68/100,000 and 0.69/100,000, respectively. Cumulative rate and truncated age-standardized rates were 0.08% and 0.88/100,000, respectively. Conclusions: Both incidence and mortality of laryngeal cancer in China were still low in 2010.

Inhibition in the central nervous systems (CNS) is mediated by two neurotransmitters: gamma-aminobutyric acid (GABA) and glycine. Inhibitory synapses are generally GABAergic or glycinergic, although there are synapses that co-release both neurotransmitter types. Compared to excitatory circuits, much less is known about the cellular and molecular mechanisms that regulate synaptic partner selection and wiring patterns of inhibitory circuits. Recent work, however, has begun to fill this gap in knowledge, providing deeper insight into whether GABAergic and glycinergic circuit assembly and maintenance rely on common or distinct mechanisms. Here we summarize and contrast the developmental mechanisms that regulate the selection of synaptic partners, and that promote the formation, refinement, maturation and maintenance of GABAergic and glycinergic synapses and their respective wiring patterns. We highlight how some parts of the CNS demonstrate developmental changes in the type of inhibitory transmitter or receptor composition at their inhibitory synapses. We also consider how perturbation of the development or maintenance of one type of inhibitory connection affects other inhibitory synapse types in the same circuit. Mechanistic insight into the development and maintenance of GABAergic and glycinergic inputs, and inputs that co-release both these neurotransmitters could help formulate comprehensive therapeutic strategies for treating disorders of synaptic inhibition.

Renal cell carcinoma (RCC) is the leading cause of death in renal malignancies. MicroRNA-590-5p (miR-590-5p) is of great importance in the processes of many cancers regarding regulation of cancer cell invasion and proliferation. In our study, alternation of miR-590-5p expression in RCC cell lines through transfection with pre-miR-590-5p (up-regulation) or anti-miR-590-5p (down-regulation) was performed. Apoptosis and viability of RCC cell lines were measured by flow cytometry and CCK-8 analysis, respectively. Cell invasion and migration were estimated by Transwell assay. The association of miR-590-5p with ARHGAP24 expression was evaluated using luciferase assays, real-time PCR and western blot assay. The expressions of apoptosis and migration-related protein were also measured by western blotting. We found that pre-miR-590-5p transfection in Caki-2 and 786-O cells showed significant increases in cell viability, invasion and migration, which were accompanied by decreased cell apoptosis, while anti-miR-590-5p transfection obviously inhibited the cell viability, migration and invasion of Caki-2 and 786-O cells as well as induced apoptosis, compared with the negative control group. Furthermore, bioinformatics combined with luciferase reporter assays indicated that ARHGAP24 is directly targeted by miR-590-5p. ARHGAP24 overexpression in 786-O and Caki-2 cells phenocopied the effects of anti-miR-590-5p transfection along with enhanced expression of active Caspase-3 and Bax/Bcl-2 ratio as well as decreased expression of MMP-2 and MMP-9. These findings suggested that miR-590-5p/ARHGAP24 seems to function as a potentially beneficial target for RCC treatment.

Nasopharyngeal carcinoma (NPC) is common in South China. Although regional epidemiological data on NPC in China is available, national epidemiological data have been unavailable up to now. The goal of this study was to analyze the NPC incidence and mortality data in some domestic cancer registries, estimate these rates in China in 2010, and provide scientific information that can be harnessed for NPC control and prevention. To accomplish this goal, NPC incidence and mortality data for 2010 were collected from 145 Chinese cancer registries from which data were included in the 2013 National Cancer Registry Annual Report. Such indices as its incident and death numbers, crude rates, age-standardized rates and truncated rates were calculated and analyzed. The incidence and mortality in China and constituent areas were estimated according to the national population in 2010. An estimated 41,503 new cases and 20,058 deaths were attributed to NPC in China in 2010, accounting for 1.34% of all new cancer cases and 1.03% of all cancer-related deaths that year in China. Crude incidence and mortality were 3.16/100,000 and 1.53/100,000, respectively. World age-standardized incidence and mortality were 2.44/100,000 and 1.18/100,000, respectively. Incidence and mortality were higher among males than among females and slightly higher in urban areas than in rural areas. Among seven Chinese administrative regions, NPC incidence and mortality were obviously higher in South China than in other regions and lowest in North China. The male and female age-specific incidence and mortality both rose quickly from age 25-29 years, but peaked at different ages and varied by location. These results demonstrated that NPC incidence and mortality in China especially in South China were at high levels in the world, and suggested that control and prevention efforts should be enhanced.

Liver cancer is a common malignant tumor in China and a major health concern. We aimed to estimate the liver cancer incidence and mortality in China in 2010 using liver cancer data from some Chinese cancer registries and provide reference for liver cancer prevention and treatment. We collected and evaluated the incidence and mortality data of liver cancer in 2010 from 145 cancer registries, which were included in the 2013 Chinese Cancer Registry Annual Report, calculated crude, standardized, and truncated incidences and mortalities, and estimated new liver cancer cases and deaths from liver cancer throughout China and in different regions in 2010 from Chinese practical population. The estimates of new liver cancer cases and deaths were 358,840 and 312,432, respectively, in China in 2010. The crude incidence, age-standardized rate by Chinese standard population (ASR China), and age-standardized rate by world standard population (ASR world) were 27.29/100,000, 21.35/100,000, and 20.87/100,000, respectively; the crude, ASR China, and ASR world mortalities were 23.76/100,000, 18.43/100,000, and 18.04/100,000, respectively. The incidence and mortality were the highest in western regions, higher in rural areas than in urban areas, and higher in males than in females. The age-specific incidence and mortality of liver cancer showed a rapid increase from age 30 and peaked at age 80-84 or 85+. Our results indicated that the 2010 incidence and mortality of liver cancer in China, especially in undeveloped rural areas and western regions, were among high levels worldwide. The strategy for liver cancer prevention and treatment should be strengthened.

The treatment of type IV-A choledochal cyst is particularly difficult and remains a challenge because of the rareness and the various presentations of the disease involving not only the extrahepatic but also the intrahepatic biliary tract. The purpose of this study is to analyze our clinical experience for surgical treatment of type IV-A choledochal cyst, and compare between children and adults.During a 10-year period of time (2000-2010), clinical data of 81 consecutive patients with type IV-A choledochal cyst were retrospectively analyzed. We divided these patients into two groups, the child group (age ≤ 18 years) and the adult group (age18 years). According to whether the patient received additional liver resection, patients were divided into a extrahepatic cystectomy (EHC) group and an additional liver resection (LR) group. The long-term outcomes after surgery were evaluated in two groups.Of all 81 patients, there were 17 children and 64 adults; 16 children and 35 adults belonged to EHC group, one child and 29 adults belonged to LR group. The morbidity of biliary stricture and/or lithiasis in the adults was significantly higher than that in the children (p = 0.0410.05). In the EHC group, the reoperation rate of adults was significantly higher than that of children (p = 0.0190.05). For adult patients, the morbidity of biliary stricture and/or lithiasis and the reoperation rate in EHC group was significantly higher than that in LR group (p = 0.0370.05 and p = 0.0260.05 respectively). Five adults were found to have cholangiocarcinoma within a follow-up period, while no child was found to. However, for adult patients, no significant discrepancy was observed between EHC group and LR group (p = 0.3660.05).The present study suggests that the children have better outcomes than adults for patients with type IV-A choledochal cyst after EHC, while LR brings better outcomes than EHC for adult patients.

Continuous theoretical and technological progress in the face of increasing expectations for quality health care has transformed the surgical paradigm. The authors systematically review these historical trends and propose the novel paradigm of "precision surgery," featuring certainty-based practice to ensure the best result for each patient with multiobjective optimization of therapeutic effectiveness, surgical safety, and minimal invasiveness. The main characteristics of precision surgery may be summarized as determinacy, predictability, controllability, integration, standardization, and individualization. The strategy of precision in liver surgery is to seek a balance of maximizing the removal of the target lesion, while maximizing the functional liver remnant and minimizing surgical invasiveness. In this article, the authors demonstrate the application of precision approaches in specific settings in complex liver surgery. They propose that the concept of precision surgery should be considered for wider application in liver surgery and other fields as a step toward the ultimate goal of perfect surgery.

Background Breast cancer is the most common cancer among women. Population‐based cancer registration data from the National Central Cancer Registry were used to analyze and evaluate the incidence and mortality rates in China in 2013, providing scientific information for cancer prevention and control. Methods Pooled data were stratified by area (urban/rural), gender, and age group. National new cases and deaths were estimated using age‐specific rates and the corresponding population in 2013. The Chinese population in 2000 and Segi's world population were used to calculate age‐standardized rates. Results The estimated number of new breast cancer cases was about 278 800 in China in 2013. The crude incidence, age‐standardized rate of incidence by Chinese standard population, and age‐standardized rate of incidence by world standard population were 42.02/100 000, 30.41/100 000, and 28.42/100 000, respectively. The estimated number of breast cancer deaths was about 64 600 in China in 2013. The crude mortality, age‐standardized rate of mortality by Chinese standard population, and age‐standardized rate of mortality by world standard population were 9.74/100 000, 6.54/100 000, and 6.34/100 000, respectively. Both incidence and mortality were higher in urban than in rural areas. Age‐specific breast cancer incidence significantly increased with age, particularly after age 20, and peaked at 50–55 years, while age‐specific mortality increased rapidly after 25 years, peaking at 85+ years. Conclusions Breast cancer is the most common cancer in Chinese women, especially women in urban areas. Comprehensive measures are needed to reduce the heavy burden of breast cancer.