Search

Autism spectrum disorder (ASD) has become one of the most common neurological developmental disorders in children. However, the study of ASD diagnostic markers faces significant challenges due to the existence of heterogeneity. In this study, genetic testing was performed on children who were clinically diagnosed with ASD. Children with ASD susceptibility genes and healthy controls were studied. The proteomics of plasma and peripheral blood mononuclear cells (PBMCs) as well as plasma metabolomics were carried out. The results showed that although there was genetic heterogeneity in children with ASD, the differentially expressed proteins (DEPs) in plasma, peripheral blood mononuclear cells, and differential metabolites in plasma could still effectively distinguish autistic children from controls. The mechanism associated with them focuses on several common and previously reported mechanisms of ASD. The biomarkers for ASD diagnosis could be found by taking differentially expressed proteins and differential metabolites into consideration. Integrating omics data, glycerophospholipid metabolism and N-glycan biosynthesis might play a critical role in the pathogenesis of ASD.

Background Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas. Objectives We aimed to evaluate whether dietary patterns are associated with NPC risk. Methods We studied 2554 newly diagnosed NPC patients aged 20–74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk. Results Compared with the lowest quartile, individuals in the highest quartile of the “plant-based factor” in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the “animal-based factor” had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend

BackgroundHigh prevalence of sleep problems have been reported in children with Autism Spectrum Disorder (ASD). This study aims to investigate the sleep conditions of ASD children in China, and explore the relationship between the common sleep problems and core symptoms and developmental levels.MethodsUsing a cross-sectional design, we included 2 to 7-year-old children from 13 cities in China: 1310 with ASD and 1158 with typically-developing (TD) children. The neurodevelopmental level was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). ASD were diagnosed with DSM-5 and Child Autism Rating Scale (CARS). the Social Responsiveness Scale (SRS), the Autism Behavior Checklist (ABC) and the communication warning behavior sub-scale in CNBS-R2016 valued autism behaviors. The children’ s sleep habits questionnaire (CSHQ) assessed sleep conditions.ResultsThe prevalence of sleep disorders in ASD children was significantly higher than that in TD (67.4% vs. 51%,p ConclusionChildren with ASD have a higher prevalence of sleep problems. Bedtime resistance, anxiety, sleep onset delay and daytime sleepiness may be related to the core symptoms, but not be related to the developmental level in ASD children. In the clinic, sleep assessment should be included in the routine of ASD visits, and during the intervention, sleep hygiene education is as important as the treatment of biological factors.Trial registrationThe study was approved by the ethics committee of the Children’s Hospital of Chongqing Medical University, Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number:ChiCTR2000031194).

Objective There is a lack of evidence on the usage of the quality assessment tool-the Risk Of Bias In Nonrandomized Studies-of Interventions (ROBINS-I). This article aimed to measure the reliability, criterion validity, and feasibility of the ROBINS-I and the Newcastle-Ottawa Scale (NOS). Methods A sample of systematic reviews or meta-analyses of observational studies were selected from Medline (2013-2017) and assessed by two reviewers using ROBINS-I and the NOS. We reported on reliability in terms of the first-order agreement coefficient (AC1) statistic. Correlation coefficient statistic was used to explore the criterion validity of the ROBINS-I. We compared the feasibility of the ROBINS-I and NOS by recording the time to complete an assessment and the instances where assessing was difficult. Results Five systematic reviews containing 41 cohort studies were finally included. Interobserver agreement on the individual domain of the ROBINS-I as well as the NOS was substantial with a mean AC1 statistic of 0.67 (95% CI: 0.50-0.83) and 0.73 (95% CI: 0.65-0.81), respectively. The criterion validity of the ROBNS-I was moderate (K = 0.52) against NOS. The time in assessing a single study by ROBINS-I varied from 7 hours initially to 3 hours compared with 30 minutes for the NOS. Both reviewers rated "bias due to departure from the intended interventions" the most time-consuming domain in the ROBINS-I, items in the NOS were equal. Conclusions The ROBINS-I and the NOS seem to provide the same reliability but vary in applicability. The over-complicated feature of ROBINS-I may limit its usage and a simplified version is needed.

Background The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. Methods The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. Results Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. Conclusions Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. Lay summary The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

Background: The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial. Methods: In a population-based case–control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose–response trends were evaluated using restricted cubic spline analysis. Results: Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93–1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95–1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64–0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose–response relation with NPC risk. Conclusions: Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose–response association complicates causal inference. Impact: Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.

Recently, flexible pressure sensors (FPSs) have attracted intensive attention owing to their ability to mimic and function as electronic skin. Some sensors are exploited with a biological structure dielectric layer for high sensitivity and detection. However, traditional sensors with bionic structures usually suffer from a limited range for high-pressure scenes due to their high sensitivity and high hysteresis in the medium pressure range. Here, a reconfigurable flea bionic structure FPS based on 3D printing technology, which can meet the needs of different scenes via tailoring of the dedicated structural parameters, is proposed. FPS exhibits high sensitivity (1.005 kPa

Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention.The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children.A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS.Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted β = 0.277, P 0.001). TCS concentration was higher in ASD children (P = 0.005), and positively correlated with ABC (Sensory subscales: P = 0.03; Social self-help subscales: P = 0.011) and SRS scale scores (Social awareness subscales: P = 0.045; Social communication subscales: P = 0.001; Autism behavior mannerisms subscales: P = 0.006; SRS total score: P = 0.003) in ASD children. This association was more pronounced in boys than in girls.To our knowledge, this is the first case-control study to examine the correlation between TCS and ASD. Our results suggest that maternal UADN during pregnancy may be a potential risk of ASD in offspring. Further detection of TCS levels showed that maternal UADN during pregnancy may be associated with excessive TCS exposure. In addition, the level of TCS in children with ASD is higher than TD children. The higher levels of TCS in children with ASD may be significantly associated with more pronounced core symptoms, and this association was more significant in male children with ASD.

Background The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock. Methods This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS. Results Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different (P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05). Conclusion Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011, registration date: March 12, 2019. Graphic Abstract

Background Adenovirus (Adv) is a frequent etiology of acute respiratory tract infections. Although rare, neurological manifestations are known to occur during Adv infection. Methods We retrospectively analyzed clinical, laboratory, outcome and the relationship between clinical characteristics and viral detection results in the cerebrospinal fluid (CSF) in children with Adv-associated central nervous system (CNS) dysfunction. Results Twenty-one (1.5%) cases had Adv-associated CNS manifestations. The median age was 1.4 years and 20 (95%) were less than 5 years of age. Six (28%) were male. The most frequently cited CNS symptoms were altered consciousness (100%) and seizure (14.3%). Fourteen cases (73.7%) had abnormal electroencephalogram examination and 6 cases (37.5%) had abnormal imaging. None of the patients had received cidofovir administration. Twenty children recovered without sequelae and 1 patient died of respiratory failure. Patients with positive Adv polymerase chain reaction (n = 11) presented lower onset age compared with that of patients with negative Adv polymerase chain reaction (n = 10) in the CSF. Clinical manifestation, laboratory findings, imaging studies and electroencephalogram showed no significant difference between the 2 groups. Conclusion Adv is a rare cause of CNS disease in children, mainly causing altered consciousness. Adv was detected in more cases in the respiratory tract than the CSF, but the majority of patients had the virus detected in both. The lack of Adv in the CSF does not exclude CNS involvement. Furthermore, the viral detection results in the CSF do not seem useful as an indicator of the severity of CNS disease.

Photodynamic therapy (PDT) is an effective oncotherapy and has been approved for clinical application. Unfortunately, its therapeutic efficacy is usually overshadowed by tumor angiogenesis. Thus, a detailed understanding of the tumor angiogenesis upon PDT is imperative. This study aimed to investigate the potential contribution and mechanism of P-21-activated kinase 1 (PAK1) in PDT-induced tumor angiogenesis. Firstly, we found that PAK1 was upregulated upon PDT and associated with tumor angiogenesis. Then, we elucidated the underlying molecular mechanism. Activation of PAK1 prevents hypoxia-inducible factor 1 alpha (HIF-1α) protein from ubiquitin-mediated degradation. Thereafter, HIF-1α accumulation results in the upregulation of vascular endothelial growth factor (VEGF), thus promoting tumor angiogenesis. More importantly, we determined that PAK1 knockdown effectually repressed tumor angiogenesis, which contributes to enhance the therapeutic effect of PDT. Together, PAK1 is a potential novel pharmaceutical target for inhibiting PDT-induced tumor angiogenesis, and PAK1 suppression in combination with PDT may be a potentially effective strategy for anti-tumor therapy.

Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged

Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine-resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine-resistant PC cells (PANC-1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild-type PC cells and in gemcitabine-resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p-Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation-quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p-Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2-mediated epigenetic modification.

Background Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. Methods We enrolled 1019 ASD preschoolers aged 2–7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. Results Based on general developmental quotient (GQ) 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55–69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. Conclusions Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. Trial registration ChiCTR2000031194, registered on 03/23/2020.

Background Distinguishing strangulated bowel obstruction (StBO) from simple bowel obstruction (SiBO) still poses a challenge for emergency surgeons. We aimed to construct a predictive model that could distinctly discriminate StBO from SiBO based on the degree of bowel ischemia. Methods The patients diagnosed with intestinal obstruction were enrolled and divided into SiBO group and StBO group. Binary logistic regression was applied to identify independent risk factors, and then predictive models based on radiological and multi-dimensional models were constructed. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were calculated to assess the accuracy of the predicted models. Via stratification analysis, we validated the multi-dimensional model in the prediction of transmural necrosis both in the training set and validation set. Results Of the 281 patients with SBO, 45 (16.0%) were found to have StBO, while 236(84.0%) with SiBO. The AUC of the radiological model was 0.706 (95%CI, 0.617–0.795). In the multivariate analysis, seven risk factors including pain duration ≤ 3 days (OR = 3.775), rebound tenderness (OR = 5.201), low-to-absent bowel sounds (OR = 5.006), low levels of potassium (OR = 3.696) and sodium (OR = 3.753), high levels of BUN (OR = 4.349), high radiological score (OR = 11.264) were identified. The AUC of the multi-dimensional model was 0.857(95%CI, 0.793–0.920). In the stratification analysis, the proportion of patients with transmural necrosis was significantly greater in the high-risk group (24%) than in the medium-risk group (3%). No transmural necrosis was found in the low-risk group. The AUC of the validation set was 0.910 (95%CI, 0.843–0.976). None of patients in the low-risk and medium-risk score group suffered with StBO. However, all patients with bowel ischemia (12%) and necrosis (24%) were resorted into high-risk score group. Conclusion The novel multi-dimensional model offers a useful tool for predicting StBO. Clinical management could be performed according to the multivariate score.

Although BHPF has been widely used in plastic manufacturing as a substitute for BPA, current evidence suggests that BHPF also causes harmful effects on reproduction. However, effects of BHPF on mammalian early pregnancy are still poorly defined. This study aimed to explore the effects of BHPF on early pregnancy, especially decidualization and embryonic development in mice and human beings. The results showed that 50 and 100 mg/kg BHPF exposure reduced birth weight, and implantation site weight on the day 8 of pregnancy in mice. Because BHPF inhibits both embryo development and artificial decidualization in mice, suggesting that the detrimental effects of BHPF should be from its effects on embryo development and decidualization. Under in vitro decidualization, 10 μM BHPF inhibits decidualization and leads to disordered expression of Lamin B1 and collagen in mice. In addition, 10 μM BHPF also inhibits decidualization, and causes disordered expression of both collagen III and Lamin B1 under human in vitro decidualization. However, collagen III supplementation can rescue BHPF inhibition on decidualization. Further, our study demonstrates that BHPF impairs human decidualization through the HB-EGF/EGFR/STAT3/Collagen III pathway. Taken together these data suggest that exposure to BHPF impairs mouse and human decidualization during early pregnancy.

Emergence agitation (EA) is a common complication in pediatric patients after general anesthesia. The effectiveness of magnesium sulfate in decreasing the incidence of EA in children remains controversial. Therefore, a systematic review and meta-analysis was performed to assess the efficacy of magnesium sulfate in preventing EA in pediatric patients following general anesthesia.Systematic review and meta-analysis.PubMed, Embase, Web of Science, and Cochrane Library were searched to identify eligible randomized controlled trials from their respective database inception dates to June 30, 2021.Pediatric patients (18 years old) undergoing general anesthesia.Intravenous administration of magnesium sulfate.The primary outcome of the meta-analysis was EA incidence. The risk of bias of the included studies was evaluated using the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Grading of Recommendations, Assessment, Development, and Evaluation was applied to assess the level of certainty.Eight studies with 635 participants were identified. The forest plot revealed no significant difference in the incidence of EA between patients treated with magnesium sulfate and the control group (risk ratio = 0.69, 95% confidence interval [0.44, 1.07]; P = 0.10, IAdministration of magnesium sulfate during general anesthesia did not affect the occurrence of EA in pediatric patients. However, magnesium sulfate can prolong the emergence time without adverse effects. PROSPERO registration number: CRD42021252924.

Background Epstein–Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. Methods The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. Results By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%–99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%–68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%–14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). Conclusions Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

Deregulation of E3 ubiquitin ligases is intimately implicated in breast cancer pathogenesis and progression, but the underlying mechanisms still remain elusive. Here we report that RING finger protein 144A (RNF144A), a poorly characterized member of the RING-in-between-RING family of E3 ubiquitin ligases, functions as a tumor suppressor in breast cancer. RNF144A was downregulated in a subset of primary breast tumors and restoration of RNF144A suppressed breast cancer cell proliferation, colony formation, migration, invasion in vitro, tumor growth, and lung metastasis in vivo. In contrast, knockdown of RNF144A promoted malignant phenotypes of breast cancer cells. Quantitative proteomics and biochemical analysis revealed that RNF144A interacted with and targeted heat-shock protein family A member 2 (HSPA2), a putative oncoprotein that is frequently upregulated in human cancer and promotes tumor growth and progression, for ubiquitination and degradation. Notably, the ligase activity-defective mutants of RNF144A impaired its ability to induce ubiquitination and degradation of HSPA2, and to suppress breast cancer cell proliferation, migration, and invasion as compared with its wild-type counterpart. Moreover, RNF144A-mediated suppression of breast cancer cell proliferation, migration, and invasion was rescued by ectopic HSPA2 expression. Clinically, low RNF144A and high HSPA2 expression in breast cancer patients was correlated with aggressive clinicopathological characteristics and decreased overall and disease-free survival. Collectively, these findings reveal a previously unappreciated role for RNF144A in suppression of breast cancer growth and metastasis, and identify RNF144A as the first, to our knowledge, E3 ubiquitin ligase for HSPA2 in human cancer.

Background: Sepsis-3 definitions have been published recently; however, their diagnostic value remains controversial. This study was to assess the accuracy of Sepsis-3 definitions compared to Sepsis-1 definitions by stratifying mortality among adult critically ill patients with suspected infection. Methods: A multicenter, prospective cohort study was conducted from November 10, 2017 to October 10, 2018, in five Intensive Care Units (ICUs) at four teaching hospitals. Thirty-day mortality was compared across categories for both Sepsis-3 definitions and Sepsis-1 definitions, which were evaluated by logistic regression analysis followed by measurement of the area under the receiver operating characteristic curve (AUROC) for predicting 30-day mortality rates. Results: Of the 749 enrolled patients, 644 (85.9%) were diagnosed with sepsis according to the Sepsis-1 definitions. Among those patients, 362 were diagnosed with septic shock (362/749, 48.3%). However, according to the Sepsis-3 definitions, there were 483 patients with a diagnosis of sepsis (483/749, 64.5%), among whom 299 patients were diagnosed with septic shock (299/749, 39.9%). According to the Sepsis-3 definitions, sepsis (sepsis and septic shock) patients had higher 30-day mortality (41.8%) than sepsis patients according to the Sepsis-1 definitions (31.8%, χ2 = 5.552, P = 0.020). The AUROC of systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA) scores with regard to 30-day mortality rates were 0.609 (0.566–0.652) and 0.694 (0.654–0.733), respectively. However, the AUROC of SOFA scores (0.828 [0.795–0.862]) were significantly higher than that of SIRS or qSOFA scores (P < 0.001). Conclusion: In adult critically ill patients with suspected infection, the Sepsis-3 definitions were relatively accurate in stratifying mortality and were superior to the Sepsis-1 definitions. Trial Registration: www.chictr.org.cn (ChiCTR-OOC-17013223). Key words: Infection; Critically ill patients; Sepsis-3; Septic shock; Mortality

Background The association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long‐term based on a prospective cohort design. Methods A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA‐IgA, EBNA1‐IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non‐NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE). Results With a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46‐6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07‐6.23) for male and 3.75 (95%CI: 1.25‐11.20) for female, respectively. Among the non‐NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3‐5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29‐2.18) for VCA‐IgA and 1.92 (95%CI: 1.42‐2.59) for EBNA1‐IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE. Conclusion Smoking could significantly increase the long‐term risk of NPC in southern China, partly by persistently reactivating EBV.

We aimed to investigate the relationship between vitamin D status and core symptoms and neurodevelopmental levels in children with ASD with a multicenter survey.We enrolled 1321 ASD children and 1279 typically developing (TD) children aged 2-7 years from 13 cities in China. ASD symptoms were assessed with the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS), and neurodevelopmental levels were evaluated with the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016).Children with ASD had lower serum 25(OH)D levels than TD children. Serum 25(OH)D levels were negatively associated with CARS and communication warning behavior of CNBS-R2016 scores, and were not associated with the development quotients of ASD children. ASD Children were grouped based on the quartiles for 25(OH)D levels in the controls, and children in the first to third quartiles had higher SRS social communication and/or CARS and communication warning behavior of CNBS-R2016 scores than those in the fourth quartile.Serum 25(OH)D levels were primarily associated with core symptoms in children with ASD, and individuals with relatively lower 25(OH)D levels displayed worse autistic symptomatology. More research is needed to determine whether vitamin D supplements would be a useful treatment for ASD.

Photothermal therapy (PTT) is a promising alternative therapy for benign or even malignant tumors. To improve the selective heating of tumor cells, target-specific photothermal conversion agents are often included, especially nanoparticles. Meanwhile, some indirect methods by manipulating the radiation and heat delivery are also adopted. Therefore, to gain a clear understanding of the mechanism, and to improve the controllability of PTT, a few issues need to be clarified, including bioheat and radiation transfer, localized and collective heating of nanoparticles, etc. In this review, we provide an introduction to the typical bioheat transfer and radiation transfer models along with the dynamic thermophysical properties of biological tissue. On this basis, we reviewed the most recent advances in the temperature control methods in PTT from macroscale to nanoscale. Most importantly, a comprehensive introduction of the localized and collective heating effects of nanoparticle clusters is provided to give a clear insight into the mechanism for PPT from the microscale and nanoscale point of view.

Shenghua Decoction (SHD) is a well-known classic herbal formula documented in traditional Chinese medicine (TCM) that has been widely applied during the postpartum period in Chinese communities for several years. We conducted this systematic review and meta-analysis to explore the influence of SHD as an adjuvant treatment for early medical abortion using a combination of mifepristone followed by misoprostol.This systematic review and meta-analysis was reported using 2020 PRISMA guidelines. Eight databases were searched from their establishment to February 28, 2022, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, the Chinese BioMedical database, the Chinese Scientific Journal Database, and the Wanfang database. The Grading of Recommendations Assessment, Development, and Evaluation estimated the quality of evidence.Sixteen RCTs involving 3016 patients were included in the meta-analysis. Overall, compared with no treatment as the control group after early medical abortion, patients treated with SHD were associated with a higher complete abortion rate (RR: 1.14; 95% CI: 1.10 - 1.18; P 0.01, IOur findings suggest that SHD supplementation may be beneficial for women seeking a medical abortion before the 7-week gestational period and no adverse events in the experimental group were reported. However, the methodological quality of the included RCTs was unsatisfactory, and therefore it is necessary to further verify the effectiveness of SHD using standardized studies of rigorous design.

The 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is limited evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock.This was a multicenter prospective observational study of adult patients with septic shock who were admitted to four intensive care units (ICUs) in a total of three Jiangsu Province teaching hospitals over a 3-year span from May 8, 2018, to June 15, 2021. Each enrolled patients with septic shock was categorized into the low-volume (below 20 mL/kg fluid), medium-volume (20-30 mL/kg fluid) or high-volume (above 30 mL/kg fluid) fluid group according to the initial infusion dose given for fluid resuscitation. Various demographic attributes and other variables were collected from medical records. Logistic regression and Kaplan-Meier curve analysis were used to determine the relationship between initial fluid resuscitation doses and patient outcomes.A total of 302 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the high-volume group (48.3%) and lowest in the medium-volume group (26.3%, P 0.05). Patients who completed 30 mL/kg initial fluid resuscitation in the first 1-2 h had the lowest 28-day mortality rate (22.8%, P 0.05). Logistic regression showed that a medium initial fluid volume dose was an independent protective factor, with the odds ratio (OR) indicating significantly decreased mortality (OR, 0.507; 95% confidence interval, 0.310-0.828; P = 0.007; P 0.05). A Kaplan-Meier curve stratified by initial fluid resuscitation dose was constructed for the probability of 28-day mortality. The medium-volume fluid group showed a significantly lower 28-day mortality rate than the high-volume group or the low-volume group (log-rank test, P = 0.0016).In septic shock patients, an initial fluid resuscitation rate of 20-30 mL/kg within the first hour may be associated with reduced 28-day mortality; however, this result needs to be confirmed by further high-quality randomized controlled clinical trials.Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674.

BACKGROUND Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein-Barr virus-based markers is possible, the performance of diagnostic methods for detecting lesions among screen-positive individuals is poorly understood. METHODS The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population-based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow-up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated. RESULTS Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; Pdifference = .021) and for early-stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early-stage disease and were more commonly observed for tumors originating from the pharyngeal recess. CONCLUSIONS MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen-positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened.

Tenosynovial giant cell tumor (TGCT) is a locally aggressive tumor with colony-stimulating factor 1 receptor (CSF1R) signal expression. However, there is a lack of better in vivo and ex vivo models for TGCT. This study aims to establish a favorable preclinical translational platform, which would enable the validation of efficient and personalized therapeutic candidates for TGCT.Histological analyses were performed for the included patients. Fresh TGCT tumors were collected and sliced into 1.0-3.0 mmThe TGCT tumor grafts that were implanted into athymic mice subrenal capsules maintained their original morphological and histological features. The "take" rate of this model was 95% (19/20). Administration of CSF1R inhibitors (PLX3397, and a novel candidate, WXFL11420306) to TGCT-PDTX mice was shown to reduce tumor size while inducing intratumoral apoptosis. In addition, the CSF1R inhibitors suppressed circulating nonspecific monocyte levels and CD163-positive cells within tumors. These response patterns of engrafts to PDTX were validated by ex vivo PDE cultures.Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.

Background:. Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. Methods:. In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. Results:. The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P

To investigate the molecular mechanism of miR-520a-3p regulating the secretion of cytokines in cervical cancer.The matching between miR-520a-3p and the NF-κB complex subunit RELA was analyzed by TargetScanHuman, and then the luciferase reporting system was used to detect whether miR-520a-3p targeted the NF-κB complex subunit RELA. After cervical cancer HELA cells stimulated by LPS, in the overexpression group or the knockout group, miR-520a-3p mimics or inhibitor were mixed with transfection reagent and dripped into HELA cells. The expression levels of colony stimulating factor (GCSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 2 (IL-2), interleukin 3 (IL-3), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 19 (IL-9), interleukin 10 (IL-10), interleukin 12 p40 (IL-12 p40), interleukin 12 p70 (IL-12 p70), interleukin 13 (IL-13), interleukin 17 (IL-17), interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-5 (MCP-5), small inducible cytokine A5 (RANTES), tumor necrosis factor-alpha (TNFα) were detected by enzyme-linked immunosorbent assay in both the overexpression group and the knockout group. Each experiment was repeated three times.miR-520a-3p targeted the 3'UTR of RELA. After activation of the NF-κB signaling pathway by lipopolysaccharide (LPS), the protein expression levels of cytokines GCSF, GM-CSF, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 p40, IL-12 p70, IL-13, IL-17, IFN-γ, MCP-1, MCP-5, RANTES, TNFα secreted by HELA cells of cervical cancer were increased significantly (miR-520a-3p inhibits cytokine secretion in HELA cells of cervical cancer by targeting RELA, a key molecule in the NF-κB signaling pathway.目的: 探讨miR-520a-3p调控宫颈癌细胞因子分泌的分子机制。方法: 通过TargetScanHuman分析miR-520a-3p与NF-κB复合体亚基RELA的匹配情况,然后通过荧光素酶报告系统检测miR-520a-3p是否靶向NF-κB复合体亚基RELA;使用LPS刺激宫颈癌HELA细胞后,将miR-520a-3p mimics与转染试剂混合后滴入HELA细胞中,此为过表达组;将miR-520a-3p inhibitor与转染试剂混合后滴入HELA细胞中,此为敲低组,通过酶联免疫吸附试验检测过表达组和敲低组GCSF, GM-CSF, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 p40, IL-12 p70, IL-13, IL-17, IFN-γ, MCP-1, MCP-5, RANTES, TNFα的表达水平。每次实验重复3次。结果: miR-520a-3p靶向RELA的3’UTR;LPS激活NF-kB信号通路后,宫颈癌HELA细胞分泌的细胞因子GCSF, GM-CSF, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 p40, IL-12 p70, IL-13, IL-17, IFN-γ, MCP-1, MCP-5, RANTES, TNFα的蛋白表达水平上升(

Objective We aimed to examine the associations between ambient air pollutants and daily mortality in Northeast China from 2014 to 2018. Methods A two-stage approach was used to estimate particulate matter with an aerodynamic diameter of 10 μm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) exposure and daily mortality. Results An increase of 10 μg/m of PM10 exposure and NO2 at lag of 0 to16 days was associated with the cumulative relative risk (RR) of 1.011 (95% confidence interval [CI]: 1.004, 1.019) and 1.026 (95% CI: 1.004, 1.049), respectively, in non-accident mortality. Meanwhile, significant association was observed in people aged under 60 years between SO2 exposure and respiratory mortality at lag of 0 to 9 days. Conclusions Our findings strengthen the evidence of PM10 and NO2 exposures were independent risk for daily mortality.

Objective Perioperative shivering (POS) is a common complication in patients undergoing spinal anaesthesia. The present study investigated the efficacy of 5-HT3 receptor antagonists in preventing POS following spinal anaesthesia. Design Systematic review and meta-analysis. Data sources Pubmed, Embase, the Web of Science and Cochrane Library were searched from database establishment on 31 July 2019. Eligibility criteria Randomised controlled trials that reported the effects of 5-HT3 receptor antagonists in the prevention of POS in patients after spinal anaesthesia. Data extraction and synthesis Two reviewers independently extracted data. The primary outcome of the present study was the incidence of POS. The risk of bias for the included studies was assessed according to the Cochrane Handbook. The quality of primary outcome was evaluated by Grading of Recommendations Assessment, Development and Evaluation. Trial sequential analysis for the primary outcome was performed to reduce the type 1 error caused by repeated meta-analysis and the required information size was calculated. Results A total of 13 randomised controlled trials consisting of 1139 patients were included. The overall incidence of POS was significantly lower in the 5-HT3 receptor antagonists group (risk ratio 0.31; 95% CI 0.26 to 0.38; p

The aim of our study was to evaluate the relationship between the 24-h blood pressure (BP) profile, plasma NT-proBNP levels and left ventricular hypertrophy (LVH) in subjects with primary aldosteronism (PA) compared to patients with essential hypertension (EH). A total of 385 consecutive patients with PA [187 with aldosterone producing adenoma (APA) and 198 with idiopathic hyperaldosteronism (IHA)] and 385 patients with EH were matched based on age, sex, body mass index (BMI), BP values and duration of hypertension. Twenty-four-hour ambulatory BP monitoring (ABPM), plasma levels of NT-proBNP, left ventricular mass index (LVMI), and other clinical medical data were assessed in all patients. No differences in age, sex, BMI, clinical BP, 24-h mean BP, daytime BP, or duration of hypertension were found between groups. Nighttime systolic BP (130 ± 16 vs. 127 ± 17 mmHg, p

Objective Previous studies reported the effect of dexmedetomidine on intrathecal anesthesia. In this review, we explored the impact of dexmedetomidine as an adjunct for lumbar anesthesia in patients undergoing cesarean section. Methods Two authors searched eligible random controlled trials in electronic databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, the Chinese BioMedical database, Chinese Scientific Journal Database, and the Wanfang database. Results Ten trials comprising 970 patients were included in this review. Intrathecal dexmedetomidine significantly reduced the onset time of sensory block (standardized mean difference (SMD), −1.50, 95% confidence interval (CI) −2.15, −0.85, I2 = 92%) and motor block (SMD −0.77, 95% CI −1.50, −0.49, I2 = 60%) and prolonged the block duration time (sensory block: SMD 2.02, 95% CI 1.29, 2.74, I2 = 93%; motor block: SMD 1.90, 95% CI 1.07, 2.74, I2 = 94%). Patients who received dexmedetomidine showed a lower incidence of shivering. No significant difference was reported for the neonatal Apgar score and other complications. Conclusion The use of intrathecal dexmedetomidine during cesarean section can shorten the onset time of spinal anesthesia and enhance the effect of local anesthetic. It has no significant impact on neonates and there were no other adverse events.

Decidualization is essential to rodent and primate pregnancy. Senescence is increased during decidualization. Failure of senescence clearance during decidualization will cause pregnancy abnormality. Caveolin-1 is located in plasmalemmal caveolae and involved in senescence. However, whether caveolin-1 is involved in decidualization remains undefined. In this study, we examined the expression, regulation and function of Caveolin-1 during mouse early pregnancy and under mouse and human in vitro decidualization. From days 1 to 8 of pregnancy, Caveolin-1 signals are mainly located in endothelium and myometrium. Estrogen stimulates Caveolin-1 expression in endothelium. Deficiency of estrogen receptor α significantly promotes Caveolin-1 level in uterine stromal cells. Progesterone upregulates Caveolin-1 expression in luminal epithelium. During mouse in vitro decidualization, Caveolin-1 is significantly increased. However, Caveolin-1 is obviously decreased during human in vitro decidualization. Caveolin-1 overexpression and siRNA suppress and upregulate IGFBP1 expression under in vitro decidualization, respectively. Blastocysts-derived tumor necrosis factor α (TNFα) and human Chorionic Gonadotropin (hCG) regulate Caveolin-1 in mouse and human decidual cells, respectively. Caveolin-1 levels are also regulated by high glucose and insulin. In conclusion, a low level of Caveolin-1 should be beneficial for human decidualization.

Background: The efficacy of low-dose hydrocortisone therapy in the management of septic shock remains controversial in critical care for many years. Hence, we performed this meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) to evaluate its effect on clinical outcome among adult patients with septic shock. Methods: We identified relevant RCTs published from inception to March 7, 2018 comparing low-dose hydrocortisone with placebo or no intervention in adults admitted to the intensive care unit (ICU) for septic shock. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Collaboration’s instrument. Trial sequential analysis was used to pool the results from the included studies for the primary outcomes. Results: Thirteen studies were retrieved by our literature search strategy. There were no significant differences in 28-day mortality (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.81-1.00; P = .05) and hospital mortality (OR = 0.91, 95% CI = 0.82-1.02; P = .09) between the 2 groups, which were confirmed by TSA. However, there was a significant improvement in shock reversal in the hydrocortisone group (OR = 1.33, 95% CI = 1.02-1.72; P = .03). Furthermore, subgroup analyses revealed that hydrocortisone plus fludrocortisone statistically reduced the rate of 28-day mortality (OR = 0.79, 95% CI = 0.64-0.97; P = .03), ICU mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .02), and hospital mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .01) in comparison with the placebo, the results were also confirmed by TSA. Conclusion: Among adult patients with septic shock, the use of low-dose hydrocortisone compared with control did not confer overall survival benefits, albeit improving shock reversal rate. The benefit of reducing 28-day mortality, ICU mortality, and hospital mortality was observed in combination use of hydrocortisone and fludrocortisone.

STUDY OBJECTIVE Previous studies reported that controlled low central venous pressure (CVP) can reduce blood loss during liver resection. This systematic review and meta-analysis sought to explore the efficacy and safety of low CVP in patients undergoing hepatectomy. DESIGN A systematic review and meta-analysis of randomized controlled trials (RCTs). REVIEW METHODS RCTs were searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical database, Chinese Scientific Journals Database, and Wanfang database from inception to April 30, 2021. Subgroup analyses were performed based on different surgical methods (open hepatectomy vs laparoscopic hepatectomy) and published countries (China vs other countries). The quality of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation. MAIN RESULTS Eighteen RCTs containing 1285 participants (626 patients in the low CVP group and 659 patients in the control group) were included in this study. The forest plot showed that low CVP effectively reduced blood loss during liver resection compared with the control group (MD = -311.92 mL, 95% CI [-429.03, -194.81]; P

Background Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial–mesenchymal transition (EMT) in cancer. Compared with the well-defined molecular events of miR-200a in EMT, the role of miR-200a in therapy resistance remains to be elucidated. Methods Breast cancer cells transfected with mimic or inhibitor for miR-200a was assayed for chemoresistance in vitro. miR-200a expression was assessed by quantitative real-time PCR (qRT-PCR) in breast cancer patients treated with preoperative chemotherapy. Luciferase assays, cell proliferation assay were performed to identify the targets of miR-200a and the mechanism by which it promotes treatment resistance. Survival analysis was used to evaluate the prognosis value of miR-200a. Results In this study, our results showed ectopic expression of miR-200a promotes chemoresistance in breast cancer cell lines to several chemotherapeutic agents, whereas inhibition of miR-200a enhances gemcitabine chemosensitivity in resistance cancer cells. We found overexpression of miR-200a was closely associated with poor response to preoperative chemotherapy and poor prognosis in breast cancer patients. Furthermore, knockdown of YAP1 and TP53INP1 phenocopied the effects of miR-200a overexpression, and confirmed that TP53INP1 is a novel target of miR-200a. Remarkably, TP53INP1 expression is inversely correlated with miR-200a expression in Breast cancer cell lines. Taken together, these clinical and experimental results demonstrate that miR-200a is a determinant of chemoresistance of breast cancer. Conclusions Upregulated miR-200a enhances treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer. Electronic supplementary material The online version of this article (10.1186/s12885-017-3930-0) contains supplementary material, which is available to authorized users.

Key Points Question What are the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS), and what is an accurate and efficient method of predicting overall survival (OS) among these patients? Findings In this prognostic study of 315 patients with HAS, 3 risk factors (perineural invasion, preoperative carcinoembryonic antigen levels ≥5 ng/mL, and pathological node category 3b) were independently associated with worse OS among patients with HAS. Based on these risk factors, a nomogram to predict postoperative OS among patients with HAS was developed. Meaning This study found that, among patients with HAS, perineural invasion, preoperative carcinoembryonic antigen levels, and pathological node category 3b were independently associated with OS; an individualized nomogram that was developed to predict postoperative OS had good prognostic value and may be useful as a supplement to the current tumor-node-metastasis staging system., Importance Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). Objective To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). Design, Setting, and Participants This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. Main Outcomes and Measures OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. Results Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P, This prognostic study examines the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma and develops an individualized nomogram based on independently associated risk factors to predict overall survival among those with this distinct cancer subtype.

Background Array CGH is the criterion standard for identifying copy number variations (CNV), but the restrictive requirement of DNA quality and relatively high cost prevent the use of this method as a general assay in hospitals in developing countries. Our principal objective was to determine whether the semiconductor sequencing platform (SSP) could be an alternative method in CNV detection for spontaneous miscarriage. Material/Methods A total of 443 spontaneous miscarriage samples were collected and subjected to low-coverage (0.1X) whole-genome analysis by SSP. These samples were verified by array CGH and 8 low-quality DNA samples were analyzed by SSP and validated by MLPA. Results SSP detected 195 chromosomal numerical abnormalities, 74 CNVs, and 9 mosaicisms among the 435 samples. Among 74 CNV abnormalities, SSP detected an equal number (56) of CNVs 56 >1 Mb with array CGH. However, SSP missed more 6 cases CNVs 1 Mb, and performs better in identifying mosaicism. With the merits of low cost and less demand of input DNA, SSP is a good alternative for use in genetic diagnosis.

QiHong Wu,1 RongRong Jin,2 Ting Feng,1 Li Liu,2 Li Yang,2 YuHong Tao,3 James M Anderson,4,5 Hua Ai,2,6 Hong Li1,3 1Key Laboratory of Obstetrics, Gynecology, Pediatric Disease, and Birth Defects, Ministry of Education, West China Second University Hospital, 2National Engineering Research Center for Biomaterials, 3Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; 4Department of Biomedical Engineering, 5Department of Pathology, Case Western Reserve University, Cleveland, OH, US; 6Department of Radiology, West China Hospital, Sichuan University, Chengdu, China Abstract: Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles. Keywords: autophagy, cytotoxicity, human monocytes, inflammation, iron oxide nanoparticles

Objective: Results from randomized controlled trials (RCTs) and real-world study (RWS) appear to be discordant. We aimed to investigate whether data derived from RCTs and RWS evaluating long-term all-cause mortality of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) were in agreement. Methods: RCTs or RWS comparing TAVI and SAVR, reporting longterm (≥2-year follow-up) all-cause mortality, were identified. We also carried out subgroup analyses to access the effect in different subgroups. A pre-designated data extraction form including 5 domains and 26 items was used to explore the relationship between RCTs and RWS. Mortality and effect in different subgroups were evaluated using random-effects meta-analyses. Results: Five RCTs (5421 participants, TAVI: 2759, SAVR: 2662) and 33 RWS (20839 participants; TAVI: 6585, SAVR: 14254) were identified. Pooled RCT analysis showed no difference in all-cause mortality between TAVI and SAVR (HR=0.97, 95% CI: 0.88-1.07; P=0.55). In RWS, TAVI was associated with an increased risk of allcause mortality (HR=1.46, 95% CI: 1.26-1.69; P

Background. Shoutai Pill (STP), a famous classic herbal formula documented in traditional Chinese medicine (TCM), is widely available in China for treating unexplained recurrent spontaneous abortion (URSA). This systematic review and meta-analysis aims at evaluating the efficacy and safety of STP in the first trimester of pregnancy in women with a history of unexplained recurrent spontaneous abortion. Methods. The following eight databases were searched from their establishment to Dec 31, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results. A total of 12 studies (916 patients) with URSA were contained in this meta-analysis. The forest plot showed that patients treated with Shoutai Pill and western medicine had a significantly lower incidence of early pregnancy loss (RR: 0.42; 95% CI: 0.34–0.52; P<0.01, I2=0%). Subgroup analysis revealed that different types of TCM syndrome differentiation had the similar results. Also, in the combined group, patients had a lower TCM syndromes and symptoms and serum D-dimer level, while higher incidence of live birth. Conclusions. Our findings suggest that cotreatment with STP and western medicine might be superior to western medicine alone in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent spontaneous abortion, and there was no adverse event in the experimental group reported. However, the methodological quality of included RCTs was unsatisfactory; it is necessary to verify its effectiveness with further more standardized researches of rigorous design.

Purpose Therapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury. Methods We searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool. Results Twenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007). Conclusions Our meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.

Background: Treatment of neonatal seizures includes etiotropic and anticonvulsant treatments. However, anticonvulsant use in neonates is off-label and requires ethical review.Objective: To investig...

Background An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated. Methods This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake. Results Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79). Conclusions Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.