Search

Parental vaccine-hesitancy can lead to delays or refusal to vaccinate children despite the availability of vaccines. This is a population-based, cross-sectional study investigating whether parents in China are hesitant to vaccinate their children with a COVID-19 vaccine booster.Parents in Taizhou, China, responded to a self-reported online questionnaire on their hesitancy to vaccinate their children with a COVID-19 vaccine booster. Of the 1252 parents who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid data for data analysis.A total of 41.8% of participants were hesitant to give their children a COVID-19 vaccine booster. After adjusting for confounders, parental gender (female vs. male parent, OR=0.56 95% CI: 0.32-0.87), parental opinion (yes vs. no, OR=0.17, 95% CI: 0.09-0.30), parental attitudes (yes vs. no, OR=0.28, 95% CI: 0.16-0.50), the presence of people around them who are generally hesitant to receive COVID-19 booster vaccines for children (yes vs. no, OR=0.14, 95%CI: 0.08-0.23), the individual hesitancy of people around them to administer booster COVID-19 vaccines to children (yes vs. no, OR=0.02, 95%CI: 0.02-0.22), and parents' hesitancy to receive a booster vaccine for their children showed significant correlation. The disparity of factors related to booster vaccine-hesitancy for children between fathers and mothers was also found.We found that a moderate proportion of parents reported that they were hesitant to give their children a COVID-19 vaccine booster. The results suggest that an in-depth, dynamic assessment and further health education planning are necessary to reduce Chinese parents' hesitancy to vaccinate their children.

Patients with clinical stage I (CS I: cN0M0) testicular germ cell tumors (TGCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I TGCT, we lack reliable means to predict relapse among pediatric and adolescent patients.We sought to identify predictors of relapse in children with CS I TGCT.We performed a pooled post hoc analysis on pediatric and adolescent AJCC CS I TGCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of events, defined as relapse, secondary malignant neoplasm, or death.106 patients were identified with outcomes data available. Most patients were pT1-2 stage. Among patients with evaluable histopathology, yolk sac tumor elements were present in all patients and lymphovascular invasion in 51% of patients. Over a median follow-up of 56 months, no patients died, and 25 patients (24%) experienced an event (median event-free survival not reached). Independent predictors of events on multivariable analysis included age ≥12 years at diagnosis (HR 8.87, p 0.001) and higher pT stage (pT2 HR 7.31, p = 0.0017; pT3 HR 13.5, p = 0.0043).Although our study population reflects the largest pooled prospective cohort of CS I pediatric and adolescent TGCT to our knowledge, the relatively low event rate limits our multivariable analysis, and longer follow-up duration would help further characterize the natural history of these patients. Centralized pathologic review was also unable to be performed for several patients.Pediatric and adolescent CS I TGCT patients exhibit remarkable 5-year survival. Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and inform personalized treatment for these patients by potentially guiding surveillance versus adjuvant treatment strategies.

Revascularisation for peripheral artery disease (PAD) is increasingly common in dialysis patients. Patients with PAD who have undergone revascularisation are at high risk of subsequent complications. Malnutrition is an important modifiable risk factor for dialysis patients, yet few data exist on the prognostic impact of malnutrition on post-procedure long term outcomes. The objective was to assess the prevalence and prognostic association of malnutrition using the Controlling Nutritional Status (CONUT) score in a prospective cohort of dialysis patients undergoing endovascular therapy (EVT) for PAD.A total of 395 consecutive dialysis patients undergoing endovascular revascularisation for lower extremity PAD between 2005 and 2019 were examined for the primary outcome of all cause death. Secondary outcomes included major adverse limb events (MALEs), defined as acute limb ischaemia, major amputation, and clinically driven revascularisation; and major adverse cardiovascular events (MACEs). Nutritional status was assessed by CONUT score, a screening tool for malnutrition, incorporating albumin, cholesterol, and total lymphocyte count.According to the CONUT score, 40.8% of patients were moderately or severely malnourished. During a median follow up of 2.2 years, 218 (55.2%) patients died; 211 (53.4%) patients had MALEs, and MACEs occurred in 135 (34.2%) patients. Compared with normal nutritional status, severe malnutrition was associated with a significantly increased risk of all cause death (adjusted hazard ration [aHR] 4.83, 95% confidence interval [CI] 2.56 - 9.12) and MALEs (aHR 2.42, 95% CI 1.23 - 4.74) but not MACEs (aHR 1.81, 95% CI 0.74 - 4.40). Similar results were observed when the CONUT score was analysed as a continuous variable.Malnutrition is common in dialysis patients with PAD requiring endovascular therapy and is strongly associated with increased death and MALEs. Clinical trials are needed to evaluate whether nutritional interventions improve outcomes for dialysis patients after peripheral revascularisation.

Human activities have significantly increased the release of thallium (Tl) to the environment. However, the study of the relationship between maternal Tl exposure during pregnancy and the risk of preterm birth (PTB) is scarce so far. We aimed to investigate the association between Tl exposure in early pregnancy and the risk of PTB. A total of 2104 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) in Wuhan, China were enrolled in the analysis. We collected the urine samples in early pregnancy ( 20 weeks) and inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary Tl levels. The association between Tl levels and the risk of PTB was evaluated by an unconditional logistic regression. The median and geometric mean values of Tl levels were 0.35 μg/L (0.47 μg/g creatinine) and 0.33 μg/L (0.47 μg/g creatinine), respectively. Compared with the lowest tertile of Tl levels (≤ 0.37 μg/g creatinine), the highest tertile ( 0.57 μg/g creatinine) was associated with an increased risk of PTB with an adjusted odds ratio (OR) of 2.11 (95% confidence interval (CI): 1.08, 4.12). Stratified analyses showed an elevated risk of PTB related to the highest tertile of Tl levels for male newborns. After excluding women with miss covariate information, gestational diabetes mellitus, pregnancy-induced hypertension, reporting fish intake, or exposed to smoke, the association remained stable. Our results suggested that maternal Tl exposure during early pregnancy was positively associated with the risk of PTB, and Tl exposure may have a sex-specific effect on PTB.

The study explored the diagnostic value of SNHG5 in diabetic nephropathy (DN) and investigated the role and mechanism on DN via establishing the in vitro HK2 cell model. This study recruited 62 types 2 diabetes mellitus (T2DM) patients, 58 DN patients and 60 healthy controls (HC). The expressions of serum SNHG5 and miR-26a-5p were measured by RT-qPCR analysis. The diagnostic value of SNHG5 in DN was assessed by ROC curve. The in vitro cell model was built to estimate the effects of SNHG5 on cell viability, cell apoptosis, inflammation response and oxidative stress. Serum SNHG5 was increased in DN patients (relative expression: 2.04±0.34) and had the diagnostic value in DN. After HK2 cells were treated with high glucose, the cell viability decreased and apoptosis increased, and the production of inflammatory cytokines and ROS enhanced significantly. It was noticed that inhibition of SNHG5 could reverse the above phenomenon caused by high glucose. Besides, serum miR-26a-5p was diminished in DN patients, and luciferase reporter gene revealed that miR-26a-5p is direct target of SNHG5. These results indicated that inhibition of SNHG5 may mitigate HG-induced renal tubular damage via targeting miR-26a-5p, which providing a new insight into the mechanism of renal tubule damage in DN patients.

Background Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia. Methods This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1–9 days of the illness course) and the late BAL layer (received BAL within 10–14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups. Results Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p p Conclusion For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications.

Background X-linked hyper-immunoglobulin M (XHIGM), a primary immunodeficiency syndrome caused by mutations in the CD40 ligand gene(CD40LG), presents with recurrent respiratory infections in pediatric patients. We aimed to evaluate the spectrum of clinical features and respiratory pathogens in pediatric patients with XHIGM in China. Methods We retrospectively reviewed seven pediatric patients who were diagnosed with XHIGM and received follow-up treatment at the Guangzhou Women and Children’s Medical Center between January 2010 and January 2021. We determined their clinical characteristics, causative pathogens, and prognosis by performing peripheral immunological and genetic tests. Results There were seven boys with age ranging from 4–20 months (median age, 13 months). Four of the seven respiratory infections were caused by Talaromyces marneffei(T. marneffei). Two patients had viral infections caused by cytomegalovirus (CMV) and human adenovirus respectively. One patient had a mixed infection caused by Pneumocystis carinii and CMV. Except for one child who died of respiratory failure, one patient received hematopoietic stem cell transplantation (HSCT) and recovered well, the other five patients survived with regular infusions of intravenous immunoglobulin (IVIg) during the follow-up period. Six patients had reduced antibody levels, especially IgG, IgA, and IgE levels. Increased serum IgM levels were detected in four cases, and three cases presented normal IgM levels at onset. All children were diagnosed with XHIGM with CD40LG variation. Three novel mutations were identified in the present study. Conclusions Our study suggests that respiratory infections usually begin within 2 years old, fungi and viruses are important pathogens causing respiratory infections in children with XHIGM. In endemic areas, T. marneffei is the common pathogen of respiratory tract infection in children with the disease.

This study aimed to investigate the role and regulatory mechanisms of Ezrin in synovial vessels in rheumatoid arthritis (RA). Synovial tissues were obtained from people with osteoarthritis people and patients with RA patients. We also used an antigen‐induced arthritis (AIA) mice model by using Freund's adjuvant injections. Ezrin expression was analysed by immunofluorescence and immunohistochemical staining in synovial vessels of patients with RA and AIA mice. We investigated the role of Ezrin on vascular endothelial cells and its regulatory mechanism in vivo and in vitro by adenoviral transfection technology. Our results suggest a role for the Ezrin protein in proliferation, migration and angiogenesis of vascular endothelial cells in RA. We also demonstrate that Ezrin plays an important role in vascular endothelial cell migration and tube formation through regulation of the Hippo‐yes‐associated protein 1 (YAP) pathway. YAP, as a key protein, can further regulate the activity of PI3K/Akt signalling pathway in vascular endothelial cells. In AIA mice experiments, we observed that the inhibition of Ezrin or of its downstream YAP pathway can affect synovial angiogenesis and may lead to progression of RA. In conclusion, Ezrin plays an important role in angiogenesis in the RA synovium by regulating YAP nuclear translocation and interacting with the PI3K/Akt signalling pathway.

Objective To investigate the effects of different lactoferrin concentrations on mid-palatal suture bone remodeling during palatal expansion and relapse in rats. Materials and methods Thirty-two 5-week-old male Wistar rats were randomly divided into four groups: EO (expansion only), E+LF1 (expansion plus 10 mg/kg/day daily LF), E+LF2 (expansion plus 100 mg/kg/day daily LF), and E+LF3 (expansion plus 1 g/kg/day daily LF). Thereafter, micro-computed tomography and micro-morphology of the mid-palatal suture were analyzed on day 7 and day 14, respectively. Results The arch widths were increased in all the four groups after expansion, and there was no significant difference among them on day 7. After relapse, however, the arch width in the E+LF3 group was significantly larger compared with EO group. In E+LF3 group and E+LF2 group, new bone formation and osteoblast number were enhanced with up-regulated expression of osteocalcin and collagen type I, while the expression of cathepsin K-positive cells was downregulated in E+LF3 group. Conclusion Lactoferrin gavage administration might increase the stability of palatal expansion and reduce relapse in a concentration-dependent manner by enhancing bone formation and inhibiting resorption. LF administration may be promising for optimizing the maxillary expansion outcome.

Vascular smooth muscle cell (VSMC) dysfunction is the main cause of aortic dissection (AD). In this study, we focused on the role and mechanism of miR-4787-5p in regulating VSMC apoptosis. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of miR-4787-5p in aorta tissues of AD (n = 10) and normal aortic tissues of donors (n = 10). Cell apoptosis was tested by TUNEL assay and Annexin V FITC/PI staining flow cytometry. The expression of PC1 and the PI3K/Akt/FKHR signaling pathway associated proteins in VSMCs was measured by Western blot. We found that the miR-4787-5p was highly expressed in aorta tissues of AD compared with 10 healthy volunteers. Meanwhile, PI3K/Akt/FKHR signaling pathway was inactive in the aortic tissue of AD. The overexpression of miR-4787-5p significantly induced VSMC apoptosis, and miR-4787-5p knockdown showed the opposite results. In addition, polycystic kidney disease 1 gene, which encodes polycystin-1 (PC1), was found to be a direct target of miR-4787-5p in the VSMCs and this was validated using a luciferase reporter assay. Overexpression of PC1 by a lentivirus packaging PC1-overexpression plasmid (LV-PC1) plasmids markedly eliminated the promotion of miR-4787-5p overexpression on VSMC apoptosis. Finally, it was found that miR-4787-5p deactivated the PI3K/Akt/FKHR pathway, as demonstrated by the down-regulation of phosphorylated (p-)PI3K, p-Akt, and p-FKHR. In conclusion, these findings confirm an important role for the miR-4787-5p/polycystic kidney disease 1 axis in AD pathobiology.

Despite all modern advances in medicine, there are few reports of effective and safe drugs to treat obesity. Our objective was to screen anti-obesity natural compounds, and to verify whether they can reduce the body weight gain and investigate their molecular mechanisms. By using drug-screening methods, Phytohemagglutinin (PHA) was found to be the most anti-obesity candidate natural compound. Six-week-old C57BL/6J mice were fed with a high-fat diet (HFD) and intraperitoneally injected with 0.25 mg/kg PHA everyday for 8 weeks. The body weight, glucose homeostasis, oxygen consumption and physical activity were assessed. We also measured the heat intensity, body temperature and the gene expression of key regulators of energy expenditure. Prevention study results showed PHA treatment not only reduced the body weight gain but also maintained glucose homeostasis in HFD-fed mice. Further study indicated energy expenditure and uncoupling protein 1 (UCP-1) expression of brown adipose tissue (BAT) and white adipose tissue (WAT) in HFD-fed mice were significantly improved by PHA. In the therapeutic study, a similar effect was observed. PHA inhibited lipid droplet formation and upregulated mitochondrial-related gene expression during adipogenesis in vitro. UCP-1 KO mice displayed no differences in body weight, glucose homeostasis and core body temperature between PHA and control groups. Our results suggest that PHA prevent and treat obesity by increasing energy expenditure through upregulation of BAT thermogenesis.

Prepubertal boys with cancer may suffer from reduced fertility and maturity following gonadotoxic chemoradiotherapy. Thus, a viable method of immature testicular tissue (ITT) preservation is required in this cohort. In this study, we used poly-L-lactic acid electrospun scaffolds with two levels of fineness to support the development of ITT transplanted from transgenic donors to wild-type recipient mice. The purpose of this study was to evaluate the potential of ITT transplantation and spermatogenesis after using the two scaffolds, employing bioluminescence imaging for evaluation. The results suggest that ITT from 4-week-old mice possessed the most potential in spermatogenesis on the 70th day, together with the fine electrospun scaffolds. Moreover, bioluminescent imaging intensity was observed in recipient mice for up to 107 days, approximately six times more than the coarse electrospun scaffold and the control group. This occurs since the fine scaffold is more akin to the microenvironment of native testicular tissue as it reduces stiffness resulting from micronization and body fluid infiltration. The thermal analysis also exhibited recrystallization during the biodegradation process, which can lead to a more stable microenvironment. Overall, these findings present the prospect of fertility preservation in prepubertal males and could serve as a framework for future applications.

Background This exploratory study aimed to investigate factors related to infant deaths using a conceptual framework that explains the risk factors of infant deaths in developing countries. Methods The study adopted a cross-sectional study design and used data from the 2012 and 2017 Indonesia Demographic and Health Surveys, with a sample of 3694 singleton live births in 2012 and 3413 in 2017. Results Female infants had a lower chance of mortality compared to male infants [adjusted odds ratio (aOR) = 0.51; 95% confidence interval (CI) = 0.34–0.77]. Infants with a smaller birth size had a higher risk of infant death compared to those with an average size (aOR = 5.66; 95% CI = 3.66–8.77). The risk of infant death with a preceding birth interval of ≥24 months was lower than that with a preceding birth interval of Conclusions A higher infant death risk was associated with male babies and a shorter birth interval (

Background The enterovirus 71 (EV-A71) vaccine has been used in Hefei for several years, and the epidemiological significance of vaccination in this area is unclear. We aims to explore the spatial–temporal-demographic and virological changes of hand, foot and mouth disease (HFMD) after vaccination in China. Methods The data for HFMD from 2012 to 2020 were downloaded with the help of HFMD reporting system of Hefei Center for Disease Control and Prevention and combined with the EV-A71 vaccination status in Hefei. The study defined the period between 2012 to 2016 as the pre-vaccination period and explored the effect of vaccination on the incidence of HFMD by comparing the changes of HFMD before and after vaccination in terms of spatial, temporal, demographic and virological aspects. Results During the study period, a higher incidence occurred in urban area and the random distribution changed to a slight cluster after vaccination. HFMD incidence had inconsistent seasonality over years, with one or two incidence peaks in varying years. The morbidity decreased from 215.22/105 in 2012–2016 to 179.81/105 in 2017–2020 (p Conclusions The EV-A71 vaccine was effective in reducing the incidence of HFMD and changing the spatial, temporal, demographic, and virological characteristic. These changes should be considered during the vaccination implementation to further reduce the disease burden of HFMD.

Pediatric cancer survivors experiencing gonadotoxic chemoradiation therapy may encounter subfertility or permanent infertility. However, previous studies of cryopreservation of immature testicular tissue (ITT) have mainly been limited to in vitro studies. In this study, we aim to evaluate in vitro and in vivo bioluminescence imaging (BLI) for solid surface-vitrified (SSV) ITT grafts until adulthood. The donors and recipients were transgenic and wild-type mice, respectively, with fresh ITT grafts used as the control group. In our study, the frozen ITT grafts remained intact as shown in the BLI, scanning electron microscopy (SEM) and immunohistochemistry (IHC) analyses. Graft survival was analyzed by BLI on days 1, 2, 5, 7, and 31 after transplantation. The signals decreased by quantum yield between days 2 and 5 in both groups, but gradually increased afterwards until day 31, which were significantly stronger than day 1 after transplantation (p = 0.008). The differences between the two groups were constantly insignificant, suggesting that both fresh and SSV ITT can survive, accompanied by spermatogenesis, until adulthood. The ITT in both groups presented similar BLI intensity and intact cells and ultrastructures for spermatogenesis. This translational model demonstrates the great potential of SSV for ITT in pre-pubertal male fertility preservation.

Background Quantitative assessment of muscle mass is a critical step in sarcopenia disease management. Expanding upon the use of ultrasound in foetal growth assessment, we established and validated an ultrasound-derived muscle assessment system for older adults at a risk of sarcopenia. Methods A total of 669 older adults were recruited in three cohorts in this cross-sectional study. In cohort 1(n = 103), the most valuable sites for skeletal muscle mass index (SMI) estimation were located among 11 ultrasound scanning sites. An ultrasound-derived SMI estimating algorithm based on muscle thickness (MT) was obtained in the modelling group composed of cohorts 1 and 2 (n = 309). The reliability of the muscle mass estimation equation and the validity of the obtained cut-off values were verified in cohort 3 (n = 257), which was selected as the verification group. Results In the modelling group, the cut-off values of ultrasound-derived e-SMI for low SMI were 7.13 kg/m2 for men and 5.81 kg/m2 for women. In the verification group, the intraclass correlation between e-SMI and SMI was 0.885. The sensitivity of the e-SMI in detecting low SMI was 93.6% for men and 89.7% for women, and the negative predictive value was 94.9% for men and 94.7% for women. Combined with the handgrip strength and gait speed, the e-SMI had an overall diagnostic sensitivity of 92.7% and a specificity of 91.0% for sarcopenia. Conclusion The ultrasound-derived muscle assessment system can be a promising muscle mass estimation tool and a potential disease classification tool.

Background The Jamar hydraulic dynamometer is a widely recognized tool for measuring grip strength. Nevertheless, the devices used most often in Asian countries are spring-type dynamometers, represented by the CAMRY dynamometer or Smedley dynamometer. We aimed to evaluate the reliability and validity of the CAMRY dynamometer compared with the Jamar dynamometer. Methods This was a cross-sectional study using a random crossover design in the grip strength test with two dynamometers. A total of 1064 healthy community-dwelling older adults aged 50–90 years old, which included 686 minorities and 378 Han Chinese, were recruited into the study from July to September 2021. We assessed the reliability and validity of the CAMRY EH101 dynamometer, and the Jamar dynamometer was regarded as the reference device. The order of testing with two dynamometers was randomized in a 1:1 ratio, with a 10-min gap between the two devices. Intraclass correlation coefficients (ICCs) and Bland–Altman analysis were calculated to assess reliability and validity between the two devices. Results The average handgrip strength (HGS) values at six times by the Jamar and CAMRY devices were 25.0 ± 7.9 kg and 24.6 ± 7.5 kg, respectively. The ICC values between the two devices were 0.815–0.854, and the systematic bias underestimated by the CAMRY dynamometer was 0.5 kg in men and 0.6 kg in women. We carried out a linear regression equation by sex, and their relationship was found as follows: male HGS (kg)Jamar = 8.001 + 0.765 × HGS (kg)CAMRY; female HGS (kg)Jamar = 3.681 + 0.840 × HGS (kg)CAMRY. Conclusions The CAMRY EH101 dynamometer provides excellent reliability and validity. This device can serve as a reliable, inexpensive, and practical device to assess grip strength in geriatric clinical practice. Clinical trial registration Chinese Clinical Trial Registry: ChiCTR2100046367; Date of clinical trial reistration: 15/05/2021.

Objective: To explore the effects of music video therapy on pain among preschool children after cardiothoracic surgery. Methods: Patients in the music video therapy (MVT) group received a 30-min music video intervention, while patients in the music therapy (MT) group received a 30-min musical intervention. Both groups were given their respective therapy three times a day for three days. Patients in the control group did not receive MVT or MV. Measures, including pain scores, vital signs (heart rate, mean arterial pressure, respiratory rate, and oxygen saturation), and other postoperative indicators were recorded and analyzed. Results: The MVT group showed a statistically significant decrease in heart rate, mean arterial pressure, and respiratory rate at the first day after surgery and pain scores at the first and second day after surgery compared to the MT group, but no significant difference was identified in oxygen saturation. The postoperative indicators including cumulative capacity of sufentanil use, the length of intensive care unit (ICU) stay, and the length of hospital stay in the MVT group were significantly lower than those in the control group. Conclusion: The findings provide further evidence to support the practice of music video therapy as a non-pharmaceutical intervention to reduce postoperative pain, reduce the dosage of analgesics, shorten the length of ICU and hospital stay in preschool children after the cardiothoracic surgery.

Background The incidence of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is low. To improve our understanding of this rare tumor type and optimally guide clinical treatment, associated risk factors, clinical manifestations, and prognosis must be explored. Aim To identify risk factors that influence the prognosis of patients with gastroenteropancreatic MiNEN (GEP-MiNEN). Methods We retrospectively analyzed the clinical data of 46 patients who were diagnosed with GEP-MiNEN at the First Affiliated Hospital of Bengbu Medical College (Anhui, China) between January 2013 and December 2017. Risk factors influencing the prognosis of the patients were assessed using Kaplan-Meier curves and cox regression models. We compared the results with 55 randomly selected patients with gastroenteropancreatic GEP neuroendocrine tumors, 47 with neuroendocrine carcinomas (NEC), and 58 with poorly differentiated adenocarcinoma. Results Among the 46 patients with GEP-MiNEN, thirty-five had gastric tumors, nine had intestinal tumors (four in the small intestine and five in the colon and rectum), and two had pancreatic tumors. The median age of the patients was 66 (41-84) years, and the male-to-female ratio was 2.83. Thirty-three (71.7%) patients had clinical stage III and IV cancers. Distant metastasis occurred in 14 patients, of which 13 had metastasis to the liver. The follow-up period was 11-72 mo, and the median overall survival was 30 mo. Ki-67 index ≥ 50%, high proportion of NEC, lymph node involvement, distant metastasis, and higher clinical stage were independent risk factors affecting the prognosis of patients with GEP-MiNEN. The median overall survival was shorter for patients with NEC than for those with MiNEN (14 mo vs 30 mo, P = 0.001), but did not significantly differ from those with poorly differentiated adenocarcinoma and MiNEN (30 mo vs 18 mo, P = 0.453). Conclusion A poor prognosis is associated with rare, aggressive GEP-MiNEN. Ki-67 index, tumor composition, lymph node involvement, distant metastasis, and clinical stage are important factors for patient prognosis.

Background Bronchiolitis is a clinical syndrome commonly encountered in practice, particularly among infants and young children. To investigate the prevalence of pathogens in hospitalized children with bronchiolitis and study the clinical characteristics of bronchiolitis with or without coinfections. Methods We investigated the respiratory specimens and clinical data of 1012 children with bronchiolitis who were treated at the Children’s Hospital of Soochow University between November 2011 and December 2018. The nasopharyngeal aspirates were examined to detect viruses by direct immunofluorescence assay or polymerase chain reaction (PCR). Mycoplasma pneumoniae (MP) was tested by PCR and enzyme-linked immunosorbent assay. Results Of the 1134 children less than 2 years with bronchiolitis, 122 were excluded by exclusion criteria. Causative pathogen was detected in 83.2% (842 of 1012). The majority of these (614 [72.9%] of 842) were single virus infection. The most common pathogens detected were respiratory syncytial virus (RSV) (44.4%), MP (15.6%), and human rhinovirus (HRV) (14.4%). Coinfection was identified in 13.5% (137 of 1012) of the patients. Coinfection included mixed virus infection and virus infection with MP infection. Children with single virus infection had a higher rate of oxygen therapy compared with single MP infection. Conclusions The most common pathogen detected in children with bronchiolitis is RSV, followed by MP and HRV. Coinfection leads to a longer period of illness, increased severity of the symptoms and increased risk of hypoxemia.

Background and Aims Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn’s disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. Methods MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. Results In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate–severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. Conclusions MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.

Introduction: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin-converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 15, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children's lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Results: It revealed that infants (< 1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (> 1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children's lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants' lungs. The ACE2+SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Conclusions: Infants (< 1 yrs.-old) with SARS-CoV-2 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from SARS-CoV-2 infection.

Arginine synthesis deficiency due to the suppressed expression of ASS1 (argininosuccinate synthetase 1) represents one of the most frequently occurring metabolic defects of tumor cells. Arginine-deprivation therapy has gained increasing attention in recent years. One challenge of ADI-PEG20 (pegylated ADI) therapy is the development of drug resistance caused by restoration of ASS1 expression and other factors. The goal of this work is to identify novel factors conferring therapy resistance. Methods: Multiple, independently derived ADI-resistant clones including derivatives of breast (MDA-MB-231 and BT-549) and prostate (PC3, CWR22Rv1, and DU145) cancer cells were developed. RNA-seq and RT-PCR were used to identify genes upregulated in the resistant clones. Unbiased genome-wide CRISPR/Cas9 knockout screening was used to identify genes whose absence confers sensitivity to these cells. shRNA and CRISPR/Cas9 knockout as well as overexpression approaches were used to validate the functions of the resistant genes both in vitro and in xenograft models. The signal pathways were verified by western blotting and cytokine release. Results: Based on unbiased CRISPR/Cas9 knockout screening and RNA-seq analyses of independently derived ADI-resistant (ADIR) clones, aberrant activation of the TREM1/CCL2 axis in addition to ASS1 expression was consistently identified as the resistant factors. Unlike ADIR, MDA-MB-231 overexpressing ASS1 cells achieved only moderate ADI resistance both in vitro and in vivo, and overexpression of ASS1 alone does not activate the TREM1/CCL2 axis. These data suggested that upregulation of TREM1 is an independent factor in the development of strong resistance, which is accompanied by activation of the AKT/mTOR/STAT3/CCL2 pathway and contributes to cell survival and overcoming the tumor suppressive effects of ASS1 overexpression. Importantly, knockdown of TREM1 or CCL2 significantly sensitized ADIR toward ADI. Similar results were obtained in BT-549 breast cancer cell line as well as castration-resistant prostate cancer cells. The present study sheds light on the detailed mechanisms of resistance to arginine-deprivation therapy and uncovers novel targets to overcome resistance. Conclusion: We uncovered TREM1/CCL2 activation, in addition to restored ASS1 expression, as a key pathway involved in full ADI-resistance in breast and prostate cancer models.

Objective Drug-induced acute interstitial nephritis (DAIN) is often associated with improved outcomes, whereas some patients may still progress to chronic kidney disease (CKD). The aim of this study was to evaluate the prognosis of patients with severe DAIN requiring renal replacement therapy (RRT) at baseline, and to explore the risk factors of progression to CKD. Methods We performed a retrospective study of patients with severe DAIN confirmed by renal biopsies in our center over a 10 years period, all the patients received RRT at presentation. The clinical and pathological characteristics at baseline were recorded, and the outcomes (renal function recovered or progressed to CKD) during follow-ups were also evaluated. Univariate and multivariate logistic regression analysis were performed to identify the independent risk factors of progression to CKD. Results Seventy-two patients who met the inclusion criteria were enrolled, 13 patients (18.0%) progressed to CKD (GFR < 60 ml/min/1.73 m2) after at least 6 months of follow-up, the remaining 59 patients achieved a favorable renal function recovery. Compared with patients who achieved renal function recovery (recovery group), the patients progressed to CKD (progression group) were older and had longer interval from symptom onset to treatment with steroids. The peak serum cystatin C concentration was higher in progression group than recovery group. Higher score of interstitial fibrosis/tubular atrophy (IFTA) and more interstitial inflammatory cells infiltration were detected in renal tissue in progression group. According to multivariable analysis, higher peak cystatin C concentration (OR = 2.443, 95% CI 1.257, 4.746, p = 0.008), longer interval to treatment with corticosteroids (OR = 1.183, 95% CI 1.035, 1.352, p = 0.014) were independent risk factors of progression to CKD. The cutoff value of cystatin C concentration was 4.34 mg/L, at which the sensitivity and specificity were 76.9% and 89.3%, respectively; the cutoff value of interval to treatment with corticosteroids was 22.5 days, at which the sensitivity and specificity were 81.8% and 79.5%, respectively. Conclusion Renal function was reversible in majority of patients with severe DAIN requiring RRT when early identification and treatment. Higher peak cystatin C concentration and longer interval to treatment with corticosteroids associated with worse renal prognosis.

Lead exposure is one of the most concerning public health problems worldwide, particularly among children. Yet the impact of chronic lead exposure on the thyroid status and related intelligence quotient performance among school-age children remained elusive.The aim of this study was to evaluate the influence of lead exposure on the thyroid hormones, amino acid neurotransmitters balances, and intelligence quotient (IQ) among school-age children living nearby a lead-zinc mining site. Other factors such as rice lead levels, mothers' smoking behavior, and diet intake were also investigated.A total of 255 children aged 7-12 years old were recruited in this study. Blood lead level (BLL), thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH), and amino acid neurotransmitters such as glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) were measured using graphite furnace atomic absorption spectroscopy (GFAAS), chemiluminescence immunoassay, high performance liquid chromatography (HPLC). Raven's standard progressive matrices (SPM) and the questionnaire were used to determine IQ and collect related influence factors.The average BLL of children was 84.8 μg/L. The occurrence of lead intoxication (defined as the BLL ≥ 100 μg/L) was 31.8%. Serum TSH levels and IQ of lead-intoxicated children were significantly lower than those without lead toxicity. The GABA level of girls with the lead intoxication was higher than those with no lead-exposed group. Correlation analyses revealed that BLL were inversely associated with the serum TSH levels (R= -0.186, p0.05), but positively related with IQ grades (R = 0.147, p0.05). Moreover, BLL and Glu were inversely correlated with IQ. In addition, this study revealed four factors that may contribute to the incidence of lead intoxication among children, including the frequency of mother smoking (OR = 3.587, p0.05) and drinking un-boiled stagnant tap water (OR = 3.716, p0.05); eating fresh fruits and vegetables (OR = 0.323, p0.05) and soy products regularly (OR = 0.181, p0.05) may protect against lead intoxication.Lead exposure affects the serum TSH, GABA levels and IQ of school-aged children. Developing good living habits, improving environment, increasing the intake of high-quality protein and fresh vegetable and fruit may improve the condition of lead intoxication.

Background: Some children hospitalized due to severe community-acquired pneumonia (CAP) require to the pediatric intensive care unit (PICU) because of severe complications. The purpose of this study was to identify the risk factors for mortality in this patient population. Methods: This study evaluated the medical records of 113 hospitalized children with severe CAP, who were transferred to the PICU within 48 h of admission at the Guangzhou Women and Children's Medical Center between 2013 and 2017. Results: The study group consisted of 87 boys (77%) and 26 girls (33%), aged between 1 month and 9 years; 72.6% (82/113) of patients were aged 3 on admission, not receiving corticosteroid therapy prior to admission, the need for mechanical ventilation, septic shock, multi-organ dysfunction (MODS), and acute renal failure (ARF) occurring prior to transfer to the PICU, increased alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, and decreased hemoglobin and albumin (ALB) levels were associated with mortality (P

Background Good self-management behaviors in patients with knee osteoarthritis can improve disease awareness, treatment effectiveness, quality of life, and reduce medical costs. However, there is a paucity of studies focusing on patients with knee osteoarthritis. Therefore, the purpose of this study was to explore the mediating effect of self-efficacy on aspects of social support and self-management behaviors in this population. Methods This study employed a cross-sectional design and convenience sampling to survey patients with knee osteoarthritis in an outpatient department of a regional hospital in northern Taiwan from February 22, 2021, to April 15, 2021. The inclusion criteria for patients were (1) those diagnosed by a physician with knee osteoarthritis and (2) who could communicate in Chinese or Taiwanese. Participants were asked to complete a demographic questionnaire, the Arthritis Self-Efficacy Scale (ASE), the Inventory of Socially Supportive Behavior (including enacted support and perceived social support), and the Arthritis Self-Management Assessment Tool (ASMAT). In addition, the Kellgren-Lawrence Grading Scale was obtained from a chart review. Data were analyzed with descriptive statistics, t-test, one-way analysis of variance, Pearson product-moment correlation, and mediation analysis. Results A total of 140 patients met the inclusion criteria. The mean age of participants was 70.21 ± 10.84years; most (73.6%) were female. The mean total score of the ASMAT was 64.27 ± 14.84. Scores for the ASE, enacted support, and perceived social support were significantly positively correlated with ASMAT (all p p p p Conclusion Our findings might suggest that perceived social support indirectly affected ASMAT through ASE. Therefore, interventions designed to increase self-efficacy and social support could enhance self-management behaviors for patients with knee osteoarthritis.

Chronic inflammation is the cause of chronic kidney disease (CKD). The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the inflammation process and is associated with the regulatory effects of NLRP3 gene polymorphisms. This study evaluated the association between NLRP3 gene polymorphisms and CKD, and further explored whether the association of environmental metals with CKD varied by the NLRP3 genotypes. A total of 218 CKD patients and 427 age- and sex-matched healthy controls were recruited in this clinic-based case–control study. Patients were identified as having CKD if their estimated glomerular filtration rate (eGFR) 2 and stage 3–5 for at least 3 months. We examined the genotypes of fifteen common ssingle-nucleotide polymorphisms in NLRP3 genes. Concentrations of total urinary arsenic were examined by summing of urinary inorganic arsenic species. Concentrations of selenium, cadmium, and lead were measured from blood samples. Associations between NLRP3 polymorphisms, environmental metals exposure, and CKD were evaluated using multivariable logistic regression while controlling for confounders. We observed that the odds of carrying NLRP3 rs4925650 GA/AA genotypes, NLRP3 rs1539019 CA/AA genotypes, and NLRP3 rs10157379 CT/TT genotypes were significantly higher among CKD cases compared to controls, with the adjusted odds ratio (95% confidence interval) were 1.54 (1.01–2.36), 1.56 (1.04–2.33), and 1.59 (1.05–2.38), respectively. The significant multiplicative interactions were identified between high levels of blood lead and NLRP3 rs4925650 GA/AA genotypes; high levels of blood cadmium or low levels of plasma selenium and the NLRP3 haplotype (rs4925648, rs4925650, rs12048215, and rs10754555) C-A-A-C multiplicatively interacted to increase the risk of CKD. Our results imply that NLRP3 polymorphisms may play an important role in the development of environmental metals exposure related CKD.

Background It remains unclear whether stress hyperglycemia is associated with delirium. We performed this cohort study to determine the association between stress hyperglycemia and delirium. Methods We consecutively enrolled patients aged ≥70 years who were admitted to the Geriatric Department of West China Hospital between March 2016 and July 2017. Stress hyperglycemia ratio (SHR) was calculated as fasting blood glucose divided by estimated average glucose derived from glycosylated hemoglobin (HbA1c) and was classified into three tertiles. Delirium was screened within 24 h of admission and three times daily thereafter, using the confusion assessment method. The Cox proportional hazards models were used to assess the association of SHR with delirium. Results Among 487 included patients (mean age 83.0 years, 72.0% male), 50 (10.3%) patients experienced delirium during hospitalization. Compared to the second tertile, both the lowest and the highest SHR tertiles were independently associated with delirium (hazard ratio [HR] 3.71, 95% confidence interval [CI] 1.45-9.51; and HR 2.97, 95% CI 1.29-6.81, respectively). Similar results were found after further adjusting for statin comedication. Multiple-adjusted restricted cubic splines revealed a nonlinear relationship between SHR and delirium (Pnonlinearity=0.04). Adding SHR to conventional risk factors improved the risk prediction of delirium (net reclassification index 0.39, P=0.01; integrated discrimination improvement 0.07, P=0.03). Subgroup analyses indicated that the relationship between SHR and delirium was more apparent in patients with HbA1c Conclusions Both lower and higher SHR were associated with increased risk of delirium but only in patients with HbA1c

Antigen-specific TRM persist and protect against skin or female reproductive tract (FRT) HSV infection. As the pathogenesis of HSV differs between humans and model organisms, we focus on humans with well-characterized recurrent genital HSV-2 infection. Human CD8+ TRM persisting at sites of healed human HSV-2 lesions have an activated phenotype but it is unclear if TRM can be cultivated in vitro. We recovered HSV-specific TRM from genital skin and ectocervix biopsies, obtained after recovery from recurrent genital HSV-2, using ex vivo activation by viral antigen. Up to several percent of local T cells were HSV-reactive ex vivo. CD4 and CD8 T cell lines were up to 50% HSV-2-specific after sorting-based enrichment. CD8 TRM displayed HLA-restricted reactivity to specific HSV-2 peptides with high functional avidities. Reactivity to defined peptides persisted locally over several month and was quite subject-specific. CD4 TRM derived from biopsies, and from an extended set of cervical cytobrush specimens, also recognized diverse HSV-2 antigens and peptides. Overall we found that HSV-2-specific TRM are abundant in the FRT between episodes of recurrent genital herpes and maintain competency for expansion. Mucosal sites are accessible for clinical monitoring during immune interventions such as therapeutic vaccination.

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson’s disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson’s disease in this animal model.

Background. Estrogen is involved in the pathophysiological process of benign prostatic hyperplasia (BPH), in which epithelial-mesenchymal transition (EMT) plays an important role. Upregulation of aquaporin (AQP) 5, which is directly activated by estrogen, has been reported to promote EMT in multiple cells. This study aimed to examine the effects of AQP5 on estrogen-induced EMT in the prostate. Methods. Normal prostate (NP) tissue samples without any histopathological changes and BPH tissue samples with pathologically confirmed hyperplasia were obtained. An EMT cell model was subsequently established by adding estradiol (E2) to RWPE-1 cells, after which AQP5 knockdown was performed. Tissue morphological and immunohistochemical features were examined using hematoxylin-eosin and immunohistochemical staining. Western blot analysis was performed to determine the expression of AQPs, estrogen receptors, and EMT-related proteins. Cell proliferation was assessed and supernatants were collected for enzyme-linked immunosorbent assay to determine transforming growth factor-β1 (TGF-β1) concentrations. Immunofluorescence staining was performed to assess protein expressions in RWPE-1 cells. Results. BPH tissues exhibited greater EMT (TGF-β1: 1.362 ± 0.196 vs. 0.107 ± 0.067, P = 0.003; vimentin: 1.581 ± 0.508 vs. 0.221 ± 0.047, P

Highlights • The detection rate of hock-a-loogie saliva was higher than nasopharyngeal swabs. • Hock-a-loogie saliva sample had a higher viral load than throat swab. • Hock-a-loogie saliva sampling for SARS-CoV-2 detection is reliable., To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P

Background Surgery is the cornerstone of treatment for single-ventricle patients, but life just begins for most when the staged procedures are completed. A package of care, including primary care, out-of-hospital specialist visits, and medication, is required for patients living with Fontan. This study quantified the current state of out-of-hospital health care use across childhood for Fontan patients using evidence from Australia. Methods Patients recruited from the Fontan Registry were linked with the administrative Medicare (universal health insurance) data. Frequency of medical and pharmaceutical care and costs were estimated. Results Data for 115 patients with 12,726 medical and 8,336 pharmaceutical claims were obtained. From age 0 to 20 years, patients on average visited a general practitioner an estimated 6.4 times per year (95% confidence interval [CI], 5.9-7.0 times per year), and specialists, including cardiologists, 2.8 times per year (95% CI, 2.5-3.0 times per year). Average use of allied health professional care peaked at age 6 to 9 years (1.0 visits per year; 95% CI, 0.7-1.4 visits per year) with psychologic services being most prominent. For pharmaceuticals, an average of 13.3 prescriptions filled per patient per year throughout childhood was observed (95% CI, 12.4-14.2 prescriptions per year). Overall, out-of-hospital doctor visits of all types averaged 11 visits per year from birth to 20 years. A decline in care was observed when patients reached 18 years across services. Conclusions Patterns of out-of-hospital health care use were observed; however, current guidelines are silent about whether this is optimal. Further research is needed to better understand the comprehensive needs of this population.

We conducted a cross-sectional study to investigate the associations between domestic pets and respiratory health in children. We randomly recruited 11,611 school children from Zhongshan, a southern city in China. Information about the respiratory symptoms and disease history of the recruited children, the status of domestic pets, and other related risk factors were collected from March to July 2016. We identified cat-keeping at home increases the risk of persistent cough (OR, 1.77; 95%CI, 1.03���3.05); poultry-keeping at home increases the risk of current asthma (OR, 3.87; 95%CI, 1.08���13.92) and allergic rhinitis (OR, 1.84; 95%CI, 1.01���3.37); sleeping with pets increases the risk of persistent phlegm (OR, 5.04; 95%CI, 1.05���24.28), doctor-diagnosed asthma (OR, 3.35; 95%CI, 1.31���8.57) and current asthma (OR, 4.94; 95%CI, 1.05���23.31) in children. Cat-keeping and molds on the wall of the house had the multiplicative and additive interaction in doctor-diagnosed asthma. In conclusion, pet-keeping increased the risk of respiratory symptoms in children.

We sought to determine whether donor-derived human herpesvirus (HHV) 6B–specific CD4+ T-cell abundance is correlated with HHV-6B detection after allogeneic hematopoietic cell transplantation. We identified 33 patients who received HLA-matched, non–T-cell–depleted, myeloablative allogeneic hematopoietic cell transplantation and underwent weekly plasma polymerase chain reaction testing for HHV-6B for 100 days thereafter. We tested donor peripheral blood mononuclear cells for HHV-6B–specific CD4+ T cells. Patients with HHV-6B detection above the median peak viral load (200 copies/mL) received approximately 10-fold fewer donor-derived total or HHV-6B–specific CD4+ T cells than those with peak HHV-6B detection at ≤200 copies/mL or with no HHV-6B detection. These data suggest the importance of donor-derived immunity for controlling HHV-6B reactivation.

Background. The importance of identifying osteoporotic vertebral endplate or/and cortex fracture (ECF), which primarily includes endplate fracture (EPF) and vertebral anterior cortex buckling, has been recognized. However, some old traumatic ECFs with healing process in the elderly may be mistaken as osteoporotic. This study analyzes the radiological features of traumatic EPF. Methods. This was a retrospective analysis of 194 spine trauma patients with 263 vertebral fractures (mean age: 42.11 ± 9.82 years, 118 males and 76 females). All patients had traumatic EPF identified by X-ray/CT/MRI. Results. The involved vertebra was mostly L1 (29.7%), followed by T12 and L2. Except EPFs involved both superior and inferior endplates (12.6%), only 1.9% involved inferior endplate alone, with the majority involved superior endplate. If each endplate was divided into five segments of equal lengths (from anterior to posterior: a1, a2, m, p2, p1), the most depressed point of superior EPFs was mostly at segment-a2 (approximately 45%), followed by segment-a1 (approximately 20%) or segment-m (approximately 20%), and very rarely at segment-p1. The upper 1/3 of anterior vertebral wall was more likely to fracture, followed by middle 1/3 of anterior wall. For posterior vertebral wall fracture, 68.5% broke the bony wall surrounding the basivertebral vain. 58.6%, 30.0%, and 11.4% of vertebral fractures had 1/3 vertebral body height loss. As the extent of vertebral height loss increased, the chance of having both superior and inferior EPFs also increased; however, the chance of having inferior EPF alone did not increase. Conclusion. Traumatic EPF features are characterized, which may help the differentiation of traumatic and osteoporotic EPFs.

Introduction Rapid palatal expansion is an effective intervention for correcting transverse maxillary deficiency in growing patients. However, relapse after treatment is often observed, and the mechanisms of tissue remodeling during expansion and relapse remain unclear. This study aimed to gain insight into such a mechanism. Methods A total of 24 5-week-old male Wistar rats were randomly divided into either the expansion or sham device (control) group. Each rat underwent 7 days of expansion and 7 days of relapse. The width of the dental arch, palatal bone, and suture, as well as the angle of the teeth, were measured. Tissue remodeling in the midpalatal suture was examined using microcomputed tomography and histologic and immunohistochemical analyses. Results The mechanical expansion force caused an increase in arch width, which relapsed after the removal of force. Bilateral tilting of the teeth and midpalatal suture expansion contributed to the widening of the maxillary arch, and only the relapse of the palatal bone width was observed. Histochemical staining showed that suture tissue remodeling was activated by mechanical force in the expansion group and reverted to the level of the control group after relapse. Immunohistochemistry staining revealed that the expression of cathepsin K, osteocalcin, and collagen type I was higher in the expansion group than that in the control group on day 7; however, the difference dissipated by day 14. Conclusions The expansion force stimulated osteogenic activity in the midpalatal suture area. After removal of the expansion force, tissue remodeling went back to the normal level.

BackgroundWashington State served as the initial epicenter of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in the United States. An understanding of the risk factors and clinical outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) may provide guidance for management.MethodsAll laboratory-confirmed COVID-19 cases in adults admitted to an academic medical center in Seattle, Washington, between 2 March and 26 March 2020 were included. We evaluated individuals with and without severe disease, defined as admission to the intensive care unit or death.ResultsOne hundred five COVID-19 patients were hospitalized. Thirty-five percent were admitted from a senior home or skilled nursing facility. The median age was 69 years, and half were women. Three or more comorbidities were present in 55% of patients, with hypertension (59%), obesity (47%), cardiovascular disease (38%), and diabetes (33%) being the most prevalent. Most (63%) had symptoms for ≥5 days prior to admission. Only 39% had fever in the first 24 hours, whereas 41% had hypoxia at admission. Seventy-three percent of patients had lymphopenia. Of 50 samples available for additional testing, no viral coinfections were identified. Severe disease occurred in 49%. Eighteen percent of patients were placed on mechanical ventilation, and the overall mortality rate was 33%.ConclusionsDuring the early days of the COVID-19 epidemic in Washington State, the disease had its greatest impact on elderly patients with medical comorbidities. We observed high rates of severe disease and mortality in our hospitalized patients.

Honey-processed Astragalus is a widely used traditional Chinese medicine that has a better effect on reinforcing "Qi" (vital energy) than the raw one. A comparative study of metabolites analysis between them in rat serum for finding the bioactive ingredients was carried out using serum pharmacochemistry and multivariate statistical analysis. The blood collection methods and time were optimized first. Then the prototypes and metabolites in serum samples after oral administration were investigated by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry integrated with principal component analysis and orthogonal partial least squares discriminant analysis. The contents of metabolites were also analyzed to evaluate the metabolic profile differences. As a result, nine prototypes and 36 metabolites were identified. Only two prototypes and 15 metabolites were different between raw and honey-processed Astragalus. Their biotransformation reactions contained the process of oxidation, demethylation, and hydrolysis in phase I and glucuronide conjugation or sulfate conjugation in phase II. Most of the detected metabolites were transformed from isoflavones and isoflavanes. Our results expand the knowledge about the influence of honey-processing on Astragalus and suggest the different curative effects between raw and honey-processed Astragalus might due to their therapeutic material discrepancy.

Mounting evidence has linked dietary capsaicin (CAP) consumption to the improvement of glucose homeostasis; however, the underlying mechanisms still need to be further elucidated. Male mice were fed a high-fat diet (HFD) with CAP administration for 8 weeks, gut microbiota, bile acid (BA) profiles and markers for BA, and glucose metabolism were investigated. CAP improved glucose homeostasis partially by enhancing the secretion of glucagon-like peptide 1 (GLP-1). The gut microbiota was remodeled by CAP and was characterized by the increased abundance of Bacteroides genera, which is related with lithocholic acid (LCA) production. LCA is an endogenous agonist of Takeda G-protein coupled receptor 5 (TGR5); it may enhance GLP-1 secretion in intestinal L cells. Meanwhile, antibiotics experiment abolished the effects of CAP on glucose homeostasis and microbiota transplantation experiments demonstrated that the CAP-induced beneficial effects were transferable, indicating that the effects of CAP on glucose homeostasis were largely dependent on the gut microbiota. Additionally, we further identified that the improvements induced by CAP were attenuated by the antagonist of GLP-1 receptor, indicating that the activation of GLP-1 signaling contributes to the CAP-induced improvement in glucose homeostasis.

We investigated the role of dynamic changes of serum levels S100B protein in brain injury and poor outcome of sepsis. This is a prospective cohort study designed to include 104 adult patients with sepsis who are admitted to ICU from Jan 2015 to Aug 2016. Sepsis was defined as sepsis 3.0. Patients with a GCS score of

Summary: Background: We report initial surgical results and learning process of single-port video-assisted thoracoscopic surgery (VATS) subsegmentectomy in comparison with segmentectomy in our institution as the presentative of minimal invasiveness and precise resection for early stage lung cancer. Methods: All patients undergoing single-port VATS sublobar anatomic resection between January 2014 and December 2018 for clinical diagnosis of lung cancer were included. The learning curve was analyzed using the cumulative summation (CUSUM) method. Comparisons were done between those who underwent single-port VATS subsegmentectomy and segmentectomy. Results: A total of 364 patients underwent single-port VATS segmentectomy and 91 patients underwent single-port VATS subsegmentectomy were included. Lung adenocarcinoma was the most common (61.1%) diagnosis. The operative time and blood loss in the subsegmentectomy group were less than the segmentectomy group. The incidence of intraoperative complication was also lower in the subsegmentectomy group. The surgical proficiency was reached at 28 cases in single-port VATS subsegmentectomy. For primary lung cancer, the tumor size in subsegmentectomy group was smaller than segmentectomy group (1.1 cm versus 1.4 cm, p = 0.026). The resection margin was smaller in subsegmentectomy group, and both groups reached adequate margin without significant difference (94.7% versus 95.5%, p = 0.737). During the follow-up period, 2 (3.5%) patients in subsegmentectomy group and 9 (4.1%) patients in segmentectomy group developed distant metastasis. Conclusion: Single-port VATS subsegmentectomy is safe and feasible for small-sized lung lesion, providing the benefit of minimal invasiveness, preservation of pulmonary function, and clearance of lymphatic drainage at the intersegmental plane. The surgical proficiency could be achieved based on the experiences in single-port VATS segmentectomy. Keywords: Single port, Single incision, Subsegmentectomy, Segmentectomy

Summary Background Colonoscopy performance varies among endoscopists, impairing the discovery of colorectal cancers and precursor lesions. We aimed to construct a real-time quality improvement system (ENDOANGEL) to monitor real-time withdrawal speed and colonoscopy withdrawal time and to remind endoscopists of blind spots caused by endoscope slipping. We also aimed to evaluate the effectiveness of this system for improving adenoma yield of everyday colonoscopy. Methods The ENDOANGEL system was developed using deep neural networks and perceptual hash algorithms. We recruited consecutive patients aged 18–75 years from Renmin Hospital of Wuhan University in China who provided written informed consent. We randomly assigned patients (1:1) using computer-generated random numbers and block randomisation (block size of four) to either colonoscopy with the ENDOANGEL system or unassisted colonoscopy (control). Endoscopists were not masked to the random assignment but analysts and patients were unaware of random assignments. The primary endpoint was the adenoma detection rate (ADR), which is the proportion of patients having one or more adenomas detected at colonoscopy. The primary analysis was done per protocol (ie, in all patients having colonoscopy done in accordance with the assigned intervention) and by intention to treat (ie, in all randomised patients). This trial is registered with http://www.chictr.org.cn , ChiCTR1900021984. Findings Between June 18, 2019, and Sept 6, 2019, 704 patients were randomly allocated colonoscopy with the ENDOANGEL system (n=355) or unassisted (control) colonoscopy (n=349). In the intention-to-treat population, ADR was significantly greater in the ENDOANGEL group than in the control group, with 58 (16%) of 355 patients allocated ENDOANGEL-assisted colonoscopy having one or more adenomas detected, compared with 27 (8%) of 349 allocated control colonoscopy (odds ratio [OR] 2·30, 95% CI 1·40–3·77; p=0·0010). In the per-protocol analysis, findings were similar, with 54 (17%) of 324 patients assigned ENDOANGEL-assisted colonoscopy and 26 (8%) of 318 patients assigned control colonoscopy having one or more adenomas detected (OR 2·18, 95% CI 1·31–3·62; p=0·0026). No adverse events were reported. Interpretation The ENDOANGEL system significantly improved the adenoma yield during colonoscopy and seems to be effective and safe for use during routine colonoscopy. Funding Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Hubei Province Major Science and Technology Innovation Project, and the National Natural Science Foundation of China.

Background The prognostic predictors of pulmonary hypertension (PH) due to advanced heart failure (HF) have yet to be explored. Objectives To examine the prognostic value of hemodynamics and comorbidities in this patient group. Methods We retrospectively enrolled consecutive patients with PH due to advanced HF diagnosed by echocardiography and right heart catheterization. Follow-up was performed every 6 months ± 2 weeks. Primary endpoints were all-cause mortality and heart or lung transplantation. Results In total, 92 patients were included. The mean age was 46.82 years and mean left ventricular ejection fraction (LVEF) was 26.63%. During a median follow-up time of 9.72 months, 66 patients (71.7%) met primary endpoints. Pulmonary arterial compliance (PAC) was a significant predictor for primary endpoints and patients burdened with more than 3 comorbidities had worse prognoses (P = 0.0114). Conclusions In these patients, PAC can be a potential prognostic predictor and patients with a higher comorbidity burden have worse outcomes.

Dual and single antiplatelet therapies are routinely used in carotid artery endarterectomy (CEA). However, the efficacy and safety of these therapies are controversial. The present study aimed to comprehensively compare the clinical outcomes between dual and single antiplatelet therapies in CEA.This study retrieved available academic studies evaluating the complications related to antiplatelet therapy between dual and single antiplatelet therapies in CEA from the databases of ScienceDirect, the Cochrane Library, EMBASE, and PubMed. References to previous reviews and related clinical trials were manually checked to retrieve potential literature that was not included in our electronic search results.A total of 10 articles (1 randomized controlled trial, 9 non-randomized controlled trials) were included in the study. The overall number of patients in the dual antiplatelet group was 14,280, and the number of patients in the single antiplatelet group was 125,850. The results revealed that the single antiplatelet group had a lower incidence of 30-day death (rate difference [RD] 0.002; 95% confidence interval [CI] 0.000-0.003; P = 0.014), neck hematoma (odds ratio [OR] 2.120; 95% CI 1.431-3.142; P0.001), myocardial infarction (RD 0.004; 95% CI 0.001-0.007; P = 0.003), and major bleeding (RD 0.005; 95% CI 0.002-0.008; P0.001). Meanwhile, the single antiplatelet group was associated with a shorter operation time (weighted mean difference 4.000; 95% CI= 2.564-5.436; P0.001). However, there was no significant difference in the rate of postoperative transient ischemic attack (P = 0.215), stroke (P = 0.130), or length of stay (P = 0.563).Based on current evidence, using single antiplatelet therapy in CEA may reduce operation time and the incidences of 30-day death, neck hematoma, major bleeding, and myocardial infarction without increasing the risks of transient ischemic attack, stroke, or a longer operation time.

Angiopoietin-2 (Ang-2) is a proangiogenic factor that mediates inflammation and atherosclerosis. We evaluated the predictive value of circulating Ang-2 levels for periprocedural myocardial injury (PMI) in 145 patients undergoing elective percutaneous coronary intervention (PCI), and investigated whether post-PCI Ang-2 levels are influenced by PMI. PMI was defined as a post-procedural troponin elevation above the 5×99th percentile upper reference limit. Blood samples for Ang-2 analysis were collected at admission and on postoperative days 1 and 3. PMI occurred in 40 patients (28%). At baseline, there was no difference in Ang-2 levels between PMI and non-PMI patients (P=0.554). However, a significant interaction effect between PMI occurrence and time on Ang-2 levels was observed (interaction P=0.036). Although serum Ang-2 levels in non-PMI patients gradually decreased, Ang-2 levels in PMI patients did not change between different time-points. Multiple logistic regression analysis revealed that age, total stent length, and serum levels of N-terminal pro-brain natriuretic peptide were independent PMI predictors. These findings indicate that pre-procedural Ang-2 levels do not impact PMI occurrence after elective PCI. However, changes in Ang-2 levels after the procedure are closely related to PMI.

Background Despite the fact that histone deacetylase (HDAC) inhibitors have been tested to treat various cardiovascular diseases, the effects of selective HDAC6 inhibitor ACY1215 on infarct size during cardiac ischemia-reperfusion (IR) injury still remain unknown. In the present study we aimed to investigate the effects of ACY1215 on infarct size in rats with cardiac IR injury, as well as to examine the association between HDAC6 inhibitors and the gene expression of hypoxia inducible factor-1α (HIF-1α), a key regulator of cellular responses to hypoxia. Methods By using computational analysis of high-throughput expression profiling dataset, the association between HDAC inhibitors (pan-HDAC inhibitors panobinostat and vorinostat, and HDAC6 inhibitor ISOX) and their effects on HIF-1α gene-expression were evaluated. The male Wistar rats treated with ligation of left coronary artery followed by reperfusion were used as a cardiac IR model. ACY1215 (50 mg/kg), pan-HDAC inhibitor MPT0E028 (25 mg/kg), and vehicle were intraperitoneally injected within 5 min before reperfusion. The infarct size in rat myocardium was determined by 2,3,5-triphenyltetrazolium chloride staining. The serum levels of transforming growth factor-β (TGF-β) and C-reactive protein (CRP) were also determined. Results The high-throughput gene expression assay showed that treatment of ISOX was associated with a more decreased gene expression of HIF-1α than that of panobinostat and vorinostat. Compared to control rats, ACY1215-treated rats had a smaller infarct size (49.75 ± 9.36% vs. 19.22 ± 1.70%, p p Conclusions Our research indicated that HDAC6 inhibition by ACY1215 might reduce infarct size in rats with cardiac IR injury possibly through modulating HIF-1α expression. TGF-β and CRP should be useful biomarkers to monitor the use of ACY1215 in cardiac IR injury.

The objective of this study was to verify the protective effect of Bifidobacterium longum (BL) and the synergistical effect of Selenium and BL on alcohol plus high fat diet (HFD) induced hepatic injury in mice. We also want to explore the mechanism of Selenium-enriched Bifidobacterium longum (SeBL). C57BL/6 mice were treated with alcohol plus HFD with or without different dosage of BL or SeBL for 4 weeks. Serum levels of ALT, AST, TC, TG, LDL-C, HDL-C, FFAs, TNF-α, IL-6 and IL-1β, hepatic MDA level, SOD activity, the mRNA levels of AMPK, PPAR-α and SREBP1 were invested. SeBL inhibited lipid accumulation in hepatocytes; reduced serum AST and ALT levels; improved dyslipidemia; decreased serum FFAs, TC, TG and LDL-C levels. SeBL also inhibited alcohol plus HFD-induced hepatocyte oxidative stress through decrease in hepatic MDA levels and increase in SOD activity. SeBL also regulated lipid metabolism related genes such as AMPK, PPAR-α and SREBP1. Although BL had similar effect as SeBL, SeBL is more effective than BL. SeBL protected mice from alcohol plus HFD-induced hepatic injury in mice because of its inhibitory effect on hepatocellular oxidative stress, lipogenesis and inflammation. Selenium enhanced the protective effect of BL.