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Background: Delayed spinal epidural hematoma (SEH) following central neuraxial block (CNB) is a rare but serious complication. The underlying causes of SEH associated with neuraxial anesthesia are still unclear. Furthermore, the decision between surgical intervention and conservative management for SEH remains a complex and unresolved issue. Case Presentation: We report a case of delayed SEH in a 73-year-old woman who underwent vaginal hysterectomy under combined spinal-epidural anesthesia, with the administration of postoperative anticoagulants to prevent deep vein thrombosis on the 1st postoperative day (POD). She experienced symptoms 56 h after CNB. Magnetic resonance imaging (MRI) revealed a dorsal SEH at the L1-L4 level with compression of the thecal sac. On conservative treatment, full recovery was achieved after six months. Conclusions: This case reminds anesthesiologists should be alert to the possible occurrence of a delayed SEH following CNB, particularly with the administration of anticoagulants. Immediate neurological evaluation of neurological deficit and MRI are advised. Conservative treatment combined with close and dynamic neurological function monitoring may be feasible for patients with mild or nonprogressive symptoms even spontaneous recovery. [ABSTRACT FROM AUTHOR]

Depression is a mental disease involving complex pathophysiological mechanisms, and there are many ways to establish depressive mouse models. The purpose of this study is to comprehensively compare the behavioral changes and its mechanism induced by two different models. This study established two depressive mouse models by maternal separation (MS) or lipopolysaccharide (LPS) administration, and added fluoxetine treatment group respectively for comparison. MS induced more apparent anxiety-like behavior while LPS induced more apparent depressive-like behavior. LPS increased peripheral inflammatory factors more apparent, which were mitigated by fluoxetine. MS inhibited the 5-HT system more obviously and was relieved by fluoxetine. LPS triggered stronger immune response in the hippocampus and prefrontal cortex (PFC). MS significantly reduced the expression of neurotrophic proteins and was alleviated by fluoxetine. Overall, LPS induced stronger system inflammation, while MS impaired the function of HPA axis and 5-HT system. Our results will contribute to a deeper understanding of the pathophysiology of different stress-induced depression and will also help researchers select appropriate models of depression for their own needs. [ABSTRACT FROM AUTHOR]

Background: This population-based cross-sectional study aimed to evaluate the prevalence of oral mucosal lesions (OMLs) in children in a rural area in China as epidemiological data on these conditions from such areas are insufficient. Methods: A total of 3145 children in Xiangyun of Yunnan were enrolled. A socio-economic questionnaire and a field survey of OMLs were administered. We gathered information on factors (sex, age, caregiver, parental education, and last-month household income) that might be associated with OMLs in these children. Results: OMLs in children in Xiangyun of Yunnan had a prevalence of 1.8% (95% CI; 1.3–2.3%). The most prevalent OML was oral ulcer (n = 11; 18.3%), followed by linea alba (n = 10; 16.7%), whereas the least prevalent OMLs were frenal tag (n = 1; 1.7%) and herpes labialis (n = 1; 1.7%). On unadjusted or adjusted regression, school-aged children had about 50% lower risk of OMLs than preschoolers. Conclusions: These findings indicate that the prevalence of OMLs in Xiangyun of Yunnan is lower than previously reported. Additionally, the age might be associated with the occurrence of OMLs in children in Xiangyun of Yunnan, China. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a relatively rare malignant tumor with a high incidence in young people. The development of tyrosine kinase inhibitors has brought the treatment of osteosarcoma into a new stage. Apatinib, a tyrosine kinase inhibitor specifically targeting VEGFR2, has been increasingly reported as a treatment for osteosarcoma with promising outcome parameters, but there has been no systematic analysis of the treatment of osteosarcoma by apatinib.Methods: A single-arm meta-analysis was performed, and published literature from PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wan Fang databases as of March 1, 2021 was systematically retrieved. Quality assessment is carried out in accordance with a 20 item checklist form prepared by the Institute of Health Economics (IHE). Double arcsine transformation is performed to stabilize the variance of the original ratio. When I2 > 50%, the random effect model is used to calculate the pooled parameters; otherwise, the fixed effect model is used. We conducted subgroup analysis according to age and apatinib dose.Results: This meta-analysis included 11 studies of 356 Chinese patients with osteosarcoma. The pooled objective remission rate (ORR) of advanced or metastatic osteosarcoma treated by oral apatinib in Chinese patients was 0.27(95%CI = 0.18-0.38). The pooled disease control rate (DCR) was 0.57 (95%CI = 0.42-0.72). The pooled median progression-free survival (mPFS) and median total survival (mOS) were 5.18 months (95%CI = 4.03-6.33) and 10.87 months (95% CI = 9.40-12.33), respectively. More than 70% of adverse reactions were mild, the most common adverse reaction was hand-foot syndrome (HFMD), with an incidence of 0.46 (95%CI = 0.35-0.58), the second was hypertension, with an incidence of 0.40 (95%CI = 0.29-0.51).Conclusions: The efficacy of apatinib in the treatment of osteosarcoma is competitive with current evidence, and it is worth noting that its low cost can significantly improve patient compliance and increase therapeutic value. [ABSTRACT FROM AUTHOR]

Background: It is well documented that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effects of endothelial cells on the behavior of tumor cells. The study here was to determine the roles of endothelial cells in HCC cell growth, migration and invasion. Methods: A mixture of highly metastatic MHCC97H cells and HUVEC cells, as well as MHCC97H cells alone were subcutaneously injected into nude mice to observe the effects of HUVECs on HCC growth. The biological characteristics of MHCC97H cells respectively treated with conditioned medium (CM) derived from HUVECs and endothelial cell basal medium (EBM) in vitro, such as proliferation, migration and invasion, invasion/metastasis associated gene expression, were comparatively analyzed. Differential cytokines between CM and EBM were screened and identified using human cytokine array. Effects of the interested differential cytokine CCL2, IL-8 and CXCL16 and its related signaling pathways were further investigated in HCC cells. Results: Subcutaneous tumorigenicity of MHCC97H cells in nude mice was promoted by HUVECs and its invasion/ metastasis associated genes were significantly upregulated. The in vitro, proliferation, migration and invasion of HCC cells treated with CM were all significantly enhanced as compared to those with EBM stimulation. Simultaneously, PI3K/Akt and ERK1/2 pathway in HCC cells were activated by CM. Total of 25 differential cytokines were identified between CM and EBM such as angiopoietin-2, CCL2 (MCP-1), uPA, endostatin, CXCL16, IL-8, pentraxin 3 etc. The selected differential cytokines CCL2, IL-8 and CXCL16 all modulated the expressions of HCC invasion/metastasis genes, especially MMP2 and MMP9. In exposure to CCL2 or CXCL16 alone, upregulation in AKT phosphorylation but no change in ERK phosphorylation were found in MHCC97H cells, moreover the contents of nuclear transcription factor NF-?B were increased as compared to the control. However, no effects on the activation of Akt and ERK pathway in MHCC97H were found in exposure to IL-8. Conclusion: This study expands the contribution of endothelial cells to the progression of HCC. It unveils a new paradigm in which endothelial cells function as initiators of molecular crosstalks that enhance survival, migration and invasion of HCC cells. [ABSTRACT FROM AUTHOR]

Background: Fluoride-resistant Streptococcus mutans (S. mutans) strains have developed due to the wide use of fluoride in dental caries prevention. However, the metabolomics of fluoride-resistant S. mutans remains unclear. Objective: This study aimed to identify metabolites that discriminate fluoride-resistant from wild-type S. mutans. Materials and methods: Cell supernatants from fluoride-resistant and wild-type S. mutans were collected and analyzed by liquid chromatography-mass spectrometry. Principal components analysis and partial least-squares discriminant analysis were performed for the statistical analysis by variable influence on projection (VIP > 2.0) and p value (Mann–Whitney test, p < 0.05). Metabolites were assessed qualitatively using the Human Metabolome Database version 2.0 (http://www.hmdb.ca), or Kyoto Encyclopedia of Genes and Genomes (http://www.kegg.jp), and Metaboanalyst 6.0 (https://www.metaboanalyst.ca). Results: Fourteen metabolites differed significantly between fluoride-resistant and wild-type strains in the early log phase. Among these metabolites, 5 were identified. There were 32 differential metabolites between the two strains in the stationary phase, 13 of which were identified. The pyrimidine metabolism for S. mutans FR was matched with the metabolic pathway. Conclusions: The fructose-1,6-bisphosphate concentration increased in fluoride-resistant strains under acidic conditions, suggesting enhanced acidogenicity and acid tolerance. This metabolite may be a promising target for elucidating the cariogenic and fluoride resistant mechanisms of S. mutans. [ABSTRACT FROM AUTHOR]

Background: Volar locked plate for distal radius fracture is one of the common procedures performed in trauma surgery. There are already some factors which can be used to predict the functional outcome after volar locked plating for distal radius fracture. However their limitations caused that the outcomes couldn't be satisfactorily predicted. Better factors for predicting the prognosis more precisely are of great interest. The aim of this study is to introduce such a new factor.Methods: A total of 56 patients suffered from unilateral distal radius fracture were managed operatively with the volar locked plate. Before operation, all CT scans of the distal radius were obtained. The ratios of soft tissue circumference to bone circumference at the watershed line in the distal radius were calculated based on the preoperative CT scans. Outcomes were evaluated after operation. The correlations between the ratio and the outcomes were analyzed using single factor linear regression analysis.Results: Statistically significant linear relationships between the ratio and flexion degrees, extension degrees also patient-rated wrist evaluation (PRWE) scores were discovered. With the increase of the ratios, the flexion and extension range increased and the PRWE scores declined.Conclusions: There are obvious linear relationships between the ratio and postoperative wrist flexion-extension degrees also PRWE scores when using volar locked plating for distal radius fracture. So the ratio can be used as a predictor aiding surgeons to predict the outcome. [ABSTRACT FROM AUTHOR]

Background: To explore whether a polypropylene mesh is suitable for application as a new material for testicular prostheses. Methods: The data of 65 patients with advanced prostate cancer who underwent surgical castration in hospital were collected and analyzed. Patients who preferred to undergo traditional orchidectomy (n = 16) were assigned to the control group, and patients who underwent subcapsular orchiectomy plus implantation of a polypropylene mesh testicular prosthesis (n = 49) were assigned to the experimental group. The presence of hematoma, infection, and other complications in patients in these two groups were investigated at 3 and 12 months following the surgery. The patients were also followed up using a self-designed testicular castration satisfaction questionnaire. Results: A higher score indicated greater satisfaction. The mean score was 15.33 ± 2.85 in the experimental group and 4.63 ± 1.45 in the control group at 3 months after the surgery. The mean score was 14.92 ± 1.74 in the experimental group and 4.25 ± 1.61 in the control group at 12 months after the surgery. The difference between the two groups was statistically significant at the two time points (P < 0.01). Conclusions: Compared with orchidectomy alone, patients were more satisfied with subcapsular orchiectomy plus the implantation of a polypropylene mesh testicular prosthesis for the treatment of advanced prostate cancer. Furthermore, the polypropylene mesh testicular prosthesis maintained its original character over the duration of the study, with a good long-term effect. Thus, implantation of a polypropylene mesh testicular prosthesis is indicated to be safe and effective, and polypropylene mesh is potentially useful as a new material for testicular prostheses. [ABSTRACT FROM AUTHOR]

Background: The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process, and ovarian aging is shown by a decrease in the number and quality of oocytes. However, little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging, especially in goats. Therefore, the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution. Results: For the first time, we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn, young and aging goats, and identified nine ovarian cell types with distinct gene-expression signatures. Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes, such as Wnt beta-catenin signalling was enriched in germ cells, whereas ovarian steroidogenesis was enriched in granulosa cells (GCs). Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system, oxidative phosphorylation, and apoptosis. Subsequently, we identified a series of dynamic genes, such as AMH, CRABP2, THBS1 and TIMP1, which determined the fate of GCs. Additionally, FOXO1, SOX4, and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging. Conclusions: This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell type-specific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases. [ABSTRACT FROM AUTHOR]

Background: To infer transmission direction of a HIV transmission chain is helpful not only in legal jurisdiction but also in precise intervention to prevent HIV spread. Recently, the direction of transmission is inferred by whether paraphyletic-monophyletic (PM) or a combination of paraphyletic and polyphyletic (PP) topologies is observed or not between the sequences of source and recipient in the phylogenetic tree. However, paraphyly between them often declines over time and may disappear between spouses due to bidirectional transmission after primary infection. In this study, our aim is to test the reliability of inferring HIV transmission direction between epidemiologically linked HIV-1 positive couples using whether or not paraphyly is observed in phylogenetic tree.Methods: HIV quasi-species were sequenced using PCR product clones, and then Bayesian analysis of molecular sequences with MCMC was employed to construct phylogenetic relationship of env, gag, pol gene fragments of HIV-1 positive couples using BEAST software.Results: Our results showed that all sequences of seven couples except pol sequences of couple 12 and 13 form their own monophyletic cluster in phylogenetic tree including the closest control sequences from GenBank or other studies on local samples, which are supported by significant Bayesian posterior probabilities more than 0.9932. Of seven couples, paraphyly is only observed in phylogenetic tree constructed with env and pol gene sequences of three couples and gag gene sequences of four couples. Paraphyly is not observed in half of HIV positive couples. Pol sequences of couple 13 is separated by Blast selected controls; pol sequences of couple 12 in phylogenetic tree is supported by a lower Bayesian posterior value.Conclusion: Paraphyly relationship between sequences of donator and recipient is only observed among partial HIV-1 positive couples with epidemiological link. Phylogenetic relationship is not always the same when various gene regions of HIV are used to conduct phylogenetic analysis. The combination of phylogenetic analysis based on various gene regions of HIV and enough epidemiology investigation is essential when inferring transmission direction of HIV in a transmission chain or in one couple. However, while observed paraphyly can be used to infer transmission direction in HIV-1 positive couple, no observed paraphyly cannot deny it. [ABSTRACT FROM AUTHOR]

Background: Zinc finger and bric-a-brac/tramtrack/broad (ZBTB) domain-containing proteins have been reported to be associated with many tumors' development. However, in tumor initiation and progression, the role of ZBTB9, one of the protein family, and its prognostic value were yet to be elucidated in Liver Hepatocellular Carcinoma (LIHC). Methods: We used R software and online bioinformatics analysis tools such as GEPIA2, cBioPortal, TIMER2, Metascape, UALCAN, STRING, TISIDB, and COSMIC to investigate ZBTB9's characteristics and function in LIHC, including abnormal expression, carcinogenic role, related signaling pathways and prognostic value. Furthermore, cell experiments (such as formation, wound healing, and transwell assays) and analyses based on clinical samples (such as immunohistochemistry (IHC) and promoter methylation analysis) were conducted to verify pivotal conclusions. Results: ZBTB9 was overexpressed in LIHC samples compared to adjacent normal tissues. Through the analysis of genomic alteration and promoter hypomethylation, the clinical value and etiology of abnormal expression of ZBTB9 were preliminarily exlpored. Subsequent evidence showed that it could result in tumor progression and poor prognosis via activating cell cycle, DNA repair, MYC, and KRAS-associated signaling pathways as well as rendering immune dysregulation. After the knockdown of ZBTB9, evidently inhibited capacities of tumor cells proliferation and migration were observed. These results together indicated that ZBTB9 could be a promising prognostic biomarker and had the potential value to offer novel therapeutic targets for LIHC treatment. Conclusions: ZBTB9 was identified as a novel biomarker to predict the prognosis and tumor progression in LIHC, and a promising therapeutic target to invert tumor development. [ABSTRACT FROM AUTHOR]

Background: Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. Methods: Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017–2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. Results: Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. Conclusions: Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi can cause important intestinal diseases in ruminants. However, data on the distribution of these three protozoan pathogens in Tibetan sheep are limited. Methods: We collected 761 fecal samples from Tibetan sheep across four seasons in Qinghai Province, China, and screened the samples for Cryptosporidium spp., G. duodenalis and E. bieneusi using PCR-based sequence analysis of the genes encoding 18S ribosomal RNA, triosephosphate isomerase and the internal transcribed spacer, respectively. Results: The positivity rates of Cryptosporidium spp., G. duodenalis and E. bieneusi in Tibetan sheep were 3.68% (28/761 samples), 1.58% (12/761) and 6.44% (49/761), respectively. Four species of Cryptosporidium were identified: C. xiaoi (n = 13 samples), C. ubiquitum (n = 8), C. bovis (n = 6) and C. ryanae (n = 1). Two G. duodenalis assemblages, namely the A (n = 2 samples) and E (n = 10) assemblages, were detected. Five zoonotic E. bieneusi genotypes were found: BEB6 (n = 21 samples), COS-I (n = 14), CHS3 (n = 11) and CGS1 (n = 2) from group 2, and PIGEBITS5 (n = 1) from group 1. Geographic differences in the distribution of E. bieneusi, and seasonal differences for all the three protozoan pathogens were noted. Conclusions: Our results elucidate the prevalence and genetic diversity of these three pathogens in Tibetan sheep across different regions and seasons, including zoonotic pathogens such as C. ubiquitum, C. ryanae, G. duodenalis assemblage A and five genotypes of E. bieneusi. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. Methods: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). Results: Five hundred and ten patients were included and grouped based on dosage as A (0.10–0.14 mg/kg/week), B (0.15–0.16 mg/kg/week), C (0.17–0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). Conclusions: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15–0.20 mg/kg/week might be preferred. Trial registration: ClinicalTrials.gov: NCT03249480, retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Seed dormancy and germination determine wheat resistance to pre-harvest sprouting and thereby affect grain yield and quality. Arabidopsis VQ genes have been shown to influence seed germination; however, the functions of wheat VQ genes have not been characterized. Results: We identified 65 TaVQ genes in common wheat and named them TaVQ1–65. We identified 48 paralogous pairs, 37 of which had Ka/Ks values greater than 1, suggesting that most TaVQ genes have experienced positive selection. Chromosome locations, gene structures, promoter element analysis, and gene ontology annotations of the TaVQs showed that their structures determined their functions and that structural changes reflected functional diversity. Transcriptome-based expression analysis of 62 TaVQ genes and microarray analysis of 11 TaVQ genes indicated that they played important roles in diverse biological processes. We compared TaVQ gene expression and seed germination index values among wheat varieties with contrasting seed dormancy and germination phenotypes and identified 21 TaVQ genes that may be involved in seed dormancy and germination. Conclusions: Sixty-five TaVQ proteins were identified for the first time in common wheat, and bioinformatics analyses were used to investigate their phylogenetic relationships and evolutionary divergence. qRT-PCR data showed that 21 TaVQ candidate genes were potentially involved in seed dormancy and germination. These findings provide useful information for further cloning and functional analysis of TaVQ genes and introduce useful candidate genes for the improvement of PHS resistance in wheat. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015.Methods: We used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation.Results: The ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0-20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases.Conclusions: The integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission. [ABSTRACT FROM AUTHOR]

Background: Atopy may be associated with disease severity and a poor prognosis of human adenovirus (HAdV) pneumonia in children. Our aim was to observe the clinical characteristics and pulmonary radiological changes in children with atopy and HAdV pneumonia in China.Methods: Children hospitalised with HAdV pneumonia from June 2018 to December 2019 were analysed. All children were divided into atopic with HAdV, non-atopic with HAdV, and atopic without HAdV infection group. Each group was further divided into the mild and severe pneumonia groups according to disease severity. Standard treatment was initiated after admission, and regular follow-up evaluations were conducted at 1 month after discharge. Baseline and clinical characteristics and pulmonary radiological changes in children with and without atopy were evaluated. Risk factors associated with small airway lesions in patients with HAdV pneumonia were analysed.Results: The eosinophil count in the atopic group was significantly higher than that in the non-atopic group (P < 0.05). Severe coughing, wheezing, and small airway lesions on chest high-resolution computed tomography (HRCT) upon admission, after discharge and 1 month after discharge were significantly higher in the atopic group (with or without HAdV infection) than in the non-atopic group (P < 0.05). There were significant differences in the number of patients with wheezing and small airway lesions during hospitalisation and after discharge among the three groups (P < 0.05). The risks of small airway lesions in children with a family or personal history of asthma, severe infection, atopy, and HAdV infection were 2.1-, 2.7-, 1.9-, 2.1-, and 1.4-times higher than those in children without these characteristics, respectively.Conclusions: Children with atopy and HAdV pneumonia may experience severe coughing in mild cases and wheezing in mild and severe cases. Children with atopy are more susceptible to the development of small airway lesions, recurrent wheezing after discharge and slower recovery of small airway lesions as observed on pulmonary imaging than non-atopic children after HAdV infection. A family or personal history of asthma, atopy, severe infection, and HAdV infection are independent risk factors associated with the development of small airway lesion as observed on chest HRCT. [ABSTRACT FROM AUTHOR]

Background: Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM. Methods: Immunohistochemistry and western blotting were used to detect the expression of USP7 in GBM tissues. In vitro apoptosis assay of USP7 inhibition was performed by western blotting, immunofluorescence, and flow cytometry. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Western blotting and IP were used to verify the relationship between USP7 and its substrate. In an in vivo experiment using an intracranial xenograft model in nude mice was constructed to assess the therapeutic effect of target USP7. Results: Immunohistochemistry and western blotting confirmed that USP7 was significantly upregulated in glioblastoma samples. In in vitro experiments, inhibition of USP7 in GBM induced significant apoptosis. Co-IP and TMT proteomics identified a key anti-apoptotic substrate of USP7, ADP-ribosylation factor 4 (ARF4). Western blotting and IP confirmed that USP7 interacted directly with ARF4 and catalyzed the removal of the K48-linked polyubiquitinated chain that binded to ARF4. In addition, in vivo experiments revealed that USP7 inhibition significantly suppressed tumor growth and promoted the expression of apoptotic genes. Conclusions: Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a novel specific inhibitor of USP7 may be an effective approach for the treatment of GBM. [ABSTRACT FROM AUTHOR]

Background: Increased physical activity level is related to lower risk of depressive symptoms, and there is an inverse association between muscle strength and risk of depressive symptoms among the elderly. Although there is evidence of an inverse association between muscle strength and depressive symptoms, the relationship between these variables in a younger population is still unknown. This study aimed to examine the association between handgrip strength, a representative indicator of skeletal muscle strength, and the risk of depressive symptoms among Chinese female college freshmen.Methods: A cross-sectional study was conducted among 867 participants aged between 16 and 23 years. Handgrip strength was measured with a handheld digital Smedley dynamometer, and handgrip strength relative to body weight (kg/kg) was calculated and was classified into tertiles as follows: low (0.32-0.50), medium (0.51-0.58), and high (0.59-0.94). Depressive symptoms were evaluated using the 20-item Zung self-rating depression scale (SDS), and three cutoff points were used to indicate different depression levels.Results: We found that 10.7% of participants were classified as having severe depressive symptoms using an SDS score of 50 as the cutoff point. After adjusting for potential confounders, the adjusted odds ratios and 95% confidence intervals (CIs) for moderate-to-severe depressive symptoms across tertiles of the relative handgrip strength were 1.00 (reference) for tertile 1, 0.614 (0.353, 1.069) for tertile 2, and 0.537 (0.292, 0.988) for tertile 3 (P for trend = 0.041). The significant associations remained when other cutoff points (SDS scores: 48 or 45) were used. Interactions between handgrip strength and potential confounders for depressive symptoms in the final models were not significant.Conclusions: Our findings indicate that handgrip strength is inversely and independently related to the risk of depressive symptoms among Chinese female college freshmen. The present findings can help develop an effective intervention strategy against depression. Further intervention studies are needed to explore the mechanisms underlying the effects of handgrip strength on depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy is widely used in peripheral T cell lymphoma (PTCL). Here we conducted a phase 2, multicenter, randomized, controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in newly diagnosed PTCL. Methods: PTCL patients, except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, were 1:1 randomly assigned to receive CEOP/IVE/GDP (CEOP, cyclophosphamide 750 mg/m2, epirubicin 70 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg] on day 1, and prednisone 60 mg/m2 [maximum 100 mg] on days 1–5 every 21 days, at the first and fourth cycle; IVE, ifosfamide 2000 mg/m2 on days 1–3, epirubicin 70 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1–3 every 21 days, at the second and fifth cycle; and GDP, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1–3, and dexamethasone 40 mg on days 1–4 every 21 days, at the third and sixth cycle) and CEOP (every 21 days for 6 cycles). Analysis of efficacy and safety was of the intent-to-treatment population. The primary endpoint was a complete response rate at the end of treatment. Meanwhile, whole exome sequencing and targeted sequencing were performed in 62 patients with available tumor samples to explore prognostic biomarkers in this cohort as an exploratory post hoc analysis. Results: Among 106 patients, 53 each were enrolled to CEOP/IVE/GDP and CEOP. With 51 evaluable patients each in two groups, a complete response rate of the CEOP/IVE/GDP group was similar to that of the CEOP group (37.3% vs. 31.4%, p = 0.532). There was no difference in median progression-free survival (PFS; 15.4 months vs. 9.2 months, p = 0.122) or overall survival (OS; 24.3 months vs. 21.9 months, p = 0.178). Grade 3–4 hematological and non-hematological adverse events were comparable. Histone modification genes were most frequently mutated (25/62, 40.3%), namely KMT2D, KMT2A, SETD2, EP300, and CREBBP. Multivariate analysis indicated that CREBBP and IDH2 mutations were independent factors predicting poor PFS and OS (all p < 0.001), while KMT2D predicting poor PFS (p = 0.002). Conclusions: CEOP/IVE/GDP alternating regimen showed no remission or survival advantage to standard chemotherapy. Future clinical trials should aim to develop alternative regimen targeting disease biology as demonstrated by recurrent mutations in epigenetic factors. Trial registration: The study was registered on ClinicalTrial.gov (NCT02533700) on August 27, 2015. [ABSTRACT FROM AUTHOR]

Background: Epoxide hydrolase can regioselectively catalyze the oxirane ring-opening hydrolysis of rac-epoxides producing the corresponding chiral diols. In our laboratory, a gene named pveh1 encoding an EH from Phaseolus vulgaris was cloned. Although the directed modification of PvEH1 was carried out, the mutant PvEH1Y3 showed a limited degree of enantioconvergence towards racemic (rac-) m-chlorostyrene oxide (mCSO). Results: PvEH1 and PvEH1Y3 were combinatively subjected to laboratory evolution to further enhance the enantioconvergence of PvEH1Y3 towards rac-mCSO. Firstly, the substrate-binding pocket of PvEH1 was identified using a CAVER 3.0 software, and divided into three zones. After all residues in zones 1 and 3 were subjected to leucine scanning, two E. coli transformants, E. coli/pveh1Y149L and /pveh1P184L, were selected, by which rac-mCSO was transformed into (R)-m-chlorophenyl-1,2-ethanediol (mCPED) having 55.1% and 27.2% eep. Secondly, two saturation mutagenesis libraries, E. coli/pveh1Y149X and /pveh1P184X (X: any one of 20 residues) were created at sites Y149 and P184 of PvEH1. Among all transformants, both E. coli/pveh1Y149L (65.8% αS and 55.1% eep) and /pveh1P184W (66.6% αS and 59.8% eep) possessed the highest enantioconvergences. Finally, the combinatorial mutagenesis was conducted by replacements of both Y149L and P184W in PvEH1Y3, constructing E. coli/pveh1Y3Z2, whose αS reached 97.5%, higher than that (75.3%) of E. coli/pveh1Y3. In addition, the enantioconvergent hydrolysis of 20 mM rac-mCSO was performed by E. coli/pveh1Y3Z2, giving (R)-mCPED with 95.2% eep and 97.2% yield. Conclusions: In summary, the enantioconvergence of PvEH1Y3Z2 was successfully improved by laboratory evolution, which was based on the study of substrate-binding pocket by leucine scanning. Our present work introduced an effective strategy for the directed modification of enantioconvergence of PvEH1. [ABSTRACT FROM AUTHOR]

Background: Patients with regional lymph node recurrence after radical resection of esophageal cancer have poor therapeutic outcomes. Currently, there is no standard treatment for regional lymph node recurrence, and its prognostic risk factors are not well-understood. This study retrospectively analyzed 83 patients with postoperative regional lymph node recurrence after radical resection of esophageal squamous cell carcinoma. The aim was to evaluate the clinical efficacy and prognostic factors of salvage radiotherapy with or without chemotherapy in these patients.Methods: The survival and prognostic factors of 83 patients with esophageal squamous cell carcinoma with regional lymph node recurrence after radical surgery were retrospectively analyzed. All patients underwent radiotherapy, of which 74 patients received volumetric modulated arc therapy (VMAT), 9 patients received three-dimensional conformal radiation therapy (3DCRT), administered using a conventional segmentation protocol with a dose distribution range of 50.4-66.2Gy (median dose of 60Gy). In total, 41 patients received radiotherapy alone, 42 received radiotherapy combined with chemotherapy, and the concurrent chemotherapy regimen was mainly composed of either platinum or fluorouracil monotherapy, except for 4 patients who were given 5-fluorouracil plus platinum (FP) or paclitaxel plus platinum (TP).Results: The median follow-up time was 24 (range, 9-75) months. The overall survival (OS) rates at 1 year, 2 years, 3 years, and 5 years were 83.0, 57.1, 40.1, and 35.1%, respectively. The median overall survival (OS) time was 18 (range, 5-75) months. The 3-year survival rate was 47.5% in patients with radiation alone and 41.9% in patients receiving concurrent chemoradiotherapy(p = 0.570), while the response rate (CR + PR) in those two groups was 73.2 and 91.4%, respectively. By multivariate analysis of OS, age (worse in younger patients, p = 0.034) was found to be significantly associated with disease prognosis. The commonly toxicities were esophagitis, neutropenia and anemia. 18% patients experienced grade 3 toxicity and no treatment-related death occurred.Conclusions: These results of this retrospective analysis suggest that radiotherapy with or without chemotherapy is an effective and feasible salvage treatment for lymph node recurrence after radical resection of esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the molecular mechanism involving lncRNA-miRNA-mRNA network underlying glioma genesis is beneficial to the treatment of glioma. This study was designed to investigate the role of lncRNA NEAT1, miR-132 and SOX2 interaction in glioma. Methods: Microarray analysis was conducted to identify the differentially expressed lncRNAs in glioma tissues. The expression levels of NEAT1, miR-132 and SOX2 were determined by qRT-PCR and western blot. Proliferation of glioma cells was detected by MTT assay, while migration and invasion were determined by transwell assay. The target relationships were predicted by miRcode algorithm, and confirmed by dual luciferase reporter gene assay. Results: NEAT1 was up-regulated in glioma. Knockdown of NEAT1 inhibited glioma cells' viability, migration and invasion. MiR-132 was down-regulated while SOX2 was up-regulated in glioma cells. NEAT1 negatively regulated the expression of miR-132 in glioma while miR-132 targeted SOX2 to down-regulate its expression. Conclusion: NEAT1 promoted glioma development by promoting SOX2 expression through suppressing miR-132. [ABSTRACT FROM AUTHOR]

Background: Global countries are suffering from a shortage of health professionals. Turnover intention is closely related to job satisfaction and burnout, making good use of these relationships could alleviate the crisis. Our research aims to examine the mediating role of job satisfaction in the relationship between burnout and turnover intention.Methods: This research was conducted in Huangpi, China. The convenience sampling method and self-administereded questionnaires were used. 1370 of valid samples were collected with 97.72% effective rate. Descriptive analyses were conducted to describe social demographic factors. The structural equation model (SEM) was performed to adjust model fitting, and the mediation effect test was carried out by using the bootstrap method. Sobel-Z test was used to verify the significance of mediation effect.Results: The mean age was 36.98 (SD = 9.84). The fitting indices of hypothetical model are not good. After the adjustments, χ2/df = 5.590, GFI = 0.932, AGFI = 0.901, CFI = 0.977, NFI = 0.973, IFI = 0.977, TLI = 0.970, RESEA = 0.058. The revised model fitted well, and the SEM was put up by using the bootstrap method. The mediating effect is partial, and Soble-Z test indicates that the mediation effect is significant. Burnout is negatively correlated with job satisfaction (p < 0.01) and the standardized path coefficient is - 0.41. Job satisfaction is also negatively correlated with turnover intention (p < 0.01) and the standardized path coefficient is - 0.18. Burnout is positively correlated with turnover intention (p < 0.01) and the standardized path coefficient is 0.83.Conclusions: Job satisfaction is a mediating variable that affects the relationship between burnout and turnover intention. The mediating effect was a partial mediating effect and has a low impact of 7.4%. Improving treatment and giving more promotion opportunities for workers to improve job satisfaction, conducting career planning course and paying attention to employee psychological health to reduce job burnout. The above measures may be helpful to reduce employee turnover rate and alleviating the current situation of a shortage of health personnel in China. [ABSTRACT FROM AUTHOR]

Abstract It was highlighted that the original article [1] contained some typesetting mistakes in the first paragraph of the Background section. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease, and it is a multifactorial disease with no definite diagnostic index. The aim of this study is to construct a molecular network to find molecules that play important roles in the progression of PD with the goal of using them diagnostically and for early intervention. Results: We downloaded two gene expression profiles (GSE54536 and GSE100054) from the Expression Omnibus (GEO) database to analyze possible markers. The Genes were analyzed with GEO2R. There were 1790 and 967 differentially expressed genes (DEGs) in GSE54536 and GSE100054 respectively. A total of 125 genes co-exist in the DEGs of the two data sets. KEGG pathway analysis showed that 125 DEGs were enriched in Aldosterone synthesis and secretion, Gap junctions, Platelet activation, Rap1 signaling pathway, and Estrogen signaling pathway. There were 20 hub genes among 125 DEGs analyzed by PPI that involved in Platelet activation, Inflammatory response, Innate immune response, B cell receptor signaling, Stimulatory C-type lectin receptor signaling, Lipopolysaccharide response, Leukocyte migration, and Regulation of cell proliferation. Additionally, 42 differences in miRNAs were found in GSE100054. We constructed a miRNA-mRNA regulatory network depicting interactions between the predicted genes and the 125 DEGs. 34 miRNA-mRNA pairs were obtained. We found GNAQ and TMTC2 were the most important mRNAs in the network analyzed by Cytoscape APP centiscape, and their degrees in centiscape2.2 were all 10. has-miR-142 was the most important miRNA (the highest degree is 4 in centiscape2.2), which forms miRNA-mRNA pairs with GNAQ, TMTC2, BEND2, and KYNU. Conclusions: This study provides data of potential biomarkers and therapeutic targets for PD diagnosis and treatment. Among them, hsa-miR-142 is a critical miRNA in the PD network, and may be involved in PD progression by regulating GNAQ, TMTC2, BEND2, and KYNU. [ABSTRACT FROM AUTHOR]

Background: Acute disseminated encephalomyelitis (ADEM) is an autoimmune disease that typically follows a monophasic course and may affect any age group. The precise population-based incidence of ADEM is still unknown in most countries. In China, there is no ADEM surveillance system. The exact incidence of ADEM is difficult to estimate, and other epidemiological characteristics of ADEM are unknown. The purpose of this study is to investigate the epidemiological characteristics of ADEM in Nanchang, China.Methods: A retrospective investigation was conducted with ADEM patients admitted to second-level and third-level hospitals in Nanchang from 2008 to 2010, aiming to analyse the epidemiologic characteristics of ADEM in the population in Nanchang. ADEM patients, defined as patients who were diagnosed according to the consensus definition of ADEM provided by the International Pediatric MS Study Group, were enrolled in the study. The data were extracted from the ADEM patients' medical records.Results: Forty-seven ADEM patients were investigated. The average annual incidence was 0.31/100,000; the incidence among males (0.31/100,000) was nearly equal to that among females (0.31/100,000). The median age of onset was 25.97 years old, and the peak incidence was observed in the 5- to 9-year-old age group (0.75/100,000), followed by the over-60 age group (0.55/100,000). ADEM occurs throughout the year, but it occurs most frequently in March (n = 7) and least frequently in April and July (both n = 2). The patient numbers are roughly even in the other months. In the 2 months before the onset of ADEM, 15 patients presented with a preceding infection, but none of the patients received a vaccination. An increased number of vaccination was not accompanied by a corresponding increased number of cases of ADEM.Conclusions: The average annual incidence of ADEM was 0.31/100,000 in Nanchang. The incidence among males was nearly equal to that among females. The peak age of onset was 5-9 years old. The peak season of onset was not apparent. There was no evidence of an association between increased number of vaccines administered and number of cases of ADEM in Nanchang, China. [ABSTRACT FROM AUTHOR]

An abstract of the study "Study of Visfatin, ASP Level in Obese Children and Their Clinical Significance" by Li Rui-Zhen et al is presented.