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Objective: The association of the triglyceride-glucose (TyG) index with intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) is unclear. This study aimed to investigate the relationship of TyG index with the distribution and severity of ICAS and ECAS. Method: Patients who underwent digital subtraction angiography (DSA) for evaluating ICAS/ECAS in Zhongnan Hospital of Wuhan University from January 2017 to October 2021 were retrospectively enrolled in our study. Clinical characteristics, DSA data, blood routine, lipid profile and fasting glucose were recorded. The association of TyG index and ICAS/ECAS status were investigated in four aspects: location and distribution of stenosis, stenosis severity and whether stenosis is symptomatic. Logistic regression models were used to evaluate the association. Restricted cubic splines were constructed to model the non-linear relationship between the TyG index and different arterial stenosis status. Results: Among 1129 included patients, the median age was 62 (IQR 55–68) years, and 71.3% were male. The median TyG index was 8.81 (8.40, 9.21). Elevated TyG index was significantly associated with ICAS, combined ICAS/ECAS, anterior circulation stenosis, posterior circulation stenosis, combined anterior/posterior circulation stenosis, severe stenosis, both asymptomatic and symptomatic stenosis. This association was maintained after adjusting for age, sex, smoking, drinking, medical history of hypertension and stroke, platelet, total cholesterol, high-density lipoprotein, and low-density lipoprotein. Multivariable-adjusted spline regression models showed that a progressively increasing risk of arterial stenosis was related to an elevated TyG index. Conclusion: Elevated TyG index was associated with ICAS/ECAS. TyG index might be a useful indicator of ICAS and severe stenosis. [ABSTRACT FROM AUTHOR]

Background: Canopy architecture is critical in determining the fruit-zone microclimate and, ultimately, in determining an orchard's success in terms of the quality and quantity of the fruit produced. However, few studies have addressed how the canopy environment leads to metabolomic and transcriptomic alterations in fruits. Designing strategies for improving the quality of pear nutritional components relies on uncovering the related regulatory mechanisms. Results: We performed an in-depth investigation of the impact of canopy architecture from physiological, metabolomic and transcriptomic perspectives by comparing pear fruits grown in a traditional freestanding system (SP) or a flat-type trellis system (DP). Physiological studies revealed relatively greater fruit sizes, soluble solid contents and titratable acidities in pear fruits from DP systems with open canopies. Nontargeted metabolite profiling was used to characterize fruits at the initial ripening stage. Significant differences in fruit metabolites, including carbohydrates, nucleic acids, alkaloids, glycerophospholipids, sterol lipids, and prenol lipids, were observed between the two groups. Transcriptomic analysis indicated that a series of organic substance catabolic processes (e.g., the glycerol-3-phosphate catabolic process, pectin catabolic process and glucan catabolic process) were overrepresented in fruits of the DP system. Moreover, integrative analysis of the metabolome and transcriptome at the pathway level showed that DP pear fruits may respond to the canopy microenvironment by upregulating phenylpropanoid biosynthesis pathway genes such as PpPOD. Transient assays revealed that the contents of malic acid and citric acid were lower in the pear flesh of PpPOD RNAi plants, which was associated with regulating the expression of organic acid metabolism-related genes. Conclusions: Our results provide fundamental evidence that at the physiological and molecular levels, open-canopy architecture contributes to improving pear fruit quality and is correlated with increased levels of carbohydrates and lipid-like molecules. This study may lead to the development of rational culture practices for enhancing the nutritional traits of pear fruits. [ABSTRACT FROM AUTHOR]

Objective: Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj. Methods: A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed. Results: Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support. Conclusion: The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent. Strengths and Limitations: This is the first study to investigate the relationship between ddPCR copy number and the clinical characteristics of patients with PCP. Droplet digital PCR was a more sensitve and accurate method than qPCR for detection of pathogens. This was a retrospective study and we did not include more samples for it. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that immune dysfunction plays an important role in the pathogenesis of schizophrenia. Meso Scale Discovery (MSD) is bioanalytical method, which can detect serum inflammatory factors in patients. MSD has higher sensitivities, capturing a narrower range of proteins compared to other methods typically used in similar studies. The present study was aimed to explore the correlation between the levels of serum inflammatory factors and psychiatric symptoms in patients with schizophrenia at different stages and investigate a wide panel of inflammatory factors as independent factors for the pathogenesis of schizophrenia. Methods: We recruited 116 participants, including patients with first-episode schizophrenia (FEG, n = 40), recurrence patients (REG, n = 40) with relapse-episode schizophrenia, and a control group (healthy people, HP, n = 36). Patients are diagnosed according to the DSM -V. The plasma levels of IFN-γ, IL-10, IL-1β, IL-2, IL-6, TNF-α, CRP, VEGF, IL-15, and IL-16 were tested by the MSD technique. Patient-related data was collected, including sociodemographic data, positive and negative symptom scale (PANSS), and brief psychiatric rating scale (BPRS) and subscale scores. The independent sample T test, χ2 test, Analysis of covariance (ANCOVA), the least significant difference method (LSD), Spearman's correlation test, binary logistic regression analysis and ROC curve analysis were used in this study. Results: There were significant differences in serum IL-1β (F = 2.37, P = 0.014) and IL-16 (F = 4.40, P < 0.001) levels among the three groups. The level of serum IL-1β in the first-episode group was significantly higher than in the recurrence group (F = 0.87, P = 0.021) and control group (F = 2.03, P = 0.013), but there was no significant difference between the recurrence group and control group (F = 1.65, P = 0.806). The serum IL-16 levels in the first-episode group (F = 1.18, P < 0.001) and the recurrence group (F = 0.83, P < 0.001) were significantly higher than in the control group, and there was no significant difference between the first-episode group and the recurrence group (F = 1.65, P = 0.61). Serum IL-1β was negatively correlated with the general psychopathological score (GPS) of PANSS (R=-0.353, P = 0.026). In the recurrence group, serum IL-16 was positively correlated with the negative score (NEG) of the PANSS scale (R = 0.335, P = 0.035) and negatively correlated with the composite score (COM) (R=-0.329, P = 0.038). In the study, IL-16 levels were an independent variable of the onset of schizophrenia both in the first-episode (OR = 1.034, P = 0.002) and recurrence groups (OR = 1.049, P = 0.003). ROC curve analysis showed that the areas under IL-16(FEG) and IL-16(REG) curves were 0.883 (95%CI:0.794–0.942) and 0.887 (95%CI:0.801–0.950). Conclusions: Serum IL-1β and IL-16 levels were different between patients with schizophrenia and healthy people. Serum IL-1β levels in first-episode schizophrenia and serum IL-16 levels in relapsing schizophrenia were correlated with the parts of psychiatric symptoms. The IL-16 level may be an independent factor associating with the onset of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Identifying cancer biomarkers from transcriptomics data is of importance to cancer research. However, transcriptomics data are often complex and heterogeneous, which complicates the identification of cancer biomarkers in practice. Currently, the heterogeneity still remains a challenge for detecting subtle but consistent changes of gene expression in cancer cells. Results: In this paper, we propose to adaptively capture the heterogeneity of expression across samples in a gene regulation space instead of in a gene expression space. Specifically, we transform gene expression profiles into gene regulation profiles and mathematically formulate gene regulation probabilities (GRPs)-based statistics for characterizing differential expression of genes between tumor and normal tissues. Finally, an unbiased estimator (aGRP) of GRPs is devised that can interrogate and adaptively capture the heterogeneity of gene expression. We also derived an asymptotical significance analysis procedure for the new statistic. Since no parameter needs to be preset, aGRP is easy and friendly to use for researchers without computer programming background. We evaluated the proposed method on both simulated data and real-world data and compared with previous methods. Experimental results demonstrated the superior performance of the proposed method in exploring the heterogeneity of expression for capturing subtle but consistent alterations of gene expression in cancer. Conclusions: Expression heterogeneity largely influences the performance of cancer biomarker identification from transcriptomics data. Models are needed that efficiently deal with the expression heterogeneity. The proposed method can be a standalone tool due to its capacity of adaptively capturing the sample heterogeneity and the simplicity in use. Software availability: The source code of aGRP can be downloaded from https://github.com/hqwang126/aGRP. [ABSTRACT FROM AUTHOR]

This article is a response to "comment on 'Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma'" by Gopal Sharma. With this comment, author highlighted the strengths and limitations of the study. With this response, we respond to this and make a comparison of the results and conclusions. [ABSTRACT FROM AUTHOR]

Background: This paper attempts to conduct a systematic review and meta-analysis of deep learning (DLs) models for cervical cancer CT image segmentation.Methods: Relevant studies were systematically searched in PubMed, Embase, The Cochrane Library, and Web of science. The literature on DLs for cervical cancer CT image segmentation were included, a meta-analysis was performed on the dice similarity coefficient (DSC) of the segmentation results of the included DLs models. We also did subgroup analyses according to the size of the sample, type of segmentation (i.e., two dimensions and three dimensions), and three organs at risk (i.e., bladder, rectum, and femur). This study was registered in PROSPERO prior to initiation (CRD42022307071).Results: A total of 1893 articles were retrieved and 14 articles were included in the meta-analysis. The pooled effect of DSC score of clinical target volume (CTV), bladder, rectum, femoral head were 0.86(95%CI 0.84 to 0.87), 0.91(95%CI 0.89 to 0.93), 0.83(95%CI 0.79 to 0.88), and 0.92(95%CI 0.91to 0.94), respectively. For the performance of segmented CTV by two dimensions (2D) and three dimensions (3D) model, the DSC score value for 2D model was 0.87 (95%CI 0.85 to 0.90), while the DSC score for 3D model was 0.85 (95%CI 0.82 to 0.87). As for the effect of the capacity of sample on segmentation performance, no matter whether the sample size is divided into two groups: greater than 100 and less than 100, or greater than 150 and less than 150, the results show no difference (P > 0.05). Four papers reported the time for segmentation from 15 s to 2 min.Conclusion: DLs have good accuracy in automatic segmentation of CT images of cervical cancer with a less time consuming and have good prospects for future radiotherapy applications, but still need public high-quality databases and large-scale research verification. [ABSTRACT FROM AUTHOR]

Background: Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders. Methods: We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov–Smirnov test was used to test the normality of six groups of S100B samples. The Mann–Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis. Results: All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation. Conclusions: In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells. [ABSTRACT FROM AUTHOR]

Objective: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. Methods: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. Results: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0–151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. Conclusions: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC. [ABSTRACT FROM AUTHOR]

Background: China has 129 dialects with Mandarin as the standard and Chaoshan as the major dialect of the Chaoshan region in Guangdong. This study aimed to describe the dialect competence and usage, communication difficulty, impact of linguistic barriers, and subjective experience in healthcare.Methods: Healthcare providers (n = 234) and healthcare consumers (n = 483) at two tertiary teaching hospitals in Shantou, Chaoshan region participated in an anonymous survey.Results: Chaoshan and Mandarin were spoken respectively by ca. 80% and 6.1% of the participants. Monolinguals accounted for 28.5%, including 16.8% of Chaoshan-speaking healthcare providers and 18% of Mandarin-speaking healthcare consumers. The monolinguals preferentially used their competent dialect (Ps < 0.001) and had significant communication difficulties (Ps < 0.0001), with the mean (SD) score of 3.06 (0.96) out of 4 with Mandarin for healthcare providers and 2.18 (1.78) and 1.64 (1.40) with Mandarin and Chaoshan, respectively, for healthcare consumers. The monolingual healthcare providers perceived significant negative impacts of linguistic barriers on the entire healthcare delivery process (Ps < 0.0001). Regression analyses showed the length of stay in the Chaoshan region as a protective factor of linguistic barrier with a limited protective effect.Conclusions: This is the first report of significant linguistic barriers in healthcare imposed by Mandarin and Chaoshan dialects in Chaoshan, China. With perceived adverse impacts on the entire healthcare delivery and risks to the healthcare quality and burden, interventions such as professional interpreter service, service-learning interpreter program, or mobile interpreting apps that are medically accurate and culturally sensitive are suggested for dialectally diverse China. [ABSTRACT FROM AUTHOR]

Background: As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs. Results: The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways. Conclusions: In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds. [ABSTRACT FROM AUTHOR]

Background: With the rapid development of the high throughput detection techniques, tumor-related Omics data has become an important source for studying the mechanism of tumor progression including breast cancer, one of the major malignancies worldwide. A previous study has shown that the G2 and S phase-expressed-1 (GTSE1) can act as an oncogene in several human cancers. However, its functional roles in breast cancer remain elusive. Method: In this study, we analyzed breast cancer data downloaded from The Cancer Genome Atlas (TCGA) databases and other online database including the Oncomine, bc-GenExMiner and PROGgeneV2 database to identify the molecules contributing to the progression of breast cancer. The GTSE1 expression levels were investigated using qRT-PCR, immunoblotting and IHC. The biological function of GTSE1 in the growth, migration and invasion of breast cancer was examined in MDA-MB-231, MDA-MB-468 and MCF7 cell lines. The in vitro cell proliferative, migratory and invasive abilities were evaluated by MTS, colony formation and transwell assay, respectively. The role of GTSE1 in the growth and metastasis of breast cancer were revealed by in vivo investigation using BALB/c nude mice. Results: We showed that the expression level of GTSE1 was upregulated in breast cancer specimens and cell lines, especially in triple negative breast cancer (TNBC) and p53 mutated breast cancer cell lines. Importantly, high GTSE1 expression was positively correlated with histological grade and poor survival. We demonstrated that GTSE1 could promote breast cancer cell growth by activating the AKT pathway and enhance metastasis by regulating the Epithelial-Mesenchymal transition (EMT) pathway. Furthermore, it could cause multidrug resistance in breast cancer cells. Interestingly, we found that GTSE1 could regulate the p53 function to alter the cell cycle distribution dependent on the mutation state of p53. Conclusion: Our results reveal that GTSE1 played a key role in the progression of breast cancer, indicating that GTSE1 could serve as a novel biomarker to aid in the assessment of the prognosis of breast cancer. [ABSTRACT FROM AUTHOR]

Background: This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20–39 years old. Methods: All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity. Results: Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as < 231 ng/dL). Multivariate logistic regression revealed the odds of low testosterone was significantly greater with increasing SSB consumption (Q4 [≥442 kcal/day] vs. Q1 [≤137 kcal/day]), adjusted odds ratio [aOR] = 2.29, p = 0.041]. After adjusting for possible confounding variables, BMI was an independent risk factor for low testosterone level; subjects with BMI ≥ 25 kg/m2 had a higher risk of having a low testosterone level than those with BMI < 25 kg/m2 (aOR = 3.68, p = 0.044). Conclusion: SSB consumption is significantly associated with low serum testosterone in men 20–39 years old in the United States. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B is a significant public health problem and complex pathologic process, and unraveling the underlying mechanisms and pathophysiology is of great significance. Data independent acquisition mass spectrometry (DIA-MS) is a label-free quantitative proteomics method that has been successfully applied to the study of a wide range of diseases. The aim of this study was to apply DIA-MS for proteomic analysis of patients with chronic hepatitis B. We performed comprehensive proteomics analysis of protein expression in serum samples from HBV patients and healthy controls by using DIA-MS. Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein network analysis were performed on differentially expressed proteins and were further combined with literature analysis. We successfully identified a total of 3786 serum proteins with a high quantitative performance from serum samples in this study. We identified 310 differentially expressed proteins (DEPs) (fold change > 1.5 and P value < 0.05 as the criteria for a significant difference) between HBV and healthy samples. A total of 242 upregulated proteins and 68 downregulated proteins were among the DEPs. Some protein expression levels were significantly elevated or decreased in patients with chronic hepatitis B, indicating a relation to chronic liver disease, which should be further investigated. [ABSTRACT FROM AUTHOR]

Background: The randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1–2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1–2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1–2 SLN macrometastases undergoing TM. Methods: The clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis. Results: A total of 273 patients with 1–2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019–1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302–36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1–2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%. Conclusions: The breast cancer patients with cT1/2N0 stage, undergoing TM and 1–2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear. Methods: Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model. Results: In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection. Conclusion: In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6. 1Hpvw1WsEdBy8VCZXh5Sc1 Video Abstract [ABSTRACT FROM AUTHOR]

Objective: This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM). Methods: Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1β) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM. Results: The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1β in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1β as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1β rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1β blockade using neutralizing IL-1β monoclonal antibody or siRNA of IL-1β suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1β and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum. Conclusion: NLRP3/caspase-1/IL-1β axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM). Methods: Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1β) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM. Results: The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1β in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1β as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1β rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1β blockade using neutralizing IL-1β monoclonal antibody or siRNA of IL-1β suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1β and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum. Conclusion: NLRP3/caspase-1/IL-1β axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM. [ABSTRACT FROM AUTHOR]

Background: Metagenomic next-generation sequencing (mNGS) is an important supplement to conventional tests for pathogen detections of pneumonia. However, mNGS pipelines were limited by irregularities, high proportion of host nucleic acids, and lack of RNA virus detection. Thus, a regulated pipeline based on mNGS for DNA and RNA pathogen detection of pneumonia is essential.Methods: We performed a retrospective study of 151 patients with pneumonia. Three conventional tests, culture, loop-mediated isothermal amplification (LAMP) and viral quantitative real-time polymerase chain reaction (qPCR) were conducted according to clinical needs, and all samples were detected using our optimized pipeline based on the mNGS (DNA and RNA) method. The performances of mNGS and three other tests were compared. Human DNA depletion was achieved respectively by MolYsis kit and pre-treatment using saponin and Turbo DNase. Three RNA library preparation methods were used to compare the detection performance of RNA viruses.Results: An optimized mNGS workflow was built, which had only 1-working-day turnaround time. The proportion of host DNA in the pre-treated samples decreased from 99 to 90% and microbiome reads achieved an approximately 20-fold enrichment compared with those without host removal. Meanwhile, saponin and Turbo DNase pre-treatment exhibited an advantage for DNA virus detection compared with MolYsis. Besides, our in-house RNA library preparation procedure showed a more robust RNA virus detection ability. Combining three conventional methods, 76 (76/151, 50.3%) cases had no clear causative pathogen, but 24 probable pathogens were successfully detected in 31 (31/76 = 40.8%) unclear cases using mNGS. The agreement of the mNGS with the culture, LAMP, and viral qPCR was 60%, 82%, and 80%, respectively. Compared with all conventional tests, mNGS had a sensitivity of 70.4%, a specificity of 72.7%, and an overall agreement of 71.5%.Conclusions: A complete and effective mNGS workflow was built to provide timely DNA and RNA pathogen detection for pneumonia, which could effectively remove the host sequence, had a higher microbial detection rate and a broader spectrum of pathogens (especially for viruses and some pathogens that are difficult to culture). Despite the advantages, there are many challenges in the clinical application of mNGS, and the mNGS report should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. Results: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. Conclusion: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD. [ABSTRACT FROM AUTHOR]

Background: A novel coronavirus pneumonia outbreak began in Wuhan, Hubei Province, in December 2019; the outbreak was caused by a novel coronavirus previously never observed in humans. China has imposed the strictest quarantine and closed management measures in history to control the spread of the disease. However, a high level of evidence to support the surgical management of potential trauma patients during the novel coronavirus outbreak is still lacking. To regulate the emergency treatment of trauma patients during the outbreak, we drafted this paper from a trauma surgeon perspective according to practical experience in Wuhan. Main body: The article illustrates the general principles for the triage and evaluation of trauma patients during the outbreak of COVID-19, indications for emergency surgery, and infection prevention and control for medical personnel, providing a practical algorithm for trauma care providers during the outbreak period. Conclusions: The measures of emergency trauma care that we have provided can protect the medical personnel involved in emergency care and ensure the timeliness of effective interventions during the outbreak of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms.Methods: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis.Results: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes.Conclusion: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC. [ABSTRACT FROM AUTHOR]

Background: Screening is the main preventive method for cervical cancer in developing countries, but each type of screening has advantages and disadvantages. To investigate the most suitable method for low-income areas in China, we conducted a health economic analysis comparing three methods: visual inspection with acetic acid and Lugol's iodine (VIA/VILI), ThinPrep cytology test (TCT), and human papillomavirus (HPV) test.Methods: We recruited 3086 women aged 35-65 years using cluster random sampling. Each participant was randomly assigned to one of three cervical cancer screening groups: VIA/VILI, TCT, or HPV test. In order to calculate the number of disability-adjusted life years (DALYs) averted by each screening method, we used Markov models to estimate the natural development of cervical cancer over a 15-year period to estimate the age of onset and duration of each disease stage. The cost-effectiveness ratios (CERs), net present values (NPVs), benefit-cost ratios (BCRs), and cost-utility ratios (CURs) were used as outcomes in the health economic analysis.Results: The positive detection rate in the VIA/VILI group was 1.39%, which was 4.6 and 2.0 times higher than the rates in the TCT and HPV test groups, respectively. The positive predictive value of VIA/VILI (10.53%) was highest while the rate of referral for colposcopy was lowest for those in the HPV + TCT group (0.60%). VIA/VILI performed the best in terms of health economic evaluation results, as the cost of per positive case detected was 8467.9 RMB, which was 24503.0 RMB lower than that for TCT and 5755.9 RMB lower than that for the HPV test. In addition, the NPV and BCR values were 258011.5 RMB and 3.18 (the highest), and the CUR was 2341.8 RMB (the lowest). The TCT performed the worst, since its NPV was <0 and the BCR was <1, indicative of being poorly cost-beneficial.Conclusions: With the best economic evaluation results and requiring minimum medical resources, VIA/VILI is recommended for cervical cancer screening in poverty-stricken areas in China with high incidence of cervical cancer and lack of medical resources. [ABSTRACT FROM AUTHOR]

Background: Smoking has been shown to reduce health-related quality of life (HRQOL) in patients with coronary artery disease (CAD) undergoing percutanous coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal stents (BMS). Drug-eluting stents (DES) have now been widely used and are related to substantial reduction of restenosis and significantly improved HRQOL compared with BMS. This study aimed to evaluate the effects of smoking on HRQOL in patients after PCI in DES era.Methods: A cohort of 649 patients admitted for CAD and treated with drug-eluting stents were included in this prospective, observational study. Patients were classified as non-smokers (n = 351, 54.1%), quitters (n = 126, 19,4%), or persistent smokers (n = 172, 26.5%) according to their smoking status at the time they first admitted to hospital and during the first year of follow-up. Each patient was prospectively interviewed at baseline, 6 months and 1 year following PCI. HRQOL was assessed with the use of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36).Results: For the overall population, HRQOL scores at 1-year follow-up were significantly higher than baseline for all 8 domains. At 1-year follow-up, the HRQOL scores in persistent smokers were still lower than that in non-smokers in 6 domains except for bodily pain and mental health, and than that in quitters in 5 domains except for bodily pain, role emotional and mental health. There were no significant differences with regard to the scores between non-smokers and quitters except role emotional for which non-smokers had higher scores. After adjustment, persistent smokers demonstrated significantly less improvements in HRQOL than non-smokers in 6 domains except for bodily pain and social functioning and significantly less improvement than quitters for general health. Improvements of quitters were comparable to that of non-smokers in all domains. Multivariate linear regression analyses showed persistent smoking was an independent risk factor for PCS and MCS improvements.Conclusions: Persistent smoking substantially diminishes the potential quality-of-life benefits of DES. Efforts should be made to promote smoking cessation after DES implantation which could greatly improve the health quality outcomes. [ABSTRACT FROM AUTHOR]

Background: Factory workers in low- and middle-income countries (LMICs) are vulnerable to HIV transmission. Interventions are needed to prevent HIV in this population. We systematically reviewed published literature on the efficacy of various HIV interventions in reducing stigma, risk behaviors and HIV transmission among factory workers.Methods: A systematic review was performed using predefined inclusion and exclusion criteria. Four databases (PubMed, PsycINFO, Scopus and EMBASE) were searched for relevant publications between January 1, 1990 and December 31, 2018. Two independent reviewers assessed the methodological quality of studies.Results: Thirteen articles were included, with 2 randomized controlled trials and 11 cohort studies. Five interventions and their combinations were summarized. Educational intervention increased condom use and reduced the use of recreational drugs and alcohol before sex. Community intervention that proactively provide HIV counselling and testing (HCT) services could increase the detection rate of HIV and other sexually transmitted diseases (STDs). Lottery intervention increased HCT uptake and decreased HIV public stigma. Education combined with community intervention reduced the proportion of workers with casual sex and enhanced HIV knowledge. Peer education combined with community intervention increased the proportion of workers who were willing to take their partners to HCT. Policy intervention combined with peer education enhanced HIV knowledge, perceived condom accessibility and condom use with regular partners.Conclusions: Various interventions improved HIV knowledge, decreased HIV stigma and reduced HIV-related risk behaviors among factory workers in LMICs. The combination of multiple interventions tended to achieve better efficacy than a single intervention. Persistent combination interventions are essential to address HIV in this population. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most lethal human cancers. N6-methyladenosine (m6A), a common eukaryotic mRNA modification, plays critical roles in both physiological and pathological processes. However, its role in pancreatic cancer remains elusive. Methods: LC/MS was used to profile m6A levels in pancreatic cancer and normal tissues. Bioinformatics analysis, real-time PCR, immunohistochemistry, and western blotting were used to identify the role of m6A regulators in pancreatic cancer. The biological effects of methyltransferase-like 14 (METTL14), an mRNA methylase, were investigated using in vitro and in vivo models. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of METTL14. Results: We found that the m6A levels were elevated in approximately 70% of the pancreatic cancer samples. Furthermore, we demonstrated that METTL14 is the major enzyme that modulates m6A methylation (frequency and site of methylation). METTL14 overexpression markedly promoted pancreatic cancer cell proliferation and migration both in vitro and in vivo, via direct targeting of the downstream PERP mRNA (p53 effector related to PMP-22) in an m6A-dependent manner. Methylation of the target adenosine lead to increased PERP mRNA turnover, thus decreasing PERP (mRNA and protein) levels in pancreatic cancer cells. Conclusions: Our data suggest that the upregulation of METTL14 leads to the decrease of PERP levels via m6A modification, promoting the growth and metastasis of pancreatic cancer; therefore METTL14 is a potential therapeutic target for its treatment. [ABSTRACT FROM AUTHOR]

Background: The global spread of mosquito-borne diseases (MBD) has presented increasing challenges to public health. The transmission of MBD is mainly attributable to the biting behaviors of female mosquitoes. However, the ecological pattern of hourly host-seeking behavior in Aedes albopictus and its association with climatic variables are still not well understood, especially for a precise requirement for establishing an effective risk prediction system of MBD transmission. Methods: Mosquito samples and data on mosquito hourly density and site-specific climatic variables, including temperature, relative humidity, illuminance and wind speed, were collected simultaneously in urban outdoor environments in Guangzhou during 2016–2018. Kernel regression models were used to assess the temporal patterns of hourly host-seeking behavior in mosquito populations, and negative binomial regression models in the Bayesian framework were used to investigate the associations of host-seeking behavior with climatic variables. Results: Aedes albopictus was abundant, constituting 82% (5569/6790) of the total collected mosquitoes. Host-seeking behavior in Ae. albopictus varied across time and was significantly influenced by climatic variables. The predicted hourly mosquito densities showed non-linear relationships with temperature and illuminance, whereas density increased with relative humidity but generally decreased with wind speed. The range of temperature estimates for female biting was 16.4–37.1 °C, peaking at 26.5 °C (95% credible interval: 25.3–28.1). During the favorable periods, biting behavior of female Ae. albopictus was estimated to occur frequently all day long, presenting a bimodal distribution with peaks within 2–3 h around both dawn and dusk (05:00–08:00 h and 16:00–19:00 h). Moreover, a short-term association in hourly density between the females and males was found. Conclusions: Our field-based modeling study reveals that hourly host-seeking behavior of Ae. albopictus exhibits a complex pattern, with hourly variation constrained significantly by climatic variables. These findings lay a foundation for improving MBD risk assessments as well as practical strategies for vector control. For instances of all-day-long frequent female biting during the favorable periods in Guangzhou, effective integrated mosquito control measures must be taken throughout the day and night. [ABSTRACT FROM AUTHOR]

Background: Aedes albopictus is among the 100 most invasive species worldwide and poses a major risk to public health. Photoperiodic diapause provides a crucial ecological basis for the adaptation of this species to adverse environments. Ae. albopictus is the vital vector transmitting dengue virus in Guangzhou, but its diapause activities herein remain obscure. Methods: In the laboratory, yeast powder and food slurry were compared for a proper diapause determination method, and the critical photoperiod (CPP) was tested at illumination times of 11, 11.5, 12, 12.5, 13, and 13.5 h. A 4-parameter logistic (4PL) regression model was selected to estimate the CPP. In the field, the seasonal dynamics of the Ae. albopictus population, egg diapause, and hatching of overwintering eggs were investigated monthly, weekly, and daily, respectively. A distributed lag non-linear model (DLNM) was used to assess the associations of diapause with meteorological factors. Results: In the laboratory, both the wild population and the Foshan strain of Ae. albopictus were induced to diapause at an incidence greater than 80%, and no significant difference (P > 0.1) was observed between the two methods for identifying diapause. The CPP of this population was estimated to be 12.312 h of light. In the field, all of the indexes of the wild population were at the lowest levels from December to February, and the Route Index was the first to increase in March. Diapause incidence displayed pronounced seasonal dynamics. It was estimated that the day lengths of 12.111 h at week2016, 43 and 12.373 h at week2017, 41 contributed to diapause in 50% of the eggs. Day length was estimated to be the main meteorological factor related to diapause. Conclusions: Photoperiodic diapause of Ae. albopictus in Guangzhou of China was confirmed and comprehensively elucidated in both the laboratory and the field. Diapause eggs are the main form for overwintering and begin to hatch in large quantities in March in Guangzhou. Furthermore, this study also established an optimized investigation system and statistical models for the study of Ae. albopictus diapause. These findings will contribute to the prevention and control of Ae. albopictus and mosquito-borne diseases. [ABSTRACT FROM AUTHOR]

Background: Routine chemotherapy often cannot achieve good therapeutic effects because of multidrug resistance (MDR). MDR is frequently caused by the elevated expression of the MDR1 gene encoding P-glycoprotein (P-gp). E2F1 is a frequently overexpressed protein in human tumor cells that increases the activity of the MDR1 promoter, resulting in higher P-gp levels. The upregulation of P-gp might contribute to the survival of tumor cells during chemotherapy. E2F1 confers anticancer drug resistance; however, we speculate whether E2F1 affects MDR through other pathways. This study investigated the possible involvement of E2F1 in anticancer drug resistance of gastric carcinoma in vitro and in vivo. Methods: A cisplatin-resistant SGC7901/DDP gastric cancer cell line with stable overexpression of E2F1 was established. Protein expression levels of E2F1, MDR1, MRP, TAp73, GAX, ZEB1, and ZEB2 were detected by western blotting. The influence of overexpression of E2F1 on anticancer drug resistance was assessed by measuring IC50 of SGC7901/DDP cells to cisplatin, doxorubicin, and 5-fluorouracil, as well as the rate of doxorubicin efflux, apoptosis, and cell cycle progression detected by flow cytometry. We determined the in vivo effects of E2F1-overexpression on tumor size in nude mice, and apoptotic cells in tumor tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and hematoxylin and eosin staining. Results: The SGC7901/DDP gastric cancer cell line stably overexpressing E2F1 exhibited significantly inhibited sensitivity to cisplatin, doxorubicin, and 5-fluorouracil. Flow cytometry confirmed that the percentage of apoptotic cells decreased after E2F1 upregulation, and that upregulation of E2F1 potentiated S phase arrest of the cell cycle. Furthermore, upregulation of E2F1 significantly decreased intracellular accumulation of doxorubicin. Western blot revealed that E2F1 upregulation suppressed expression of GAX, and increased the expression of MDR1, MRP, ZEB1, TAp73, and ZEB2. Conclusions: Overexpression of E2F1 promotes the development of MDR in gastric carcinoma, suggesting that E2F1 may represent an efficacious target for gastric cancer therapy. [ABSTRACT FROM AUTHOR]