Prevalence and genetic diversity of human rhinovirus among patients with acute respiratory infections in China, 2012-2021.

To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.

Combined sedation in pediatric magnetic resonance imaging: determination of median effective dose of intranasal dexmedetomidine combined with oral midazolam.

BACKGROUND: The exact median effective dose (ED50) of intranasal dexmedetomidine combined with oral midazolam sedation for magnetic resonance imaging (MRI) examination in children remains unknow and the aim of this study was to determine the ED50 of their combination. METHODS: This is a prospective dose-finding study. A total of 53 children aged from 2 months to 6 years scheduled for MRI examination from February 2023 to April 2023 were randomly divided into group D (to determine the ED50 of intranasal dexmedetomidine) and group M (to determine the ED50 of oral midazolam). The dosage of dexmedetomidine and midazolam was adjusted according to the modified Dixon's up-and-down method, and the ED50 was calculated with a probit regression approach. RESULTS: The ED50 of intranasal dexmedetomidine when combined with 0.5 mg∙kg- 1 oral midazolam was 0.39 µg∙kg- 1 [95% confidence interval (CI) 0.30 to 0.46 µg∙kg- 1] while the ED50 of oral midazolam was 0.17 mg∙kg- 1 (95% CI 0.01 to 0.29 mg∙kg- 1) when combined with 1 µg∙kg- 1 intranasal dexmedetomidine. The sedation onset time of children with successful sedation in group D was longer than in group M (30.0[25.0, 38.0]vs 19.5[15.0, 35.0] min, P < 0.05). No other adverse effects were observed in the day and 24 h after medication except one dysphoria. CONCLUSION: This drug combination sedation regimen appears suitable for children scheduled for MRI examinations, offering a more precise approach to guide the clinical use of sedative drugs in children. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2300068611(24/02/2023).

2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages.

Inhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an inhibitor of glycolysis in silicosis mouse models and its molecular mechanisms remain unclear. Therefore, we used 2-DG to observe its effect on pulmonary inflammation and fibrosis in a silicosis mouse model. Furthermore, in vitro cell experiments were conducted to explore the specific mechanisms of HIF-1α. Our study found that 2-DG down-regulated HIF-1α levels in alveolar macrophages induced by silica exposure and reduced the interleukin-1ß (IL-1ß) level in pulmonary inflammation. Additionally, 2-DG reduced silica-induced pulmonary fibrosis. From these findings, we hypothesize that 2-DG reduced glucose transporter 1 (GLUT1) expression by inhibiting glycolysis, which inhibits the expression of HIF-1α and ultimately reduces transcription of the inflammatory cytokine, IL-1ß, thus alleviating lung damage. Therefore, we elucidated the important regulatory role of HIF-1α in an experimental silicosis model and the potential defense mechanisms of 2-DG. These results provide a possible effective strategy for 2-DG in the treatment of silicosis.

VX-765 attenuates silica-induced lung inflammatory injury and fibrosis by modulating alveolar macrophages pyroptosis in mice.

Silicosis is a diffuse fibrotic lung disease in which excessive inflammatory responses are triggered by silica exposure. Pyroptosis, a pro-inflammatory mode of programmed cell death, is mediated by gasdermin and may play a pivotal role in the development of silicosis. The caspase-1 inhibitor, VX-765, was used in vivo and in vitro to investigate the effects of silica-induced early inflammatory injury and later lung fibrosis. Our findings show that VX-765 reduces inflammatory lung injury by inhibiting silica-induced pyroptosis of alveolar macrophages in a silicosis mouse model. VX-765 limits the infiltration of inflammatory M1 alveolar macrophages, decreasing expression of inflammatory cytokines, including IL-1ß, TNF-α, IL-6, CCL2, and CCL3, and down-regulating endogenous DAMPs and inflammatory immune-related cell pattern recognition receptors TLR4 and NLRP3. Furthermore, VX-765 alleviates fibrosis by down-regulating α-smooth muscle actin (α-SMA), collagen, and fibronectin. In this study, we illustrate that Alveolar macrophages pyroptosis occur in the early stages of silicosis, and VX-765 can alleviate the development of silicosis by inhibiting the pyroptosis signaling pathway. These results may provide new insight into the prevention and treatment of early-stage silicosis.

Label-free Raman spectroscopy characterizes signatures of inflammation and fibrosis in the silicosis.

Silicosis is an occupational disease that seriously damages the life and health of miners. Herein, we constructed a mouse model of silicosis and used label-free confocal Raman spectroscopy to analyze the biomolecular variations in lung fibrous nodules and inflammatory sites. The mice were exposed to silica particles for 1 month (SIL-1M group), 3 months (SIL-3M group), or no exposure (control tissues, NS). Raman spectra obtained from treated and untreated lung tissue were subjected to chemometric analysis to quantify biochemical composition differences in the silicosis. Simultaneously, immunohistochemistry and collagen staining were used to evaluate inflammation, fibrosis, and apoptosis. As a result, the SIL-1M and SIL-3M groups showed significant differences in cholesterol, lipids, amino acids, nucleic acids, and cytochrome C, and the collagen peaks at 1248 cm-1 and 1448 cm-1 were significantly higher than in the NS group. Notably, glycogen and phospholipid may be an inflammatory indicator consistent with NF-κB expression. In addition, significant differences in collagen and cytochrome C content in silicosis lung tissue were found using Raman spectroscopy and were verified by Masson's staining and Bax/Bcl-2 expression ratio. In summary, our findings provide a label-free technique to understand the biochemical changes in lung inflammatory and fibrosis microenvironment after exposure to silica particles and provide a valuable reference for studying the mechanism of silicosis.

Surgical Treatment is Still Recommended for Patients Over 75 Years with IA NSCLC: A Predictive Model Based on Surveillance, Epidemiology and End Results Database.

BACKGROUND: To determine the populations who suitable for surgical treatment in elderly patients (age ≥ 75 y) with IA stage. METHODS: The clinical data of NSCLC patients diagnosed from 2010 to 2015 were collected from the SEER database and divided into surgery group (SG) and no-surgery groups (NSG). The confounders were balanced and differences in survival were compared between groups using PSM (Propensity score matching, PSM). Cox regression analysis was used to screen the independent factors that affect the Cancer-specific survival (CSS). The surgery group was defined as the patients who surgery-benefit and surgery-no benefit according to the median CSS of the no-surgery group, and then randomly divided into training and validation groups. A surgical benefit prediction model was constructed in the training and validation group. Finally, the model is evaluated using a variety of methods. RESULTS: A total of 7297 patients were included. Before PSM (SG: n = 3630; NSG: n = 3665) and after PSM (SG: n = 1725, NSG: n = 1725) confirmed that the CSS of the surgery group was longer than the no-surgery group (before PSM: 82 vs. 31 months, P < .0001; after PSM: 55 vs. 39 months, P < .0001). Independent prognostic factors included age, gender, race, marrital, tumor grade, histology, and surgery. In the surgery cohort after PSM, 1005 patients (58.27%) who survived for more than 39 months were defined as surgery beneficiaries, and the 720 patients (41.73%) were defined surgery-no beneficiaries. The surgery group was divided into training group 1207 (70%) and validation group 518 (30%). Independent prognostic factors were used to construct a prediction model. In training group (AUC = .678) and validation group (AUC = .622). Calibration curve and decision curve prove that the model has better performance. CONCLUSIONS: This predictive model can well identify elderly patients with stage IA NSCLC who would benefit from surgery, thus providing a basis for clinical treatment decisions.

Relationship Between Neutrophil-To-Lymphocyte Ratio and Brain Metastasis in Non-Small Cell Lung Cancer Patients.

OBJECTIVE: To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) of patients with non-small cell lung cancer (NSCLC) and their risk of developing brain metastases after adjusting for confounding factors. METHODS: A retrospective observational study of the general data of patients with NSCLC diagnosed from January 2016 to December 2020. Multivariate logistic regression was used to calculate the dominance ratio (OR) with 95% confidence interval (CI) for NLR and NSCLC brain metastases with subgroup analysis. Generalized summation models and smoothed curve fitting were used to identify whether there was a nonlinear relationship between them. RESULTS: In all 3 models, NLR levels were positively correlated with NSCLC brain metastasis (model 1: OR: 1.12, 95% CI: 1.01-1.23, P = .025; model 2: OR: 1.16, 95% CI: 1.04-1.29, P = .007; model 3: OR: 1.20, 95% CI: 1.05-1.37, P = .006). Stratified analysis showed that this positive correlation was present in patients with adenocarcinoma (LUAD) and female patients (LUAD: OR: 1.30, 95% CI: 1.10-1.54, P = .002; female: OR: 1.52, 95% CI: 1.05-2.20, P = .026), while there was no significant correlation in patients with squamous carcinoma (LUSC) and male patients (LUSC: OR:0.76,95% CI:0.38- 1.53, P = .443; male: OR:1.13, 95% CI:0.95-1.33, P = .159). CONCLUSION: This study showed that elevated levels of NLR were independently associated with an increased risk of developing brain metastases in patients with NSCLC, and that this correlation varied by TYPE and SEX, with a significant correlation in female patients and patients with LUAD.

Development and Validation of Machine Learning Models to Predict Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Cancer: A Multi-Center Retrospective Radiomics Study.

OBJECTIVE: To develop and validate a generalized prediction model that can classify epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer patients. METHODS: A total of 346 patients (296 in the training cohort and 50 in the validation cohort) from four centers were included in this retrospective study. First, 1085 features were extracted using IBEX from the computed tomography images. The features were screened using the intraclass correlation coefficient, hypothesis tests and least absolute shrinkage and selection operator. Logistic regression (LR), decision tree (DT), random forest (RF), and support vector machine (SVM) were used to build a radiomics model for classification. The models were evaluated using the following metrics: area under the curve (AUC), calibration curve (CAL), decision curve analysis (DCA), concordance index (C-index), and Brier score. RESULTS: Sixteen features were selected, and models were built using LR, DT, RF, and SVM. In the training cohort, the AUCs was .723, .842, .995, and .883; In the validation cohort, the AUCs were .658, 0567, .88, and .765. RF model with the best AUC, its CAL, C-index (training cohort=.998; validation cohort=.883), and Brier score (training cohort=.007; validation cohort=0.137) showed a satisfactory predictive accuracy; DCA indicated that the RF model has better clinical application value. CONCLUSION: Machine learning models based on computed tomography images can be used to evaluate EGFR status in patients with non-small cell lung cancer, and the RF model outperformed LR, DT, and SVM.

Adipose-specific knockout of Protein Kinase D1 suppresses de novo lipogenesis in mice via SREBP1c-dependent signaling.

Having healthy adipose tissue is essential for metabolic health, as excessive adipose tissue in the body can cause its dysregulation and driving chronic metabolic diseases. Protein kinase D1 (PKD1) is considered to be a key kinase in signal transduction, which regulates multiple cellular functions, but its physiological functions in adipose are still not fully understood. This study aimed at elucidating the function of adipocyte PKD1 on lipogenesis. From RNA-Sequencing data, we found that the fatty acid biosynthesis pathway in white adipose tissue lacking PKD1 was significantly affected. Critical rate-limiting enzymes for de novo lipogenesis in adipocytes, such as FASN, ACCα, and SCD1, were significantly repressed after deleting PKD1 in vivo and in vitro. Further studies revealed that blockade of PKD1 significantly increased phosphorylation of SREBP1c at serine 372 site. Co-immunoprecipitation analysis showed that PKD1 interacts with SREBP1c in vitro and in vivo. Importantly, overexpression of SREBP1c reversed the inhibition of FASN and ACCα expression caused by PKD1 silencing. Together, adipocyte PKD1 promotes de novo lipogenesis via SREBP1c-dependent manner in visceral white adipose tissue and might provide a new target for the development of anti-obesity therapies.

Coal dust exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis and Vitamin D remedies.

BACKGROUND: Coal dust particles (CDP), an inevitable by-product of coal mining for the environment, mainly causes coal workers' pneumoconiosis (CWP). Long-term exposure to coal dust leads to a complex alternation of biological processes during regeneration and repair in the healing lung. However, the cellular and complete molecular changes associated with pulmonary homeostasis caused by respiratory coal dust particles remain unclear. METHODS: This study mainly investigated the pulmonary toxicity of respirable-sized CDP in mice using unbiased single-cell RNA sequencing. CDP (< 5 µm) collected from the coal mine was analyzed by Scanning Electron Microscope (SEM) and Mass Spectrometer. In addition, western blotting, Elisa, QPCR was used to detect gene expression at mRNA or protein levels. Pathological analysis including HE staining, Masson staining, immunohistochemistry, and immunofluorescence staining were performed to characterize the structure and functional alternation in the pneumoconiosis mouse and verify the reliability of single-cell sequencing results. RESULTS: SEM image and Mass Spectrometer analysis showed that coal dust particles generated during coal mine production have been crushed and screened with a diameter of less than 5 µm and contained less than 10% silica. Alveolar structure and pulmonary microenvironment were destroyed, inflammatory and death (apoptosis, autophagy, and necrosis) pathways were activated, leading to pneumoconiosis in post 9 months coal dust stimulation. A distinct abnormally increased alveolar type 2 epithelial cell (AT2) were classified with a highly active state but reduced the antimicrobial-related protein expression of LYZ and Chia1 after CDP exposure. Beclin1, LC3B, LAMP2, TGF-ß, and MLPH were up-regulated induced by CDP, promoting autophagy and pulmonary fibrosis. A new subset of macrophages with M2-type polarization double expressed MLPH + /CD206 + was found in mice having pneumoconiosis but markedly decreased after the Vitamin D treatment. Activated MLPH + /CD206 + M2 macrophages secreted TGF-ß1 and are sensitive to Vitamin D treatment. CONCLUSIONS: This is the first study to reconstruct the pathologic progression and transcriptome pattern of coal pneumoconiosis in mice. Coal dust had obvious toxic effects on lung epithelial cells and macrophages and eventually induced pulmonary fibrosis. CDP-induced M2-type macrophages could be inhibited by VD, which may be related to the alleviation of the pulmonary fibrosis process.

Serum amyloid a, C-reactive protein, and procalcitonin levels in children with Mycoplasma pneumoniae infection.

BACKGROUND: Mycoplasma pneumoniae (MP) is a common pathogen of community-acquired pneumonia in children. In the present study, serum amyloid A (SAA), C-reactive protein (CRP), and procalcitonin (PCT) levels in children with MP infection were analyzed and the differential diagnoses of MP evaluated. METHODS: The study included 152 children with MP infection hospitalized in Tai'an Central Hospital in Shandong Province and 50 healthy children as controls. SAA, CRP, and PCT, as well as serum immunoglobulins and T lymphocyte subsets were analyzed during the acute and convalescent phases. Among the MP-infected children, 30 cases were selected to monitor the SAA, immunoglobulins, and T lymphocyte subset levels for a week. RESULTS: The SAA, CRP, PCT, IgA, and IgM levels were significantly higher in the MP-infected group than in the control group (F(SAA) = 83.91, p < 0.05; F(CRP) = 40.79, p < 0.05; F(PCT) = 60.58, p < 0.05; F(IgA) = 43.45, p < 0.05; F(IgM) = 233.88, p < 0.05). In addition, the levels of these factors were significantly higher in the acute phase than in the convalescent phase (p < 0.05). However, significant difference was not observed in the IgG level between these two groups (p > 0.05). The CD3+ and CD4+ levels in the MP-infected group were lower than in the control group ( F(CD3+) = 60.58, P < 0.05; F(CD4+) = 89.05, p < 0.05), and the CD8+ level was higher than in the control group ( F(CD8+) = 96.96, p < 0.05). The CD3+ , CD4+ , and CD8+ levels were significantly different between the acute phase and the convalescent phase (CD3+ : acute phase vs. convalescent phase, q = 2.79, p < 0.05; CD4+ : acute phase vs. convalescent phase, q = 2.83, p < 0.05; CD8+ : acute phase vs. convalescent phase, q = 3.15, p < 0.05). The changes in serum SAA levels in the MP-infected group positively correlated with the changes in IgA, IgM, and CD8+ levels and negatively correlated with CD3+ , CD4+ , and CD4+ /CD8+ . CONCLUSION: SAA, CRP, and PCT were specific markers for diagnosing early MP infection in children. These findings are important in the differential diagnosis of MP infection and clinical guidance for MP treatment.

Differential expression of Chitinase 3-Like 1 protein in appendicitis and appendix carcinomas.

BACKGROUND: Chitinase 3-Like 1 (CHI3L1) has been used as an inflammatory biomarker for a variety of diseases, but its expression in acute appendicitis and appendix carcinomas remains unclear. METHODS: Sixty cases of patients were studied, including 46 acute appendicitis and 14 appendix carcinomas. We divided the acute appendicitis group into acute uncomplicated appendicitis (AUA), suppurative appendicitis (SA), and gangrenous appendicitis (GA). The appendix carcinoma group was divided into appendiceal neuroendocrine neoplasms (ANENs) and appendiceal mucinous neoplasms (AMN). Controls were 32 healthy donors. Blood neutrophil to lymphocyte ratio (NLR), CHI3L1, C-reactive protein (CRP), interleukin-6 (IL-6), and serum amyloid A (SAA) were measured in the patients. Meanwhile, immunohistochemistry and immunofluorescence were used to identify the expression level and location of CHI3L1 in different cell types in appendix tissues. RESULTS: Compared with the controls, CHI3L1 serum levels were up-regulated in SA, GA, and AMN groups, while no significant difference was observed in the AUA and ANEN groups. Immunofluorescence revealed that CHI3L1 expression was high in macrophages and adenocarcinoma cells of appendix tissues but not in the neuroendocrine carcinoma tissues. Moreover, levels of NLR and CRP in the SA and GA groups were considerably higher than in the control group. IL-6 and SAA in SA, GA, ANENs, and AMN groups were also increased compared with the control group. In addition, CHI3L1 displayed good performance in predicting appendicitis, with an AUC of 0.862. CONCLUSION: CHI3L1 was highly expressed in acute appendicitis and appendiceal mucinous neoplasms, which can be used as a novel biomarker predicting appendicitis.

Glycogen metabolism reprogramming promotes inflammation in coal dust-exposed lung.

Long-term coal dust exposure triggers complex inflammatory processes in the coal workers' pneumoconiosis (CWP) lungs. The progress of the inflammation is reported to be affected by disordered cell metabolism. However, the changes in the metabolic reprogramming associated with the pulmonary inflammation induced by the coal dust particles are unknown. Herein, we show that coal dust exposure causes glycogen accumulation and the reprogramming of glucose metabolism in the CWP lung. The glycogen accumulation caused by coal dust is mainly due to macrophages, which reprogram glycogen metabolism and trigger an inflammatory response. In addition, 2-deoxy-D-glucose (2-DG) reduced glycogen content in macrophages, which was accompanied by mitigated inflammation and restrained NF-κB activation. Accordingly, we have pinpointed a novel and crucial metabolic pathway that is an essential regulator of the inflammatory phenotype of coal dust-exposed macrophages. These results shed light on new ways to regulate CWP inflammation.

Genome-Wide Investigation and Functional Verification of the ZIP Family Transporters in Wild Emmer Wheat.

The zinc/iron-regulated transporter-like protein (ZIP) family has a crucial role in Zn homeostasis of plants. Although the ZIP genes have been systematically studied in many plant species, the significance of this family in wild emmer wheat (Triticum turgidum ssp. dicoccoides) is not yet well understood. In this study, a genome-wide investigation of ZIPs genes based on the wild emmer reference genome was conducted, and 33 TdZIP genes were identified. Protein structure analysis revealed that TdZIP proteins had 1 to 13 transmembrane (TM) domains and most of them were predicted to be located on the plasma membrane. These TdZIPs can be classified into three clades in a phylogenetic tree. They were annotated as being involved in inorganic ion transport and metabolism. Cis-acting analysis showed that several elements were involved in hormone, stresses, grain-filling, and plant development. Expression pattern analysis indicated that TdZIP genes were highly expressed in different tissues. TdZIP genes showed different expression patterns in response to Zn deficiency and that 11 genes were significantly induced in either roots or both roots and shoots of Zn-deficient plants. Yeast complementation analysis showed that TdZIP1A-3, TdZIP6B-1, TdZIP6B-2, TdZIP7A-3, and TdZIP7B-2 have the capacity to transport Zn. Overexpression of TdZIP6B-1 in rice showed increased Zn concentration in roots compared with wild-type plants. The expression levels of TdZIP6B-1 in transgenic rice were upregulated in normal Zn concentration compared to that of no Zn. This work provides a comprehensive understanding of the ZIP gene family in wild emmer wheat and paves the way for future functional analysis and genetic improvement of Zn deficiency tolerance in wheat.

Characteristics of thin InAlAs digital alloy avalanche photodiodes.

InP-based avalanche photodiodes (APDs) are widely used in short-wave infrared (SWIR) communications. In this work, a thin (200 nm nominal) InAlAs digital alloy layer consisting of two monolayer (ML) InAs and two ML AlAs was grown on InP substrate and investigated in detail. APDs with p-i-n and n-i-p structures were fabricated and characterized. The current-voltage, capacitance-voltage characteristics, and excess noise were measured at room temperature with different laser wavelengths, and the measured effective k value (ratio of impact ionization coefficients) is about 0.15 with the multiplication gain up to 12. The randomly-generated path length (RPL) model was carried out to analyze the dead space effect. Our thin digital alloy successfully reduced excess noise compared with conventional In0.52Al0.48As random alloy without introducing new elements and shows the potential for high-speed, low noise APD applications.

A novel Cys328-terminator mutant implicated in severe coagulation factor XIII deficiency: a case report.

BACKGROUND: Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder that is commonly due to mutations in the FXIIIA subunit gene (F13A1), and it has been reported to have a prevalence of one per 2 million. We describe a new genetic variant in the F13A1 gene that caused a patient to suffer from lifelong hemorrhagic diathesis. CASE PRESENTATION: We evaluated a 20-year-old female with umbilical cord bleeding after birth, an intracerebral hemorrhage at age 6, and other bleeding episodes, including hematuria and cephalohematoma, who suffered from a lifelong hemorrhagic diathesis. The clot solubility test showed that the clot of the patient was dissolved in urea solution at 10 h. Genetic testing identified a novel homozygous mutation, c.984C > A(p. Cys328stop), resulting in a premature stop codon in exon 8 of the F13A1 gene. The results obtained with ClusterX software showed that Cys328 of exon 8 in the F13A1 gene is highly conserved among species. CONCLUSION: We reported a novel homozygous mutation in the F13A1 gene in a factor XIII (FXIII)-deficient patient, which adds a new point mutation to the mutant library. In this paper, we discuss other aspects of the disease, including laboratory examination, homogeneous sequence alignment and molecular modeling.

ß2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells.

BACKGROUND: Chronic stress is well known to promote tumor progression, however, little is known whether chronic stress-mediated regulation of osteoblasts contributes to the migration and invasion of metastatic cancer cells. METHODS: The proliferation, migration and invasion of prostate cancer cells were assessed by CCK-8 and transwell assay. HIF-1α expression of osteoblasts and epithelial-mesenchymal transition (EMT) markers of prostate cancer cells were examined by Western blot. The mRNA level of cytokines associated with bone metastasis in osteoblasts and EMT markers in PC-3 and DU145 cells were performed by qRT-PCR. Functional rescue experiment of cells were performed by using siRNA, plasmid transfection and inhibitor treatment. RESULTS: Isoproterenol (ISO), a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibited no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promoted EMT, migration and invasion of PC-3 and DU145 cells, which could be inhibited by ß2AR inhibitor. Mechanistically, ISO increased the secretion of CXCL12 via the ß2AR-HIF-1α signaling in osteoblasts. Moreover, overexpression of HIF-1α osteoblasts promoted migration and invasion of PC-3 and DU145 cells, which was inhibited by addition of recombinant knockdown of CXCR4 in PC-3 and DU145 cells, and inhibiting CXCL12-CXCR4 signaling with LY2510924 blunted the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. CONCLUSIONS: These findings demonstrated that ß2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.

Hereditary protein C deficiency caused by novel compound heterozygous mutants in a Chinese pedigree: A case report.

Purpura fulminans (PF) is a neonatal presentation of homozygous or compound heterozygous protein C (PC) deficiency; infants who are diagnosed with it are determined to have a major defect in coagulation regulation which is associated with undetectable levels of PC. We report a pedigree who suffered from the hereditary PC deficiency with compound heterozygous mutants; genetic analysis revealed compound heterozygous mutations of 262 G > T(Asp88Tyr) and 400 + 5G > A that were identified in the proband; moreover, Asp88Tyr and 400 + 5G > A were also detected in the father and the mother, respectively. A bioinformatics analysis revealed 262 G > T is probably damaging, and structural analysis indicated a possible mechanism for the functional impairment of PC in this pedigree.

Clinical Application of 3-Dimensional Continuous Suturing Technique for Triangular Wounds.

BACKGROUND: Although there are numerous skin closure methods, there is no special method for suturing triangular skin wounds. The authors have summarized and modified their experience with a 3-dimensional (3D) continuous suturing technique for triangular wounds. METHODS: From December 2015 to September 2017, the 3D continuous suturing technique for triangular wounds has been used in 32 cleft lip repairs (48 surgical triangular incisions) and 11 cases of facial trauma (15 traumatic triangular wounds). The patients, 3 months to 39 years of age, had triangular flaps designed for esthetic purposes or triangular defects secondary to accidents. To evaluate the effectiveness of this technique, the mean follow-up was 7 months (range, 1-15 months). RESULTS: The 3D continuous suturing technique for triangular wounds can shorten the suturing time, decrease the number of thread knots, and shorten the time of surgery. All patients healed well and the stitches were removed 7 days postoperatively. The wound on both sides of the triangle was well arranged, with a good appearance and no scar hyperplasia. CONCLUSIONS: Our experience showed that the 3D continuous suturing technique for triangular wounds is a time-saving and convenient method and can make the wounds closed tighter, more stable, and reliable. The technique can be applied to any type of triangular wounds or incisions and is not limited to the clinical scenarios described in this article.

Clinical diagnostic value of viable Schistosoma japonicum eggs detected in host tissues.

BACKGROUND: Schistosomiasis, one of the neglected tropical diseases, is endemic in more than 70 countries. However, the clinical diagnosis of patients with a low degree of infection is an unsolved technical problem. In areas endemic for schistosomiasis japonica, proctoscopy detection of eggs has been one method used for clinical diagnosis. However, it is often a challenge to find typical live eggs and it is difficult to distinguish live eggs from large numbers of partially degraded and/or completely degraded eggs within colon biopsy tissue. To address this problem, we tested six different morphological and biochemical/molecular markers (ALP; morphological characteristics of egg; CalS (calcified substance); AOS (antioxidase); SDHG (succinic dehydrogenase) and SjR2 mRNA (retrotransposons 2 of S.japonicum genome mRNA)), including four new markers (CalS; AOS; SDHG and SjR2 mRNA.), to determine the viability of S. japonicum eggs deposited in human and mouse colon tissues. Our ultimate aim is to obtain a new method that is more sensitive, practical and accurate to clinically diagnose schistosomiasis. METHODS: Tissue samples were collected from mice at six different time points during S. japonicum infection with or without treatment with praziquantel (PZQ). Four new biochemical or molecular markers were used for the detection of egg viability from mouse liver and intestinal samples: CalS; AOS; SDHG and SjR2 mRNA. Subsequently, all markers were employed for the detection and analysis of eggs deposited in biopsy materials from patients with suspected schistosomiasis japonica for clinical evaluation. Microscopic examination of the egg morphology, worm burden in vivo and ALP (alkaline phosphatase) levels were used as a reference standard to evaluate the sensitivity and reliability of four new markers detecting egg viability. RESULTS: The results of the study showed that the morphology of S. japonicum eggs deposited in tissues of hosts with schistosomiasis, especially cases with chronic schistosomiasis, is complex and egg viability is difficult to judge morphologically, particularly eggs with a fuzzy structure or partially modified eggs. We found that the majority of the viable schistosome eggs determined by four new markers (CalS, AOS, SDHG and SjR2 mRNA) were morphologically difficult to identify. CONCLUSIONS: Among the markers, the most sensitive and specific method was the detection of SjR2 mRNA and the most simple, rapid and practical method was the detection of SDHG. Therefore, the detection of SDHG is the most practical for clinical application and its use could improve the accuracy in diagnosing active schistosome infection.