In addition to its well established role as a neurotransmitter, extracellular ATP has been considered as a paracrine/autocrine factor, either released from sperm or epithelial cells, in the male reproductive tract and shown to play a versatile role in modulating various reproductive functions. This review summarizes the signal pathways through which ATP induces anion secretion by the epithelia of the epididymis, as well as its epithelium-dependent modulation of smooth muscle contraction of the vas deferens. Finally, the overall role of ATP in coordinating various reproductive events in the male genital tract is discussed.
Adenosine Triphosphate ; physiology ; Animals ; Epididymis ; physiology ; Epithelium ; physiology ; Humans ; Male ; Muscle Contraction ; Muscle, Smooth ; physiology ; Signal Transduction ; Urogenital System ; physiology ; Vas Deferens ; physiology

Objective To investigate the prevalence of fusidic acid ( FA) resistance among Staphylococcus aureus clinical isolates.Methods Five hundred fifty -five Staphylococcus aureus isolates were isolated from the various specimens of patients at the first affiliated hospital of Wenzhou medical university from January , 2009 to September , 2013. The susceptibility of Staphylococcus aureus isolates to FA and clinically often used antimicrobials was determined by disc diffusion method .The minimal inhibitory concentrations ( MICs ) of FA and vancomycin for FA-resistant isolates was determined by agar dilution method . Results Among 555 Staphylococcus aureus isolates, 293 were methici-llin-resistant Staphylococcus aureus ( MRSA) and 262 were methicillin-susceptible Staphylococcus aureus ( MSSA ) .Seventy -seven of 555 ( 13.87%) isolates including 60 MRSA and 17 MSSA isolates were resistant to FA.The rates of FA resistance among MRSA and MSSA iso-lates were 22.90% ( 60/262 ) and 5.80% ( 17/293 ) . The rates of FA resistance among Staphylococcus aureus isolates from 2009 to 2013 were 7.81% ( 5/64 ) , 9.80% ( 5/51 ) , 22.92%(11/48), 5.21%(11/211) and 24.86%(45/181), respectively.The MICs of FA for 77 FA -resistant isolates ranged from 2 to >64 μg? mL-1 , among which 44 with fusidic acid MIC of >64 μg? mL-1 .All FA-resis-tant isolates were susceptible to quinupristin -dalfopristin , vancomycin , linezolid and nitrofurantoin .While more than 50% of theses isolates were resistant to penicillin , tetracycline , clindamycin , erythromycin and ciprofloxacin . Conclusion FA has fine antimicrobial activity in vitro against Staphylococcus aureus isolates, but the FA resistance among these isolates was increasing , especially increased high -level FA resistance.

Objective To investigate the resistance of Staphylococcus epidermidis isolates to mupirocin and its resistant characteristics to anti-bacterial agents used in clinical.Methods A total of 489 Staphyloco-ccus epidermidis isoliates were isolated from the various specimens of pa-tients in our Hospital.The identification and antimicrobial susceptibility testing of Staphylococcus epidermidis isolates were determined by Vitek-2 Compact full automated Microbiology Analyzer.The susceptibility of 489 Staphylococcus epidermidis isolates to mupirocin was determined by disc-diffusion method.Results Among 489 Staphylococcus epidermidis clini-cal isolates, 39 methicillin -resistant Staphylococcus epidermidis ( MRSE) were resistant to mupirocin.The prevalence of mupirocin resis-tance among Staphylococcus epidermidis clinical isolates was 7.8%(39/498).All mupirocin-resistant isolates were susceptible to quinu-pristin/dalfopristin, linezolid, vancomycin and nitrofurantoin. While more than 60%of mupirocin-resistant isolates were resistant to penici-llin, clindamycin, erythromycin and trimethoprim/sulfamethoxazole.The resistance rates of mupirocin -resistant isolates to gentamicin and rifapin were more than 35%. Conclusion Mupirocin is an effective agent against Staphylococcus epidermidis isolates in vitro.However, the mupiro-cin-resistant Staphylococcus epidermidis has appeared in clinical isolates which is of concern.

Objective To investigate the antibacterial activity of quinu-prisitin/dalfopristin on the clinical isolates of Enterococcus faecium in vitro.Methods A total of 2217 Enterococcus faecium isolates were isola-ted from the various specimens of patients at the first affiliated hospital of Wenzhou medical university from January , 2011 to December , 2015.The susceptibility of 2217 Enterococcus faecium isolates to quinuprisitin/dalfopristin and the susceptibility of quinuprisitin/dalfopristin -non -susceptible isolates to clinically often used antimicrobials were determined by full automated Microbiology Analyzer.Results Among 2217 Entero-coccus faecium isolates, 115 (5.2%) were non -susceptible to quinu-prisitin/dalfopristin, among which 25 with quinuprisitin/dalfopristin re-sistance and 90 with quinuprisitin/dalfopristin intermediate.The rates of quinuprisitin/dalfopristin non -susceptibility among tested clinical iso-lates from 2011 to 2015 were 4.3%(25/588), 3.1%(18/581), 6.2%(22/353), 6.3%( 25/394 ) and 8.3%( 25/301 ), respectively.All non-susceptible isolates were susceptible to vancomycin , linezolid , teicoplanin and tigecycline.However , more than 80% of theses isolates were resistant to ampicllin, penicillin, levofloxacin, ciprofloxacin, moxifloxacin and erythromycin.Conclusion Quinuprisitin/dalfopristin has good antimicrobial activity in vitro against Enterococcus faecium clinical isolates.The prevalence of quinuprisitin/dalfopristin resistance remained relatively stable and low , but non-susceptible rate showed an upward trend.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Neuroblastoma/drug therapy* ; Positron-Emission Tomography ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome

Anemia, Aplastic ; therapy ; Bone Marrow Transplantation ; statistics & numerical data ; China ; Cooperative Behavior ; Family ; Hematopoietic Stem Cell Transplantation ; statistics & numerical data ; Hemoglobinopathies ; therapy ; Hong Kong ; Humans ; Immunologic Deficiency Syndromes ; therapy ; Leukemia ; therapy ; Lymphoma ; therapy ; Malaysia ; Myelodysplastic Syndromes ; therapy ; Peripheral Blood Stem Cell Transplantation ; statistics & numerical data ; Philippines ; Singapore ; Thailand ; Tissue Donors ; statistics & numerical data ; Transplantation, Autologous ; statistics & numerical data ; Transplantation, Homologous ; statistics & numerical data

Among the types of lung cancer, lung adenocarcinoma accounts for the majority, and its overall survival rate is poor. B-cell translocation gene 2 (BTG2) is a member of the antiproliferative gene family, belonging to the BTG/TOB family. Many studies have shown that BTG2 was abnormally expressed in many types of tumors, but its regulatory role in the radiosensitivity of lung adenocarcinoma remained unclear. In this study, we explored the expression level of BTG2 in patients with lung adenocarcinoma and its correlation with clinical prognosis through online database and tissue samples of lung adenocarcinoma patient. The results indicated that the expression level of BTG2 decreased significantly in lung adenocarcinoma patient with radiation resistance. Bioinformatics analysis confirmed that BTG2 could respond to radiotherapy in lung adenocarcinoma cell lines, and its low expression in lung adenocarcinoma patients was associated with poor prognosis (P < 0.05). The lentivirus overexpressing BTG2 (OE-BTG2) was transfected into human lung adenocarcinoma cell lines to increase the expression level of BTG2 including A549 and H1299. And the effect of BTG2 overexpression on the radiosensitivity of lung adenocarcinoma cell lines was detected by clone formation assay. Clone formation experiment confirmed that overexpression of BTG2 could significantly enhance the radiosensitivity of A549 and H1299 cell lines (P < 0.05). The expression levels of BTG2 and apoptosis related protein-Bax were detected by Western blotting (WB) and immunohistochemistry (IHC). The effect of BTG2 on radiation sensitivity of lung adenocarcinoma was further detected via nude mouse in vivo. WB experiment confirmed that BTG2 upregulation could significantly increase the apoptosis level of A549 and H1299 cells after radiation. Moreover, BTG2 overexpression can markedly enhance the radiosensitivity of lung adenocarcinoma (P < 0.05) and increase the protein level of Bax after radiation in vivo. In conclusion, BTG2 had low expression in lung adenocarcinoma patients and its low expression level was closely related to the poor clinical prognosis. Overexpression of BTG2 can increase the radiosensitivity of lung adenocarcinoma cell lines and promote the process of apoptosis after radiation, indicating a new target for overcoming the radiation resistance of lung adenocarcinoma.

OBJECTIVEThis report aims to investigate the Toll-like receptor (TLR) signaling pathways and induced antiviral activity in hepatocytes.

METHODSWe isolated primary hepatocytes from wild-type C57BL/6 mice and examined the expression of TLR by realtime RT-PCR. Hepatocytes were stimulated with TLR 1-9 agonists and the supernatants were harvested. The secretion of cytokines were tested by ELISA. The antiviral effectors in supernatants were assayed via virus protection assay (in EMCV system) and the control of HBV replication were assessed via Southern blotting (in HBV system).

RESULTSWe demonstrated that hepatocytes expressed TLR1-9. In accordance with these TLR expression profiles, hepatocytes responded to all TLR ligands by producing inflammatory cytokines (TNF-α or IL-6), to TLR -1,-3,-7 and -9 ligands by producing type I IFN (IFN-α or IFN-β). Only TLR 3 and TLR 7 agonists could stimulate the production of high amounts of antiviral mediators by hepatocytes in virus protection assay. By contrast, supernatants from TLR1, -3 and -4 directly stimulated hepatocytes and TLR 3, -7 and -9 transfected hepatocytes were able to potently suppress HBV replication.

CONCLUSIONPrimary hepatocytes display a unique TLR signaling pathway and can control HBV replication after stimulation by TLR agonists in mice. It may be helpful for the development of TLR-based therapeutic approaches against hepatotropic virus.

Animals ; Cells, Cultured ; Hepatitis B virus ; immunology ; physiology ; Hepatocytes ; immunology ; metabolism ; Immunity, Innate ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; Toll-Like Receptors ; immunology ; metabolism ; Virus Replication

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.
Asia* ; Blood Platelets ; Delayed-Action Preparations ; Delivery of Health Care ; Dexlansoprazole* ; Efficiency ; Esophagitis ; Gastroesophageal Reflux* ; Healthy Volunteers ; Plasma ; Prevalence ; Proton Pump Inhibitors ; Proton Pumps* ; Protons*