Chinese military medical teams in the Ebola outbreak of Sierra Leone.

The 2014-2015 Ebola virus disease (EVD) epidemic in West Africa was the largest in history. The three most affected countries, Guinea, Liberia and Sierra Leone, have faced enormous challenges in controlling transmission and providing clinical care for patients with EVD. The Chinese government, in response to the requests of the WHO and the governments of the affected countries, responded rapidly by deploying Chinese military medical teams (CMMTs) to the areas struck by the deadly epidemic. A total of three CMMTs, comprising 115 military medical professionals, were rotationally deployed to Freetown, Sierra Leone to assist with infection prevention and control, clinical care and health promotion and training. Between 1 October 2014 and 22 March 2015, the CMMTs in Sierra Leone admitted and treated a total of 773 suspected and 285 confirmed EVD cases. Among the 285 confirmed cases, 146 (51.2%) patients survived after treatment. In addition, the CMMTs maintained the record of zero infections among healthcare workers and zero cross-infections between quarantined patients. In this manuscript, we aim to give an overview of the mission, and share our best practices experience on predeployment preparedness, EVD holding and treatment centre building and EVD case management.

[Identification of potential targets and synergistic mechanism of Kushen Decoction for the treatment of cryptosporidiosis].

OBJECTIVE: To explore the potential targets and synergistic mechanisms of Kushen Decoction for the treatment of cryptosporidiosis using network pharmacology and molecular docking methods. METHODS: The main active ingredients of Kushen Decoction were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TC-MSP) and the Universal Protein Resource (UniProt) database, and the potential targets were predicted. In addition, the active ingredients of Kushen Decoction that were not included in the TCMSP database were retrieved in CNKI, WanFang Data, CBM, PubMed and Web of Science databases, and the target genes of all supplemented active ingredients were predicted using the online TargetNet database. Network construction and analysis were performed using the Cytoscape software, and cryptosporidiosis-related targets were retrieved in the Comparative Toxicogenomics Database and GeneCards database. The protein-protein interaction (PPI) network was created using the STRING database, and the DAVID database was used for GO enrichment and KEGG pathway analyses. The tissue distribution of key targets was investigated using the BioGPS database, and the AutoDockTools software was employed to verify the molecular docking results. RESULTS: A total of 38 active ingredients of Kushen Decoction were screened, and the core ingredients included quercetin, (+)-14α-hydroxymatrine and apigenin. A total of 831 targets of Kushen Decoction and 512 cryptosporidiosis-related targets were predicted, and PPI network analysis revealed 69 key targets, including AKT1, TNF and IL-6. There were 303 biological processes, 46 molecular functions and 29 cellular components involved in the treatment of cryptosporidiosis with Kushen Decoction, and 13 KEGG pathways played a therapeutic role in the synergistic mechanisms of multiple targets, such as Toll-like receptor (TLR), nuclear factor kappa B(NF)-κB, nucleotide binding oligomerization domain like receptor (NLR) signal pathways. The core targets were mainly distributed in the hematologic and immune systems. Molecular docking analysis showed that the binding energy between active ingredients and key targets were all less than 0 kJ/mol, indicating the strong binding of ligands to receptors. CONCLUSIONS: The active ingredients of Kushen Decoction, such as quercetin, (+)-14α-hydroxymatrine and apigenin, may act on targets like AKT1, TNF, IL-6 to modulate TLR, NLR and NF-κB signaling pathways to play a synergistic role in the treatment of cryptosporidiosis in the hematologic and immune system.

Transcription factor 7-like 1 dysregulates keratinocyte differentiation through upregulating lipocalin 2.

Recent studies strongly suggested that transcription factor 7-like 1 (Tcf7l1, also known as Tcf3) is involved in the differentiation of several types of cells, and demonstrated that Tcf7l1 modulates keratinocytes physiologically through regulating lipocalin 2 (LCN2), a key regulator of cell differentiation. To reveal the potential role of Tcf7l1 in the dysregulation of keratinocyte differentiation, both Tcf7l1 and LCN2 were determined in a variety of skin disorders. The in vitro effect of Tcf7l1 on keratinocyte differentiation was studied by culturing SCC-13 cells, and the human foreskin keratinocytes (HFKs) that were transfected with vectors for overexpressing human papillomavirus E6/E7 or Tcf7l1 genes. We found that both Tcf7l1 and LCN2 were highly expressed in those diseases characterized by defective keratinocyte differentiation (especially psoriasis vulgaris, condyloma acuminatum, squamous cell carcinoma, etc). Moreover, compared with control HFKs, SCC-13 cells and E6/E7-harboring HFKs expressed more Tcf7l1 and LCN2. Tcf7l1 siRNA transfection decreased LCN2 but increased involucrin and loricrin in HFKs under calcium stimuli. Conversely, Tcf7l1 overexpression in SCC-13 cells or vector-transfected HFKs induced lower involucrin and loricrin expression and less keratinocyte apoptosis, both of which, however, were partially abrogated by LCN2 siRNA or neutralizing anti-LCN2 antibody. Interestingly, the Tcf7l1 expression in HFKs correlated positively with the MMP-2 level, and the inhibition of MMP-2 decreased the LCN2 level and even attenuated the effect of Tcf7l1 on LCN2 expression. Therefore, Tcf7l1 dysregulates keratinocyte differentiation, possibly through upregulating the LCN2 pathway in an MMP-2 mediated manner. Elucidating the interaction between Tcf7l1 and LCN2 may help understand disordered cell differentiation in some skin diseases.

Expression of Smad4, TGF-ßRII, and p21waf1 in esophageal squamous cell carcinoma tissue.

Esophageal squamous cell carcinoma (SCC) possesses one of the worst prognoses out of the digestive carcinomas. Several studies have suggested that transforming growth factor ß receptor type II (TGF-ßRII), Smad family member 4 (Smad4) and p21 wild-type p53-activated factor 1 (p21waf1) are associated with esophageal SCC. The aim of the present study was to evaluate the effect of Smad4, TGF-ßRII and p21waf1 in esophageal squamous cancer tissue and the pathological significance of the effect. An immunohistochemical method was used to evaluate the expression levels of Smad4, TGF-ßRII and p21waf1 in specimens of esophageal SCC lesions obtained from 80 patients. It was found that the expression of Smad4, TGF-ßRII and p21waf1 in histologically-classified grade I esophageal SCC, without invasion or lymph node metastasis, was markedly higher compared with grade III esophageal SCC that had invaded into the deep muscular or serous layer and metastasized to the lymph nodes (P<0.05). Analysis of the expression level of Smad4, TGF-ßRII and p21waf1, as well as the clinical and pathological characteristics of esophageal SCC, revealed that the three proteins may be associated with the carcinogenesis, biological behavior and prognosis of esophageal SCC, parallel to the pathological stage and cell grade.

[Effects of phoxim on sperm production and motility of rats].

The effects of phoxim at various dosage levels on sperm production and motility in rats were studied. Sperm motility was measured by computer assisted sperm analysis (CASA). The results showed that rats exposed to phoxim at higher doses(24.5 and 73.5 mg/kgBW) for 60 successive days showed significant reduction of daily sperm production as compared with the control (P < 0.05, P < 0.01). Sperm motion parameters such as currilinear velocity (VCL), straight line velocity(VSL), beat cross frequency(BCF), linearity(LIN) and straightness(STR) were significantly decreased than those of the control(P < 0.05, P < 0.01) which indicated a dose-dependent relationship to some extent. However, there was no obvious change in body weight, testis weight and the rate of motile sperm in epididymis. It suggests that the male reproductive toxicilIty of phoxim at higher doses (24.5 and 73.5 mg/kgBW) mainly induces a reduction of sperm production and motility.

Reduced EBP50 expression or mis-localization of the EBP50 protein is associated with the malignant progression of esophageal squamous cell carcinoma.

PURPOSE: The aim of this study was to examine the significance of EBP50 (ezrin-radixin-moesin binding phosphoprotein 50) expression in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Real-time PCR (qRT-PCR), western blotting, and immunohistochemical staining were performed to detect EBP50 expression in pairs of ESCCs and matched non-tumor tissues, and the relationships between EBP50 expression and other clinical factors in ESCC were analyzed. An iRNA targeting EBP50 was transfected into EC9706 cells. MTT and plate colony assays were performed to assess the effects of EBP50 down-regulation on cell growth, and flow cytometry was used to evaluate the influence of inhibiting EBP50 on cell cycle progression. RESULTS: The real-time PCR (qRT-PCR), western blotting, and immunohistochemical staining results showed that EBP50 expression was significantly lower in ESCCs compared to matched non-tumor tissues. In addition, decreased EBP50 expression correlated with differentiation, T stage, lymph node (LN) metastasis, and poor prognosis in patients with ESCC. The down-regulation of EBP50 may significantly promote the growth and proliferation of EC9706 cells while accelerating cell cycle progression from the G1to S phase. CONCLUSIONS: EBP50 expression was decreased in ESCC, indicating that EBP50 might play a significant role in the malignant progression of ESCC and be a prognostic marker for patients with ESCC.