SPARC promotes self-renewal of limbal epithelial stem cells and ocular surface restoration through JNK and p38-MAPK signaling pathways.

The purpose of this study was to investigate the effects of secreted protein acidic and rich in cysteine (SPARC) on the maintenance of limbal epithelial stem cell (LESC) stemness and restoration of ocular surface. To determine the suitable concentration of SPARC for LESC culture, the marker expression, mitogenic effect, and holoclone-forming capacity of LESCs treated with different concentrations of SPARC were analyzed. To investigate the mechanism of SPARC's action on the preservation of LESCs stemness, the phosphorylation of related signaling pathways was evaluated by Western blotting. A corneal wound model was established to verify the function of SPARC in ocular surface repair. Consecutive subculturing, colony-forming efficiency, immunofluorescence, and 5-ethynyl-2-deoxyuridine incorporation assays indicated that 1 µg/mL SPARC was a suitable concentration to stimulate LESC proliferation and preserve their proliferative potential. Compared with a control group, 1 µg/mL SPARC effectively increased the expression of ABCG-2, Bmi-1, and Ki67, while decreasing that of CK3/12. The mitogenic effect of SPARC on LESCs was found to be mediated by the phosphorylation of c-Jun N-terminal kinase (JNK) and p38-MAPK signaling pathways, whereas the inhibitors of JNK and p38 MAPK reduced the marker expression and mitogenic capacity of LESCs. In a corneal injury model, SPARC facilitated corneal epithelial wound healing and promoted the proliferation of p63α-positive cells both in the limbus and in the epithelial healing front. SPARC promotes proliferation while suppressing spontaneous differentiation of LESCs through JNK and p38-MAPK signaling pathways, suggesting that SPARC is a promising factor for the improvement of LESCs culture in vitro and in vivo.

Current status of group B Streptococcus infection in neonates: a multicenter prospective study. / 新生儿Bæ—é“¾çƒèŒæ„ŸæŸ“çŽ°çŠ¶çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of maternal group B Streptococcus (GBS) colonization and neonatal early-onset GBS disease (GBS-EOD), and to study the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. METHODS: A total of 16 384 pregnant women and 16 634 neonates delivered by them were enrolled prospectively who had medical records in Xiamen Maternal and Child Care Hospital, Beijing Obstetrics and Gynecology Hospital of Capital Medical University, and Zhangzhou Zhengxing Hospital from May 1, 2019 to April 30, 2020. Unified GBS screening time, culture method, and indication for intrapartum antibiotic prophylaxis (IAP) were adopted in the three hospitals. The incidence rates of maternal GBS colonization and neonatal GBS-EOD were investigated. A multivariate logistic regression analysis was used to identify the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. RESULTS: In these three hospitals, the positive rate of GBS culture among the pregnant women in late pregnancy was 11.29% (1 850/16 384), and the incidence rate of neonatal GBS-EOD was 0.96‰ (16/16 634). The admission rate of live infants born to the GBS-positive pregnant women was higher than that of those born to the GBS-negative ones (P<0.05). The live infants born to the GBS-positive pregnant women had a higher incidence rate of GBS-EOD than those born to the GBS-negative ones [6.38‰ (12/1 881) vs 0.27‰ (4/14 725), P<0.05]. The multivariate logistic regression analysis showed that placental swabs positive for GBS and positive GBS in neonatal gastric juice at birth were independent predictive factors for the development of GBS-EOD (P<0.05), while adequate IAP was a protective factor (P<0.05) in the offspring of pregnant women with GBS colonization. CONCLUSIONS: GBS colonization of pregnant women in late pregnancy has adverse effects on their offspring. It is important to determine prenatal GBS colonization status of pregnant women and administer with adequate IAP based on the indications of IAP to reduce the incidence of neonatal GBS-EOD. Citation.

[Clinical features and drug resistance in children with Salmonella infection].

OBJECTIVE: To study the clinical features and drug resistance in children with Salmonella infection. METHODS: A total of 163 children with positive fecal cultures for Salmonella who were hospitalized between 2013 and 2017 were enrolled. A retrospective analysis was performed for their data on clinical features, distribution of Salmonella serotypes, and drug sensitivity test results. RESULTS: Among the 163 children with Salmonella infection, 79 (48.5%) were aged ≤1 year. Main clinical manifestations included fever and diarrhea. Of all the children, 121 (74.2%) reached a body temperature of above 39°C, 52 (31.9%) had diarrhea more than 10 times a day, and 56 (34.4%) had respiratory infection. Salmonella infection often occurred in summer and autumn. Of all the children, 131 (80.4%) had the infection in May to October. Salmonella typhimurium was observed in 100 children (61.3%) and Salmonella enteritidis was observed 15 children (9.2%). All serotypes of Salmonella had a drug resistance rate of >20% to cefotaxime, as well as high sensitivities to ß-lactamase inhibitors (amoxicillin/clavulanic acid and piperacillin/tazobactam). There were no strains resistant to carbapenems including imipenem. CONCLUSIONS: Infants aged ≤1 year are susceptible to Salmonella infection in summer and autumn, and the most common serotype is Salmonella typhimurium. Main clinical manifestations are fever and diarrhea in children with Salmonella infection, and most children also have respiratory infection. Salmonella has an increased rate of drug resistance to third-generation cephalosporins. In clinical treatment, antimicrobial drugs should be used according to the results of drug sensitivity test.

Epidemiology, species distribution and outcome of nosocomial Candida spp. bloodstream infection in Shanghai.

BACKGROUND: Yeasts, mostly Candida, are important causes of bloodstream infections (BSI), responsible for significant mortality and morbidity among hospitalized patients. The epidemiology and species distribution vary from different regions. The goals of this study were to report the current epidemiology of Candida BSI in a Shanghai Teaching Hospital and estimate the impact of appropriate antifungal therapy on the outcome. METHODS: From January 2008 to December 2012, all consecutive patients who developed Candida BSI at Ruijin University Hospital were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy and its impact on the outcome were analyzed. RESULTS: A total of 121 episodes of Candida BSI were identified, with an incidence of 0.32 episodes/1,000 admissions (0.21 in 2008 and 0.42 in 2012) The proportion of candidemia caused by non-albicans species (62.8%), including C. parapsilosis (19.8%), C. tropicalis (14.9%), C. glabrata (7.4%), C. guilliermondii (5.8%), C. sake (5.0%) was higher than that of candidemia caused by C. albicans (37.2%). The overall crude 28-day mortality was 28.1% and significantly reduced with appropriate empiric antifungal therapy administered within 5 days (P = 0.006). Advanced age (OR 1.04; P = 0.014), neutropenia < 500/mm3 (OR 17.44; P < 0.001) were independent risk factors for 28-day mortality, while appropriate empiric antifungal therapy (OR 0.369; P = 0.035) was protective against 28-day mortality. CONCLUSION: The epidemiology of candidemia in Shanghai differed from that observed in Western countries. Appropriate empiric antifungal therapy influenced the short-term survival.

Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis.

AIM: To investigate the potential interactions of thymic stromal lymphopoietin (TSLP) with interleukin-4 (IL-4) in adaptive immunity during fungal keratitis (FK). METHODS: An FK mouse model was induced with Aspergillus fumigatus (AF) hyphal infection. Mice were divided into several groups: untreated, phosphate buffer saline (PBS), infected with AF, and pretreated with a scrambled siRNA, a TSLP-specific siRNA (TSLP siRNA), murine recombinant TSLP (rTSLP), immunoglobulin G (IgG), murine recombinant IFN (rIFN-γ), murine recombinant IL-4 (rIL-4), rIL-13, murine recombinant IL-17A (rIL-17A), and murine recombinant IL-17F (rIL-17F) groups. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) or Western blot were performed to determine mRNA and protein levels in the inflamed cornea. Cytokine locations were observed by immunofluoresence staining after AF hyphal infection. RESULTS: Compared to those in the untreated group, TSLP and T helper type 1 (Th1) cytokine levels in the AF group were upregulated at 24h post infection (hpi), and those of T helper type 2 (Th2) and T helper type 17 (Th17) cytokines were increased at 5d post infection (dpi). Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF group. The TSLP level was increased in the rIL-4-pretreated group, but there were no significant changes among the other groups. Immunofluorescence staining showed cytokine locations after AF hyphal infection. CONCLUSION: TSLP induces a Th2 immune response and promots Th2 T cell differentiation in vivo. IL-4 promotes TSLP secretion. Therefore, TSLP with IL-4 regulates adaptive immunity in FK.