The RNA binding protein MEX3A promotes tumor progression of breast cancer by post-transcriptional regulation of IGFBP4.

PURPOSE: Breast cancer (BC) is the most frequent malignant tumor in women worldwide with exceptionally high morbidity. The RNA-binding protein MEX3A plays a crucial role in genesis and progression of multiple cancers. We attempted to explore its clinicopathological and functional significance in BC in which MEX3A is expressed. METHODS: The expression of MEX3A detected by RT-qPCR and correlated the results with clinicopathological variables in 53 BC patients. MEX3A and IGFBP4 profile data of BC patients were downloaded from TCGA and GEO database. Kaplan-Meier (KM) analysis was used to estimate the survival rate of BC patients. Western Blot, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MEX3A and IGFBP4 in BC cell proliferation, invasion and cell cycle in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of BC cells after MEX3A knockdown. The interactions among MEX3A and IGFBP4 were measured by RNA pull-down and RNA immunoprecipitation. RESULTS: The expression of MEX3A was upregulated in BC tissues compared to adjacent tissues and high expression of MEX3A was associated with poor prognosis. Subsequent in vitro studies demonstrated that MEX3A knockdown inhibited BC cells proliferation and migration, as well as xenograft tumor growth in vivo. The expression of IGFBP4 was significantly negatively correlated with MEX3A in BC tissues. Mechanistic investigation showed that MEX3A binds to IGFBP4 mRNA in BC cells, decreasing IGFBP4 mRNA levels, which further activated the PI3K/AKT and other downstream signaling pathways implicated cell cycle progression and cell migration. CONCLUSION: Our results indicate that MEX3A plays a prominent oncogenic role in BC tumorigenesis and progression by targeting IGFBP4 mRNA and activating PI3K/AKT signaling, which can be used as a novel therapeutic target for BC.

miR-335-5p suppresses gastric cancer progression by targeting MAPK10.

BACKGROUND: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. METHODS: Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p. CONCLUSIONS: These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

miR-5701 promoted apoptosis of clear cell renal cell carcinoma cells by targeting phosphodiesterase-1B.

Increasing evidence has demonstrated that microRNAs play critical roles in malignant biological behaviors, including cancerogenesis, cancer progression and metastasis, through the regulation of target genes expression. As miR-5701 has recently been identified to play roles as tumor suppressor miRNA in the development of some kinds of cancers, in this study we sought to investigate the role of miR-5701 in clear cell renal cell carcinoma (ccRCC). Colony formation, cell apoptosis and proliferation assays were employed, and the results showed that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells. Western blotting and dual-luciferase reporter assays were used to confirm that PDE1B is a new direct target of miR-5701. Furthermore, overexpression of PDE1B attenuated the effects of miR-5701, indicating that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells via targeting PDE1B. Taken together, the data presented here indicate that t miR-5701 is a tumor suppressor in ccRCC and PDE1B is a new target of miR-5701.

MicroRNA-33a-5p suppresses colorectal cancer cell growth by inhibiting MTHFD2.

Colorectal cancer (CRC) is one of the most common malignancies with high levels of invasiveness, drug resistance and mortality, but the internal mechanisms of CRC are largely unknown. MicroRNAs (miRs) have been reported to be involved in the development of CRC, and numerous studies have demonstrated that the abnormal expression of miR-33a-5p might be associated with CRC. However, the function and downstream mechanism of miR-33a-5p in colorectal cancer (CRC) remains unclear. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme involved in folic acid metabolism, interestingly was confirmed to be one of the target genes of miR-33a-5p in the present study. We first confirmed that miR-33a-5p in CRC tissues and cell lines were downregulated (P < 0.05), and that the proliferation, clone formation capacities, G1/S progression, and migration capacities of the two CRC cell lines HCT116 cells and HT29 were suppressed by miR-33a-5p overexpression in vitro (P < 0.05). Ctrl HCT116 and miR-33a-5p-overexpressing HCT116 were injected into nude mice. In vivo tumour formation was significantly suppressed by miR-33a-5p overexpression (P < 0.05) as well as the proliferation marker Ki67 (P < 0.05). Additionally, MTHFD2 protein expression was significantly enhanced in CRC tissues. From bioinformatics predictions and a luciferase report analysis, MTHFD2 was confirmed to be one of the target genes of miR-33a-5p. In contrast to the role of miR-33a-5p overexpression, MTHFD2 overexpression promoted the proliferation and migration of HCT116 and HT29 cells (P < 0.05), which confirmed that MTHFD2 was a functional target gene of miR-33a-5p. In conclusion, miR-33a-5p inhibits the growth and migration of CRC by targeting MTHFD2.

An easy operating pathogen microarray (EOPM) platform for rapid screening of vertebrate pathogens.

BACKGROUND: Infectious diseases emerge frequently in China, partly because of its large and highly mobile population. Therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. The availability of a large number of microbial genome sequences generated by conventional Sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale screening of vertebrate pathogens. METHODS: An easy operating pathogen microarray (EOPM) was designed to detect almost all known pathogens and related species based on their genomic sequences. For effective identification of pathogens from EOPM data, a statistical enrichment algorithm has been proposed, and further implemented in a user-friendly web-based interface. RESULTS: Using multiple probes designed to specifically detect a microbial genus or species, EOPM can correctly identify known pathogens at the species or genus level in blinded testing. Despite a lower sensitivity than PCR, EOPM is sufficiently sensitive to detect the predominant pathogens causing clinical symptoms. During application in two recent clinical infectious disease outbreaks in China, EOPM successfully identified the responsible pathogens. CONCLUSIONS: EOPM is an effective surveillance platform for infectious diseases, and can play an important role in infectious disease control.

Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.

Panton-Valentine leukocidin gene sequence variation and phage in methicillin-resistant and methicillin-susceptible Staphylococcus aureus from children in mainland China.

To determine the variation in the Panton-Valentine leukocidin (PVL) gene sequences and different PVL-encoding phages of Staphylococcus aureus strains collected from children in mainland China, fifty-eight strains with PVL collected from 2007 to 2009 were used. Their molecular characteristics were examined. Primers were designed to sequence the PVL genes. Six PVL-encoding phages (ϕPVL, ϕ108PVL, ϕSLT, ϕSa2MW, ϕSa2958, and ϕSa2USA) were identified by PCR. Eleven sequence types (ST) were detected with ST59 (39.7%, 23/58) the most frequent ST, followed by 910 (22.4%, 13/58), and 338 (12.1%, 7/58). Single nucleotide polymorphisms (SNP) were identified at 11 locations in the PVL genes. SNP (nucleotide 1396, A→G) and SNP (nucleotide 1546, A→G) were observed in >10 sequences. Four additional SNP were non-synonymous. Both SNP (nucleotide 16, C→A) and SNP (nucleotide 62, C→T) were present in the same ST59 strain. SNP (nucleotide 527, A→G) was present in five strains belonging to ST30, 121, 1, and 93. SNP (nucleotide 1436, A→C) was present in one ST30 strain. Fifteen strains belonging to ST910, ST217, and ST30 carried a PVL phage that had an icosahedral head morphology. Nine ST59 strains carried ϕ108PVL. Three ST88 strains carried a PVL phage that had an elongated head morphology. Twenty-seven strains, including 60.9% (14/23) of ST59 and all ST338 strains, had no detectable phage. In conclusion, sequence variation in PVL genes and PVL-encoding phages was generally related to the lineage. ST59 strains may indeed carry novel PVL phages.

Abdominal bronchogenic cyst: A rare case report.

BACKGROUND: Bronchogenic cysts are cystic masses caused by congenital abnormal development of the respiratory system, and usually occur in the pulmonary parenchyma or mediastinum. CASE SUMMARY: A rare case of a bronchogenic cyst discovered in the abdominal cavity of a 35-year-old man is reported. Physical examination found a space-occupying lesion in the patient's abdomen for 4 d. Laparoscopic exploration found the cyst tightly adhered to the stomach and its peripheral blood vessels; therefore, intraoperative laparotomy was performed. The cystic mass was resected en bloc with an Endo-GIA stapler. The final postoperative pathological diagnosis confirmed an abdominal bronchogenic cyst. CONCLUSION: This is a rare case of a bronchogenic cyst that was discovered within the abdominal cavity of a male patient. The cyst is easily confused with or misdiagnosed as other lesions. Therefore, it is necessary to distinguish abdominal bronchogenic cyst from gastrointestinal stromal tumor, Meckel's diverticulum, enteric duplication cyst, or lymphangioma. Although computer tomography and magnetic resonance imaging were the primary diagnostic approaches, endoscopic ultrasound-guided fine-needle aspiration could assist with clarification of the cytological or histopathological diagnosis before surgery.

FERM domain-containing protein 6 exerts a tumor-inhibiting role in thyroid cancer by antagonizing oncogenic YAP1.

The emerging role of FERM domain-containing protein 6 (FRMD6) in cancer progression has been revealed in several malignancies. However, its relevance on thyroid cancer is not well understood. This work evaluated the possible role and mechanism of FRMD6 in thyroid cancer. We demonstrated that FRMD6 expression was downregulated in thyroid cancer by analyzing the Cancer Genome Atlas data. Remarkable reductions in FRMD6 expression were also confirmed in the clinical specimens and cell lines of thyroid cancer. The upregulation of FRMD6 restrained the proliferation, epithelial-mesenchymal transition, and invasion of thyroid cancer. Moreover, FRMD6 overexpression significantly increased the apoptosis and cell cycle arrest. Further molecular research demonstrated that the overexpression of FRMD6 increased the phosphorylation levels of mammalian STE20-like protein kinase 1, large tumor suppressor 1, and Yes-associated protein 1 (YAP1) and prohibited the activation of YAP1. The re-expression of constitutively active YAP1 strikingly reversed FRMD6-induced tumor-inhibiting effects. Thyroid cancer cells overexpressing FRMD6 had a weakened ability to form xenograft tumors in vivo in nude mice. Overall, the overexpression of FRMD6 produces remarkable tumor-inhibiting effects in thyroid cancer by inhibiting oncogenic YAP1.

MBD1/HDAC3-miR-5701-FGFR2 axis promotes the development of gastric cancer.

Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide due to the lack of specific biomarkers for the early diagnosis and universal accepted therapy for advanced GC. Lower levels of miR-5701 were found in the GC tissue from the online sequencing data and confirmed in the GC tissues and GC cell lines. Overexpression of miR-5701 inhibited the proliferation and migration of GC cells and promoted the apoptosis of these cells. Bioinformatics analyses and luciferase assay showed that miR-5701 targeted FGFR2, which acted as an oncogene in GC. Nude mice with GC cells overexpressing miR-5701 exhibited smaller tumor sizes and less lung metastases. The miR-5701 expression was directly, transcriptionally inhibited by MBD1 together with HDAC3 by binding together to form a complex. Knocked down MBD1 or HDAC3 increased the miR-5701 expression. These results indicated the potential use of exogenously administered miR-5701 or agents that elevated endogenous miR-5701 to inhibit GC, improving the prognosis of patients with GC.

FOCAD/miR-491-5p, downregulated by EGR1, function as tumor suppressor by inhibiting the proliferation and migration of gastric cancer cells.

Gastric cancer is a common malignant tumor in China; however, its carcinogenesis remains unknown. Focadhesin (FOCAD) is a tumor suppressor gene in gliomas, its expression, role, and mechanism in gastric cancer have not been defined. The aim of the present study was to explore the expression pattern of FOCAD in human normal tissues and cancer tissues and elucidate the role and regulatory mechanism of Early Growth Response 1 (EGR1) in FOCAD and its intron, miR-491-5p, in gastric cancer. Immuno histochemical staining revealed that FOCAD is widely and highly expressed in normal gastric mucosa, but is absent in gastric cancer tissue. Based on an association analysis FOCAD expression was found to be negatively associated with lymph node metastasis (P = 0.004); higher FOCAD levels were associated with longer survival in patients with gastric cancer (P = 0.001). MTT, colony, Transwell chamber, and flow cytometry assays revealed that siFOCAD promoted cell proliferation, growth, and migration, and inhibited apoptosis. Furthermore, bioinformatic analysis, Fluorescence reporter gene and chromatin immunoprecipitation analyses confirmed that EGR1 binds to the promoter and negatively regulates FOCAD and miR-491-5p at the transcriptional level. The overexpression of EGR1 was also found to promote cell proliferation, growth, and migration, and inhibit apoptosis. Overall, FOCAD is specifically overexpressed in the gastric mucosa and is significantly downregulated in gastric cancer. To our knowledge, this is the first study to demonstrate that FOCAD is a tumor suppressor, higher FOCAD levels might be a better prognostic marker of gastric cancer, and FOCAD/miR-491-5p may be negatively regulated by EGR1.

TDG suppresses the migration and invasion of human colon cancer cells via the DNMT3A/TIMP2 axis.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors with high rates of recurrence and mortality. Thymine DNA glycosylase (TDG) is a key molecule in the base excision repair pathway. Recently, increasing attention has been paid to the role of TDG in tumor development. However, the specific functions of TDG in CRC remain unclear. Methods: The biological functions of TDG and DNA methyltransferase 3 alpha (DNMT3A) in CRC were evaluated using migration and invasion assays, respectively. A tumor metastasis assay was performed in nude mice to determine the in vivo role of TDG. The interaction between TDG and DNMT3A was determined via co-immunoprecipitation (Co-IP). Chromatin immunoprecipitation analysis (ChIP) was used to predict the DNA-binding site of DNMT3A. We also performed methylation-specific PCR (MSP) to detect changes in TIMP2 methylation. Results: TDG inhibited the migration and invasion of human colon cancer cells both in vitro and in vivo. TDG promoted the ubiquitination and degradation of DNMT3A by binding to it. Its interference with siDNMT3A also inhibits the migration and invasion of human colon cancer cells. Furthermore, the ChIP, MSP, and rescue experiments results confirmed that TDG accelerated the degradation of DNMT3A and significantly regulated the transcription and expression of TIMP2, thereby affecting the migration and invasion of human colon cancer cells. Conclusion: Our findings reveal that TDG inhibits the migration and invasion of human colon cancer cells through the DNMT3A-TIMP2 axis, which may be a potential therapeutic strategy for the development and treatment of CRC.

LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma.

Small nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous "sponge" competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.

Molecular characterisation of the faecal microbiota in patients with type II diabetes.

The investigation provides molecular analyses of the faecal microbiota in type 2 diabetic patients. In order to characterise the gut microbiota in diabetic patients and to assess whether there are changes in the diversity and similarity of gut microbiota in diabetic patients when compared with healthy individuals, bacterial DNAs from 16 type 2 diabetic patients and 12 healthy individuals were extracted from faecal samples and characterised by PCR-denaturing gradient gel electrophoresis (DGGE) with primers specifically targeting V3 region of the 16S rRNA gene, as well as been sequenced for excised gel bands. The counts of Bacteroides vulgatus, Clostridium leptum subgroup and Bifidobacterium genus were assessed using quantitative PCR. By comparing species diversity profiles of two groups, we observed that there were no significant differences between diabetic and healthy group, although a few diabetic individuals (D6, D8) exhibited a remarkable decrease in species profiles. As for the similarity index, it was lower in inter-group than that in intra-group, which showed that the composition of gut microbiota in diabetic group might be changed due to diabetes status. Sequencing results also revealed that bacterial composition of diabetic group was different from that of the healthy group. B. vulgatus and Bifidobacterium genus were low represented in the microbiota of diabetic group, and the significant decrease was observed for Bifidobacterium by real-time PCR. Taken together, in this work we observed the characterisation of gut microbiota in diabetic patients, which suggests that the gut microbiota of diabetes patients have some changes associated with occurrence and development of diabetes.

FOXN3 suppresses the growth and invasion of papillary thyroid cancer through the inactivation of Wnt/ß-catenin pathway.

Forkhead box N3 (FOXN3) is a subtype of FOX family that has been demonstrated to be implicated in several cancers. However, the role of FOXN3 in papillary thyroid carcinoma (PTC) and its mechanisms have not yet been investigated. Our results showed that FOXN3 was markedly down regulated in PTC tissues and cell lines. Overexpression of FOXN3 suppressed the proliferation, colony formation, migration, and invasion in PTC cells. Overexpression of FOXN3 also prevented EMT process in PTC cells, as shown by the increased E-cadherin expression level and decreased expression levels of N-cadherin and vimentin. In addition, overexpression of FOXN3 inhibited tumor growth of PTC in vivo. Furthermore, overexpression of FOXN3 caused significant decreases in expression levels of ß-catenin, c-Myc, and cyclin D1. Additionally, activation of Wnt/ß-catenin pathway reversed the effects of FOXN3 on PTC cells. In conclusion, these findings indicated that FOXN3 exerted a tumor suppressive activity in PTC, which was mediated by Wnt/ß-catenin pathway.

Risk factors for mortality from severe community-acquired pneumonia in hospitalized children transferred to the pediatric intensive care unit.

BACKGROUND: Some children hospitalized due to severe community-acquired pneumonia (CAP) require to the pediatric intensive care unit (PICU) because of severe complications. The purpose of this study was to identify the risk factors for mortality in this patient population. METHODS: This study evaluated the medical records of 113 hospitalized children with severe CAP, who were transferred to the PICU within 48 h of admission at the Guangzhou Women and Children's Medical Center between 2013 and 2017. RESULTS: The study group consisted of 87 boys (77%) and 26 girls (33%), aged between 1 month and 9 years; 72.6% (82/113) of patients were aged <12 months. The mortality rate was 12.3% (14/113). The most common viral and bacterial pathogens isolated were adenovirus (17.7%, 20/113) and Haemophilus influenzae (8.8%, 10/113). Wheezing, cyanosis, oxygen saturation <90%, Pediatric Early Warning Score (PEWS) >3 on admission, not receiving corticosteroid therapy prior to admission, the need for mechanical ventilation, septic shock, multi-organ dysfunction (MODS), and acute renal failure (ARF) occurring prior to transfer to the PICU, increased alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, and decreased hemoglobin and albumin (ALB) levels were associated with mortality (P < 0.05). Non-survivors were more likely to have an oxygen saturation <90% on admission and lower levels of ALB prior to transfer to the PICU than survivors (P < 0.05). CONCLUSIONS: Our results showed that hospitalized children with severe CAP who were transferred to the PICU within 48 h of hospital admission were mainly aged <1 year. Additionally, an oxygen saturation <90% and decreased ALB levels were early prognostic variables independently associated with death.

[Changes of some elements in rat's tissues except nerve centre with both ovariectomy and chronic aluminum toxication and the effects of estrogen supplement].

OBJECTIVE: To reveal the influence of ovariectomy and chronic Aluminum toxication in combination on the distribution in tissues except nerve centre and excretion in urine of somel elements. The study will supply the basis for study of Alzheimers disease. METHODS: Forty 6-month-old female S-D rats were divided randomly into 4 groups: group OVX, group OVX + Al and group OVX + Al + E2. After 3 months, urine of 24 h were collected by metabolic cages; liver, kidney, heart, bone, tibia and skeletal muscle, were got from the rats. The content of the elements in these tissues and urine was detected by ICP-AES. RESULTS: Compared of group OVX with group sham, the content of Zn decreased (P < 0.001). Compared of group OVX + Al + E2 with group sham, the content of Al, Cd, Si and Se in heart increased (P < 0.05, P < 0.01, P < 0.01, P < 0.001). The content of Se and Cd in tibia increased (P < 0.01, P < 0.001). The content of Al in kidney increased (P < 0.05). The content of Mn and Cu increased (P < 0.05, P < 0.001), Se decreased (P < 0.001) in skeletal muscle. The content of Al, Se and Ca in spinal cord decreased (P < 0.05, P < 0.01, P < 0.05). The content of Mn, Zn and Si in liver increased (P < 0.01, P < 0.05, P < 0.05). The content of Cd, Mg, Se, Al and Ca in urine increased (P < 0.05, P < 0.05, P < 0.01, P < 0.001, P < 0.001). Compared of group OVX + Al + E2 with group OVX + Al, the content of Cd, Mn and Se in heart increased (P < 0.05, P < 0.05, P < 0.01). The content of Al, Mg, Se, Cd and Mn in tibia increased (P < 0.05, P < 0.01, P < 0.001, P < 0.001, P < 0.001). The content of Mn and Cu increased (P < 0.05, P < 0.001), Se decreased (P < 0.001), in skeletal muscle. The content of Se in spinal cord decreased (P < 0.05). The content of Al and Ca decreased (P < 0.05, P < 0.01), the content of Cu, Si, Fe, Mg, Mn and Zn incraesed(P <0.05, P < 0.05, P <0.01, P < 0.01, P < 0.001, P < 0.001), in liver. The content of Se, Al, Cd, Mg, Si and Ca in urine increased (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01). CONCLUSION: Zn in heart can transfer to other tissues after a long time ovariectomy. Heart, skeletal muscle and liver, are mainly affected tissues except nerve centre by ovariectomy and chronic aluminum toxication in combination; and mainly affected elements are Zn, Si, Cu and Se. Chronic aluminum toxication make Si transfer to heart of ovariectomized rats, and facilitate Zn in heart transfer to other tissues. Supply estrogen can promote aluminum excretion in urine. distribution in tissues except nerve centre and excretion in urine of somel elements. The study will supply the basis for study of Alzheimers disease. METHODS: Forty 6-month-old female S-D rats were divided randomly into 4 groups: group OVX, group OVX + Al and group OVX + Al + E2. After 3 months, urine of 24h were collected by metabolic cages; Liver, kidney, heart, bone, tibia and skeletal muscle, were got from the rats. The content of the elements in these tissues and urine was detected by ICP-AES. RESULTS: Compared of group OVX with group sham, the content of Zn decreased (P < 0.001). Compared of group OVX + Al + E2 with group sham, the content of Al, Cd, Si and Se in heart increased (P < 0.05, P < 0.01, P < 0.01, P < 0.001). The content of Se and Cd in tibia increased (P < 0.01, P < 0.001). The content of Al in kidney increased (P < 0.05). The content of Mn and Cu increased (P < 0.05, P < 0.001),Se decreased (P < 0.001) in skeletal muscle. The content of Al, Se and Ca in spinal cord decreased (P < 0.05, P < 0.01, P < 0.05). The content of Mn, Zn and Si in liver increased (P < 0.01, P < 0.05, P < 0.05). The content of Cd, Mg, Se, Al and Ca in urine increased (P < 0.05, P < 0.05, P < 0.01, P < 0.001, P < 0.001). Compared of group OVX + Al + E2 with group OVX + Al, the content of Cd, Mn and Se in heart increased (P < 0.05, P < 0.05, P < 0.01). The content of Al, Mg, Se, Cd and Mn in tibia increased (P < 0.05, P < 0.01, P < 0.001, P < 0.001, P < 0.001). The content of Mn and Cu increased (P < 0.05, P < 0.001), Se decreased (P < 0.001), in skeletal muscle. The content of Se in spinal cord decreased (P < 0.05). The content of Al and Ca decreased (P < 0.05, P < 0.01), the content of Cu, Si, Fe, Mg, Mn and Zn incraesed(P <0.05, P < 0.05, P <0.01, P < 0.01, P < 0.001, P < 0.001), in liver. The content of Se, Al, Cd, Mg, Si and Ca in urine increased (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01). CONCLUSION: Zn in heart can transfer to other tissues after a long time ovariectomy. Heart, skeletal muscle and liver, are mainly affected tissues except nerve centre by ovariectomy and chronic aluminum toxication in combination; and mainly affected elements are Zn, Si, Cu and Se. Chronic aluminum toxication make Si transfer to heart of ovariectomized rats, and facilitate Zn in heart transfer to other tissues. Supply estrogen can promote aluminum excretion in urine.

[Antimicrobial resistance and penicillin resistance-associated genes of Streptococcus pneumoniae isolated from children with respiratory tract infection].

OBJECTIVE: To investigate the antimicrobial resistance and penicillin resistance-associated genes (TEM and pbp2B) of Streptococcus pneumoniae (S. pneumoniae) isolated from sputum specimens of Guangzhou children with respiratory tract infection. METHODS: E-test and Kirby-Bauer methods were applied to detect the antibiotic susceptibility of 44 strains of S. pneumoniae. PCR was used to detect resistance genes pbp2B and TEM, followed by DNA sequence analysis of pbp2B gene. The sequence results were compared to those of penicillin-susceptible S. pneumoniae R6. RESULTS: Of the 44 isolates of S. pneumoniae, only 5 (11.4%) were susceptible to penicillin. All strains were resistant to erythromycin but susceptible to ofloxacin and vancomycin. The resistance rate of the isolates to clindamycin and trimoxazole was more than 90%. The S. pneumoniae isolates showed a high susceptibility to amoxicillin, imipenem and ceftriaxone, with a resistance rate of 0, 2.6% and 3.9%, respectively. The sequence analysis showed that more than 99% nucleotide sequence of pbp2B gene of five penicillin-susceptible isolates was the same as penicillin-susceptible S. pneumoniae R6, without any amino acid replacement. Site mutation was found in the remaining 39 penicillin-nonsusceptible isolates with a nucleotide mutation rate ranging from 13.2% to 23.1% and amino acid replacement rate from 6.5% to 10.9%. The 39 penicillin-nonsusceptible isolates were classified into 4 types according to the mutation site between Ser391 and Thr492 of pbp2B: type I (n=30), type II (n=7), type III (n=1) and type IV (n=1). No TEM gene was detected in all the 44 S. pneumoniae isolates. CONCLUSIONS: The S.pneumoniae isolates from Guangzhou children with respiratory tract infection are resistant to penicillin and erythromycin. Amoxicillin and the third generation cephalosporin may be recommended for treating S. pneumoniae infection. The mutation of pbp2B gene plays an important role in the development of S. pneumoniae resistance to penicillin.

Antibiotic usage in Chinese children: a point prevalence survey.

BACKGROUND: Children as a population have high antimicrobial prescribing rates which may lead to high resistance of bacteria according to data from some single-center surveys of antibiotic prescribing rates in China. The acquirement of baseline data of antibiotic prescribing is the basis of developing intervention strategies on inappropriate antimicrobial prescriptions. Few studies show clearly the pattern and detailed information on classes of antibiotics and distribution of indications of antibiotic prescriptions in children in China. This study aims to assess the antibiotic prescribing patterns among children and neonates hospitalized in 18 hospitals in China. METHODS: A 24-hour point prevalence survey on antimicrobial prescribing was conducted in hospitalized neonates and children in China from December 1st, 2016 to February 28th, 2017. Information on the antibiotic use of patients under 18 years of age who were administered one or more on-going antibiotics in the selected wards over a 24-hour period was collected. These data were submitted to the GARPEC (Global Antimicrobial Resistance, Prescribing and Efficacy in Children and Neonates) web-based application ( https://pidrg-database.sgul.ac.uk/redcap/ ). For statistical analysis, Microsoft Excel 2007 and SPSS 22.0 were used. RESULTS: The antibiotic data were collected in 35 wards in 18 hospitals from 9 provinces. In total, 67.76% (975/1439) of the patients (n = 1439) were given at least one antibiotic, including 58.1% (173/298) of neonates (n = 298) and 70.3% (802/1141) of children (n = 1141). In neonates, the three most frequently prescribed antibiotics were third-generation cephalosporins (41.7%), penicillins plus enzyme inhibitor (23.8%), and carbapenems (11.2%). In children, the three most frequently prescribed antibiotics were third-generation cephalosporins (35.5%), macrolides (23.2%), and penicillins plus enzyme inhibitors (15.9%). The most common indication for antibiotics was proven or probable bacterial lower respiratory tract infection (30.9% in neonates and 66.6% in children). CONCLUSIONS: Antibiotics are commonly prescribed in the Chinese children population. It is likely that the third-generation cephalosporins and macrolides are currently overused in Chinese children. Efforts must be made to ensure safe and appropriate antibiotic prescribing to reduce and prevent the future development of antibiotic resistance.

Molecular and clinical characteristics of clonal complex 59 methicillin-resistant Staphylococcus aureus infections in Mainland China.

Detailed molecular analyses of Clonal Complex 59 (CC59) methicillin-resistant Staphylococcus aureus (MRSA) isolates from children in seven major cities across Mainland China were examined. A total of 110 CC59 isolates from invasive and non-invasive diseases were analyzed by multilocus sequence typing (MLST), Staphylococcus cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing and pulsed-field gel electrophoresis (PFGE). Antibiotics susceptibilities, carriage of plasmids and 42 virulence genes and the expression of virulence factors were examined. ST59 (101/110, 91.8%) was the predominant sequence type (ST), while single locus variants (SLVs) belonging to ST338 (8/110, 7.3%) and ST375 (1/110, 0.9%) were obtained. Three SCCmec types were found, namely type III (2.7%), type IV (74.5%) and type V (22.7%). Seven spa types including t437, which accounted for 87.3%, were determined. Thirteen PFGE types were obtained. PFGE types A and B were the major types totally accounting for 81.8%. The dominant clone was ST59-t437-IVa (65.5%), followed by ST59-t437-V (14.5%). The positive rate of luks-PV and lukF-PV PVL encoding (pvl) gene was 55.5%. Plasmids were detected in 83.6% (92/110) of the strains. The plasmid size ranging from 23.4 kb to 50 kb was most prevalent which accounted for 83.7% (77/92). A significantly lower expression of hla was found in ST59-t437-IVa compared with ST59-t437-V. Among the 110 cases, 61.8% of the patients were less than 1 year old. A total of 90 cases (81.8%) were community-associated (CA) infections whereas 20 cases (18.2%) were hospital-associated (HA) infections. Out of the 110 patients, 36.4% (40/110) were diagnosed with invasive infectious diseases in which ST59-t437-IVa accounted for 67.5% (27/40). In brief, ST59-t437-IVa was proved as the dominant clone in CC59 MRSA strains. The carriage rate of pvl gene was high. CC59 MRSA could result in CA and HA infections. The majortiy of MRSA infection children were in young age.