Clioquinol has been shown to have anticancer activity both in vitro and in vivo. The present study compared the cytotoxicity of clioquinol with six analogues, using human cancer cell lines. Of the analogues tested, 8-hydroxy-5-nitroquinoline (NQ) was the most toxic, with an IC50 that was 5-10 fold lower than other congeners. Its activity was enhanced by copper, but not zinc, and the use of a zinc-sensitive fluorophore showed that unlike clioquinol, NQ is not a zinc ionophore. NQ increased intracellular reactive oxygen species generation, an effect that was significantly enhanced by the addition of copper at levels that approximate those found in human plasma. NQ has been used in humans for the treatment of urinary infections. NQ is an 8-hydroxyquinoline derivative that is more potent than the halogenated 8-hydroxyquinolines, and may be less neurotoxic because it lacks zinc ionophore activity. NQ is another clinical used anti-microbial agent whose properties suggest that it may be useful in treating cancer.

Acute bacterial meningitis is still considered one of the most dangerous infectious diseases in children. To investigate the prevalence and antibiotic resistance profiles of cerebrospinal fluid (CSF) pathogens in children with acute bacterial meningitis in Southwest China, CSF samples from 179 meningitis patients (3 days to 12 years old) with positive culture results were collected from 2012 to 2015. Isolated pathogens were identified using the Vitek-32 system. Gram stain results were used to guide subcultures and susceptibility testing. The antimicrobial susceptibility of isolates was determined using the disc diffusion method. Of the isolates, 50.8% were Gram-positive bacteria, and 49.2% were Gram-negative bacteria. The most prevalent pathogens were E. coli (28.5%), Streptococcus pneumoniae (17.8%), Staphylococcus epidermidis (10.0%), Haemophilus influenzae type b (9.5%), and group B streptococcus (7.2%). In young infants aged ≤3 months, E. coli was the organism most frequently isolated from CSF (39/76; 51.3%), followed by group B streptococcus (13/76; 17.1%) and Streptococcus pneumoniae (8/76; 10.5%). However, in young infants aged >3 months, the most frequently isolated organism was Streptococcus pneumoniae (24/103; 23.3%), followed by Staphylococcus epidermidis (18/103; 17.5%) and Haemophilus influenzae type b (16/103; 15.5%). Antimicrobial susceptibility tests indicated that for E. coli isolates, the susceptibility rates to aminoglycosides ranged from 56.8% to 100.0%, among them, amikacin was identified as the most effective against E. coli. As for cephalosporins, the susceptibility rates ranged from 29.4% to 78.4%, and cefoxitin was identified as the most effective cephalosporin. In addition, the susceptibility rates of piperacillin/tazobactam and imipenem against E. coli were 86.3% and 100%. Meanwhile, the susceptibility rates of Streptococcus pneumoniae isolates to penicillin G, erythromycin, chloramphenicol, ceftriaxone and tetracycline were 68.8%, 0.0%, 87.5%, 81.3% and 0.0%, respectively. Gentamycin, ofloxacin, linezolid and vancomycin were identified as the most effective antibiotics for Streptococcus pneumoniae, each with susceptibility rates of 100%. It was notable that other emerging pathogens, such as Listeria monocytogenes and group D streptococcus, cannot be underestimated in meningitis.

Enterovirus A71 (EV-A71) inactivated vaccines have been widely inoculated among children in Kunming City after it was approved. However, there was a large-scale outbreak of Enteroviruses (EVs) infection in Kunming, 2018.The epidemiological characteristics of HFMD and EVs were analyzed during 2008 to 2018, which are before and three years after EV-A71 vaccine starting to use. The changes of infection spectrum were also investigated, especially for severe HFMD in 2018.The incidence of EV-A71 decreased dramatically after EV-A71 vaccine starting use. The proportion of non CV-A16/EV-A71 EVs positive patients raised up to 77.17% to 85.82%, while, EV-A71 and CV-A16 only accounted for 3.41% to 7.24% and 6.94% to 19.42% in 2017 and 2018. CV-A6 was the most important causative agent in all clinical symptoms (Severe HFMD, HFMD, Herpangina and fever), accounting from 42.13% to 62.33%. EV-A71 only account for 0.36% to 2.05%. In sever HFMD, CV-A6 (62.33%), CV-A10 (11.64%), CV-A16 (10.96%) were the major causative agent in 2018. EV-A71 inactivated vaccine has a good protective effect against EV-A71 and induced EVs infection spectrum changefully. EV-A71 vaccine has no or insignificant cross-protection effect on CV-A6, CV-A10 and CV-A16. Herein, developing 4-valent combined vaccines is urgently needed.

BackgroundSemaphorin 4D (Sema4D) is highly expressed in certain types of tumors and functions in the regulation of tumor angiogenesis and growth. However, it is still not clear regarding the roles of Sema4D in breast cancer. This study was designed to explore the effects of Sema4D on proliferation, cell cycle progression, apoptosis, invasion, migration, tumor growth, and angiogenesis in breast cancer.Materials and methodsThe expression level of Sema4D was investigated in MCF10A, 184A1, HCC1937, MDA-MB-468, MDA-MB-231, Hs578T, BT474, MCF-7, and T47D breast cancer cell lines by Western blotting analysis. Sema4D downregulation or overexpression was established by infection with lentiviruses-encoding Sema4D short hairpin RNA (shRNA) or Sema4D. To evaluate the effects of Sema4D on cell proliferation, cell cycle progression, apoptosis, invasion, and migration of MDA-MB-231 and MDA-MB-468 cells, methods including MTT assay, flow cytometry, wound healing assay, and transwell experiments were applied. BALB/c nude mice were injected with MDA-MB-231 cells, which were respectively infected with lentiviruses-encoding Sema4D, Sema4D shRNA, and GFP, followed by tumor angiogenesis assay.ResultsSema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines, especially in MDA-MB-231 and MDA-MB-468 cells. Cell proliferation ability was remarkably inhibited in Sema4D downregulated condition, whereas the proportions of cells in the G0/G1 phase and apoptosis increased in MDA-MB-231 and MDA-MB-468 cells. In addition, the invasion and migration abilities of these cells were obviously reduced. Xenograft growth as well as angiogenesis was inhibited when infected with lentiviruses-encoding Sema4D shRNA in vivo.ConclusionDownregulation of Sema4D had notable influence on cell proliferation ability, invasion, migration, and apoptosis of both MDA-MB-231 and MDA-MB-468 cells. Furthermore, infection with lentiviruses-encoding Sema4D shRNA obviously inhibited tumor growth and angiogenesis in BALB/c nude mice. Our results showed that Sema4D may represent a novel therapeutic target for human breast cancer.

Semaphorin 4D (Sema4D) is highly expressed in a variety of tumors and is associated with high invasion, poor prognosis and poor therapeutic response. However, the expression and role of Sema4D in leukemia remains unclear. The present study investigated the expression of Sema4D in pediatric leukemia and its effects in leukemia cells. The results demonstrated that Sema4D protein was highly expressed in peripheral blood mononuclear cells of patients with pediatric leukemia, and high levels of soluble Sema4D were also observed in the plasma of these patients. Sema4D knockdown induced cell cycle arrest in G 0 /G 1 phase, inhibited proliferation and promoted apoptosis in BALL-1 cells, while Sema4D overexpression exhibited the opposite effect. In Jurkat cells, Sema4D knockdown inhibited proliferation and promoted apoptosis, while Sema4D overexpression decreased the abundance of the cells in the G 0 /G 1 phase of the cell cycle and promoted proliferation. Sema4D overexpression also increased the migratory capacity of Jurkat cells and the invasive capacity of BALL-1 cells. The phosphorylation level of PI3K was decreased in both Sema4D knocked-down Jurkat and BALL-1 cells, and the phosphorylation level of ERK was decreased in Sema4D knocked-down BALL-1 cells. The phosphorylation levels of PI3K, ERK and AKT were elevated in patients with pediatric leukemia, and were correlated to the increased Sema4D expression. Sema4D overexpression was associated with a shorter overall survival in patients with acute myeloid leukemia. Overall, the results of the present study indicated that Sema4D serves an important role in leukemia development by activating PI3K/AKT and ERK signaling, and it may be used as a potential target for the diagnosis and treatment of leukemia.

Background/aim: MiR-125b plays an important role in breast cancer. The current study was to explore the expression and function of miR-125b in triple negative breast cancer cells. Materials and methods: The expression of miR-125b in human TNBC samples and cell lines were examined by qRT-PCR. MTT, scratch assays and transwell assays were utilized to observe the proliferation, migration and invasion ability. MiR-125b’s target gene and downstream signaling pathways were investigated by Luciferase Reporter Assays, qRT-PCR, immunofluorescence assays and western bolt. Results: MiR-125b was highly expressed in human TNBC tissues and cell lines. Inhibiting miR-125b expression suppressed the proliferation, cell migration and invasion. The three-prime untranslated region (3´-UTR) of adenomatous polyposis coli (APC) mRNA contains miR-125b binding sites, and inhibiting miR-125b expression suppressed the activity of the intracellular Wnt/β-catenin pathways and EMT. Conclusion: Inhibiting miR-125b regulates the Wnt/β-catenin pathway and EMT to suppress the proliferation and migration of MDA-MB-468 TNBC cells.

Background Since 2016, enterovirus 71 (EV71) vaccines have been approved for market entry, and little is known about how the epidemiology of hand, foot, and mouth disease (HFMD) has been affected by the introduction of the vaccines in Yunnan Province. The study describes the epidemiological characteristics of HFMD before and after the introduction of EV71 vaccination in Yunnan Province. Methods Surveillance data collected between 2008 and 2019 were analyzed to produce epidemiological distribution on cases, etiologic composition, and EV71 vaccination coverage, as well as to compare these characteristics before and after EV71 vaccination. Results A total of 1,653,533 children received EV71 vaccines from 2016 through 2019 in Yunnan. The annual EV71 vaccination coverage rate ranged from 5.53 to 15.01% among children ≤5 years old. After the introduction of EV71 vaccines, the overall incidence of HFMD increased and reached over 200 cases per 100,000 population-years in 2018 and 2019. However, the case severity and case fatality rate decreased and remained lower than 1 and 0.005% after 2016, respectively. EV71-associated mild, severe and fatal cases sharply decreased. The predominant viral serotype changed to non-EV71/non-CV-A16 enteroviruses which were detected across the whole province. Conclusions Non-EV71/non-CV-A16 enteroviruses became the predominant strain and led to a higher incidence in Yunnan. Expanding EV71 vaccination and strengthening laboratory-based surveillance could further decrease the burden of severe HFMD and detect and monitor emerging enteroviruses.

The association between dietary carbohydrate intake and colorectal cancer (CRC) risk remains controversial. We therefore conducted this meta-analysis to assess the relationship between them. A literature search from the databases of PubMed, Embase, Web of Science and Medline was performed for available articles published in English (up to September 2016). Pooled relative risk (RR) with 95% confidence interval (CI) was calculated to evaluate the association between dietary carbohydrate intake and CRC risk. The random-effect model (REM) was selected as the pooling method. Publication bias was estimated using Egger’s regression asymmetry test and funnel plot. A total of 17 articles involving 14402 CRC patients and 846004 participants were eligible with the inclusion criteria in this meta-analysis. The pooled RR with 95% CI of dietary carbohydrate intake for CRC, colon cancer and rectum cancer risk were 1.08 (95% CI =0.93–1.23, I2 =68.3%, Pheterogeneity<0.001), 1.09 (95% CI =0.95–1.25, I2 =48.3%) and 1.17 (95% CI =0.98–1.39, I2 =17.8%) respectively. When we conducted the subgroup analysis by gender, the significant association was found in men’s populations (summary RR =1.23, 95% CI =1.01–1.57), but not in the women’s populations. In the further subgroup analyses for study design and geographic locations, we did not find any association between dietary carbohydrate intake and CRC risk in the subgroup results respectively. No significant publication bias was found either by the Egger’s regression asymmetry test or by the funnel plot. This meta-analysis suggested that higher dietary carbohydrate intake may be an increased factor for CRC risk in men populations. Further studies are wanted to confirm this relationship.