The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

Clinical characteristics of 84 children with invasive Haemophilus influenzae infection from 2014 to 2018 / 中华儿科杂志

Objective@#To investigate the clinical characteristics of invasive Haemophilus influenzae (HI) infection in children.@*Methods@#The clinical manifestations, laboratory examinations and treatment outcomes of 84 children with HI infection confirmed by bacterial culture in 7 tertiary children′s hospitals from 2014 to 2018 were analyzed retrospectively.@*Results@#Among the 84 cases, 50 were males. The age was 1.54 years (ranged from 5 days to 13 years).Twenty cases (24%) had underlying diseases and 48 cases (57%) had not received antibiotics before collecting specimens. Eighty-two cases (98%) had fever and 75 cases (89%) had clear infection foci, among which 31 cases (37%) had meningitis and 27 cases (32%) had pneumonia. Blood culture was positive in 62 cases (74%), cerebrospinal fluid culture was positive in 10 cases (12%), blood culture and cerebrospinal fluid culture were both positive in 11 cases (13%). Antibiotics susceptibility test showed that 27% (22/82) of all HI strains produced β-lactamases and 48% (37/77) strains were resistant to ampicillin. The drug resistance rates to cefuroxime, ampicillin-sulbactam, trimethoprim-sulfamethoxazole and azithromycin were 25% (20/80) , 20% (9/45) , 71% (44/62) and 19%(11/58), respectively. All strains were sensitive to meropenem, levofloxacin and ceftriaxone. After sensitive antibiotic therapy, 83% (70/84) of all patients were cured and improved, the mortality rate and loss of follow-up rate were 13% (11/84) and 4% (3/84) respectively.@*Conclusions@#Meningitis and pneumonia are common presentation of invasive HI infections in children. Mortality in HI meningitis children is high and the third generation of cephalosporins, such as ceftriaxone can be used as the first choice for the treatment of invasive HI infection.

Advances in researches on β-carbonic anhydrases as anti-parasitic drug tar-gets / 中国血吸虫病防治杂志

β?carbonic anhydrases(β?CAs)are ubiquitous metalloenzymes which active site contains a zinc ion(Zn2+),and they could catalyze the hydration of carbon dioxide to bicarbonate and protons efficiently and are involved in many biological pro?cesses,such as respiration,pH and CO2 homeostasis,biosynthetic reactions,virulence regulation and so on,and may play a critical role in the life activity of many organisms which contain these enzymes. β?CAs are widely distributed in fungi,bacteria, algae,plants and a small number of protozoan and metazoan except vertebrates. Therefore,as potential drug targets for design?ing and developing antibacterial and anti?parasitic drugs,β?CAs promise a broad application prospect. This paper focuses on the distribution,physiological function and the progress of researches on β?CAs in parasites and their vectors.

Curative effects of breast conserving operation in treatment of triple negative breast cancer / 中国基层医药

Objective To investigate the safety and clinical prognosis of breast conserving operation in treat-ment of triple negative breast cancer.Methods 157 patients with breast cancer were divided into the non triple nega-tive breast cancer group (n=76) and triple negative breast cancer (n=81) according to its receptor expression,clin-ical pathological features, local recurrence after 5 years.Distant metastasis and survival situation were compared between two groups.Results The age0.05);The 5 year dis-ease free survival rate of the triple negative group was 80.25%,significantly lower than 94.74%of the non triple neg-ative group (χ2 =6.572,P<0.05).Conclusion The patients with triple negative breast cancer is younger,their tumor size is large and has a high proportion of family history.Their recurrence rate,distant metastasis rate and 5 year overall survival rate are as better as the patients with non triple negative breast cancer after breast preservation opera-tion,which has high security and good clinical application value.