ObjectiveTo summarize functions and mechanisms of poly ADP-ribose polymerase (PARP) inhibitors and its application in germline BRCA mutated breast cancer.MethodThe literatures about the PARP inhibitors and their applications in the treatment of germline BRCA mutated breast cancer at home and abroad in recent years were collected to make a review.ResultsAs a DNA repair enzyme, the PARP played an important role in the DNA repair pathway. Based on this mechanism, the PARP inhibitors had been developed and widely used in the clinic. On the other hand, the previous studies had shown that the PARP inhibitors marked the synthetic lethal effect in the cancers with homologous recombination deficiency mechanism. By inhibiting the PARP activity in the tumor cells with BRCA mutation, all the DNA damage repair pathways were blocked, which could induce the cell apoptosis or increase the sensitivity of tumor cells to chemoradiotherapy, resulting in the cell death.ConclusionIn patients with germline BRCA mutated breast cancer, PARP inhibitors can selectively kill breast cancer cells and show a high potential for individualized treatment.
ObjectiveTo understand the drug resistance of Mycobacterium tuberculosis complex in West China Hospital, Sichuan University, analyze its drug resistance characteristics, and provide reference for the monitoring of drug-resistant tuberculosis.MethodsFrom January 2016 to March 2018, Mycobacterium tuberculosis drug susceptibility testing kit was used to detect the drug susceptibility of Mycobacterium tuberculosis culture-positive strains in Department of Laboratory Medicine, West China Hospital, Sichuan University. The tested drugs included four of the first-line anti-tuberculosis drugs: rifampicin, isoniazid, ethambutol, and streptomycin, and ten of the second-line anti-tuberculosis drugs: capreomycin, ofloxacin, ethionamide, p-aminosalicylic acid, levofloxacin, moxifloxacin, rifabutin, amikacin, kanamycin, and chlorine phenazine.ResultsA total of 130 patients (130 strains) were enrolled, including 82 newly diagnosed patients (82 strains) and 48 re-treated patients (42 strains). The drug resistance rate of the 130 patients was 37.69%. The drug resistance rate of the newly diagnosed patients (28.05%) was significantly lower than that of the re-treated patients (54.17%), and there was a statistical difference (χ2=8.794, P=0.003). The multi-drug resistance rate of the newly diagnosed patients (6.10%) was significantly lower than that of the re-treated patients (25.00%), and the difference was statistically significant (χ2=9.517, P=0.002). The resistance rate of isoniazid, rifampicin, and streptomycin in newly diagnosed patients (23.17%, 8.54%, and 7.32%, respectively) were significantly lower than those in the re-treated patients (45.83%, 41.67%, and 29.17%, respectively), and the differences were statistically significant (P<0.05). The resistance rate of ofloxacin, moxifloxacin, rifabutin and ethionamide in the newly diagnosed patients (9.76%, 8.54%, 7.31%, and 4.88%, respectively) were significantly lower than those in the re-treated patients (39.58%, 27.08%, 25.00%, and 22.92%, respectively), and the differences were statistically significant (P<0.05).ConclusionIt is necessary to strengthen the standardized treatment of patients with newly diagnosed tuberculosis, increase the treatment and management of re-treated tuberculosis patients, and prevent the generation and spread of drug-resistant patients, especially multidrug-resistant patients.
Objective
To probe the distribution and drug resistance of pathogens causing surgical site infection in patients after gynecologic operation, and provide reference for prevention and treatment.
Methods
Seventy patients with incision infection after gynecologic operation in West China Second University Hospital of Sichuan University from January 2010 to May 2015 were selected. Species of the pathogens from the submitted specimens and the results of the drug susceptibility testing were analyzed.
Results
Seventy-two strains of pathogens were isolated, including 36 strains (50.0%) of Gram-negative (G–) bacteria and 36 strains (50.0%) of Gram-positive (G+) bacteria. The main G– bacteria were Escherichia coli (36.1%) and Enterobacter cloacae (5.6%); the main G+ bacteria were Staphylococcus aureus (18.1%), Staphylococcus epidermidis (12.5%), and Enterococcus faecalis (8.3%). Escherichia coli showed low sensitivities to ampicillin, ceftriaxone, and gentamicin, with resistance rates of 76.9%, 61.5%, and 61.5%, respectively. Staphylococcus aureus showed low sensitivities to penicillin G, clindamycin, and erythromycin, with resistance rates of 92.3%, 69.2%, and 61.5%, respectively. Staphylococcus epidermidis showed low sensitivities to erythromycin, penicillin G, and ciprofloxacin, with resistance rates of 88.9%, 77.8%, and 77.8%, respectively. No carbapenem-resistant G– bacteria or vancomycin-resistant G+ bacteria were detected.
Conclusion
Postoperative surgical site infection is the most common nosocomial infection. The main bacteria related to postoperative incision infection in the gynecology department of the hospital are Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis, which become resistant to common antibiotics currently. Therefore more attention should be paid to bacterial isolation and drug susceptibility test results for rational use of antimicrobial drugs and effectiveness of the treatment to nosocomial infection.
Cryptococcosis, mainly caused by Cryptococcus neoformans/gattii species complexes, is a lethal infection in both immunosuppressive and immunocompetent populations. With the upgrade of detection methods and the increase of clinical knowledge, the incidence rate of cryptococcosis is increasing, and it has become one of the most important fungi threatening human health. In recent years, great progress has been made in this field, including the taxonomy and nomenclature of Cryptococcus spp., laboratory diagnostic methods and antifungal susceptibility tests, as well as the characteristics and treatments of cryptococcosis. This article reviews the above contents, in order to improve the clinical and laboratory understanding of the Cryptococcus spp., and realize the timely diagnosis and early treatment of cryptococcosis.
Objective To summarize the advancement of hereditary thrombophilia. Methods Relevant literatures about hereditary thrombophilia published recently domestic and abroad were reviewed and analyzed. Results The hereditary risk factors of venous thromboembolism were different among different races. In western population, the main risk factors were activated protein C resistance (APC-R) and mutation of factor V Leiden, methylene tetrahydrofolate reductase polymorphism (C677T) and prothrombin G20210A. While in Chinese population, the disorder of protein C system and hyperhomocysteinemia were the major genetic risk factor. The existence of multiple genetic risk factors increased the incidence of primary and recurrent venous thromboembolism. Conclusion Further study on the relations between the hereditary risk factors and thrombophilia will be very important for prediction and prevention of the venous thromboembolism.
Inappropriate and irrational prescription of antimicrobial agents has led to increasing bacterial resistance, which has become a major concern around the world. Clinical microbiology service provides a basis and guarantee for the rational application of antimicrobial agents and an important technical support for antimicrobial stewardship, and plays an important role in promoting the rational use of antimicrobial agents. This paper summarizes and evaluates the specific role and technical requirements of clinical microbiology service in the diagnosis of infectious diseases, rational application of antimicrobial agents, hospital infection control and training of medical staff, so as to provide a technical guidance for clinical microbiology service in the antimicrobial stewardship.
Objective
To investigate the pathogen distribution and drug resistance in ICU patients, provide reference for prevention of severe infection and empirical antibacterial treatment.
Methods
The patients admitted in ICU between January 2013 and December 2014 were retrospectively analyzed. The pathogenic data were collected including bacterial and fungal culture results, the flora distribution and drug resistance of pathogenic bacteria.
Results
A total of 2088 non-repeated strains were isolated, including 1403 (67.2%) strains of Gram-positive bacteria, 496 (23.8%) strains of Gram-negative bacteria, and 189 (9.0%) strains of fungus. There were 1324 (63.42%) strains isolated from sputum or other respiratory specimens, 487 (23.33%) strains from blood specimens, 277 (13.27%) strains from other specimens. The bacteria included Acinetobacter baumannii (17.2%), Klebsiella pneumoniae (14.8%), Pseudomonas aeruginosa (9.9%), C. albicans (6.3%), E. coli (5.6%), E. cloacae (5.4%), Epidermis staphylococcus (5.0%) and Staphylococcus aureus (4.7%). There were 15 strains of penicillium carbon resistant enterobacteriaceae bacteria (CRE) accounting for 2.3%, including 5 strains of Pneumonia klebsiella, 4 strains of E. cloacae. In 117 strains of E. coli, drug-resistant strains accounted for 86.4% including 85.5% of multiple drug-resistant strains (MDR) and 0.9% of extremely-drug resistant (XDR) strains. In 359 strains of Acinetobacter baumannii, drug-resistant strains accounted for 75.2% including 72.1% of XDR strains and 3.1% of MDR strains. MDR strains accounted for 10.6% in Pseudomonas aeruginosa. Detection rate of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase-negative Staphylococci (MRCNS) was 49.0% and 95.5%, respectively. There were 4 strains of vancomycin resistant Enterococcus faecalis. There were 131 (69.3%) strains of C. albicans, 23 (12.2%) strains of smooth candida. C. albicans was sensitive to amphotericin and 5-fluorine cytosine, and the resistance rate was less than 1% to other antifungle agents. The resistance rate of smooth ball candida was higher than C. albicans and nearly smooth candida, but still less than 15%.
Conclusions
The predominant pathogens in ICU was gram-negative bacteria. The top eight pathogenic bacteria were Acinetobacter baumanni, Klebsiella pneumoniae, Pseudomonas aeruginosa, C. albicans, E. coli, E. cloacae, Epidermis staphylococcus and S. aureus. Sputum and blood are common specimens. CRE accounts for 2.3%. Drug-resistant strains are most common in E. coli mainly by MDR, followed by Acinetobacter baumannii mainly by XDR, and least in Pseudomonas aeruginosa. C. albicans is the most common fungus with low drug resitance.
Objective To explore the association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and breast cancer risk and to investigate the interaction with menopausal status by meta-analysis. Methods Such databases as The Cochrane Libtary (Issue1, 2010), Pubmed, CBM, CNKI and WanFang Data were searched from the date of their establishment to October, 2010, and the case-control studies of MnSOD Val-9Ala polymorphism and breast cancer risk were collected according to the inclusion and exclusion criteria. Then the quality of the included trials was assessed and meta-analysis was performed by RevMan 4.2.10 software. Results A total of 14 studies involving 17 842 patients were included. The results of meta-analyses showed no significant relation between MnSOD Val-9Ala polymorphism and the breast cancer susceptibility (Val/Ala vs. Val/Val: OR=1.04, 95%CI 0.93 to 1.17; Ala/Ala vs. Val/Val: OR=1.12, 95%CI 0.95 to 1.33; Ala/Ala vs. Val/Ala+Val/Val: OR=1.06, 95%CI 0.93 to 1.20; Val/Ala+ Ala/Ala vs. Val/Val: OR=1.06, 95%CI 0.94 to 1.10). However, in the subgroup analysis, the breast cancer risk significantly increased for premenopausal women (Val/Ala+Ala/Ala vs. Val/Val: OR=1.15, 95%CI 1.01 to1.31). Conclusion This meta-analysis suggests that the MnSOD Val-9Ala polymorphism is not significantly associated with the breast cancer susceptibility, but it may increase the risk of breast cancer in the presence of menopausal state.
ObjectiveThrough Sequenom iPEX system analyzed the genetic susceptibility in patients with Medial temporal lobe epilepsy (MTLE) which screening hyperpolarization-activated cyclic nucleotide gated channel (HCN) subunit HCN1 and HCN2 single nucleotide polymorphism blood samples.
MethodsPatients with epilepsy who were diagnosed MTLE in our epileptic clinic from December 2013 to April 2016 were included in this study, total 143 cases. Healthy volunteers who received annual physical checkups were recruited to serve as controls total 120 cases. The group enter criterion according to a 2004 ILAE report mainly:①12~55 years old; ②attack forms:partial onset seizures or secondary tonic-closure-clonus attack, a common onset symptoms such as stomach gas rise feeling, sense of deja vu, automatism etc.; ③with or without febrile convulsions history; ④EEG displayed unilateral or bilateral temporal spike, sharp slow wave, or their spines slow-wave sample such as epilepsy wave; ⑤head MRI displayed hippocampal sclerosis. Exclusion criteria:①tumors; ②head MRI display focal cortical dysplasia (FCD). Using sequenom iPLEX technology platform to detect all the object of study of gene polymorphism sites total ten sites. All statistical tests were conducted using SPSS version 16.0.
Resultsall sites fulfilled Hardy-Weinberg genetic balance. The results showed that HCN1 rs17344896 C/T, rs6451973 A/G and HCN2 rs12977194 A/G three polypeptide sites associated with MTLE, with statistical differences(P < 0.05).
ConclusionHCN1 and HCN2 genetic suscepibility is one of possible mechanism of MTLE.
ObjectiveTo investigate the clinical settings, antibiotic susceptibilities, management and outcomes of streptococcal endophthalmitis. MethodsA retrospective observational case series study. Fifty six eyes of 56 patients diagnosed with streptococcal endophthalmitis in Eye & ENT Hospital, Fudan University from 2012 to 2022 were collected. The treatment followed the general principles of relevant guidelines, including pars plana vitrectomy (PPV), vitreous injection of antibiotics (IVI), vitreous injection of glucocorticoids and systemic application of antibiotics. The follow-up time was (11.9±17.0) months. Patients' clinical characteristics, pathogenic distribution and antibiotic susceptibilities, treatment and outcomes in their medical records were retrospectively collected and analyzed. ResultsAll 56 patients had monocular onset, including 39 (69.6%, 39/56) males and 17 (30.4%, 17/56) females, 26 (46.4%, 26/56) with left eyes involved and 30 (53.6%, 30/56) with right eyes involved. Their average age was (25.0±24.4) years. Ocular trauma was the leading cause of streptococcal endophthalmitis (73.2%, 41/56), followed by ophthalmic surgery (23.2%, 13/56) and endogenous infection (3.6%, 2/56). The streptococcal species included Streptococcus viridans (50.0%, 28/56), Streptococcus pneumoniae (18/56, 32.1%) and β-hemolytic Streptococcus (17.9%, 10/56). The susceptibility rates of Streptococcus to penicillin, cefatriaxone, vancomycin and levofloxacin were 66.0%, 57.1%, 94.1% and 92.4%, respectively. Patients received PPV+IVI and IVI as initial treatment were 49 eyes (87.5%, 49/56) and 7 eyes (12.5%, 7/56), respectively. Vitreous injection of glucocorticoids were performed in 17 eyes (30.4%, 17/56); and systemic antibiotics were applied in 52 cases (92.9%, 52/56). At the final follow-up, 47 eyes were recorded with visual acuity. Twenty (35.7%, 20/56) had best corrected visual acuity (BCVA)≥0.05 and 27 (48.2%, 27/56) had BCVA ＜0.05, of which 1 (1.8%, 1/56) had an eyeball enucleation. The etiology of endophthalmitis, streptococcal species, initial treatment with PPV, vitreous injection of glucocorticoids, and systemic antibiotics did not significantly affect patients' visual outcomes (P＞0.05). Timely visit to the hospital after the onset of symptoms (≤3 days) was significantly associated with achieving a final BCVA above 0.05 (P=0.025). ConclusionsOcular trauma was the primary cause of streptococcal endophthalmitis. Streptococcus viridans is the most common pathogenic bacterium. Streptococci had high susceptibility to vancomycin, but patients' visual outcomes were poor.
