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.
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.
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.
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 investigate the relationship between p53 codon 72 polymorphism and susceptibility to keloid. Methods The p53 genotypes were detected by polymerase chain reactionreverse dot blot(PCRRDB) and DNA direct sequencing among 15 healthy controls and 15 patients with keloid. Results The frequency of the Proallele(P=0.035) and Pro/Pro genotype(P=0.030) in patients was significantly higher than that in the controlls. There was no significant difference in the frequency of Pro/Arg and Arg/Arg genotypes between patients and controls. Conclusion The p53 gene codon 72 polymorphism may play a role in susceptibility to keloid.
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.
Magnetic induction method aims at the noninvasive detection of liver iron overload by measuring the hepatic magnetic susceptibility. To solve the difficulty that eddy current effects interfere with the measurement of magnetic susceptibility, we proposed an improved coil system based on the static field magnetization principle in this study. We used a direct current excitation to eliminate the eddy current effect, and a rotary receiver coil to get the induced voltage. The magnetic field for a cylindrical object due to the magnetization effect was calculated and the relative change of maximum induced voltage was derived. The correlation between magnetic susceptibility of object and maximum magnetic flux, maximum induced voltage and relative change of maximum induced voltage of the receiver coil were obtained by simulation experiments, and the results were compared with those of the theory calculation. The contrast shows that the simulation results fit the theory results well, which proves our method can eliminate the eddy current effect effectively.
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.
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.
Antimicrobial resistance is a rigorous health issue around the world. Because of the short turn-around-time and broad pathogen spectrum, culture-independent metagenomic next-generation sequencing (mNGS) is a powerful and highly efficient tool for clinical pathogen detection. The increasing question is whether mNGS is practical in the prediction of antimicrobial susceptibility. This review summarizes the current mNGS-based antimicrobial susceptibility testing technologies. The critical determinants of mNGS-based antibacterial resistance prediction have been comprehensively analyzed, including antimicrobial resistance databases, sequence alignment tools, detection tools for genomic antimicrobial resistance determinants, as well as resistance prediction models. The clinical challenges for mNGS-based antibacterial resistance prediction have also been reviewed and discussed.