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 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.
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.
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 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.
To assess the background field removal method usually used in quantitative susceptibility mapping (QSM), and to analyze the cause of serious artifacts generated in the truncated k-space division (TKD) method, this paper discusses a variety of background field removal methods and proposes an improved method to suppress the artifacts of susceptibility inversion. Firstly, we scanned phase images with the gradient echo sequence and then compared the quality and the speed of reconstructed images of sophisticated harmonic artifact reduction for phase data (SHARP), regularization enable of SHARP (RESHARP) and laplacian boundary value (LBV) methods. Secondly, we analyzed the reasons for reconstruction artifacts caused by the multiple truncations and discontinuity of the TKD method, and an improved TKD method was proposed by increasing threshold truncation range and improving data continuity. Finally, the result of susceptibility inversion from the improved and original TKD method was compared. The results show that the reconstruction of SHARP and RESHARP are very fast, but SHARP reconstruction artifacts are serious and the reconstruction precision is not high and implementation of RESHARP is complicated. The reconstruction speed of LBV method is slow, but the detail of the reconstructed image is prominent and the precision is high. In the QSM inversion methods, the reconstruction artifact of the original TKD method is serious, while the improved method obtains good artifact suppression image and good inversion result of artifact regions.
Quantitative susceptibility mapping (QSM) can provide tissue susceptibility information and has been adapted for clinical research and diagnosis. QSM of monkey brain in vivo at 9.4 T has not been demonstrated so far. In this study 9.4 T in vivo monkey brain QSM was performed with 200 μm isotropic high-resolution. It was found that the inherent singularity problem for QSM diverged significantly at ultra-high image resolution during regularization process and resulted in severe image artifacts. The K-space division (TKD) was applied to eliminate the artifacts, with an optimal threshold level between 0.2 and 0.3. High resolution QSM of monkey brain in vivo can thus provide a novel tool for brain research.
【Abstract】ObjectiveTo investigate the expressions of hTERT mRNA and BRCA1 protein and to analyze the correlation between these two factors in breast cancer. MethodsThe expression of hTERT mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). The expression of BRCA1 protein was examined by immunohistochemistry. ResultsThe positive rates of hTERT mRNA and BRCA1 protein were 72.1%（31/43） and 34.9%（15/43） in breast cancer tissue, were 5.0%(2/40) and 77.5%(31/40) in paracancerous breast tissue respectively. Significant difference existed between breast cancer tissue and paracancerous breast tissue (P＜0.05). Significant negative correlation existed between the expression of BRCA1 protein and expression of hTERT mRNA （r=-0.995, P＜0.01）. ConclusionThe expression of hTERT mRNA is upregulated in breast cancer, and expression of BRCA1 protein is downregulated in breast cancer. BRCA1 protein expression may be associated with expression of hTERT mRNA in breast cancer, which may be involved in the carcinogenesis of breast cancer.
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.
Objective To investigate association between –174C/G genetic polymorphism of interleukin-6 (IL-6) and susceptibility to gastric cancer by conducting a meta-analysis. Methods Such databases as PubMed, Embase, The Cochrane Library, Web of Science, CNKI, VIP, and Wanfang Data were searched from inception to January 2017 to collect case-control studies about the correlation between the –174C/G genetic polymorphism of IL-6 and susceptibility to gastric cancer. For the population genotype distributions of both the gastric cancer group and the control group, their odds ratios (OR) and 95% confidence intervals (CI) were taken as the effect indexes were applied to conduct meta-analysis in the homozygote model (CC vs. GG), heterozygote model (GC vs. GG), dominant model (CC+CG vs. GG), recessive model (CG+GG vs. CC), and allelic genetic model (C vs. G). Two reviewers independently screened the literatures, extracted the data, and evaluated the quality of the included studies. The meta-analysis was performed using Stata 12.0 software. Results Thirteen articles were included in the final meta-analysis, covering a total of 2 062 gastric cancer cases and 3 152 controls. The results of meta-analysis showed that there was no correlation between the IL-6 –174C/G genetic polymorphism and the risk of gastric cancer〔CC vs. GG: OR=1.33, 95% CI (0.92, 1.94); GC vs. GG: OR=1.32, 95% CI (0.96, 1.82); CC+CG vs. GG: OR=1.32, 95% CI (0.97, 1.80); CG+GG vs. CC: OR=0.89, 95% CI (0.67, 1.17); C vs. G: OR=1.22, 95% CI (0.98, 1.54)〕. But the results of the subgroup analysis showed there was a significant association between the IL-6 –174 C/G genetic polymorphism and the risk of gastric cancer in Asians〔CC vs. GG: OR=1.80, 95% CI (1.29, 2.50); GC vs. GG: OR=1.51, 95% CI (1.20, 1.90); CC+CG vs. GG: OR=1.60, 95% CI (1.30, 1.96); CG+GG vs. CC: OR=0.60, 95% CI (0.44, 0.83); C vs. G: OR=1.59, 95% CI (1.24, 2.03)〕. However, no association was found in Europeans〔CC vs. GG: OR=1.11, 95% CI (0.90, 1.39); GC vs. GG: OR=1.16, 95% CI (0.98, 1.37); CC+CG vs. GG: OR=1.12, 95% CI (0.96, 1.32); CG+GG vs. CC: OR=1.07, 95% CI (0.88, 1.30); C vs. G: OR=1.04, 95% CI (0.78, 1.41)〕 . Conclusion IL-6 –174C/G genetic polymorphism is associated with susceptibility to gastric cancer in Asians, which is not associated with susceptibility to gastric cancer in Europeans.