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 investigate the correlation of ascorbic acid distribution and retinal susceptibility to iron toxicity of the retina.Methods Autoclaved iron particles of 5 mg and 15 mg were implanted into the vitreous cavities of 32 Spragu-Dawley (SD) rats and 9 rabbits, respectively. The retinal sections of rats and rabbits were examined after hemotoxylin-eosin (HE) staining. Apoptos is of rabbits′retinal neurons was investigated by TdT-mediated dUTP-biotin nick-end labeling (TUNEL). Chinoy′s method was used to observe the distribution of as corbic acid in the retinae of the 2 kinds of animals.Results In rats, histological and structural densification was observed only in the photoreceptor cells after implantation of the iron particles. In rabbits, however, histological and structural destruction as well as TUNEL-positive nuclei were observed in all neuronal layers of the retina 3 days after the implantation of the iron particles. Silver granules reduced by ascorbic acid from silver nitrate were observed only in the outer nuclear layer in normal rats retinae, while they were observed evenly throu ghout all layers of rabbits′retinae. Conclusions The suscept ibility of retina to iron toxicity is correlated to the distribution of ascorbic acid in retina. (Chin J Ocul Fundus Dis，2003，19：269-332)
Objective To detect the apoptosis of vascular endothelial cells and retinal pigment epithelial (RPE) cells in vitro induced by verteporfin-photodynamic therapy. Methods Cultured vascular endothelial cells and human RPE cells were incubated with verteporfin at a concentration of 1.0 mu;g/ml which was equivalent to the initial plasma level of verteporfin in clinical therapy. Each kind of cells were divided into 6 groups according to different time of incubation: 0, 5, 15, 30, 60, and 120 minutes group. After incubated, the cells were illuminated by the laser light with the maximum wavelength of absorption of verteporfin (wavelength: 689 nm, power density: 600 mW/cm2) with the power of 2.4 J/cm 2for 83 seconds. The percentage of cellular apoptosis was measured by flow cytometry 3 hours after PDT, and the measurement was repeated thrice. Results The proportion of cellular apoptosis 3 hours after PDT were 0.01plusmn;0.01, 0.25plusmn;0.02, 0.32plusmn;0.02, 0.41plusmn;0.04, 0.49plusmn;0.03 and 0.61plusmn;0.02, respectively in 0-120 minutes group of vascular endothelial cells; and 0.02plusmn;0.01, 0.22plusmn;0.01, 0.31plusmn;0.02, 0.38plusmn;0.03, 0.47plusmn;0.05 and 0.58plusmn;0.03 respectively in 0-120 minutes group of RPE cells. The proportion of cellular apoptosis of both kinds of the cells increased as the incubation time was prolonged. There was no significant difference of the percentage of cellular apoptosis between the accordant time groups in the two kinds of cells (P＞0.05). Conclusions Cellular apoptosis can be quickly induced by verteporfin-PDT both in human vascular endothelial cells and RPE cells; under the same condition in vitro, PDT has no obvious selection for the apoptosis of the two kinds of cells. (Chin J Ocul Fundus Dis, 2006, 22: 253-255)
Immunotherapy is an important treatment method in tumor therapy. Among them, programmed death-1/programmed death ligand-1 inhibitors are the immune preparations with mature application and great survival benefit at present. Programmed death-1/programmed death ligand-1 inhibitors brought better clinical benefits to patients with esophageal cancer and provided more favorable choice for the treatment of esophageal cancer. This article introduces the mechanism of action, application in esophageal cancer, and efficacy predictors of programmed death protein-1/programmed death protein ligand-1 inhibitors, aiming to provide a theoretical basis for the more rational use of programmed death protein-1/programmed death protein ligand-1 inhibitors in patients with esophageal cancer.
Objective To present the pooled quantitative evidence of clinical features and current treatments of programmed death 1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitor-associated vasculitis. Methods Medline, Embase, EBM, CNKI, WanFang Data and VIP databases were searched for all available studies reporting PD-1/PD-L1 inhibitor-associated vasculitis till March 23, 2022. We summarized and systematically reviewed the included articles, and analyzed the data results with descriptive statistical methods. Results A total of 38 articles were included, including 43 patients. The median age [median (minimum, maximum)] was 62 (31, 89) years, and most of patients were male (64.3%). Lung cancer was the most common tumor (47.6%). The median onset time of vasculitis [median (minimum, maximum)] was 12 (1, 120) weeks after medication. Small vasculitis (62.8%) and cutaneous vasculitis (26.7%) were the most common types. The Common Terminology Criteria for Adverse Events of vasculitis was predominantly 3-4 (83.7%). After diagnosed with vasculitis, PD-1/PD-L1 inhibitors were discontinued in 81.6% of patients, and glucocorticoid was administrated in 88.4% of patients. After treatment, 90.0% of patients had significant improvement during follow-up. However, when the discontinuation of PD-1/PD-L1 inhibitors, 55.6% of patients tumor progressions, and 35.0% of patients dead. Conclusions Special attention should be paid to the occurrence of vasculitis when using PD-1/PD-L1 inhibitors for malignant tumor therapies. Stopping PD-1/PD-L1 inhibitors and using glucocorticoid are the essential methods to treat vasculitis, but the above treatments may bring a high risk of tumor progression.
Objective To analyze detailed records of peasants’ hospitalization and compensation due to external causes of illness and death based on a county’s new rural cooperative medical scheme (NRCMS) from 2009 to 2010. Methods We systematically acquired the relevant record data of all inpatients via the management information system of NRCMS in this county. According to ICD-10 coding, we categorized and divided diseases into groups in basis of discharge diagnosis of each inpatient. Data were analyzed using SPSS 17.0. Results Inpatients due to external causes of illness and death who participated in the NRCMS accounted for 17.4% (7 913/45 432) of the total inpatient person-time in 2009 and 20.7% (12 568/60 643) in 2010. External causes of illness and death ranked the first in the hospitalization disease spectrum, which mainly were animal bites and accidental injuries. About 20% of their hospitalization expense was compensated by the NRCMS. More than half of the inpatients could be hospitalized for the treatment in the county township health center (59.6% in 2009 and 66.8% in 2010). Conclusion The result of this study indicates that external causes of illness and death including animal bites and accidental injuries have been a major health problem that peasants in this county face.
Lung cancer is the most frequent cancer and the leading cause of cancer death all around the world. Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapies have significantly improved the outcomes of non-small cell lung cancer (NSCLC) patients in recent years. However, the objective response rate in non-screened patients is only about 20%. It is very important to screen out the potential patients suitable for immunotherapy. Immunohistochemical staining of tumor tissue biopsies with PD-L1 antibodies can predict the therapeutic response to immunotherapy to some extent, but it still has some limitations. Recently some clinical studies have shown that PD-L1 expression in circulating tumor cells (CTC-PD-L1) is a potential independent biomarker and may provide important information for immunotherapy in NSCLC. This article will review technology for CTC-PD-L1 detection and the predictive value of CTC-PD-L1 for immunotherapy in NSCLC and review the latest clinical research progress.
In recent years, the incidence of primary liver cancer has been increasing, among which hepatocellular carcinoma (HCC) being the most common subtype. The treatment of early HCC is mainly surgery, but most patients are not diagnosed until the late stage of the disease. The treatment methods and effects are very limited and the prognosis is very poor. Although targeted therapy has prolonged the overall survival of patients with HCC, the overall efficacy is unsatisfactory. The emergence of immunotherapy has brought new therapeutic prospects for HCC. Immune checkpoint inhibitors, among which programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte associated antigen-4 are the representative immunological checkpoints, have attracted more attention. This article will introduce the application of immune checkpoint inhibitors in the treatment of advanced HCC, in order to provide a theoretical basis for the use of immune checkpoint inhibitors in the treatment of advanced HCC.
ObjectiveTo explore the risk factors of intraabdominal complications (IACs), pancreatic fistula (PF), and operative death after pancreatoduodenectomy (PD), and to provide a theoretical basis in reducing the rates of them. MethodsClinical data of 78 patients who underwent standard PD surgery in The Third People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from Jun. 2003 to Nov. 2011 were collected to analyze the influence factors of IACs, PF, and operative death. ResultsThere were 29 cases suffered IACs (13 cases of PF included), and 6 case died during 1 month after operation. Univariate analysis results showed that IACs and PF occurred more often in patients with soft friable pancreas, diameter of main pancreatic duct less than 3 mm, preoperative biliary drainage, no pancreatic duct stenting, and without employment of somatostatin (P < 0.05), no influence factor was found to be related to operative death. Multivariate analysis results showed that patients with no pancreatic duct stenting (OR=1.867, P=0.000), soft texture of remnant stump (OR=1.356, P=0.046), and diameter of main pancreatic duct less than 3 mm (OR=2.874, P=0.015) suffered more IACs; PF was more frequent in patient with no pancreatic duct stenting (OR=1.672, P=0.030), soft texture of remnant stump (OR=1.946, P=0.042), and diameter of main pancreatic duct less than 3 mm (OR=1.782, P=0.002);no independent factor was found to have relationship with operative death. ConclusionsSoft texture of remnant stump, diameter of main pancreatic duct less than 3 mm, and no pancreatic duct stenting are independent risk factors that should be considered in indications for PD surgery.
摘要:目的:探討急診醫療過程中意外死亡的原因,以引起廣大同道的重視。方法:對急診就診過程中24 h內死亡且符合入選標準的68例患者進行死亡原因分析,分析意外死亡常見的病因并探討死亡原因與就診之初臨床特征的關系。結果:68例意外死亡患者占同期死亡人數的4.39％,其中主動脈夾層31例,占同期死亡2％,占意外死亡的45.6％;心臟性猝死(急性心肌梗塞9例,心肌炎4例,)13例占同期死亡病人的0.84％,占意外死亡總數的191％;急性腦血管病(小腦出血5例,小腦梗塞8例)13例,占同期死亡人數的0.84％,占意外死亡總數的19.1％;重癥哮喘3例;不明原因死亡5例。臨床特征多為胸痛、胸背痛、頭痛、上腹痛、眩暈等為首發癥狀。結論:急診就診過程意外死亡發生取決于多種因素,由于這些病例癥狀多不典型,病情復雜多樣,臨床醫師極易忽視,臨床極易漏診、誤診,一旦發生,都將引起較大的醫療糾紛,耗費大量的人力物力。因此對急診就診過程中的不典型特征高度重視及時考慮主動脈夾層、心臟性猝死、急性腦血管病,早期治療,避免意外死亡的發生。Abstract: Objective: To explore the character of accidental death during treatment in emergency department, and get more attention of other emergent doctors to avoid death in emergent treatment.Methods: To analysis death causes of 68 qualified patients, who died within 24 hours after they went to hospital; To analysis familiar accidental death causes and the relationship between them and initial clinical signs. Results:These 68 accidental dead patients occupied 4.39% in all dead patients during the same period, including 31 cases of aortic dissecting hematoma(2% in all dead patients vs 45.6% in accidental dead patients); 13 cases of sudden cardiac death(0.84% in all dead patients vs 19.1% in accidental dead patients), which included 9 cases of acute myocardial infaction, 4 cases of myocarditis; 13 cases of acute cerebravascular diseases(0.84% in all dead patients vs 19.1% in accidental dead patients),which included 5 cases of cerebella hemorrhage and 8 cases of cerebella infarction; 3 severe asthma and other 5 cases without exact reasons. Clinical initial showed frequently the pain of breast, breast and back, head and upper belly, and dizzling. Conclusion: The happening of accidental death during treatment in emergent department was decided by many complicated factors. Because being nontypical and complicated, these factors always were ignored by clinical doctors, resulting wrong diagnosis or leaked diagnosis, which brought many clinical dissensions. Clinical dissensions cost much money and energy. So to know and pay more attention to these nontypical signs is very important to diagnosis aortic dissecting hematoma, sudden cardiac death and acute cerebravascular diseases, and is helpful to treat in time, and consequently the death was avoided.