This work demonstrates the clinical utility of multiplex dPCR to screen for multiple mutations simultaneously with a sensitivity sufficient to detect mutations in circulating DNA obtained by noninvasive blood collection.
Secondary degeneration in areas beyond ischemic foci can inhibit poststroke recovery. The cysteine protease Cathepsin B (CathB) regulates cell death and intracellular protein catabolism. To investigate the roles of CathB in the development of secondary degeneration in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after focal cerebral infarction, infarct volumes, immunohistochemistry and immunofluorescence, and Western blotting analyses were conducted in a distal middle cerebral artery occlusion (dMCAO) stroke model in adult rats. We observed marked neuron loss and gliosis in the ipsilateral thalamus after dMCAO, and the expression of CathB and cleaved caspase-3 in the VPN was significantly upregulated; glial cells were the major source of CathB. Although it had no effect on infarct volume, delayed intracerebroventricular treatment with the membrane-permeable CathB inhibitor CA-074Me suppressed the expression of CathB and cleaved caspase-3 in ipsilateral VPN and accordingly alleviated the secondary degeneration. These data indicate that CathB mediates a novel mechanism of secondary degeneration in the VPN of the ipsilateral thalamus after focal cortical infarction and suggest that CathB might be a therapeutic target for the prevention of secondary degeneration in patients after stroke.
Objective: Hepatocellular carcinoma (HCC) is a genetically and phenotypically heterogeneous tumor, and the prediction of its prognosis remains a challenge. In the past decade, studies elucidating the mechanisms that induce tumor cell pyroptosis has rapidly increased. The elucidation of their mechanisms is essential for the clinical development optimal application of anti-hepatocellular carcinoma therapeutics.Methods: Based on the different expression profiles of pyroptosis-related genes in HCC, we constructed a LASSO Cox regression pyroptosis-related genes signature that could more accurately predict the prognosis of HCC patients.Results: We identified seven pyroptosis-related genes signature (BAK1, CHMP4B, GSDMC, NLRP6, NOD2, PLCG1, SCAF11) in predicting the prognosis of HCC patients. Kaplan Meier survival analysis showed that the pyroptosis-related high-risk gene signature was associated with poor prognosis HCC patients. Moreover, the pyroptosis-related genes signature performed well in the survival analysis and ICGC validation group. The hybrid nomogram and calibration curve further demonstrated their feasibility and accuracy for predicting the prognosis of HCC patients. Meanwhile, the evaluation revealed that our novel signature predicted the prognosis of HCC patients more accurately than traditional clinicopathological features. GSEA analysis further revealed the novel signature associated mechanisms of immunity response in high-risk groups. Moreover, analysis of immune cell subsets with relevant functions revealed significant differences in aDCs, APC co-stimulation, CCR, check-point, iDCs, Macrophages, MHC class-I, Treg, and type II INF response between high- and low-risk groups. Finally, the expression of Immune checkpoints was enhanced in high-risk group, and m6A-related modifications were expressed differently between low- and high-risk groups.Conclusion: The novel pyroptosis-related genes signature can predict the prognosis of patients with HCC and insight into new cell death targeted therapies.
ObjectiveTo investigate prognostic factors of more than 10 years of survival for liver cancer patients after liver transplantation.MethodsFrom May 2000 to May 2007, a total of 134 liver cancer patients who underwent liver transplantation in the Department of Hepatobiliary Surgery, Peking University People’s Hospital, were continuously and retrospectively enrolled. The patients included 120 males and 14 females. There were 124 cases (92.5%) of primary hepatocellular carcinoma, 9 cases (6.7%) of cholangiocarcinoma, and 1 case of mixed hepatocellular carcinoma and cholangiocarcinoma. Patients with perioperative death were excluded. Follow-up was performed until May 31st, 2017 or the time of death. According to the data on postoperative survival time, patients were divided into a < 10 years group (81 cases) and a ≥ 10 years group (53 cases). Patients’ clinical data were recorded and analyzed, including alpha-fetoprotein (AFP) level (≥ 400 µg/L or < 400 µg/L), number of tumor lesions (< 3 or ≥ 3), tumor size (≤ 5 cm or > 5 cm), vascular tumor thrombus (large blood vessel or non-large blood vessel), and histological differentiation degree. The Kaplan–Meier method was used to calculate survival rates. The log-rank method was used to compare the differences between survival curves. The Cox proportional hazards regression model was used to perform multivariate analyses of possibly influential factors.Results(1) Follow-up was conducted with all 134 liver cancer patients after liver transplantation. The follow-up periods were 1–201 months, with a median of 18 (8.75, 132.5) months. The Kaplan–Meier survival analysis results showed that the 1-year, 3-year, 5-year, and 10-year cumulative survival rates were 70.3%, 48.6%, 46.8%, and 46.8%, respectively. (2) The differences in the age of patients, the incidence rate of AFP ≥ 400 µg/L, tumor histological differentiation, vascular tumor thrombi, tumor lesion size, and number of tumor lesions between two groups were all statistically significant (all P < 0.01). (3) The cumulative survival rates were different in AFP (log-rank χ2 = 13.428), histopathologic differentiation (log-rank χ2 = 33.592), large blood vessel tumor thrombi (log-rank χ2 = 36.470), tumor lesion size (log-rank χ2 = 39.835), and number of tumor lesions (log-rank χ2 = 47.016), and there were statistically significant differences between groups (all P < 0.01). (4) Multivariate Cox proportional hazards regression analyses showed that ≥ 3 tumor lesions [hazard ratio (HR) = 2.879, 95% confidence interval (CI) 1.566–5.422], tumor lesion size > 5 cm (HR = 2.682, 95% CI 1.382–5.366), large blood vessel tumor thrombi (HR = 1.831, 95% CI 1.010–3.341), and poor histological differentiation (HR = 2.150, 95% CI 1.372–3.394), were risk factors affecting the 10-year survival of liver cancer patients after liver transplantation (all P < 0.05).ConclusionTumor size, tumor number, large blood vessel tumor thrombi, and low tumor differentiation were all found to be independent risk factors affecting the 10-year survival rate after li...
Objectives: Our aim is to evaluate initial efficacy, safety, and durable response of eltrombopag in the treatment of Chinese children with chronic immune thrombocytopenia (cITP). Methods: This was a retrospective, single-center cohort study including 30 pediatric patients with cITP administered eltrombopag between 1 July 2017 and 1 January 2019. Patients with at least 12 weeks of eltrombopag treatment and available follow-up data were included. Initial response rate, durable response rate, bleeding events, and adverse events were assessed during the follow-up period. Results: The median duration of eltrombopag administration was 6 months (range 3-8 months). The initial response rate was 73.3%. Patients with megakaryocyte count ≥100/slide or Treg <4.5% were more likely to achieve initial response. The median follow-up period was 10 months (range 6-20 months). A total of 53.2% of pediatric patients had a durable response of up to 20 months. Patients with megakaryocyte count ≥100/slide and Treg<4.5% had more than 60% durable response rates compared with individuals with megakaryocyte count<100/slide and Treg≥4.5%, respectively. No serious bleeding events or serious adverse events occurred during the study period. Conclusion:Eltrombopag not only shows excellent initial response but also has continued efficacy and safety. Patients with megakaryocyte count ≥100/slide and Treg<4.5% achieve increased initial response and more frequent durable response.
Objectives. The study aimed to evaluate the preliminary effect and efficacy of auricular point acupressure (APA) on the quality of sleep in women with breast cancer who were undergoing chemotherapy. Sample & Setting. We conducted a randomized controlled trial on 68 patients with breast cancer who reported poor sleep quality based on the Pittsburgh Sleep Quality Index (PSQI) scores (>7). Methods & Variables. Participants were randomly assigned to an APA treatment group or a control group. Patients in the APA group had magnetic pellets attached to selected auricular points and were instructed to apply pressure to these points 4×/day for three consecutive weeks. We objectively measured sleep quality using the Actiwatch Spectrum and the PSQI at the baseline and postintervention. Statistical analyses of changes in sleep data were performed using the t-test, a rank-sum test, and analyses of covariance. Results. In patients treated with APA, the PSQI total score and sleep onset latency had significantly decreased, while the total sleep time and sleep efficiency had significantly increased. Although the total PSQI score differed between groups at the baseline, ANCOVA results showed that the APA group had a significantly lower total PSQI score. Conclusion. APA could be an inexpensive and effective approach to improving sleep quality and reducing sleep disturbance in patients with breast cancer. Further research needs a larger sample size to verify our findings.
Background: Microsatellite instability (MSI) remains a focus of interest in cancer research, but the characteristics of MSI in gastric cancer (GC) are ambiguous. Methods:In this retrospective study, we analyzed the prevalence of MSI and the expression of programmed death-ligand 1 (PD-L1) and cluster of differentiation 8 (CD8) cells in Chinese GC patients. A total of 393 GC patients admitted to two centers from January 2010 to December 2017 were enrolled. Results:The prevalence of MSI in this cohort was 3.4% and most frequently occurred in females, patients aged between 59 and 69 years, and patients at a lower clinical stage. All MSI GCs had CD8 expression but lacked PD-L1 expression, indicating that MSI was related to CD8 expression but irrelevant to PD-L1 expression. However, there was no significant difference in the expression of CD8/PD-L1 between MSI GC and microsatellite stable (MSS) GC. Kaplan-Meier survival curves revealed that patients with MSI had a significantly longer overall survival (OS) than patients with MSS.Conclusions: In Chinese GC patients, MSI frequently occurred in females, patients aged between 59 and 69, and patients with lower clinical stages. Patients with MSI-High (MSI-H) and MSI-Low (MSI-L) had a longer OS than patients with MSS. MSI was related to CD8 expression but irrelevant to PD-L1 expression.
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