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Patients who underwent arterio-arterial graft (AAG) surgery at Beijing Haidian Hospital from March 2021 to December 2023 were prospectively included. A total of 13 cases (6 males and 7 females) aged (59±13) years were collected, with a dialysis history of 4.0 (1.8, 10.0) years. Nine cases of "bow"-type AAG and 4 cases of "α"-type AAG were established. The follow-up time was 10 (7, 16) months. The primary patency and secondary patency rates at 3, 6 and 12 months after surgery were 92.3% and 100%, 81.8% and 90.9%, 57.1% and 57.1%, respectively. Stenosis, thrombosis and infection occurred in 2, 5 and 2 cases, respectively. The current study indicates that AAG surgery is simple, minimally invasive, and has a high long-term patency rate. It can be used as a new type of vascular access for patients who fail to establish conventional dialysis access.
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Derivação Arteriovenosa Cirúrgica , Diálise Renal , Grau de Desobstrução Vascular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Derivação Arteriovenosa Cirúrgica/métodos , Idoso , Estudos ProspectivosRESUMO
Objective: To investigate the inplementation of cardiovascular surgery for congenital heart disease (CHD) in China. Methods: A cross-sectional study was carried out. The CHD cardiovascular surgery data collected by the Chinese Society of Extracorporeal Circulation from 2017 to 2021 in 31 provinces (autonomous regions/municipalities) of China were retrospectively reviewed, the implementation of CHD cardiovascular surgery in different provinces, regions, general/specialized hospitals, and different age groups (whether≤18 years old) were summarized, and the correlation analysis between the number of surgeries carried out in each province/region and the gross regional product and the number of the regional population was performed. Results: Between 2017 and 2021, the annual volume of CHD cardiovascular surgery was 77 120, 77 634, 81 161, 62 663 and 71 492, respectively, showing a decreasing trend. Meanwhile, the proportion of CHD patients aged≤18 years who underwent cardiovascular surgery also showed a downward trend, from 79.8% (61 557/77 120) in 2017 to 58.6% (41 871/71 492) in 2021 (P=0.027). The number of surgical cases varied greatly among different provinces, including 4 provinces with≥5 000 cases and 9 provinces with 2 000-5 000 cases. In the five years, the number of CHD cardiovascular surgeries in Central and East China was the largest, accounting for 41.1%-45.5% of the total surgical cases. The proportion of CHD surgery cases≤18 years old was the highest in Southwest China (69.7%-87.4%) and the lowest in Northeast China (28.2%-68.9%). Except for 2021, the number of cases carried out by each region between 2017 and 2020 was correlated with the gross regional product (r=0.929, 0.929, 0.893 and 0.964, respectively, all P<0.05) and the population (r=0.821, 0.893, 0.821 and 0.857, respectively, all P<0.05). Hospitals that performed more than 100 operations (20.5%±1.2% of the total number of hospitals) completed 86.2%±1.2% of the total number of operations in China during the 5-year period. In 2017 and 2021, the number of CHD cardiovascular surgeries preformed in children's/women's and children's specialized hospitals accounted for 24.3% (18 772/77 120) and 23.8% (17 012/71 492) of the total number of cases in China, respectively. Conclusions: From 2017 to 2021, the number of cardiovascular surgery for CHD decreases slightly, but the proportion of surgery for adult CHD patients increases significantly.There is a strong correlation between the number of CHD operations in each region and their economic development status. The scale of CHD cardiovascular surgery performed in children's hospitals/women's and children's hospitals accounts for about a quarter of the total volume in China.
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Cardiopatias Congênitas , Humanos , Cardiopatias Congênitas/cirurgia , China , Inquéritos e Questionários , Procedimentos Cirúrgicos Cardiovasculares/tendências , Adolescente , Criança , Procedimentos Cirúrgicos CardíacosRESUMO
OBJECTIVE: To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey (dmPAG) in regulating excessive defensive behaviors in mice with post-traumatic stress disorder (PTSD). METHODS: Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno- associated viral vectors (rAAV2/9-CaMKII-mCherry, rAAV2/9-CaMKII-hM3Dq-mCherry and rAAV2/9-CaMKII-hM4Di-mCherry) into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons, followed 2 weeks later by PTSD modeling by single prolonged stress. The looming test, response to whisker stimulation test and contextual fear conditioning (CFC) test were used to observe changes in defensive behaviors of the PTSD mice. The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining. RESULTS: Compared with the control mice, the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest, response scores of defensive behaviors and freezing time (all P<0.01). Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors. Activation of the glutamatergic neurons in the dmPAG (in PTSD hM3Dq group) did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice, whereas inhibiting the glutamatergic neurons in the dmPAG (in PTSD hM4Di group) caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice (P<0.05 or 0.01). CONCLUSION: Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.
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Substância Cinzenta Periaquedutal , Transtornos de Estresse Pós-Traumáticos , Ratos , Camundongos , Masculino , Animais , Substância Cinzenta Periaquedutal/fisiologia , Ratos Wistar , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Camundongos Endogâmicos C57BL , NeurôniosRESUMO
A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation. RNA interference-mediated silencing of Ty expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington's disease model, and expanded the replicative lifespan of yeast in a partially Hsp104-dependent manner. The results are in line with recent data demonstrating that VLPs might act as aging factors in mammals, including humans, and extend these findings by linking VLPs to a toxic accumulation of protein aggregates and raising the possibility that they might negatively influence neurological disease progression.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Humanos , Animais , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Agregados Proteicos , Longevidade , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Replicação do DNA , Mamíferos/metabolismoRESUMO
Objective: To explore the value of the aMAP risk score (age, male, albumin-bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors. Results: Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group (P=0.001). Conclusions: The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..
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Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Ablação por Cateter/métodos , Recidiva Local de Neoplasia/cirurgiaRESUMO
Objective: To screen the differential metabolites and metabolic pathways in silicosis model by analyzing plasma metabolomics of silicosis rats. Methods: In May 2021, twenty male SD rats were randomly divided into control group (C), 1-week silicosis group (S1W), 2-week silicosis group (S2W) and 4-week silicosis group (S4W), with 5 rats in each group. Rats were intratracheally instillated with 1ml crystalline SiO(2) suspension (50 mg/ml) or normal saline and were sacrificed after 1 week, 2 weeks and 4 weeks, HE staining was used to observe the lung pathology of rats. The plasma samples were analyzed by UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze their lipid enrichment. Results: HE results showed that nodules formed in the silicosis model group, and with the extension of time, nodules gradually increased and alveolar structure was gradually destroyed. Metabolomics screened out 14 differential metabolites in S1W, 24 in S2W, and 28 in S4W, and found that the differential metabolites were mainly enriched in the metabolism of glycerophospholipid metabolism, fatty acid degradation, Glycosylphosphatidylinositol (GPI) -anchor biosynthesis, fatty acid elongation and other metabolic pathways. Conclusion: There are significant changes in plasma lipid metabolites in silicosis rat models.
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Dióxido de Silício , Silicose , Masculino , Animais , Ratos , Ratos Sprague-Dawley , Metabolômica , Ácidos Graxos , LipídeosRESUMO
Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage â ¢-â £ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.
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Linfoma de Célula do Manto , Masculino , Adulto , Humanos , Idoso , Linfoma de Célula do Manto/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Medula Óssea/patologia , Fatores de RiscoRESUMO
Objective: To explore risk factors associated with in-hospital mortality in patients requiring extracorporeal membrane oxygenation (ECMO) in the perioperative period of heart transplantation. Methods: The data of ECMO cases in the perioperative period of heart transplantation from the Chinese Society of Extracorporeal Life Support (CSECLS) between January 2017 and December 2021 were retrospectively analyzed. These patients were divided into the survival group and non-survival group according to their outcomes at discharge. The demographics, indications and complications of ECMO between the two groups were compared, and the related risk factors of poor prognosis were analyzed. Results: A total of 77 patients were included in the study, including 67 males and 10 females, with a median age [M(Q1, Q3)] of 48 (36, 59) years. Sixty-three patients (81.8%) were successfully withdrawn from the ECMO and 46 patients (59.7%) survived to discharge. The median ECMO time was 139 (92, 253) hours. Compared with the survival group, the non-survival group (n=31) had more patients with chronic kidney disease before surgery [22.6% (7/31) vs 4.3% (2/46), P=0.034], and a higher proportion of continuous renal replacement therapy (CRRT) during ECMO [74.2% (23/31) vs 50.0% (23/46), P=0.034]. Moreover, the non-survival group had longer duration of extracorporeal circulation [262 (195, 312) vs 201 (155, 261) min, P=0.056] and higher lactate value in the first 24 hours of ECMO support [2.7 (2.1, 4.7) vs 2.3 (1.4, 3.8) mmol/L, P=0.060], but the differences were not statistically significant. Multivariate logistic regression analysis showed that perioperative application of CRRT was an independent risk factor for poor prognosis in ECMO patients during heart transplantation (OR=19.345, 95%CI: 1.209-309.440, P=0.036). Conclusion: CRRT treatment during ECMO is a risk factor for in-hospital mortality in patients undergoing heart transplantation.
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Oxigenação por Membrana Extracorpórea , Transplante de Coração , Feminino , Masculino , Humanos , Mortalidade Hospitalar , Estudos Retrospectivos , Período Perioperatório , Ácido Láctico , Fatores de RiscoRESUMO
OBJECTIVE: The study aimed to analyze the efficacy of aparatinib and carrilizumab combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 150 patients with primary HCC admitted to our hospital from March 1, 2019, to March 1, 2022 was chosen and randomized as the control and treatment group. The control group went through TACE treatment, and the treatment group experienced apatinib + karilizumab + TACE treatment. The near and long-term efficacy of the two groups were compared. The total survival time (OS), time to progression (TTP), and hospital costs were compared between the two groups. Fasting venous blood was collected before and one month after treatment in the two groups, and liver and kidney functions were tested using automatic biochemical analyzer. The levels of CD3+, CD4+ and CD8+ were detected by flow cytometry, and CD4+/CD8+ was calculated. The levels of cysteinyl aspartate specific protease-8 (Caspase-8), vascular endothelial growth factor (VEGF) and alpha fetoprotein (AFP) were detected by enzyme-linked immunosorbent assay (ELISA). The patients' conditions were closely observed and the adverse reaction rates of diarrhea, hand foot syndrome, bone marrow suppression, proteinuria, fever and pain were compared between the two groups. RESULTS: The disease control rate (DCR) of short-term treatment in the treatment group was 97.33%, which was much higher than 88.00% in the control group. The survival ratios of the treatment group in September and December were 65.33% and 42.67% respectively, which were also much higher than 48.00% and 20.00% in the control group (p < 0.05). The TTP and OS of patients in the treatment group were significantly longer than those in the control group (p < 0.05), and the hospital expenses were significantly higher than those in the control group (p < 0.05). The levels of liver function indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were largely decreased in both groups after treatment, and more significant difference was detected in the treatment group (p < 0.05). Renal function between the two groups had no significant difference after treatment (p > 0.05). After treatment, the levels AFP and VEGF were strongly decreased and the level of Caspase-8 was markedly increased in both groups, and the treatment group had lower levels of AFP and VEGF and higher level of Caspase-8 than the control group (p < 0.05). The CD3+ and CD4+/CD8+ levels in two groups were dramatically elevated after treatment, and the treatment group had much higher CD3+ and CD4+/CD8+ levels than the control group (p < 0.05). There was no statistically significant difference in the rates of adverse reactions such as diarrhea, hand-foot syndrome, bone marrow suppression, proteinuria, fever, and pain between the two groups (p > 0.05). CONCLUSIONS: The combination of apatinib and carrilizumab with TACE had better near- and long-term efficacy in the treatment of primary HCC by effectively inhibiting tumor vascular regeneration, inducing tumor cell apoptosis, and improving patients' liver function and immune function with higher safety, which could be widely used in clinical practice.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas , Caspase 8 , Fator A de Crescimento do Endotélio Vascular , Terapia Combinada , DiarreiaRESUMO
We present the electronics developed for a sensitive and stable atomic vector magnetometer used in low-field detections. These electronics are required to be not only highly reliable and sophisticated for signal processing but also compact in size and low cost in resource consumption for the purpose of miniaturization. In addition, this magnetometer works with multiple modulations, where the interferences between harmonics of modulation fields often disturb the long-term measurements of the sensor. We work out a robust method to eliminate this problem by choosing the modulation frequencies with separations to match the minimum response points of the low-pass filters used in the demodulation processes. We validate the performance of the electronics and the frequency-selection scheme of the modulation fields with corresponding experimental results.
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The recently updated "Guidelines for the Prevention and Treatment of Chronic Hepatitis B" in China have brought about significant changes. The new treatment indications almost mandate the implementation of a Treat-all strategy for the chronically HBV-infected population in China. While simultaneous negativity for hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA has long been an accepted criterion for treatment discontinuation, there has been controversies over the initiation of treatment criteria starting with HBsAg and HBV DNA positivity. Despite the inconsistent treatment criteria, the academic community has started supporting treat-all strategies in recent years due to the decreasing cost of treatment, prolonged management duration, and growing evidence of poor outcomes in untreated populations. Therefore, this update to the Chinese HBV guidelines represents a new direction that suggests "The greatest truths are the simplest." However, in the process of rolling out the Treat-all strategy, we must remain cautious of possible issues arising from the new strategy. Among them, the problem of partial response or low-level viremia following treatment may become more prominent due to the inclusion of a significant number of patients with normal or low levels of alanine transaminase. As existing evidence suggests that low-level viremia increases the risk of HCC in patients, it is essential to monitor and explore optimal therapeutic options for these patients.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Antígenos de Superfície da Hepatite B , Viremia , DNA Viral , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Antígenos E da Hepatite BRESUMO
Objective: To observe the clinical efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with chemotherapy as first-line treatment for EGFR mutant advanced non-small cell lung cancer (NSCLC). Methods: It was a retrospective, single-arm real-world study and a total of 39 patients with stage â ¢B to â £ EGFR mutant NSCLC diagnosed in Cancer Hospital of Chinese Academy of Medical Sciences from July 2018 to December 2020 were collected. There were 16 males and 23 females, the age ranged from 25 to 73 years, with a median age of 53 years. All patients received EGFR-TKIs synchronously combined with pemetrexed and platinum-containing chemotherapy for 4-6 cycles as first-line treatment, followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse reactions were evaluated. Median follow-up time was 18.6 months (95%CI: 16.2-21.0 months). The Kaplan-Meier method was used for survival analysis. Results: The ORR was 61.5% (24/39), the DCR was 94.9% (37/39) and the median PFS was 16.4 months (95%CI: 12.1-20.7 months). The main adverse reactions were liver function injury (59.0%, 23/39), myelosuppression (43.6%, 17/39), skin reaction (25.6%, 10/39), gastrointestinal reaction (17.9%, 7/39), fatigue (12.8%, 5/39) and kidney injury (5.1%, 2/39). Most of the patients had grade 1-2 adverse reactions, and the rate of grade 3 adverse events were 12.8%(5/39), which were effectively alleviated after symptomatic support treatment, no grade 4 serious adverse events occurred. Conclusion: EGFR-TKIs synchronously combined with chemotherapy followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy has a certain therapeutic effect and fairly good safety, which can prolong PFS in patients with EGFR mutated advanced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Pemetrexede/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB/genética , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The incidence and mortality of HCC in China account for approximately 50% of all cases worldwide. Low early diagnosis rate and high postoperative recurrence rate are two major causes for poor 5-year survival rate of HCC patients in China. At present, multiple problems such as low performance and compliance of screening technology and lack of effective markers for predicting postoperative recurrence, remain to be resolved. Due to the simplicity and accuracy, new molecular markers, such as liquid biopsy, are expected to serve as supplementary tools to traditional screening and early warning approaches, thereby realizing early detection and accurate treatment of HCC. In this article, research progress upon the clinical application of liquid biopsy in early screening and prediction of postoperative recurrence of HCC was reviewed, and prospects the future research.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Carcinoma Hepatocelular/patologia , Humanos , Biópsia Líquida , Neoplasias Hepáticas/patologia , Programas de Rastreamento , Recidiva Local de NeoplasiaRESUMO
Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.
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Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/patologia , Prognóstico , Receptor de Morte Celular Programada 1 , Estudos RetrospectivosRESUMO
OBJECTIVE: Sepsis has a high morbidity and mortality and is prone to cause acute kidney injury (AKI). Here, we aimed to demonstrate the function and molecular mechanism of microRNA-543 (miR-543) in septic AKI. MATERIALS AND METHODS: MiR-543 inhibitor or NC was transfected into LPS-treated HK-2 cells to observe lipopolysaccharide (LPS)-induced inflammation and apoptosis. The detection of inflammation and apoptosis of HK-2 cells relies on Western blot, quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: MiR-543 expression was increased in LPS-treated HK-2 cells. By transfecting miR-543 inhibitor into HK-2 cells, miR-543 expression was dramatically reduced. The downregulation of miR-543 remarkably inhibited the inflammation and apoptosis, which was manifested by the reduction of inflammatory cytokines (TNF-α, IL-6, IL-1ß), the reversal of apoptosis-related proteins expression (Bcl-1, Bax), the increase of cell viability and the decrease of the proportion of apoptotic cells. The result of Luciferase activity assay demonstrated that miR-543 directly targets Bcl-2. CONCLUSIONS: MiR-543 expression was increased in LPS-treated HK-2 cells, and silencing miR-543 could inhibit LPS-induced inflammation and apoptosis in HK-2 cells via targeting Bcl-2.
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Injúria Renal Aguda , MicroRNAs , Sepse , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose , Feminino , Humanos , Inflamação , Lipopolissacarídeos/toxicidade , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Sepse/complicações , Sepse/metabolismoRESUMO
OBJECTIVE: Accumulating evidence has been revealed that miR-590 is involved in the progression and carcinogenesis of various cancers. However, the molecular mechanism of miR-590 in non-small-cell lung cancer (NSCLC) remains unclear. METHODS: Quantitative reverse transcription-PCR (qRT-PCR), western blot, MTT, and transwell assay were applied to investigate the functional role of miR-590 in this study. Dual luciferase reporter assay was utilized to investigate the interaction between YAP1 and miR-590 expression. Cells transfected with miR-590 mimic or inhibitor were subjected to western blot to investigate the role of Wnt/ß-catenin signaling in NSCLC modulated by miR-590. RESULTS: MiR-590 was down-regulated in NSCLC tissues and cells. Kaplan-Meier analysis found that the higher expression of miR-590 in NSCLC patients, the more improved survival rate of NSCLC patients. Over-expression of miR-590 inhibited NSCLC cell proliferation, migration, and invasion. Moreover, increasing miR-590 suppressed Yes-associated protein 1 (YAP1) expression and inhibited the Wnt/ß-catenin pathway in NSCLC cells. Furthermore, miR-590 was negatively correlated with YAP1 expression. CONCLUSION: These findings demonstrated that the miR-590/YAP1 axis exerted an important role in the progression of NSCLC, suggesting that miR-590 might be the appealing prognostic marker for NSCLC treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/fisiologia , Via de Sinalização Wnt/fisiologia , Proteínas de Sinalização YAP/fisiologia , Progressão da Doença , Humanos , Células Tumorais CultivadasRESUMO
BACKGROUND: To accurately identify ABO blood typing in pre-transfusion testing is very important to ensure blood transfusion safely, which is a major responsibility of blood station. METHODS: Eighty-one blood donors samples with ABO blood group typing discrepancy was collected among 61952 donor samples in our blood station from January 2019 to July 2020. Blood group serological method was used to detect ABO blood group. DNA Sequencing was used to determine the genotype. The antibody screening test detects antibodies other than ABO. RESULTS: In total, 61,952 donor samples were analysed for ABO typing discrepancies. The incidence among blood donors was 0.13% (81/61952). The most common reason of ABO typing discrepancies was due to specific antibody or non-specific agglutination (54.32%, 44/81), mainly anti-M antibody, cold autoantibody, anti-D antibody, anti-N antibody and anti-Lea antibody. The major cause of forward typing discrepancies among blood donors was ABO subgroups (25.93%, 21/81), including 10 cases of A subtype (1 case of A2, 2 cases of A3, 2 cases of Ax, 3 cases of AxB, 1 case of Ael, 1 case of Ahm), 6 cases of B subtype (2 cases of B3, 1 case of Bel, 3 cases of AB3), 2 cases of B subtype (A), 1 case of cisAB, and 2 cases of acquired B. The serum antibody was weakened in 16 cases (19.75%). CONCLUSIONS: The blood types should be correctly identified by combining serology with gene sequencing to ensure the safety of clinical blood transfusion, when the forward and reverse typing discrepancies among the blood donors.
Assuntos
Sistema ABO de Grupos Sanguíneos , Tipagem e Reações Cruzadas Sanguíneas , Sistema ABO de Grupos Sanguíneos/genética , Doadores de Sangue , Genótipo , Humanos , Biologia Molecular , Estudos RetrospectivosRESUMO
Objective: To investigate the changes of occlusal delay time, percentage of occlusal force and patients' subjective satisfaction of masticatory function for single implant crown in one year after the application of space reserved occlusion design. To provide data support and suggestions for clinical occlusion design. Methods: Patients who had received single posterior dental implant restoration in Department of Prosthodontics, Capital Medical University School of Stomatology from January 2019 to December 2019 were selected. At 0.5, 3, 6 and 12 months after restoration, the T-scan â ¢ occlusal analyzer was used to detect and record the initial occlusal contact time of the natural tooth and implanted single crown, the occlusal force percentage of single implant prosthesis and corresponding tooth on the contralateral side (control teeth) on the contralateral side (control teeth) were also recorded. Subjective satisfaction with the masticatory function of the implants was recorded using visual analogue scale (VAS). The changes of occlusal delay time (the difference of the initial occlusal time between implant restoration and the natural teeth), percentage of occlusal force and patients' subjective feeling with time were analyzed. All data were analyzed by repeated measurement analysis of variance, bilatteral P<0.01 was considered statistically significant. Results: A total of 48 patients aged (36.8±8.4) years (23 males, 25 females, aged 23-50 years) were recruited. The occlusal delay time at 0.5 months was 0.15 (0.08, 0.20) s, at 3 months was 0.11 (0.06, 0.16) s, at 6 months was 0.07 (0.03, 0.13) s and at 12 months was 0.06 (0.03, 0.10) s. The occlusal delay time was shortened at every two time points, and the occlusal force percentage of the implant crown increased significantly. The percentage of occlusal force of implant prosthesis at 0.5 months was (7.7±4.8)%, at 3 months was (10.6±5.9)%, at 6 months was (12.3±6.2)% and at 12 months was (13.2±6.7)%. The most significant change was during the period of 0.5-3 months. At 0.5 months, the occlusal force of implant prosthesis was significantly lower than that of control teeth (14.3±6.5)% (P<0.01). The VAS score at 0.5 months was (7.06±1.64) and was (8.71±0.74) at 12 months. The score was increased and the difference was statistically significant from 3 month to 12 month (P<0.01). Conclusions: The change of occlusal force percentage of single posterior dental implant is most obvious within 3 months after restoration. The occlusal condition should be reexamined and adjust occlusal after 3 months of implant restoration as appropriate.