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The influence of acute glycemic variability (GV) on early outcomes of patients after cardiac surgery remains not fully determined. We performed a systematic review and meta-analysis to evaluate the association between acute GV and in-hospital outcomes of patients after cardiac surgery. Relevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library, and Web of Science. A randomized-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. Nine cohort studies involving 16 411 patients after cardiac surgery were included in this meta-analysis. Pooled results showed that a high acute GV was associated with an increased risk of major adverse events (MAE) during hospitalization for patients after cardiac surgery [odds ratio [OR]: 1.29, 95% CI: 1.15 to 1.45, p<0.001, I22=38%]. Sensitivity analysis limited to studies of on-pump surgery and GV evaluated by coefficient of variation of blood glucose showed similar results. Subgroup analysis suggested that a high acute GV was related to an increased incidence of MAE in patients after coronary artery bypass graft, but not for those after isolated valvular surgery (p=0.04), and the association was weakened after adjustment of glycosylated hemoglobin (p=0.01). Moreover, a high acute GV was also related to an increased risk of in-hospital mortality (OR: 1.55, 95% CI: 1.15 to 2.09, p=0.004; I22=0%). A high acute GV may be associated with poor in-hospital outcomes in patients after cardiac surgery.
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Procedimientos Quirúrgicos Cardíacos , Hiperglucemia , Humanos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Glucemia , Hemoglobina Glucada , Hospitalización , Hiperglucemia/etiologíaRESUMEN
In mild acidic or alkaline solutions with limited buffer capacity, the pH at the electrode/electrolyte interface (pHs) may change significantly when the supply of H+ (or OH-) is slower than its consumption or production by the electrode reaction. Buffer pairs are usually applied to resist the change of pHs during the electrochemical reaction. In this work, by taking H2X â 2H+ + X + 2e- under a rotating disk electrode configuration as a model reaction, numerical simulations are carried out to figure out how pHs changes with the reaction rate in solutions of different bulk pHs (pHb in the range from 0 to 14) and in the presence of buffer pairs with different pKa values and concentrations. The quantitative relation of pHs, pHb, pKa, and concentration of buffer pairs as well as of the reaction current density is established. Diagrams of pHs and ΔpH (ΔpH = pHs - pHb) as a function of pHb and the reaction current density as well as of the jmax-pHb plots are provided, where jmax is defined as the maximum allowable current density within the acceptable tolerance of deviation of pHs from that of pHb (e.g., ΔpH < 0.2). The j-pHs diagrams allow one to estimate the pHs and ΔpH without direct measurement. The jmax-pHb plots may serve as a guideline for choosing buffer pairs with appropriate pKa and concentration to mitigate the pHs shift induced by electrode reactions.
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AIMS: Molecular profiling of hepatocellular carcinoma (HCC) has helped identify actionable genomic alterations that could guide therapeutic decision-making and clinical trial enrollment. However, in clinical practice, next-generation sequencing (NGS) is not extensively used in routine clinical care to identify patients with HCC who are likely to benefit from genome-directed targeted therapies. METHODS: Here, we describe the case of a 66-year-old man with advanced HCC. After rapid progression on transarterial chemoembolization, the tissue sample obtained from biopsy was subjected to NGS to verify whether precision therapy was an option. RESULTS: Our analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response. CONCLUSIONS: Our case report suggests NGS could help identify patients with high MET amplification in HCC who were likely to benefit from MET inhibitors; moreover, this requires further investigation in clinical trials.
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Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet-to-lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single-center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)-19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single-center case series of the 30 hospitalized patients with confirmed COVID-19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID-19.
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COVID-19/sangre , COVID-19/mortalidad , Recuento de Linfocitos , Recuento de Plaquetas , SARS-CoV-2 , Adulto , Anciano , Biomarcadores , COVID-19/diagnóstico , COVID-19/virología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/mortalidad , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XRESUMEN
The control of toxic chromate (Cr6+) formation is still a significant challenge in solid fuel combustion. In particular, the mechanism of chromium transformation from Cr3+ to chromate or other unoxidized forms remains unclear. The present study confirms the formation of a significant unoxidized Cr-containing compound CaCr2O4(Cr3+) during solid fuel combustion. Experiments were conducted, for the first time, to clarify the mechanism of CaCr2O4 oxidation, which is quite different from Cr2O3 oxidation. The findings demonstrate that CaCr2O4 was formed at temperatures above 1200 K, through rapid decomposition of CaCrO4 or slow and direct interaction between CaO and Cr2O3. Compared to Cr2O3, CaCr2O4 could be oxidized at lower temperatures under the influence of free CaO. In the absence of free CaO, the oxidation of CaCr2O4 was minimal; however, in the presence of CaSO4, calcium in the form of CaCr2O4 participated in the oxidation of CaCr2O4. Thus, chromium in the form of CaCr2O4 was more likely to be oxidized when CaCr2O4-containing fly ash was reheated. Fortunately, CaCr2O4 showed slight basicity on the surface, allowing it to react with acidic gases. Accordingly, measures were proposed to suppress the oxidation of CaCr2O4 by stimulating the reactions between CaCr2O4 and acidic substances, like SO2 and Si/Al-compounds. These compounds competed with chromium at high temperatures to react with calcium in the fly ash and in CaCr2O4. As a result, the unoxidized chromium was transformed into highly stable Cr2O3 or Ca3Cr2 (SiO4)3.
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Cromo , Ceniza del Carbón , Gases , Oxidación-Reducción , TemperaturaAsunto(s)
Adenocarcinoma del Pulmón/genética , Quinasa de Linfoma Anaplásico/genética , Fusión Génica , Neoplasias Pulmonares/genética , Esfingomielina Fosfodiesterasa/genética , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Trop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. This study aimed to explore the mutational characteristics and significance of Trop2 in breast cancer (BC). METHODS: Patients diagnosed with BC (n = 77) were enrolled to investigate expression level and clinical characteristics of Trop2. Database of cBioPortal and Kaplan-Meier Plotter were used to evaluate the effects of Trop2 (TACSTD2) genomic ateration and mRNA expression levels on disease-free survival (DFS) and relapse-free survival (RFS), respectively. Based on next generation sequencing analysis, the Trop2 mutation characteristics of BC patients were deeply depicted. In addition, Trop2 expression, mutation and methylation signature associated with Trop2 mutations were analyzed. RESULTS: Trop2 mutation and high expression of Trop2 were predictive biomarker for shorter DFS and RFS in BC. The positive rate of Trop2 expression in these 77 BC patients was 96.1% (74/77). Based on the Trop2 expression level, the patients were classified into Trop2 negative group, medium expression group and high expression group. The mutation frequencies of MAP3K1, NOTCH2, PTEN and MAGI2 were significantly higher in Trop2 medium expression group than high expression group. Moreover, we investigated the effect of the Trop2 mutations on other genes, including co-expressed genes, differentially mutated genes, differentially expressed genes, gene methylation and phosphorylation. We found that MED8, DPH2, KDM4A, EBNA1BP2, USP1, IPO13, CGAS, PRKAA2, NCOA7, ASCC3 and ABRACL were differentially expressed, mutated and methylated between Trop2 mutation group and wild group. CONCLUSION: MAP3K1, NOTCH2, PTEN and MAGI2 mutations were significantly different between Trop2 medium expression and Trop2 high expression BC patients. The effects of Trop2 mutation on the expression, variation, methylation, and phosphorylation of other genes were comprehensively revealed. High expression level of Trop2 and Trop2 mutation were predictive biomarker for poor prognosis and targeted therapy in BC.
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The lockdowns implemented during the coronavirus disease 2019 (COVID-19) pandemic provide a unique opportunity to investigate the impact of emission sources and meteorological conditions on the trans-boundary transportation of black carbon (BC) aerosols to the Tibetan Plateau (TP). In this study, we conducted an integrative analysis, including in-situ observational data, reanalysis datasets, and numerical simulations, and found a significant reduction in the trans-boundary transport of BC to the TP during the 2020 pre-monsoon season as a result of the lockdowns and restrictive measures. Specifically, we observed a decrease of 0.0211 µgm-3 in surface BC concentration over the TP compared to the 2016 pre-monsoon period. Of this reduction, approximately 6.04 % can be attributed to the decrease in emissions during the COVID-19 pandemic, surpassing the 4.47 % decrease caused by changes in meteorological conditions. Additionally, the emission reductions have weakened the trans-boundary transport of South Asia BC to the TP by 0.0179 µgm-2s-1; indicating that the recurring spring atmospheric pollution from South Asia to the TP will be alleviated through the reduction of anthropogenic emissions. Moreover, it is important to note that BC deposition on glaciers contributes significantly to glacier melting due to its enrichment, posing a threat to the water sustainability of the TP. Therefore, urgent measures are needed to reduce emissions from adjacent regions to preserve the TP as the "Asian Water Tower."
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Contaminantes Atmosféricos , COVID-19 , Humanos , Tibet/epidemiología , Pandemias , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Aerosoles y Gotitas Respiratorias , Hollín/análisis , Carbono/análisis , Agua/análisisRESUMEN
Adenosquamous carcinoma of the pancreas (ASCP) is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate. However, little is known about its genomic landscape and prognostic biomarkers. A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma (PDAC) tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers. The homozygous deletion of the 9p21.3 region (including CDKN2A, CDKN2B, and MTAP) (9p21 loss) occurred in both ASCP and PDAC, and a higher frequency of 9p21 loss was observed in ASCP (12.5% vs 2.0%, P = 0.022). Notably, 9p21 loss was significantly associated with poor disease-free survival (DFS) in ASCP patients (mDFS (Median DFS) = 4.17 vs 7.33 months, HR (Hazard Ratio) = 3.70, P = 0.009). The most common gene alterations in patients with ASCP were KRAS (96%), TP53 (81%), CDKN2A (42%), SMAD4 (21%), CDKN2B (13%), and FAT3 (13%). The mutation rates of ACVR2A (6.25% vs 0%), FANCA (6.25% vs 0%), RBM10 (6.25% vs 0%), and SPTA1 (8.33% vs 1.02%) were significantly higher in ASCP than in PDAC. In conclusion, we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP, which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.
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BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Studies have shown that the DNA damage response (DDR) mutation is strongly associated with microsatellite instability (MSI) status and is an indication for patients with CRCs receiving immune checkpoint inhibitor (ICI) treatment. However, DDR mutation in microsatellite stable (MSS) CRC remains unclear. METHODS: In this study, Fisher's exact test, Student'st-test, Wilcoxon rank-sum test and Cox proportional hazards regression model were performed, and a p value of < 0.05 was considered statistically significant. RESULTS: The most common gene alterations were APC (77%), TP53 (73%), KRAS (48%), and PIK3CA (25%). The mutationfrequency of APC and TP53 in left-sided CRC was significantly higher than that for right-sided CRC, while the mutation frequency of PIK3CA, ACVR2A, FAT4, and RNF43 in right-sided CRC was significantly higher than that for left-sided CRC. DDR mutations occurred in100% of MSI CRCs and in 83.77% of MSS CRCs, with the most frequently mutated DDR genes being ARID1A (7.5%), ATM (5.7%,) and BRCA2 (2.6%). When right- and left-sided CRCs were compared, no significant difference was observed for DDR genes and pathways. A survival analysis indicated that the DDR mutation was not associated with overall survival (OS) in MSS CRCs, while left-sided patients with homologous recombination repair (HRR) pathway mutations had a significantly prolonged OS compared with right-sided CRCs. CONCLUSIONS: Here, we found that stage and grade were statistically significant independent prognostic factors in the left-sided CRC and the right-sided CRC, recommending treatment for these patients stratified by stage. For the future, utilizing DDR gene defects for expanding treatment options and improving prognosis is an issue worth exploring.
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Neoplasias Colorrectales , Humanos , Mutación , Inestabilidad de Microsatélites , Pronóstico , Daño del ADN , Fosfatidilinositol 3-Quinasa Clase I/genéticaRESUMEN
RATIONALE: Rhabdomyosarcoma (RMS) is a rare sarcoma that rarely occurs in adults and accounts for only 1% of all adult tumors. The standard treatment for RMS is surgical resection, radiotherapy, and chemotherapy. PATIENT CONCERNS: Adult patients often present with an aggressive course and poor prognosis. DIAGNOSES: The patient was diagnosed with RMS in September 2019 and was confirmed by hematoxylin-eosin staining and immunohistochemistry after surgical resection. INTERVENTIONS: The patient received surgical resection in September 2019. He was admitted to another hospital after the first recurrence in November 2019. After the second routine surgical resection, the patient underwent chemotherapy, radiotherapy, and anlotinib maintenance treatment. He relapsed again in October 2020 and was admitted to our hospital. Next-generation sequencing was performed on the punctured tissue of the patient's lung metastatic lesion, and high tumor mutational burden (TMB-H), high microsatellite instability (MSI-H), and positive programmed death-ligand 1 (PD-L1) were observed. The patient then received toripalimab and anlotinib combined therapy and was evaluated for a partial response after 2 months. OUTCOMES: This benefit has persisted for more than 17 months. LESSONS: This is the longest progression-free survival for PD-1 inhibitors in RMS, and there is a trend of continued extension of progression-free survival in this patient. This case supports the hypothesis that positive PD-L1, TMB-H, and MSI-H could be beneficial biomarkers for immunotherapy in adult RMS.
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Antígeno B7-H1 , Rabdomiosarcoma , Masculino , Humanos , Adulto , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Rabdomiosarcoma/genética , Rabdomiosarcoma/terapia , Inestabilidad de Microsatélites , Inmunoterapia , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: There is evidence suggesting that sirolimus, in combination with tacrolimus, is active in the prevention of graft-versus-host disease. Sirolimus-based immune suppression may suppress alloreactive T cells, while sparing the survival and function of regulatory T cells. DESIGN AND METHODS: We conducted a randomized trial to compare the impact of sirolimus/tacrolimus against that of methotrexate/tacrolimus on the prevention of graft-versus-host disease and regulatory T-cell reconstitution. RESULTS: Seventy-four patients were randomized 1:1 to sirolimus/tacrolimus or methotrexate/tacrolimus, stratified for type of donor (sibling or unrelated) and the patients' age. The rate of grade II-IV acute graft-versus-host disease at 100 days was 43% (95% CI: 27-59%) in the sirolimus/tacrolimus group and 89% (95% CI: 72-96%) in the methotrexate/tacrolimus group (P<0.001). The rate of moderate/severe chronic graft-versus-host disease was 24% (95% CI: 7-47%) in the sirolimus/tacrolimus group and 64% (95% CI: 41-79%) in the methotrexate/tacrolimus group (P=0.008). Overall survival and patient-reported quality of life did not differ between the two groups. On days 30 and 90 post-transplant, sirolimus-treated patients had a significantly greater proportion of regulatory T cells among the CD4(+) cells in the peripheral blood, and isolated regulatory T cells were functional. CONCLUSIONS: These data demonstrate that sirolimus/tacrolimus prevents grade II-IV acute graft-versus-host disease and moderate-severe chronic graft-versus-host disease more effectively than does methotrexate/tacrolimus, and supports regulatory T-cell reconstitution following allogeneic hematopoietic cell transplantation.
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Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Metotrexato/uso terapéutico , Recurrencia Local de Neoplasia/diagnóstico , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Anciano , Estudios de Casos y Controles , Terapia Combinada , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Estudios Prospectivos , Calidad de Vida , Tasa de Supervivencia , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in gastrointestinal tract, with striking features of morphology and immunohistochemistry. But GISTs in pregnancy could seldom be found. Pathogenic activating mutations of the proto-oncogene KIT and PDGFRA are detected in majority GISTs, and adjuvant imatinib therapy targeting KIT and PDGFRA mutations is recommended for patients with high-risk GIST. However, some rare subgroups with distinct molecular features remain uncovered and more therapeutic targets need to be revealed. METHODS: The DNA/RNA samples were detected using the NGS-based YuanSu450 gene panel. After identifying the CDC42BPB-ALK fusion by NGS, this novel fusion was further confirmed by Sanger sequencing. Subsequently, FISH analysis was performed using the Vysis ALK Break Apart FISH Probe kit to testify the ALK status. ALK protein expression was confirmed by IHC (D5F3 and 5A4). RESULTS: Herein, we reported the first case of quadruple wild-type (WT) GIST with ALK-CDC42BPB fusion and ALK (D5F3) overexpression. In this study, we described a 33-year-old pregnant patient in lactation who had a massive space occupying lesion (with the maximum diameter of 22 cm) in the stomach and was eventually diagnosed as quadruple WT GIST (KITWT /PDGFRAWT /SDHWT /RAS-PWT ). CONCLUSION: We unexpectedly found that this GIST patient showed ALK (D5F3) overexpression and harbored a novel fusion CDC42BPB exon 24-ALK in exon 20.
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Tumores del Estroma Gastrointestinal , Adulto , Femenino , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Humanos , Mutación , Proteína Quinasa de Distrofia Miotónica/genética , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Proto-Oncogénicas c-kit/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismoRESUMEN
Soft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma (ASPS), and leiomyosarcoma (LMS). However, efficacy is difficult to predict. High tumor mutational burden (TMB-H) and programmed death-ligand 1 (PD-L1) expression are the strongest features associated with the efficacy of immunotherapy, although they are rarely found in STS patients. Until now, whether or not PD-L1 expression and TMB are related to the efficacy of immunotherapy has not been determined. In this study, we report data obtained from two STS patients, one ASPS and one UPS with a high TMB, that benefited from anlotinib combined with toripalimab following resistance to anlotinib monotherapy. A 26 year-old female patient was diagnosed with ASPS. PD-L1 was negative. Next generation sequencing (NSG) revealed ASPSCR1-TFE3 fusion and TMB-H. Following eight months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab for 19 months. Another 63 year-old male patient was diagnosed with UPS. PD-L1 was positive and NGS revealed TMB-H. Following 19 months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab. DFS is 23 months to follow-up time. The results presented are the first to report the relationship between TMB and the efficacy of immunotherapy in STS. Based on our results, we hypothesis that anlotinib combined with toripalimab is effective for the treatment of some advanced ASPS or UPS. TMB may be a potential predictive biomarker for ICI treatment and deserves additional study.
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Antígeno B7-H1 , Sarcoma , Adulto , Anticuerpos Monoclonales Humanizados , Antígeno B7-H1/genética , Biomarcadores de Tumor/genética , Preescolar , Femenino , Humanos , Indoles , Masculino , Quinolinas , Sarcoma/diagnóstico , Sarcoma/tratamiento farmacológico , Sarcoma/genéticaRESUMEN
Background: Colorectal leiomyosarcoma (LMS) is a rare colorectal malignancy accounting for approximately 1% of all colorectal malignancies with a poor prognosis and limited treatment options. Targeted therapies have been applied for breast cancer 2 (BRCA2) alterations, but their role remains to be explored in colorectal LMS. This case could provide clinical proof for the application of olaparib for LMS patients. Case Description: Here, we present a case of colorectal LMS with BRCA2 alterations who was treated with olaparib and achieved progression-free survival (PFS) for 1 year. In August 2016, a 46-year-old female patient was admitted to hospital due to a mass in the left lower abdomen and was diagnosed with LMS of the sigmoid colon. After surgical resection, chemotherapy with ifosfamide or ifosfamide combined with pirarubicin was given and achieved stable disease (SD) until the disease progressed 1.5 years later. Afterwards, a multi-target tyrosine kinase inhibitor, anlotinib, was taken. Before the observation of lung and liver metastasis, the patient's disease was stable for 1 year. BRCA2 mutation and rearrangement was revealed by next-generation sequencing (NGS), and the targeted therapy, olaparib, was given. Efficacy evaluation showed SD for 1 year, and no obvious toxic and side effects were observed. Conclusions: Our case suggested that NGS should be considered for further treatment of patients with colorectal LMS, and poly (ADP-ribose) polymerase (PARP) inhibitors could be a feasible therapy for LMS patients with BRCA2 alterations.
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The Arctic has experienced several extreme springtime stratospheric ozone depletion events over the past four decades, particularly in 1997, 2011 and 2020. However, the impact of this stratospheric ozone depletion on the climate system remains poorly understood. Here we show that the stratospheric ozone depletion causes significant reductions in the sea ice concentration (SIC) and the sea ice thickness (SIT) over the Kara Sea, Laptev Sea and East Siberian Sea from spring to summer. This is partially caused by enhanced ice transport from Barents-Kara Sea and East Siberian Sea to the Fram Strait, which is induced by a strengthened and longer lived polar vortex associated with stratospheric ozone depletion. Additionally, cloud longwave radiation and surface albedo feedbacks enhance the melting of Arctic sea ice, particularly along the coast of the Eurasian continent. This study highlights the need for realistic representation of stratosphere-troposphere interactions in order to accurately predict Arctic sea ice loss.
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Pérdida de Ozono , Ozono Estratosférico , Cubierta de Hielo , Regiones Árticas , Estaciones del AñoRESUMEN
Purpose: Although mutational analysis of pancreatic cancer has provided valuable clinical information, it has not significantly changed treatment prospects. The purpose of this study is to further investigate molecular alterations in locally advanced pancreatic cancer and identify predictors of the efficacy of nab-paclitaxel plus gemcitabine (AG) chemotherapy. Experimental design: Tumor samples from 118 pancreatic cancer patients who received AG chemotherapy as first-line treatment were sequenced and genomic profile was generated. Molecular alterations and the involved signaling pathways were analyzed. Genes with a significant difference in mutation frequency between primary and metastatic tumors were identified, and prognostic-related mutant genes were screened using SPSS version 22.0. Results: The most common altered genes in the patients were KRAS (94.9%), TP53 (81.4%), CDKN2A (36.4%), and SMAD4 (22.9%). The mutational frequencies of CDKN2B (14.8% vs. 0%, p = 0.001), FAT3 (7.4% vs. 0%, p = 0.041), MTAP (13% vs. 1.6%, p = 0.023), and SMAD4 (31.4% vs. 15.6%, p = 0.049) in metastatic tumors were significantly higher than that in primary tumors. TP35 and KRAS mutations were significantly correlated with objective response rate, while EPHA7, RNF43, and HMGA2 mutations were significantly correlated with disease control rate. Additionally, patients with TGFR2B, FGF23, EPHA7, SMARCA4, CARD11, ADGRA2, CCNE1, and ACVR2A alterations had a worse overall survival. Further, EPHA7, CARD11, NOTCH1, GATA6, ACVR2A, and HMGA2 mutations indicated undesirable progression-free survival. Conclusions: CDKN2B, FAT3, MTAP, and SMAD4 may be biomarkers that distinguish primary tumors from metastases. EPHA7 mutation may serve as a prognostic biomarker to predict the treatment efficacy of AG chemotherapy in locally advanced pancreatic cancer.
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OBJECTIVE: A multicenter, randomized, controlled and open-labeled clinical trial was performed to compare the efficacy and safety of recombinant human insulin injection (Yousilin R) and Novolin R in diabetic patients. METHODS: A total of 211 cases were randomized into two groups (1:1) treated with Yousilin R versus Novolin R for 12 weeks respectively. RESULTS: Compared with baseline, the levels of glycosylated hemoglobin A1c (HbA1c) at the end of 12 weeks treatment decreased from 10.77% to 7.72%(P < 0.05) in Yousilin R group and from 10.33% to 7.62% (P < 0.05) in Novolin R group, 2-hour postprandial plasma glucose (2hPG) decreased from 15.49 mmol/L to 9.72 mmol/L (P < 0.05) in Yousilin R group and from 15.33 mmol/L to 10.07 mmol/L (P < 0.05) in Novolin R group, and fasting plasma glucose (FPG) decreased from 10.90 mmol/L to 7.31 mmol/L (P < 0.05) in Yousilin R group and from 10.22 mmol/L to 7.21 mmol/L (P < 0.05) in Novolin R group. The changes of HbA1c, 2hPG and FPG from baseline to endpoint in Yousilin R group was similar to those in Novolin R group (P > 0.05). Furthermore, hypoglycemic events (26.42% vs 30.48%), other adverse events (13.21% vs 16.19%), and serious adverse events (1.89% vs 1.90%) were comparable between Yousilin R and Novolin R groups (P > 0.05). CONCLUSIONS: Yousilin R has similar efficacy, safety and compliance profiles to Novolin R group in the treatment of diabetic patients.
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Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Adulto , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Reproducibilidad de los ResultadosRESUMEN
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard treatment for patients with advanced non-small-cell lung cancer (NSCLC) harboring classic EGFR mutations. However, resistance to TKIs remains a major clinical challenge. The transformation from adenocarcinoma to small-cell lung cancer (SCLC) is a rare resistance mechanism to EGFR-TKIs. In this article, we report on 2 lung adenocarcinoma patients with EGFR mutations who developed EGFR-TKI resistance. In case one, the patient was initially diagnosed as lung adenocarcinoma with EGFR L858R, RB1 R445*, and TP53 Y205C mutations. EGFR-TKI failed to bring satisfactory curative effect with the emergence of EGFR T790M mutation and MET amplification and finally passed away. In case two, the patient was diagnosed with lung cancer harboring EGFR L747 and TP53 R342* mutations, and EGFR-TKIs brought a progression-free survival for nine months. However, EGFR-TKI resistance was acquired, and adenocarcinoma transformed into a complex of neuroendocrine carcinoma, SCLC, and lung adenocarcinoma, with the emergence of the EGFR L747, TP53 R342*, and RB1 mutations. Follow-up treatments failed to prevent tumor progression, and the patient died These 2 cases expand our understanding of EGFR-TKI resistance, SCLC transformation, and highlight the importance of histopathology and molecular characteristics for therapeutic strategies for transformed SCLC patients.
Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas de Unión a Retinoblastoma , Proteína p53 Supresora de Tumor , Ubiquitina-Proteína LigasasRESUMEN
Pancreatic cancer is one of the most leading causes of cancer death worldwide. The rapid development of next-generation sequencing (NGS) and precision medicine promote us to seek potential targets for the treatment of pancreatic cancer. Here, we report a female pancreatic cancer patient who underwent radical surgical excision after neoadjuvant chemotherapy. After the surgery, the patient underwent gemcitabine + S-1 therapy, capecitabine + albumin paclitaxel therapy and irinotecan therapy successively, however, MRI review revealed tumor progression. The surgical tissue sample was subjected to next-generation sequencing (NGS), and PALB2 germline mutation and KRAS somatic mutation were identified. The patient then received olaparib (a PARP inhibitor) + irinotecan and the disease stabilized for one year. Due to the increased CA19-9, treatment of the patient with a combination of trametinib (a MEK inhibitor) and hydroxychloroquine resulted in stable disease (SD) with a significant decrease of CA19-9. This case demonstrated that the NGS may be a reliable method for finding potential therapeutic targets for pancreatic cancer.