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1.
Hypertens Res ; 47(7): 1842-1851, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38750217

RESUMO

Limited research exists on identifying risk factors for preeclampsia (PE) in the chronic kidney disease (CKD) population, especially across different patient sources. This study aimed to address this gap by analyzing clinical data from CKD pregnant women admitted to Peking University Third Hospital from January 2012 to December 2022. Logistic regression analysis identified independent risk factors for PE in the CKD population and assessed variations among patients from different sources. Additionally, a predictive model for PE was established using data from the registered group. The study included 524 CKD patients. Hypertension, proteinuria, fibrinogen >4 g/L, serum albumin ≤30 g/L, and uric acid >260 µmol/L were independent risk factors for PE in the overall CKD population. Subgroup analysis revealed that hypertension, serum albumin ≤30 g/L, and uric acid >260 µmol/L were independent risk factors in the referred group, while hypertension, uric acid >260 µmol/L, and fibrinogen >4 g/L were independent risk factors in the registered group. The prediction model based on registered group risk factors showed good predictive efficiency, with the area under the curve of 0.774 in the training set and 0.714 in the validation set. In conclusion, this study revealed that hypertension and elevated uric acid are independent risk factors for PE in CKD patients regardless of patient source, while serum albumin and fibrinogen levels are associated with PE risk in specific patient subgroups. Our predictive model enables clinicians to quickly identify the risk of PE in CKD patients, and early intervention treatment to improve pregnancy outcomes.


Assuntos
Pré-Eclâmpsia , Insuficiência Renal Crônica , Ácido Úrico , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Adulto , Ácido Úrico/sangue , Hipertensão/complicações , Hipertensão/epidemiologia , Fibrinogênio/análise , Fibrinogênio/metabolismo , Albumina Sérica/análise , Proteinúria , Adulto Jovem
2.
Placenta ; 145: 107-116, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128221

RESUMO

INTRODUCTION: Uterine spiral artery remodeling is the prerequisite for ensuring adequate blood supply to the maternal-fetal interface during human pregnancy. One crucial cellular event in this process involves the extensive replacement of the spiral artery endothelial cells by endovascular extravillous trophoblasts (enEVTs), a subtype of extravillous trophoblasts (EVTs). However, our understanding of the properties of enEVTs remains limited. METHODS: Human enEVTs in decidual tissues during early pregnancy was purified using flow sorting by specific makers, NCAM1 and HLA-G. The high-throughput RNA sequencing analysis as well as the cytokine antibody array experiments were carried out to analyze for cell properties. Gene ontology (GO) enrichment, kyoto encyclopedia of genes and genomes (KEGG) enrichment, and gene set enrichment analysis (GSEA) were performed on differentially expressed genes of enEVTs. Immunofluorescent assays were used to verify the analysis results. RESULTS: Both enEVTs and interstitial EVTs (iEVTs) exhibited gene expression patterns typifying EVT characteristics. Intriguingly, enEVTs displayed gene expression associated with immune responses, particularly reminiscent of M2 macrophage characteristics. The active secretion of multiple cytokines and chemokines by enEVTs provided partial validation for their expression pattern of immune-regulatory genes. DISCUSSION: Our study reveals the immune-regulatory properties of human enEVTs and provides new insights into their functions and mechanisms involved in spiral artery remodeling.


Assuntos
Células Endoteliais , Trofoblastos Extravilosos , Gravidez , Feminino , Humanos , Trofoblastos/metabolismo , Placenta/irrigação sanguínea , Artérias/metabolismo
3.
Immun Inflamm Dis ; 11(10): e1057, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37904702

RESUMO

OBJECTIVE: Recurrent pregnancy loss (RPL) and pre-eclampsia (PE) are immune-related pregnancy complications that have been linked to CD4+ T cells and their cytokines, which can be influenced by genetic polymorphisms. This meta-analysis aimed to investigate the relationship between interleukin (IL)-17 and -27 polymorphisms and the susceptibility to RPL and PE. METHODS: All eligible case-control studies published up to February 2023 were identified by searching PubMed, EMBASE, Cochrane, Web of Science, and Google Scholar. The risk of recurrent pregnancy loss and PE associated with the IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were estimated for each study. RESULTS: The meta-analysis incorporated a total of 13 studies. The overall analysis indicated that IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with immune-related pregnancy complications, including RPL and PE. However, when the analysis was stratified by disease type, the IL-17 rs2275913 polymorphism was found to be associated with an increased risk of RPL (recessive model AA/GA + GG: OR = 1.68, 95% confidence interval [CI]: 1.13-2.49, p = .01). CONCLUSIONS: The IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with RPL and PE, whereas the IL-17 rs2275913 polymorphism was associated with the susceptibility to recurrent miscarriage.


Assuntos
Aborto Habitual , Interleucina-27 , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Aborto Habitual/genética , Interleucina-17/genética , Interleucina-27/genética , Interleucinas/genética , Polimorfismo Genético , Pré-Eclâmpsia/genética
4.
Front Med (Lausanne) ; 10: 1113127, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168263

RESUMO

Background: Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients. Methods: The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes. Results: (i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p < 0.001). (iii) A total of 185 just ANA-positive patients were stratified according to titers. Among them, the rate of HCQ usage was significantly higher than that in the weakly positive group (81.03% vs. 58.27%, p = 0.003). (vi) Stratified univariate analysis showed that HCQ usage in the ANA-positive group could reduce the incidence of preeclampsia (2.13% vs. 27.27%, p = 0.019) and prolong gestation (38.29 ± 2.54 vs. 34.48 ± 7.68 weeks, p = 0.006). In the ANA-weakly positive group, HCQ significantly reduced the incidence of preeclampsia (6.76% vs. 28.30%, p = 0.002), early-onset preeclampsia (1.35% vs. 13.21%, p = 0.027), and small-for-gestational-age infants (7.89% vs. 35.19%, p < 0.001). Multivariate regression analysis showed that HCQ significantly reduced the incidence of preeclampsia in both groups. Intergroup interaction analysis showed no significant difference in the value of HCQ in reducing the incidence of preeclampsia between the two groups. Conclusion: ANAs positivity is an important abnormal autoimmunity type in pregnancy. HCQ can be considered as a choice for improving adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia, in this population.

5.
Clin Rheumatol ; 42(4): 1137-1150, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36507975

RESUMO

OBJECTIVE: This study was conducted to analyse the medication indications of hydroxychloroquine (HCQ) and to explore the clinical characteristics and perinatal outcomes of pregnancy in women with autoimmune abnormalities. The value of HCQ against placental dysfunction-related pregnancy outcomes in people with autoimmune abnormalities was also explored. METHODS: ① To collect HCQ application cases during pregnancy who were hospitalized and delivered from 2016 to 2020. The classification and distribution of HCQ indications were analysed. The characteristics of cases and pregnancy outcomes were discussed. ② To include pregnancy combined with autoimmune abnormalities population during the period. Demographic information, clinical characteristics, classification, medication time frame, and pregnancy outcomes were discussed. RESULTS: ① There were 741 cases of HCQ use during pregnancy. Classification by drug indication was as follows: 257 cases (34.68%) had clear indications for autoimmune diseases. There were 359 controversial cases, as follows: 140 (18.89%) cases of antiphospholipid syndrome and 219 (29.55%) cases of autoantibody-positive cases who had no clear drug indication and also used HCQ during pregnancy. No indications were found for 125 cases (16.87%), without autoimmune abnormalities and empirical medication of HCQ during pregnancy. ② In 853 pregnancies with autoimmune abnormalities, women with systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease had clear indications for HCQ. The proportions of HCQ applied during pregnancy were 86.67%, 85.71%, 73.53%, and 75.00%. The start of medication before pregnancy only accounted for 74.44%, 65.31%, 64.71%, and 43.38%. ③ Medication indicated antiphospholipid syndrome and simple autoantibody-positive cases in the controversial population. The proportions of cases in which HCQ was used during pregnancy were 74.47% (140/188) and 64.79% (219/338). Application of HCQ during pregnancy significantly reduced pre-eclampsia (19.8% vs. 8.91%, P < 0.001), early-onset pre-eclampsia (7.78% vs. 2.51%, P = 0.007), and pregnancy loss during the middle and late pregnancy stages (2.99% vs. 0.56%, P = 0.036) in this controversial population. CONCLUSION: Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. The strength of standardized and specialist management are needed in populations with clear HCQ indications. HCQ-indicated controversial population should avoid overdiagnosis and guard against the potential risks of combined anticoagulation and glucocorticoid therapy. The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. HCQ application may alleviate the incidence of adverse pregnancy outcomes in this population. Key Points •The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. •Our work have discovered the unique value of HCQ in improving placental dysfunction diseases in autoimmune abnormal cases, not just in AID such as SLE, SS, UTCD, and RA. •HCQ is a potential drug option for autoimmune abnormalities to improve placental function, by providing synergistic prevention and treatment of these disorders, not just single target of antispasmodic, anti-hypertensive, and circulatory improvement. •Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. However, the strength of standardized and specialist management are needed in populations with clear HCQ indications.


Assuntos
Síndrome Antifosfolipídica , Antirreumáticos , Lúpus Eritematoso Sistêmico , Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Hidroxicloroquina/uso terapêutico , Antirreumáticos/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Placenta , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado da Gravidez , Autoanticorpos
6.
Clin Exp Metastasis ; 40(1): 5-32, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36318440

RESUMO

Portal vein tumor thrombosis (PVTT), a common complication of advanced hepatocellular carcinoma (HCC), remains the bottleneck of the treatments. Liver cancer cells potentially experienced multi-steps during PVTT process, including cancer cells leave from cancer nest, migrate in extracellular matrix, invade the vascular barrier, and colonize in the portal vein. Accumulated evidences have revealed numerous of molecular mechanisms including genetic and epigenetic regulation, cancer stem cells, immunosuppressive microenvironment, hypoxia, et al. contributed to the PVTT formation. In this review, we discuss state-of-the-art PVTT research on the potential molecular mechanisms and experimental models. In addition, we summarize PVTT-associated clinical trials and current treatments for PVTT and suppose perspectives exploring the molecular mechanisms and improving PVTT-related treatment for the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose Venosa , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Veia Porta/patologia , Epigênese Genética , Trombose Venosa/terapia , Trombose Venosa/complicações , Resultado do Tratamento , Estudos Retrospectivos , Microambiente Tumoral
7.
J Clin Transl Hepatol ; 11(7): 1553-1564, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38161496

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

8.
Heliyon ; 7(4): e06886, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33903853

RESUMO

RT-LAMP detection of SARS-CoV-2 has been demonstrated to be a valuable diagnostic method for the diagnosis of COVID-191,2, which can rapidly screen carriers of the virus to effectively control the spread of the SARS-CoV-2. Here, we present a combination of dyes for isothermal detection of SARS-CoV-2 as a commercial alternative, with expanded colorimetric spectrum. We compared them with commercial reagents and proved their suitability and sensitivity through clinical RNA samples. In addition, together with commercial single dye indicators, we believe the expanded color spectrum developed here as an indicator of rapid detection will promote the diagnosis of COVID-19.

9.
Sci Rep ; 11(1): 1820, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469065

RESUMO

RT-LAMP detection of SARS-CoV-2 has been shown to be a valuable approach to scale up COVID-19 diagnostics and thus contribute to limiting the spread of the disease. Here we present the optimization of highly cost-effective in-house produced enzymes, and we benchmark their performance against commercial alternatives. We explore the compatibility between multiple DNA polymerases with high strand-displacement activity and thermostable reverse transcriptases required for RT-LAMP. We optimize reaction conditions and demonstrate their applicability using both synthetic RNA and clinical patient samples. Finally, we validate the optimized RT-LAMP assay for the detection of SARS-CoV-2 in unextracted heat-inactivated nasopharyngeal samples from 184 patients. We anticipate that optimized and affordable reagents for RT-LAMP will facilitate the expansion of SARS-CoV-2 testing globally, especially in sites and settings where the need for large scale testing cannot be met by commercial alternatives.


Assuntos
COVID-19/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , SARS-CoV-2/genética , COVID-19/virologia , Temperatura Alta , Humanos , Nasofaringe/virologia , RNA Viral/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Kit de Reagentes para Diagnóstico , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Inativação de Vírus
10.
Liver Cancer ; 9(3): 245-260, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32647629

RESUMO

The Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement on the treatment strategy for patients with intermediate-stage hepatocellular carcinoma (HCC) was established on August 31, 2019, in Sapporo, Hokkaido during the 10th Annual APPLE Meeting. This manuscript summarizes the international consensus statements developed at APPLE 2019. Transarterial chemoembolization (TACE) is the only guideline-recommended global standard of care for intermediate-stage HCC. However, not all patients benefit from TACE because intermediate-stage HCC is a heterogeneous disease in terms of tumor burden and liver function. Ten important clinical questions regarding this stage of HCC were raised, and consensus statements were generated based on high-quality evidence. In intermediate-stage HCC, preservation of liver function is as important as achieving a high objective response (OR) because the treatment goal is to prolong overall survival. Superselective conventional TACE (cTACE) is recommended as the first choice of treatment in patients eligible for effective (curative) TACE, whereas in patients who are not eligible, systemic therapy is recommended as the first choice of treatment. TACE is not indicated as the first-line therapy in TACE-unsuitable patients. Another important statement is that TACE should not be continued in patients who develop TACE failure/refractoriness in order to preserve liver function. Targeted therapy is the recommended first-line treatment for TACE-unsuitable patients. Especially, the drug, which can have higher OR rate, is preferred. Immunotherapy, transarterial radioembolization, TACE + targeted therapy or other modalities may be considered alternative options in TACE-unsuitable patients who are not candidates for targeted therapy. Better liver function, such as albumin-bilirubin grade 1, is an important factor for maximizing the therapeutic effect of systemic therapy.

11.
Int J Mol Sci ; 21(14)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659969

RESUMO

Wood, which is mainly composed of lignified secondary cell wall, is the most abundant biomass in woody plants. Previous studies have revealed that R2R3-type MYB transcription factors are important regulators of the formation of the secondary cell wall in vascular plants. In this study, we isolated the R2R3-type MYB transcription factor gene PtoMYB055, which is mainly expressed in xylem and phloem tissue, from Populus tomentosa and demonstrate that PtoMYB055 is a key regulator of lignin biosynthesis. PtoMYB055 as a transcriptional activator is localized to the nucleus. Overexpression of PtoMYB055 upregulates expression of lignin biosynthetic genes in transgenic poplar plants, resulting in ectopic deposition of lignin in phloem tissue and an increase in thickness of the secondary cell wall. In sum, PtoMYB055 is a transcriptional activator that is involved in regulating lignin biosynthesis during the formation of the secondary cell wall in poplar.


Assuntos
Vias Biossintéticas/genética , Lignina/biossíntese , Lignina/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Populus/genética , Núcleo Celular/genética , Parede Celular/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Floema/genética , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Ativação Transcricional/genética , Regulação para Cima/genética , Madeira/genética , Xilema/genética
12.
Tree Physiol ; 40(1): 46-59, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31728530

RESUMO

In plants, R2R3 MYB transcription factors (TFs) consist of one large gene family and are involved in the regulation of many developmental processes and various stresses. However, the functions of most of MYB TFs in woody plants remain unknown. Here, PtrMYB94, an R2R3 MYB TF from Populus trichocarpa, is characterized to be involved in the regulation of drought responses and abscisic acid (ABA) signaling. PtrMYB94 encodes a nuclear-localized R2R3 MYB TF. RT-PCR results showed that the PtrMYB94 transcripts were relatively abundant in leaves and stems, and were induced rapidly in response to dehydration stress. Overexpression of PtrMYB94 improved plant drought responses, suggesting that this MYB TF may functionally regulate poplar adaptability to drought stress. Furthermore, the analysis of transcriptional expression and PtrMYB94 promoter: GUS activity showed that PtrMYB94 responded to ABA induction. PtrMYB94-overexpressing plants exhibited the inhibition of seed germination compared with the wild-type (WT) control under ABA exposure condition. The ABA content was evidently increased in the PtrMYB94-overexpressing plants relative to the WT plants. In addition, transcript levels of several ABA- and drought-responsive genes, such as ABA1 and DREB2B, were up-regulated. Taken together, our results suggest that PtrMYB94 is involved in an ABA-dependent drought stress regulation in Populus.


Assuntos
Arabidopsis/genética , Populus/genética , Ácido Abscísico , Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico , Fatores de Transcrição/genética
13.
J Cancer ; 10(26): 6535-6542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777583

RESUMO

Purpose: The prognosis of patients with intermediate-stage hepatocellular carcinoma (HCC) treated by conventional TACE (cTACE) is greatly heterogeneous. This study aimed to develop a new survival prediction model to help select patients who would benefit better from cTACE treatment. Methods: We collected data of 848 treatment-naïve patients with BCLC B HCC who received cTACE as first-line therapy. The prognostic model's variables were derived from univariate and multivariate Cox regression analyses. The concordance index (C-statistic) calculated through cross-validation and bootstrap resampling was used for the model selection. The calibration of our final prediction model was also assessed. Results: The model showed a better discrimination ability than Bolondi's BCLC B1-B4 subclassification to predict the prognosis of BCLC B patients (C-statistic, 0.66 vs. 0.60; difference, 0.05, 95% CI, 0.03-0.07). In cross-validation, bootstrap resampling demonstrated that the model maintained sufficiently discriminant (an average of C-statistic, 0.66; 95% CI, 0.65-0.68). The model calibration was accurate in predicting survival of patients matched well with the observed outcomes. On the basis of the improved survival of 18 months or more as the responding patient, the observations of patients in each response category (responder and non-responder) were fair-moderately matched with those predicted by the model (κ=0.40, P<0.001). Conclusions: Based on clinically available features of patient, tumor and liver function, we developed an alternative prediction model with better performance than the Bolondi's substaging system for intermediate HCC patients after cTACE, which could help define the distinct subgroup of BCLC B patients who are suitable for cTACE treatment.

14.
Liver Cancer ; 7(3): 235-260, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30319983

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

15.
BMC Cancer ; 18(1): 247, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29499662

RESUMO

BACKGROUND: This study aimed to investigate the safety of sorafenib for the treatment of unresectable hepatocellular carcinoma in Chinese patients. METHODS: A subgroup of 345 Chinese patients from the international database of the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study was included in this analysis. Safety assessment measures were adverse events (AEs) and serious adverse events (SAEs) graded using the National Cancer Institute Common Terminology Criteria version 3.0. RESULTS: Of 331 evaluable patients, 98% started sorafenib at 800 mg/day. The median treatment duration was 22 weeks (range, 0.1-116 weeks), and median overall survival (OS) was 322 days (10.7 months). Approximately 50% of patients had at least one adverse event, and 6% had grade 3-4 adverse events. Drug-related adverse events were experienced by 29% of patients, and 3.6% had grade 3-4 drug-related adverse events. Overall, 23% of patients (n = 77) experienced serious adverse events, among which only 1 event was drug-related (0.3%). No differences in overall adverse events, serious adverse events, and deaths were observed between Child-Pugh A and Child-Pugh B patients. The most frequent drug-related adverse events were dermatological/skin (24%), hand-foot skin reaction (20%), gastrointestinal (11%), and diarrhea (11%). The majority of adverse events occurred within 30 days of beginning sorafenib. CONCLUSION: Sorafenib has satisfactory efficacy and safety in Chinese Child-Pugh A and B patients with unresectable HCC using the recommended dosage of 800 mg/day, and the safety of sorafenib is not affected by liver function. Prophylaxis for gastrointestinal adverse events may help to decrease dose interruptions or discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov ; Identifier: NCT00812175. Date of registration: December 19, 2008.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Estudos Retrospectivos , Segurança , Sorafenibe , Resultado do Tratamento
16.
Cancer Med ; 7(3): 820-830, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29383859

RESUMO

Transarterial chemoembolization (TACE) is the standard treatment for unresectable hepatocellular carcinoma (HCC). Hypoxia-induced angiogenesis by TACE is linked to treatment failure; however, whether the chemotherapeutic damage of TACE to HCC could increase tumor angiogenesis has not been explored. The molecular effects of chemotherapy-damaged HCC cells on the neo-angiogenesis were investigated in vitro and in vivo. The expression of growth differentiation factor 15 (GDF15) was significantly upregulated in HCC cells exposed to chemotherapeutic agents. GDF15 from chemotherapy-damaged HCC cells promoted the in vitro proliferation, migration, and tube formation of endothelial cells. The pro-angiogenic effect of GDF15 was through the activation of Src and its downstream AKT, MAPK, and NF-κB signaling, which was blocked by thalidomide. The use of thalidomide significantly attenuated the in vivo chemotherapy-damaged HCC cells-promoted angiogenesis in nude mice. In conclusion, the chemotherapeutic damage in TACE to HCC could promote tumor angiogenesis via the increased release of GDF15. Thalidomide could reverse these pro-angiogenic effects.


Assuntos
Carcinoma Hepatocelular/complicações , Quimioembolização Terapêutica/efeitos adversos , Fator 15 de Diferenciação de Crescimento/efeitos adversos , Neoplasias Hepáticas/complicações , Neovascularização Patológica/etiologia , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Quimioembolização Terapêutica/métodos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus
17.
Arch Gynecol Obstet ; 296(6): 1085-1090, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28948341

RESUMO

PURPOSE: To analyze the clinical outcomes following the implementation of a new standard labor procedure. METHODS: This was a retrospective analysis that included a study group consisting of patients managed based on a new standard labor protocol and a control group comprising patients managed under an old standard labor protocol. The following maternal and perinatal outcomes were compared in the two groups: the indications for a cesarean section and the incidence of cesarean section, postpartum hemorrhage, fetal distress, neonatal asphyxia and pediatric intervention. We also compared the average number of days spent in the hospital, the incidence of medical disputes and hospitalization expenses. RESULTS: The cesarean section rates for the study and control groups were 19.29% (401/2079) and 33.53% (753/2246), respectively (P < 0.05). The main indications for a cesarean section in the study group were arrest of the active phase of labor, fetal distress and intrapartum fever; the percentages of each indication were significantly different from those of the control group (P < 0.001). The rates of postpartum hemorrhage in the study group and control group were 7.74% (130/1678) and 8.1% (121/1493), respectively (P = 0.710). The incidence rates of severe perineal lacerations were 0.48% (8/1678) for the study group and 0.2% (3/1493) for the control group (P = 0.187). The rates of forceps use were 4.29% (72/1678) in the study group and 2.41% (36/1493) in the control group (P = 0.004). The incidence rate of fetal distress in the study group was 6.24% (169/2709) and 4.67% (105/2246) (P = 0.006) in the control group. No significant difference was observed in the incidence of neonatal asphyxia and pediatric interventions between the two groups (0.74% (20/2709) vs. 8.12% (220/2709) and 17 (0.76%) vs. 161 (7.17%), respectively). The average length of hospital stay was 4.74 ± 1.15 and 2.13 ± 1.23 days (P < 0.01). The incidence of medical disputes was significantly different between the two groups: 1.44% (30/2079) in the study group and 0.53% (12/2246) in the control group (P < 0.01). The hospitalization expenses were 5401.29 ± 296.33 yuan in the study group and 5253.53 ± 3655.79 yuan in the control group (P = 0.06). CONCLUSIONS: The implementation of the new labor protocol reduced the cesarean section rate without negatively impacting maternal and neonatal outcomes. In practice, bed turnover and the hospital utilization rate should be better controlled, patient-doctor communication should be strengthened and the quality of obstetrical service should be improved.


Assuntos
Parto Obstétrico/métodos , Trabalho de Parto , Guias de Prática Clínica como Assunto , Cesárea/estatística & dados numéricos , China , Feminino , Sofrimento Fetal , Fidelidade a Diretrizes , Humanos , Tempo de Internação , Hemorragia Pós-Parto/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos
18.
Chin Med J (Engl) ; 130(12): 1395-1399, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28584200

RESUMO

BACKGROUND: Antiphospholipid syndrome (APS)-related immune factors are considered as an important cause of recurrent spontaneous abortion (RSA). Anticoagulant and anti-inflammatory treatments are believed to effectively improve adverse pregnancy outcomes by affecting the abnormal autoimmune response of the maternal-fetal interface. The aim of this study was to observe the clinical characteristics and treatment outcomes of anticoagulant regimens and anti-inflammatory plus anticoagulation regimens for APS-related RSA. METHODS: APS-related RSA cases from September 2011 to September 2016 at Peking University Third Hospital were retrospectively analyzed. The patients were assigned to study group (anti-inflammation plus anticoagulation) and control group (simple anticoagulation). The incidence of repeat abortion, the incidence of placental dysfunction, the gestational weeks of pregnancy, and the mean weight of the fetus were observed. RESULTS: The pregnancy and neonatal outcome indicators of the repeat pregnancy loss rate (11.11% vs. 22.70%), placental dysfunction-related diseases (6.35% vs. 15.60%), the mean birth weight of infants born after 24 weeks gestation (3152.41 ± 844.67 g vs. 2765.76 ± 816.40 g), full-term delivery weight (3456.28 ± 419.79 g vs. 3076.18 ± 518.79 g), the proportions of low birth weight infants (12.70% vs. 21.98%), and small for gestational age (6.35% vs. 14.18%) differed significantly between the study and control groups (all P< 0.05). The incidence of preterm delivery, term delivery, and stillbirth was not significantly different between the two groups, and there was no significant difference between the study and control groups in gestational age at birth (37.6 ± 3.3 weeks vs. 36.9 ± 3.2 weeks; P > 0.05). CONCLUSION: The anti-inflammatory and anticoagulation regimen is more effective than the simple anticoagulation regimen in the treatment of APS recurrent abortion.


Assuntos
Aborto Habitual/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Aborto Habitual/etiologia , Adulto , Síndrome Antifosfolipídica/complicações , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Prednisona/uso terapêutico , Gravidez , Resultado da Gravidez , Estudos Retrospectivos
19.
Tumour Biol ; 39(3): 1010428317695030, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28349781

RESUMO

The purpose of this study was to examine the safety and efficacy of sorafenib in Chinese patients with unresectable hepatocellular carcinoma. Data of 338 Chinese patients from the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib study database were included. Patients were divided into those who received and did not receive sorafenib prior to surgical resection and those with and without portal vein tumor thrombosis. In the non-surgery group, the median survival was 302 days (95% confidence interval: 244-371), and the median time from diagnosis to death was 428 days (95% confidence interval: 352-556); in the surgery group, half of the patients survived for 345 days and the median time from diagnosis to death was 1000 days (95% confidence interval: 750-2816). Median progression-free survival and median time to progression were not different between the two groups. Median overall survival was 360 days (95% confidence interval: 309-435) in the non-portal vein tumor thrombosis group and 240 days (95% confidence interval: 181-296) in the portal vein tumor thrombosis group; median time between hepatocellular carcinoma diagnosis and death was 750 days (95% confidence interval: 472-1000) and 420 days (95% confidence interval: 252-567), respectively, in the two groups. Median progression-free survival was 209 days (95% confidence interval: 166-264) for patients without portal vein tumor thrombosis and 154 days (95% confidence interval: 112-202) for patients with portal vein tumor thrombosis; median time to progression was 295 days (95% confidence interval: 209-463) and 221 days, respectively. Adverse events were generally comparable regardless of prior surgery and portal vein tumor thrombosis status. We thus conclude that earlier administration of sorafenib may result in improved outcomes in patients with unresectable hepatocellular carcinoma and portal vein tumor thrombosis.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Trombose Venosa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , China , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Veia Porta/efeitos dos fármacos , Veia Porta/patologia , Sorafenibe , Resultado do Tratamento , Trombose Venosa/etiologia , Trombose Venosa/patologia
20.
J Vasc Interv Radiol ; 27(12): 1829-1836, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27553917

RESUMO

PURPOSE: To compare outcomes of transarterial chemoembolization with radiofrequency (RF) ablation in treatment of recurrent hepatocellular carcinoma (HCC) after resection within Barcelona Clinic Liver Cancer (BCLC) stage 0/A. MATERIALS AND METHODS: From January 2007 to December 2011, 110 consecutive patients with recurrent HCC meeting BCLC stage 0/A criteria underwent transarterial chemoembolization (n = 78; mean tumor size, 1.9 cm ± 1.0) or RF ablation (n = 32; mean tumor size, 1.9 cm ± 0.6) as initial treatment. The primary outcome was overall survival (OS). Kaplan-Meier method was used to construct survival curves, which were compared by log-rank test. Prognostic factors for OS were analyzed using univariate and multivariate Cox proportional hazard models. RESULTS: No significant differences between baseline clinical characteristics of the 2 treatment groups were identified. The 1-, 3-, and 5-year OS rates were 89.7%, 61.0%, and 36.6% for the transarterial chemoembolization group and 90.1%, 72.8%, and 60.0% for the RF ablation group. There was no significant difference in OS rates between the groups (P = .159). Subgroup analysis indicated that RF ablation achieved better survival than transarterial chemoembolization among patients ≤ 55 years old and patients with BCLC stage 0 (P = .036 and P = .045). Multivariate analysis revealed that serum albumin (≤ 35 g/L) (hazard ratio = 2.797; 95% confidence interval, 1.366-2.726; P = .005) and α-fetoprotein (> 400 ng/mL) (HR = 2.336; 95% CI, 1.210-4.508; P = .011) levels before treatment were 2 significant risk factors for poor prognosis. CONCLUSIONS: Transarterial chemoembolization might provide a similar OS as RF ablation in patients with recurrent BCLC stage A HCC. However, RF ablation could provide better OS in patients with recurrent BCLC stage 0 HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Ablação por Cateter , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Distribuição de Qui-Quadrado , China , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Seleção de Pacientes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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