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1.
Curr Med Sci ; 44(5): 1006-1017, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39347922

RESUMO

BACKGROUND AND OBJECTIVE: The effectiveness of radiofrequency ablation (RFA) in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma (HCC) measuring 5 cm or less remains uncertain. This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA. METHODS: This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, focusing on patients diagnosed with a solitary HCC lesion ≤5 cm in size. We compared the overall survival (OS) and cancer-specific survival (CSS) rates of these patients with those of patients who received hepatectomy, radiotherapy, or chemotherapy or who were part of a blank control group. To enhance the reliability of our findings, we employed stabilized inverse probability treatment weighting (sIPTW) and stratified analyses. Additionally, we conducted a Cox regression analysis to identify prognostic factors. XGBoost models were developed to predict 1-, 3-, and 5-year CSS. The XGBoost models were evaluated via receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) curves and so on. RESULTS: Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs, the 5-year OS (46.7%) and CSS (58.9%) rates were greater in the RFA group than in the radiotherapy (27.1%/35.8%), chemotherapy (32.9%/43.7%), and blank control (18.6%/30.7%) groups, but these rates were lower than those in the hepatectomy group (69.4%/78.9%). Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years. Age, race, marital status, grade, cirrhosis status, tumor size, and AFP level were selected to construct the XGBoost models based on the training cohort. The areas under the curve (AUCs) for 1, 3, and 5 years in the validation cohort were 0.88, 0.81, and 0.79, respectively. Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts. CONCLUSION: RFA can improve the survival of patients diagnosed with a solitary HCC lesion ≤5 cm. In certain clinical scenarios, RFA achieves survival outcomes comparable to those of hepatectomy. The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizado de Máquina , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Ablação por Radiofrequência/métodos , Idoso , Prognóstico , Estudos Retrospectivos , Programa de SEER , Resultado do Tratamento , Adulto , Curva ROC
2.
Clin Cosmet Investig Dermatol ; 17: 1793-1797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39132031

RESUMO

Prurigo nodularis (PN) is a debilitating chronic neuroimmunologic skin condition due to the intense pruritus and difficult to treat. The pruritogenic cytokines, particularly IL-4, IL-13, IL-22, IL-31, and oncostatin M (OSM), play a crucial role in the pathogenesis of PN, potentially involving the JAK1-STAT pathway. An oral JAK1 inhibitor, abrocitinib, is presently undergoing Phase 2 trials for the treatment of PN. We evaluated the efficacy of abrocitinib at a daily dosage of 100 mg in treating two patients with PN affecting both lower limbs: a 50-year-old male with a 16-year disease history and a 38-year-old female with over three years of disease history, both of whom had failed to respond to multiple conventional treatments. Both patients responded rapidly after one week of treatment and exhibited a marked improvement. Following eight weeks of therapy, near-complete resolution of both pruritus and lesions was achieved, and no adverse effects were reported. Additionally, there were no reported side effects during the initial four months of continued treatment. Abrocitinib is an effective targeted therapy for PN, offering a promising new option for refractory patients.

3.
Huan Jing Ke Xue ; 45(7): 4082-4089, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022956

RESUMO

The rapid cultivation of partial nitritation/ANAMMOX (PN/A) granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX (AMX) bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors (CSTR) (R1-R3) by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·ï¼ˆm3·d)-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria (AMX) by introducing abundant ammonium-oxidizing bacteria (AOB) and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB (genus Nitrosomonas), AMX (genera Candidatus Kuenenia and Candidatus Brocadia), and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.


Assuntos
Processos Autotróficos , Reatores Biológicos , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos , Reatores Biológicos/microbiologia , Nitrogênio/metabolismo , Nitrogênio/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Esgotos/microbiologia , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética , Águas Residuárias/química , Compostos de Amônio/metabolismo , Compostos de Amônio/isolamento & purificação
4.
J Dermatolog Treat ; 35(1): 2313090, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38317538

RESUMO

Aim: To evaluate the therapeutic efficacy and safety of JAK inhibitor abrocitinib in patients with localized granuloma annulare (GA) and to review the available cases documented in English.Methods: We presented a patient who had a persistent, localized granuloma anulare (GA) for one year and did not respond to traditional therapies. This patient was treated with oral abrocitinib at a dosage of 150 mg daily.Results: After 6 weeks of treatment with abrocitinib, the patient exhibited notable symptom improvement with no new lesions. No adverse events or recurrences were reported during the 5-month follow-up period.Conclusions: Abrocitinib may be a promising and safe treatment option for patients with localized GA who do not respond to traditional therapies.


Assuntos
Granuloma Anular , Inibidores de Janus Quinases , Humanos , Granuloma Anular/tratamento farmacológico , Granuloma Anular/patologia , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Resultado do Tratamento
6.
Clin Res Hepatol Gastroenterol ; 48(2): 102283, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219821

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) is one of the primary treatment methods for T1/2 hepatocellular carcinoma (HCC), but the risk factors after RFA remain controversial. This study aims to identify the key factors associated with cancer-specific mortality (CSM) in patients with T1/2 HCC after RFA using competing risk analysis and to establish a prognostic nomogram for improved clinical management. METHODS: A total of 2,135 T1/2 HCC patients treated with RFA were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and randomly categorized into training and validation sets. Univariate and multivariable competing risk analyses were performed to identify risk factors associated with CSM and construct a competing risk nomogram. Receiver operating characteristic (ROC) curves, concordance indices (C-indexes), calibration plots, and decision curve analysis (DCA) were conducted to evaluate the predictive efficiency and clinical applicability of the nomogram in the training and validation sets. Patients were stratified according to their nomogram score, and the different risk groups were compared using cumulative incidence function (CIF) curves and Gray's validation . RESULTS: The 5-year CSM rate for HCC patients treated with RFA was 30.1 %. Grade, tumor size, tumor number, cirrhosis, and AFP level were identified as independent risk factors for CSM. A prognostic nomogram was developed based on these risk factors. The time-dependent C-indexes (0.65) were greater than those of the AJCC stage model (0.55) during the 12 to 60 months of follow-up. The calibration plots of the competing risk nomograms demonstrated excellent consistency between actual survival and nomogram predictions. ROC analyses showed that the 1-, 3-, and 5-year AUC values in both the training and validation cohorts were all greater than 0.63 and exceeded those of the AJCC stage model. DCA demonstrated the clinical usefulness of the nomogram. Patients were classified into low-, moderate-, and high-risk groups based on the nomogram scores, with the high-risk group showing significantly higher CSM rates after RFA compared to the other two groups. CONCLUSIONS: We identified Grade, AFP, cirrhosis, tumor size, and tumor number as independent risk factors associated with CSM. The competing risk nomogram exhibited high performance in predicting the probability of CSM for HCC patients undergoing RFA.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/cirurgia , Nomogramas , alfa-Fetoproteínas , Neoplasias Hepáticas/cirurgia , Cirrose Hepática , Prognóstico
8.
J Infect Chemother ; 29(9): 927-929, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37295648

RESUMO

The increasing antibiotic resistance of Neisseria gonorrhoeae (NG) is an urgent need to explore new and effective drugs. The antibacterial activities of spectinomycin and sanguinarine against 117 clinical NG isolates and time-kill curve of sanguinarine were evaluated. Almost all isolates were resistant to penicillin (91.5%) and ciprofloxacin (96.5%), 8.5% showed resistance to azithromycin, 10.3% and 10.3% had decreased susceptibility/resistance to ceftriaxone and cefixime, respectively, whereas 100% were susceptible to spectinomycin. The minimum inhibitory concentration (MIC) ranges, MIC50, MIC90 and MICmean values of sanguinarine were 2-64 µg/ml, 16 µg/ml, 32 µg/ml and 16.9 µg/ml, respectively, and time-kill curve showed killing of bacteria in a dose-dependent manner during the assay time of 6h, very similar to spectinomycin. Sanguinarine has great potential as an effective and novel anti-NG agent.


Assuntos
Gonorreia , Espectinomicina , Humanos , Espectinomicina/farmacologia , Espectinomicina/uso terapêutico , Neisseria gonorrhoeae , Gonorreia/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Ciprofloxacina/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
9.
Cell Death Dis ; 14(5): 335, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217473

RESUMO

Necroptosis is a caspase-independent form of programmed cell death. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in the initiation of necroptosis and the formation of the necrotic complex. Vasculogenic mimicry (VM) provides a blood supply to tumor cells that is not dependent on endothelial cells. However, the relationship between necroptosis and VM in triple-negative breast cancer (TNBC) is not fully understood. In this study, we found that RIPK1-dependent necroptosis promoted VM formation in TNBC. Knockdown of RIPK1 significantly suppressed the number of necroptotic cells and VM formation. Moreover, RIPK1 activated the p-AKT/eIF4E signaling pathway during necroptosis in TNBC. eIF4E was blocked by knockdown of RIPK1 or AKT inhibitors. Furthermore, we found that eIF4E promoted VM formation by promoting epithelial-mesenchymal transition (EMT) and the expression and activity of MMP2. In addition to its critical role in necroptosis-mediated VM, eIF4E was essential for VM formation. Knockdown of eIF4E significantly suppressed VM formation during necroptosis. Finally, through clinical significance, the results found that eIF4E expression in TNBC was positively correlated with the mesenchymal marker vimentin, the VM marker MMP2, and the necroptosis markers MLKL and AKT. In conclusion, RIPK1-dependent necroptosis promotes VM formation in TNBC. Necroptosis promotes VM formation by activating RIPK1/p-AKT/eIF4E signaling in TNBC. eIF4E promotes EMT and MMP2 expression and activity, leading to VM formation. Our study provides a rationale for necroptosis-mediated VM and also providing a potential therapeutic target for TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Células Endoteliais/metabolismo , Necroptose/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
10.
Heliyon ; 9(4): e15240, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37089316

RESUMO

The formation of left gastric artery aneurysms (LGAAs) is a very rare complication of microscopic polyangiitis (MPA). Hemorrhage due to ruptured LGAAs is life threatening. In this case report, an 81-year-old female patient diagnosed with MPA developed massive bleeding from a ruptured LGAA and hemorrhagic shock during hospitalization. The patient underwent endovascular therapy to successfully embolize the aneurysm with microcoils and recovered postoperatively.

11.
Exp Dermatol ; 32(6): 889-899, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36999576

RESUMO

Recent metabolic studies have indicated that several metabolites in blood and urine of psoriasis functionally involved in the pathogenesis of psoriasis, but the skin metabonomics research of psoriasis is limited. We aimed to investigate the metabolic profiling of lesional and nonlesional skin and screen out potential biomarkers for psoriasis. We performed liquid chromatography-mass spectrometry (LC-MS)-based nontargeted metabolomic analysis to compare metabolic profile between lesional and nonlesional skin from 12 patients with psoriasis vulgaris. A total of 3463 metabolites were detected, of which 769 (346 named and 423 unnamed) in positive ion mode and 179 (80 named and 99 unnamed) in negative ion mode were significantly different between lesional and nonlesional skin. These different metabolites were mainly derived from amino acid, lipid and nucleotide metabolism, and involved in cell proliferation and apoptosis regulation. Fourteen metabolites (10 upregulated and 4 downregulated) were identified as the most potentially significant biomarkers. Interestingly, seven of them were positively (l-gamma-glutamyl-l-leucine, 2-methylcitric acid, l-palmitoylcarnitine, inosine, eicosapentaenoic acid and 13-hydroxy-octadecaenoic acid) or negatively (l-serine) correlated with disease severity. Significant differences of metabolic characteristics were found between lesional and nonlesional skin, which may contribute to assess the severity of psoriasis and therapeutic responses.


Assuntos
Psoríase , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , Psoríase/metabolismo , Metabolômica/métodos , Biomarcadores
12.
Carbohydr Polym ; 305: 120549, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36737198

RESUMO

Vitiligo can cause serious damage to the appearance of patients and affect physical and mental health, but there is currently no simple and effective treatment. According to the theory of autoimmune disorder, the separable hydrogel microneedles delivering alpha-melanocyte-stimulating hormone (α-MSH) and tofacitinib were designed to treat vitiligo. This hydrogel microneedles were formed by dextran methacrylate (DexMA) and cyclodextrin-adamantane based host-guest supramolecules (HGSM) through CC double bond polymerization and host-guest assembly. The microneedle tips formed by the double cross-linked hydrogel can pierce the stratum corneum and deliver melanocyte protector α-MSH and JAK inhibitor tofacitinib directly to the epidermis and dermis. Under the treatment of α-MSH/tofacitinib microneedles, massive deposition of melanin in epidermis and hair follicles significantly accelerated skin and hair pigmentation.


Assuntos
Vitiligo , alfa-MSH , Humanos , alfa-MSH/farmacologia , Vitiligo/tratamento farmacológico , Dextranos , Hidrogéis , Melanócitos
14.
Transl Cancer Res ; 11(5): 1297-1308, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35706808

RESUMO

Background: Transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) intervention in prolonging the long-term survival and prognosis of patients with liver cancer are still controversy compared with the traditional interventional therapy of RFA alone. This meta-analysis aimed to compare the efficacy and safety of combination therapy versus RFA alone. Methods: The related articles were searched in PubMed, Embase, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Science and Technology Journal Database, and China Biomedical Literature Database (CBM). The Chinese and English search keywords included transcatheter arterial chemoembolization, TACE, radiofrequency ablation, RFA, primary liver cancer, and liver tumor. The five evaluation criteria of randomized controlled trials (RCTs) in Cochrane RoB 2.0 repeatedly independently evaluated the bias risks involved in the study and cross-checked the results. Results: A total of 7 articles were included, and the results of bias risk assessment show that 6 articles described the generation of random sequences in detail; There were 3 articles describing allocation concealment in detail; Operator blindness was used in 4 articles; The outcome indicators of 7 documents were complete. The 3-year overall survival rate of the RFA combined with TACE group was significantly better than that of the RFA group [odds ratio (OR) =1.97, 95% confidence interval (CI): 1.42-2.74, Z=4.05, P<0.0001]. The 1-year and 3-year tumor recurrence-free survival rates in the RFA combined with TACE group were significantly better than those in the RFA group (OR =1.88, 95% CI: 1.28-2.76, Z=3.23, P=0.001; OR =2.11, 95% CI: 1.37-3.24, Z=3.38, P=0.0007). There was no significant difference in the complication rate of patients with primary liver cancer between the RFA combined with TACE group and the RFA group (OR =0.79, 95% CI: 0.45-1.39, Z=0.81, P=0.42). Discussion: Meta-analysis results confirmed that TACE combined with RFA was safe and effective in the treatment of primary liver cancer, and can improve the overall survival and recurrence-free survival of patients with primary liver cancer.

15.
Dermatol Ther ; 35(8): e15599, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35614844

RESUMO

Although secukinumab has demonstrated high efficacy and favorable safety in moderate-to-severe psoriasis and psoriatic arthritis, patients developing adverse events of special interest (AESI) were reported increasingly in real-world practice. A systematic literature search of the PubMed database was conducted to identify clinical studies or case reports on secukinumab-induced AESI. More than 1077 patients (aged 18-74 years) from 55 studies were reported to have 24 AESI 3 days to 96 weeks after secukinumab treatment. The four most common AESI was inflammatory bowel disease (n > 1000), eczematous drug eruption (n > 30), drug-associated vasculitis (n = 8), and drug-induced lupus erythematosus (n = 4). Most of these AESI were only mild to moderately severe and resolved after secukinumab discontinuation without or with symptomatic treatment. Secukinumab has the potential to develop a number of AESI by probably dysregulating the different expression of polar T-cell axes (Th1, Th2, Th17, Th22, and/or Treg) and driving various cytokines in some patients. Physicians should be aware of these AESI for timely diagnosis and proper treatment.


Assuntos
Artrite Psoriásica , Psoríase , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Humanos , Psoríase/induzido quimicamente , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Biomed Res Int ; 2020: 7256862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32420365

RESUMO

Cardiac hypertrophy and ventricular remodeling following heart failure are important causes of high mortality in heart disease patients. The cardiac lymphatic system has been associated with limited research, but it plays an important role in the improvement of myocardial edema and the promotion of fluid balance. LCZ696 is a novel combination of angiotensin and neprilysin inhibitors. Here, we studied the role played by LCZ696 during transverse aortic constriction (TAC) induced cardiac hypertrophy and changes in the lymphatic system. Mice undergoing aortic coarctation were constructed to represent a cardiac hypertrophy model and then divided into random groups that either received treatment with LCZ696 (60 mg/kg/d) or no treatment. Cardiac ultrasonography was used to detect cardiac function, and hematoxylin and eosin (H&E) and Masson staining were used to detect myocardial hypertrophy and fibrosis. The proinflammatory factors interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) were detected in the blood and heart tissues of mice. The protein expression levels of lymphatic-specific markers, such as vascular endothelial growth factor C (VEGF-C), VEGF receptor 3 (VEGFR3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) were detected in mouse heart tissues. We also examined the colocalization of lymphatic vessels and macrophages by immunofluorescence. The results showed that LCZ696 significantly improved heart dysfunction, cardiac hypertrophy, and fibrosis and inhibited the expression of proinflammatory factors IL-6, IL-1ß, and TNF-α in the circulating blood and heart tissues of mice. LCZ696 also decreased the protein expression levels of VEGF-C, VEGFR3, and LYVE-1 in mouse heart tissues, ameliorated the transport load of lymphatic vessels to macrophages, and improved the remodeling of the lymphatic system in the hypertrophic cardiomyopathy model induced by TAC.


Assuntos
Aminobutiratos/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Doenças da Aorta , Cardiomegalia , Neprilisina/antagonistas & inibidores , Receptores de Angiotensina/metabolismo , Tetrazóis/farmacologia , Animais , Doenças da Aorta/tratamento farmacológico , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Doenças da Aorta/fisiopatologia , Compostos de Bifenilo , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Constrição Patológica , Modelos Animais de Doenças , Combinação de Medicamentos , Fibrose , Masculino , Camundongos , Neprilisina/metabolismo , Valsartana
17.
Mol Cell Biochem ; 450(1-2): 25-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29790114

RESUMO

This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva-10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed. Hematoxylin-eosin (H&E), Masson's trichome staining, and TUNEL assays were conducted to evaluate cardiac hypertrophy, fibrosis, and apoptosis, respectively. Western blotting was performed to detect the expression of proteins related to the PI3K/Akt/mTOR/p70S6K pathway. Ivabradine could effectively improve left ventricular dysfunction and hypertrophy induced by TAC in a dose-independent manner. Moreover, no obvious change in heart rate (HR) was observed in the TAC and Rap groups, whereas a significant decrease in HR was found after ivabradine treatment (P < 0.05). Cardiac hypertrophy, fibrosis, and apoptosis induced by TAC were notably suppressed after either rapamycin or ivabradine treatment (P < 0.05). Ivabradine and rapamycin also decreased the expression of PI3K/Akt and mTOR induced by TAC. Ivabradine improved cardiac hypertrophy and fibrosis as well as reduced cardiomyocyte apoptosis via the PI3K/Akt/mTOR/p70S6K pathway in TAC model mice.


Assuntos
Doenças da Aorta/fisiopatologia , Apoptose , Constrição Patológica/fisiopatologia , Modelos Animais de Doenças , Hipertrofia Ventricular Esquerda/prevenção & controle , Ivabradina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Disfunção Ventricular Esquerda/prevenção & controle , Animais , Fármacos Cardiovasculares/farmacologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/patologia , Pressão , Disfunção Ventricular Esquerda/patologia
18.
Chin J Traumatol ; 19(2): 104-8, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27140218

RESUMO

OBJECTIVE: To evaluate the feasibility and efficiency of one-stage external fixation by using locking plate in distal tibial fractures. METHODS: In this non-control prospective study, 28 patients with distal tibial fractures were included and underwent one-stage external fixation by using locking plate. There were 21 males and 7 females, with a mean age of 43 years (19-63). According to AO/OTA fracture classification, there were 9 cases of Type A1, 9 of Type A2, 10 of Type A3 fractures. There were 21 close and 7 open fractures. The locking plate was placed on the anteromedial aspect of the tibia with 4-5 bicortical screws inserted in both distal met- aphysis and diaphysis. The radiographic and clinic results were evaluated. RESULTS: All patients were followed up for the average of 16 months (ranging from 12 to 21 months). The average surgery duration was 38 (25-60) minutes. The mean time to fracture healing were 14.6 ± 2.67, 17.5 ± 3.66, and 18.4 ± 3.37 (p < 0.05) weeks in type A1, A2, and A3 fractures respectively. By the end of the follow-ups, the mean AOFAS score were 96.11 ± 2.32, 92.67 ± 1.80 and 92.00 ± 2.06 (p > 0.05) in type A1, A2, and A3 fractures respectively. None of nonunion, deep infection, or breakage of screw or plate were observed. CONCLUSIONS: Distal tibial fracture was the ideal indication for external fixation using locking plate. The external plating is characterized by ease of performance, less invasive, fewer soft tissue impingement, improved cosmesis, and convenient for removal.


Assuntos
Placas Ósseas , Fixadores Externos/estatística & dados numéricos , Consolidação da Fratura/fisiologia , Fraturas da Tíbia/cirurgia , Adulto , Análise de Variância , Estudos de Coortes , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Cuidados Pós-Operatórios/métodos , Prognóstico , Estudos Prospectivos , Medição de Risco , Fraturas da Tíbia/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
19.
Diabetes Res Clin Pract ; 115: 140-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26997210

RESUMO

AIMS: Insulin resistance (IR) and sympathetic over-activation play a critical role in diabetic cardiomyopathy (DCM). Percutaneous renal sympathetic denervation (RDN) was tested to treat refractory hypertension. However, the benefits of RDN for DCM and IR still remain unknown. The present study aimed to investigate the effect and associated mechanisms of bilateral surgical RDN (bsRDN) on cardiac function and glucose metabolism in animals with diabetes. METHODS: Thirty-two male New Zealand white rabbits were randomly assigned to Chow (n=8, normal diet) and TEST (n=24, high-fructose fat diet [HFD]) groups. At 48 weeks after HFD feeding, animals in the TEST group were randomized to the Sham, HFD, and RDN subgroups and were fed a HFD for an additional 8 weeks. Repeated measurements of cardiac function, IR, apoptosis/autophagy, and histopathological assessment were performed at 48 and 56 weeks. RESULTS: HFD feeding for 56 weeks induced IR and diastolic cardiac dysfunction with hypertrophy in septum but well preserved eject fraction in the animals. Impaired IR further deteriorated over the time in the RDN group, featured by a more profound reduction in GLUT4 mRNA and its translocation to the plasma membrane. Successful denervation was associated with improvement of cardiac function via preventing myocardial fibrosis and over-expression of procollagen III, mammalian target of rapamycin, and cardiac apoptosis. Cardiac autophagy, assessed by either electron microscopy or Western blot, was enhanced by bsRDN. CONCLUSIONS: Renal sympathetic denervation led to a significant improvement of HFD-induced cardiac dysfunction by shifting the cardiac apoptosis to autophagy, but worsening IR. Further study is required to identify the clinical benefits of RDN.


Assuntos
Denervação/métodos , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/terapia , Rim/inervação , Disfunção Ventricular Esquerda/terapia , Animais , Apoptose , Autofagia , Cardiomiopatias Diabéticas/complicações , Cardiomiopatias Diabéticas/diagnóstico , Dieta Hiperlipídica/efeitos adversos , Ecocardiografia , Frutose/toxicidade , Ventrículos do Coração/ultraestrutura , Masculino , Microscopia Eletrônica , Miocárdio/ultraestrutura , Coelhos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia
20.
J Orthop Trauma ; 29(11): e454-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26492454

RESUMO

The surgical treatment of distal tibial fractures is still challenging. The purpose of this study was to evaluate the clinical and radiographic results associated with the use of a precontoured distal femoral locking plate as an external fixator in treating distal tibial fractures. From August 2011 to October 2012, 28 patients with distal tibial fractures were consecutively enrolled in this study. There were 9 OTA 43.A1, 9 43.A2, and 10 43.A3, including 21 closed and 7 open fractures. The precontoured distal femoral locking plate was placed on the anteromedial aspect of the tibia as an external fixator. All patients were followed for an average of 16 months. The mean surgical duration was 38 (25-60) minutes. The mean time until fracture healing was 16.7 (12-24) weeks. At final follow-up, the mean American Orthopaedic Foot and Ankle Society score was 93 (88-100). There were no nonunions, deep infections, or implant fractures. Three patients had transient superficial pin site infection, but these did not change the clinical outcome. External fixation using a precontoured distal femoral locking plate is a reliable option in treating distal tibial fracture. The procedure is easy to perform, is less invasive, and the low profile plate can be concealed under stockings and can be conveniently removed.


Assuntos
Placas Ósseas , Fixação de Fratura/instrumentação , Fraturas da Tíbia/cirurgia , Adulto , Fixadores Externos , Feminino , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Tíbia/cirurgia , Adulto Jovem
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