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This work aims to expand the structure-property relationships of bromo-containing polyimides and the influence of bromine atoms on the gas separation properties of such materials. A series of intrinsically microporous polyimides were synthesized from 2,2'-dibromo-4,4',5,5'-bipohenyltetracarboxylic dianhydride (Br-BPDA) and five bulky diamines, (7,7'-(mesitylmethylene)bis(8-methyldibenzo[b,e][1,4]dioxin-2-amine) (MMBMA), 7,7'-(Mesitylmethylene)bis(1,8-dimethyldibenzo[b,e][1,4] dioxin-2-amine) (MMBDA), 4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diamine (TBDA1), 4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-3,9-diamine (TBDA2), and (9R,10R)-9,10-dihydro-9,10-[1,2]benzenoanthracene-2,6-diamine (DAT). The Br-BPDA-derived polyimides exhibited excellent solubility, high thermal stability, and good mechanical properties, with their tensile strength and modulus being 59.2-109.3 MPa and 1.8-2.2 GPa, respectively. The fractional free volumes (FFVs) and surface areas (SBET) of the Br-BPDA-derived polyimides were in the range of 0.169-0.216 and 211-342 m2 g-1, following the order of MMBDA > MMBMA > TBDA2 > DAT > TBDA1, wherein the Br-BPDA-MMBDA exhibited the highest SBET and FFV and thus highest CO2 permeability of 724.5 Barrer. Moreover, Br-BPDA-DAT displayed the best gas separation performance, with CO2, H2, O2, N2, and CH4 permeabilities of 349.8, 384.4, 69.8, 16.3, and 19.7 Barrer, and H2/N2 selectivity of 21.4. This can be ascribed to the ultra-micropores (<0.7 nm) caused by the high rigidity of Br-BPDA-DAT. In addition, all the bromo-containing polymers of intrinsic microporosity membranes exhibited excellent resistance to physical ageing.
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OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.
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Gasderminas , Pulmão , Piroptose , Quinuclidinas , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Ratos , Quinuclidinas/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Superóxido Dismutase/metabolismo , Peroxidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Caspase 1/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismoRESUMO
Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.
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Congenital anomalies of the kidney and urinary tract (CAKUT) are primarily causal for end-stage renal disease and have significant implications for long-term survival. A total of 39 healthy controls and 94 children with chronic kidney disease (CKD) were enrolled (3-12 years old as children, 13-18 years old as adolescents), who were divided into CAKUT and Non-CAKUT according to the etiology of CKD. CKD group was further classified according to estimating glomerular filtration rate (eGFR). Circulating levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemokine-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) were analyzed. The relationship between these inflammatory markers with eGFR and the kidney injury parameter (urine protein) was investigated to assess their potential as early markers of disease progression. All circulating levels of these inflammatory cytokines were increased in CKD patients (including CAKUT and Non-CAKUT) compared with healthy subjects. The circulating levels of MCP-1 and TGF-ß1 were increased in CAKUT adolescents compared with CAKUT children. In CAKUT children, levels of MCP-1 and TGF-ß1 increased as CKD progressed, and MCP-1 and TGF-ß1 were negatively and significantly correlated with eGFR and positively with urine protein. MCP-1 and TGF-ß1 may contribute to the early detection of CKD and disease stage/progression in CAKUT children.
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There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.
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Combinação Besilato de Anlodipino e Olmesartana Medoxomila , Hipertensão , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/induzido quimicamente , Olmesartana Medoxomila/farmacologia , Anlodipino/efeitos adversos , Hidroclorotiazida/uso terapêutico , Tetrazóis/farmacologia , Imidazóis/efeitos adversos , Quimioterapia Combinada , Método Duplo-Cego , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/fisiologia , Hipertensão Essencial/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/tratamento farmacológicoRESUMO
Chronic lymphocytic leukemia (CLL) is a hematological malignancy with high metabolic heterogeneity. N6-methyladenosine (m6A) modification plays an important role in metabolism through regulating circular RNAs (circRNAs). However, the underlying mechanism is not yet fully understood in CLL. Herein, an m6A scoring system and an m6A-related circRNA prognostic signature are established, and circTET2 as a potential prognostic biomarker for CLL is identified. The level of m6A modification is found to affect the transport of circTET2 out of the nucleus. By interacting with the RNA-binding protein (RBP) heterogeneous nuclear ribonucleoprotein C (HNRNPC), circTET2 regulates the stability of CPT1A and participates in the lipid metabolism and proliferation of CLL cells through mTORC1 signaling pathway. The mTOR inhibitor dactolisib and FAO inhibitor perhexiline exert a synergistic effect on CLL cells. In addition, the biogenesis of circTET2 can be affected by the splicing process and the RBPs RBMX and YTHDC1. CP028, a splicing inhibitor, modulates the expression of circTET2 and shows pronounced inhibitory effects. In summary, circTET2 plays an important role in the modulation of lipid metabolism and cell proliferation in CLL. This study demonstrates the clinical value of circTET2 as a prognostic indicator as well as provides novel insights in targeting treatment for CLL.
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Ácidos Graxos , Ribonucleoproteínas Nucleares Heterogêneas Grupo C , Leucemia Linfocítica Crônica de Células B , RNA Circular , Humanos , Proliferação de Células , Ácidos Graxos/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Leucemia Linfocítica Crônica de Células B/genética , Metabolismo dos Lipídeos/genética , RNA Circular/metabolismoRESUMO
Background: Primary pulmonary sarcoma (PPS) is very rare relative to other subtypes of lung cancer. Therefore, evidence-based treatment options for PPS patients have remained unclear. Identification of actionable cancer driver mutations in patients with non-small cell lung cancer (NSCLC) has provided the chance to use targeted treatments and improve patient clinical outcomes. In addition to epidermal growth factor receptor (EGFR), the wide use of high-throughput genomic profiling with next-generation sequencing (NGS) has also identified other cancer driver genes such as Kirsten rat sarcoma (KRAS), human epidermal growth factor receptor 2 (HER2), and mesenchymal epithelial transition (MET). Case Description: In our study, we reported a locally advanced PPS patient harboring KRAS G12C mutation. The clinical stage before neoadjuvant treatment was stage IIIB (c.T3N2M0). The direct KRAS G12C inhibitor sotorasib (AMG-510) was used as neoadjuvant treatment and the patient achieved complete response (CR). Then, the patient underwent video-assisted thoracoscopic surgery (VATS) with reserved spontaneous breathing for surgical resection. The pathological evaluation was indicative of pathological CR (pCR). Further follow-ups are required to evaluate the long-term clinical benefit of neoadjuvant treatment with sotorasib and surgical resection with VATS. Conclusions: To our knowledge, it was the first study to use sotorasib for a PPS patient harboring KRAS G12C mutation in a neoadjuvant setting. Further follow-ups are required to evaluate the long-term clinical benefit of neoadjuvant treatment with sotorasib and surgical resection with VATS.
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BACKGROUND: Recently, circular RNAs (circRNAs) have been emerging as new regulators in the propofol-induced tumor-suppressive role. Here, we intended to investigate the involvement of circRNA-Mediator of cell motility 1 (circ-MEMO1; hsa_circ_0007385) in propofol role in cancer hallmarks of lung adenocarcinoma (LUAD). METHODS: Real-time quantitative PCR and western blotting examined transcriptional and translational levels of circ-MEMO1, microRNA (miR)-485-3p, and NIMA-related kinase-4 (NEK4), and markers of growth and metastasis including E-cadherin, CyclinD1, and Vimentin. Cancer hallmarks were measured by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, 5-ethynyl-2-deoxyuridine assay, and transwell assay. The interaction among circ-MEMO1, miR-485-3p, NEK4 was determined by dual-luciferase reporter assay and Pearson's correlation analysis. RESULTS: Circ-MEMO1 and NEK4 were high-expressed, and miR-485-3p was low-expressed in LUAD patients and cells; moreover, circ-MEMO1 and NEK4 expression in LUAD cells could be suppressed, whereas miR-485-3p could be elevated with propofol anesthesia. Functionally, propofol restrained cell viability, cell cycle entrance, cell proliferation, migration, and invasion of LUAD cells, accompanied by promoted E-cadherin and depressed CyclinD1 and Vimentin. Coincidently, high circ-MEMO1 was associated with low overall survival of LUAD patients, and overexpressing circ-MEMO1 could overall attenuate propofol effects in LUAD cells. Of note, upregulating miR-485-3p and/or interfering NEK4 could partially countermand the adverse impacts of circ-MEMO1 on propofol's role in LUAD cells. Importantly, circ-MEMO1 acted as a sponge for miR-485-3p to modulate the expression of miR-485-3p-targeted oncogene NEK4. CONCLUSION: Promoting the circ-MEMO1-miR-485-3p-NEK4 axis might halt the tumor-inhibiting role of propofol in LUAD cells in vitro, suggesting a potential epigenetic pathway of propofol.
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Adenocarcinoma de Pulmão , Anestésicos , Neoplasias Pulmonares , MicroRNAs , Propofol , Humanos , Propofol/farmacologia , Vimentina , Adenocarcinoma de Pulmão/genética , Proliferação de Células/genética , Caderinas , Neoplasias Pulmonares/genética , MicroRNAs/genética , Linhagem Celular Tumoral , Peptídeos e Proteínas de Sinalização Intracelular , Quinases Relacionadas a NIMARESUMO
In this study, we aimed to investigate the effect of gap junction (GJ) on apoptosis of smooth muscle. Forty adult male guinea pigs were randomly divided into four groups with 10 guinea pigs in each group. Adeno-associated virus (AAV) and Gap27 were injected at the root of the corpus cavernosum. Two weeks later, the corpus cavernosum tissue was taken to be tested. The expression of Cx43 and α-SMC protein was detected by immunofluorescence and Western blotting. The content of corpus cavernosum smooth muscle was detected by Masson trichrome staining. Apoptosis was detected by TUNEL staining and Western blotting. The results showed that Gap27 did not affect Cx43 but decreased the expression of smooth muscle. The results of TUNEL staining and detection of apoptosis-related proteins showed that apoptosis was induced by Gap27. In addition, we found that corpus cavernosum injection of AAV could induce obvious apoptosis. In this study, we examined the effect of inhibition of gap junction on smooth muscle, and suggested that the decrease of gap junction function may be a potential mechanism of smooth muscle apoptosis.
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Disfunção Erétil , Miócitos de Músculo Liso , Animais , Apoptose , Comunicação , Junções Comunicantes , Cobaias , Humanos , Masculino , Músculo Liso , Pênis , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Propofol is commonly used for providing procedural sedation during pediatric colonoscopy. Intravenous (i.v.) lidocaine can mitigate visceral pain and reduce propofol requirements during surgery. The aim of this study is to investigate the effect of i.v. lidocaine on perioperative propofol and sufentanil dose, pulse oxygen saturation, postoperative pain score, and recovery time during pediatric colonoscopy. METHODS: We designed a randomized, double-blind, placebo-controlled study and enrolled 40 children aged from 3 to 10 years who underwent colonoscopy. After titration of propofol to achieve unconsciousness, the patients were given i.v. lidocaine (1.5 mg/kg later 2 mg/kg/hour) or the same volume of saline. Sedation was standardized and combined propofol with sufentanil. The primary outcome variables were intraoperative propofol and sufentanil requirements, and the number of oxygen desaturation episodes. Secondary outcome variables were recovery time after colonoscopy and post-colonoscopy pain. RESULTS: Lidocaine infusion resulted in a significant reduction in propofol requirements: (median (quartile) 1.8 (1.5-2.0) vs. 3.0 (2.8-3.3) mg/kg respectively; P < 0.001) and sufentanil requirements: (median (quartile) 0.06 (0.05-0.08) vs. 0.1 (0.1-0.1) µg/kg respectively; P < 0.001). The number of subjects who experienced oxygen desaturation below 95% in the lidocaine group was also significantly less than that in the control group: 1 vs. 6 (P = 0.04). The mean (SD) recovery time was significantly shorter in the lidocaine group: (19.2 (2.6) vs. 13.3 (2.6) min respectively; P < 0.001). There was no significant difference in post-colonoscopy pain. CONCLUSION: Continuous infusion of lidocaine resulted in reduction of propofol and sufentanil requirements, recovery time, and risk of hypoxemia during pediatric colonoscopy.
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Lidocaína , Propofol , Anestésicos Intravenosos , Criança , Pré-Escolar , Colonoscopia/métodos , Método Duplo-Cego , HumanosRESUMO
BACKGROUND The pathogenesis of chemotherapy-induced neuropathy, a dose-dependent adverse effect of cisplatin, involves mitochondrial dysfunction. PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy removes damaged mitochondria under various pathological conditions. The objective of this study was to determine mitophagy status and its effects on mitochondrial function and neuronal cell damage after cisplatin treatment using an in vitro model of cisplatin-induced neurotoxicity. MATERIAL AND METHODS PC12 cells were transfected with Parkin or Parkin siRNA using lentiviral particles and Lipofectamine 3000™, respectively, and then were exposed to 10 µM cisplatin. The expression of autophagic proteins was measured by Western blot analysis. Mitophagy in PC12 cells was detected by confocal microscopy analysis of mitochondria-lysosomes colocalization and autophagic flux. The effects of PINK1/Parkin-mediated mitophagy on cisplatin-induced neurotoxicity were assessed via mitochondrial function, neuritic length, nuclear diameter, and apoptosis. RESULTS Cisplatin activated PINK1/Parkin-mediated mitophagy in PC12 cells. Autophagic flux analysis revealed that cisplatin inhibits the late stage of the autophagic process. The knockdown of Parkin suppressed cisplatin-induced mitophagy, aggravating cisplatin-induced depolarization of mitochondria, cellular ATP deficits, reactive oxygen species outburst, neuritic shortening, nuclear diameter reduction, and apoptosis, while Parkin overexpression enhanced mitophagy and reversed these effects. CONCLUSIONS PINK1/Parkin-regulated mitophagy can protect against cisplatin-related neurotoxicity, suggesting therapeutic enhancement of mitophagy as a potential intervention for cisplatin-induced peripheral neuropathies. The interference of cisplatin with autophagosome-lysosome fusion may be partly responsible for cisplatin-induced neurotoxicity.
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Cisplatino/toxicidade , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cisplatino/farmacologia , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Mitofagia/fisiologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/genética , Células PC12 , PTEN Fosfo-Hidrolase/metabolismo , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transfecção , Ubiquitina-Proteína Ligases/administração & dosagem , Ubiquitina-Proteína Ligases/genéticaRESUMO
Accurately modeling gas-surface collision dynamics presents a great challenge for theory, especially in the low-energy (or temperature) regime where quantum effects are important. Here, a path integral-based nonequilibrium ring polymer molecular dynamics (NE-RPMD) approach is adapted to calculate dissociative initial sticking probabilities (S0) of H2 on Cu(111) and D2O on Ni(111), revealing the distinct quantum nature in the two benchmark surface reactions. NE-RPMD successfully captures quantum tunneling in H2 dissociation at very low energies, where the quasi-classical trajectory (QCT) method suddenly fails. Additionally, QCT substantially overestimates S0 of D2O because of severe zero point energy (ZPE) leakage, even at collision energies greater than the ZPE-corrected barrier. Instead, NE-RPMD predicts S0 values of D2O in much improved agreement with reference results obtained by the quantum wavepacket method with reasonable corrections of the thermal contribution. Our results suggest NE-RPMD as a promising approach to model quantum effects in gas-surface reactions.
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Patients with ST-segment elevation myocardial infarction (STEMI) who are treated by primary percutaneous coronary intervention (PPCI) have an increased risk of developing contrast-induced nephropathy (CIN) when compared with patients undergoing elective percutaneous coronary intervention (PCI). However, CIN prevention measures are less frequently applied in PPCI than in elective PCI. At present, no preventive strategy has been recommended by the current guidelines for patients with STEMI undergoing PPCI.Published research was scanned by formal searches of electronic databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials) from 1966 to July 2018. Internet-based sources of information on the results of clinical trials in cardiology were also searched.A total of three randomized trials involving 924 patients were included in the present meta-analysis, of whom 462 received hydration with isotonic saline (hydration group) and 462 received no hydration (control group). Periprocedural hydration with isotonic saline was associated with a significant decrease in the rate of CIN (16.9% in the hydration group versus 26.4% in the control group; summary risk ratio: 0.64, 95% confidence interval: 0.50-0.82, P = 0.0005). There was no difference in the rate of postprocedural hemodialysis or death between the groups.Intravenous saline hydration during PPCI reduced the risk of CIN without significantly altering the rate of requirement for renal replacement therapy or mortality.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Meios de Contraste/efeitos adversos , Hidratação/métodos , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Injúria Renal Aguda/prevenção & controle , Idoso , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Patients with cancer are vulnerable to depression or other depressive conditions. The aim of this paper was to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for the treatment of depression or depressive symptoms in cancer patients. METHODS: CENTRAL, MEDLINE, EMBASE, PsycINFO, CNKI, VIP, SinoMed, and online clinical trial registry websites were searched for relevant RCTs until May 2017. The methodological quality of each included study was assessed with the "risk of bias" tool. Review Manager 5.3.5 was used to analyze the data. RESULTS: We identified 18 RCTs that included data from 1441 participants. Twelve different types of Chinese herbal preparations were investigated by these studies, and they showed a better therapeutic effect in most comparisons when measured in terms of depression rating scale scores, with SMDs (95% CI) of - 2.30 (- 3.54, - 1.05) (CHM versus no treatment), - 0.61 (- 1.03, - 0.18) (CHM versus antidepressants), and - 0.55 (- 1.07, - 0.02) (CHM plus psychological treatments versus psychological treatments), or when measured in terms of treatment response rate, with RRs (95% CI) of 1.65 (1.19, 2.29) (CHM versus no treatment), 1.15 (1.03, 1.28) (CHM versus psychological treatments), 1.32 (1.07, 1.63) (CHM plus antidepressants versus antidepressants), and 1.70 (1.02, 2.85) (CHM plus psychological treatments versus psychological treatments). Compared with antidepressants, these CHMs showed borderline superiority for improving the response rate, with an RR (95% CI) of 1.08 (0.93, 1.26). Subgroup analysis based on psychiatric diagnosis (depression versus depressive symptoms) did not modify the direction of these estimates and neither could it explain the high level of heterogeneity. Patients in the CHM group experienced fewer adverse events of cardiac toxicity (P = 0.02), functional gastrointestinal disorders (P = 0.008), sleep disturbances (P = 0.02), blurred vision (P = 0.02) and fatigue (P = 0.03) than the patients in the no treatment group or the antidepressants group. CONCLUSIONS: According to the investigation of the twelve herbal preparations, the CHM intervention appears to alleviate depressive symptoms in cancer patients, either alone or combined with antidepressants or psychological treatments. However, a high risk of bias and high heterogeneity made the mean estimates uncertain. Well-designed trials with comprehensive and transparent reporting are warranted in the future.
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Depressão/tratamento farmacológico , Depressão/etiologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neoplasias/psicologiaRESUMO
OBJECTIVE: To investigate the efficacy of Zhonglun'a-decoction-containing serum (ZHONGL-CS) on the in vitro apoptosis of fibroblast-like synoviocytes (FLS) from rats with collagen-induced arthritis (CIA) by investigating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. METHODS: A CIA rat model was established using bovine type â ¡ collagen. FLS were isolated, cultured and identified. A cell counting kit-8 was used to detect cell activity. The half maximal inhibitory concentration (IC50) was calculated. Experimental subjects were divided into control, CIA, ZHONGL-CS, JAK2 inhibitor AG490, and ZHONGLCS with AG490 groups. The in vitro cell cycle and apoptosis rate were detected in FLS by flow cytometry. Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3, cyclin D1, phosphorylated JAK2, STAT1, and STAT3 protein expressions in FLS were examined by Western blotting. JAK2, STAT1 and STAT3 mRNA levels were examined by quantitative real-time polymerase chain reaction. RESULTS: Compared with the CIA group, FLS proliferation was inhibited, the FLS G0/G1 cell cycle was arrested, and the rate of FLS apoptosis was increased in the ZHONGL-CS group. In the ZHONGLCS group, the protein levels of Bcl-2 and cyclin D1 were reduced compared with the CIA group and the levels of Bax and caspase-3 in FLS were increased. In the ZHONGL-CS group, the expressions of JAK2, STAT1, and STAT3 mRNA and the levels of phosphorylated JAK2, STAT1, and STAT3 proteins were reduced. CONCLUSION: ZHONGL-CS may induce FLS apoptosis in CIA rats. Activation of the JAK/STAT signaling pathway was inhibited in FLS in vitro.
Assuntos
Apoptose/efeitos dos fármacos , Artrite Experimental/patologia , Medicamentos de Ervas Chinesas/farmacologia , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Soro/química , Transdução de Sinais/efeitos dos fármacos , Sinoviócitos/patologia , Animais , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Fibroblastos/patologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Sinoviócitos/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To observe the anesthetic effect and safety of different doses of dexmedetomidine combined with ropivacaine for brachial plexus nerve block in children undergoing polydactyly surgery. METHODS: Eighty children undergoing polydactyly surgery were randomized into 4 groups to receive brachial plexus nerve block with dexmedetomidine at 0.25, 0.50 or 0.75 µg/kg combined with 0.25% ropivacaine (0.20 mL/kg) (D1, D2, and D3 groups, respectively) or with 0.25% ropivacaine (0.20 mL/kg) only (control group). The onset time, duration of brachial plexus nerve block, awakening time, success rate, and incidence of complications were compared among the groups. Results In D2 and D3 groups, the onset time and awakening time were shorter and anesthesia lasted longer than those in the control group. The onset time and awakening time were shorter and anesthesia maintenance time was longer in D3 group than in D1 group. The success rates of brachial plexus nerve block were significantly higher in D1-3 groups than in the control group (P<0.05). Hematoma was found in one of the patients. In each of the 4 groups, laryngeal nerve block occurred in 1 child and respiratory depression in another; 2 or 3 patients had Horner syndrome, and 1 patient in D3 group experienced an episode of lowered heart beat to below 70 min-1. All the complications were managed properly and the patients all recovered uneventfully. CONCLUSION: Brachial plexus nerve block with 0.5 µg/kg dexmedetomidine combined with 0.25% ropivacaine (0.20 mL/kg) is safe for effective anesthesia in children undergoing surgery for polydactyly.
Assuntos
Amidas/administração & dosagem , Anestésicos Locais/administração & dosagem , Plexo Braquial/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Bloqueio Nervoso , Polidactilia/cirurgia , Criança , Método Duplo-Cego , Humanos , RopivacainaRESUMO
The role of homocysteine (Hcy) in the pathogenesis of coronary artery disease (CAD) is controversial, as decreased Hcy levels have not demonstrated consistent clinical benefits. Recent studies propose that S-adenosylhomocysteine (SAH), and not Hcy, plays a role in cardiovascular disease (CVD). We aimed to assess the relationship between plasma SAH and coronary artery lesions. Participants (n=160; aged 40-80years) with chest pain and suspected CAD underwent coronary angiography (CAG) for assessment of coronary artery stenosis, and were assigned to either the atherosclerosis (AS) or CAD group. Plasma SAH and S-adenosylmethionine (SAM) concentrations were measured and the association between coronary artery lesions and SAH was assessed. SAH levels were significantly higher in the CAD group (23.09±2.4nmol/L) than in the AS group (19.2±1.5nmol/L). While the AS group had higher values for SAM/SAH (5.1±0.7 vs. 4.1±1.1), levels of SAM, Hcy, folate, and vitamin B12 were similar in the two groups. Coronary artery lesions were associated with SAH (ß=11.8 [95% CI: 5.88, 17.7, P<0.05]. Plasma SAH concentrations are independently associated with coronary artery lesions among patients undergoing coronary angiography. Plasma SAH might be a novel biomarker for the early clinical identification of CVD.
Assuntos
Doença da Artéria Coronariana/sangue , S-Adenosil-Homocisteína/sangue , S-Adenosilmetionina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: An increasing number of studies have shown that low tidal volume (TV) with positive end-expiratory pressure (PEEP) offers lung protection during one-lung ventilation (OLV). Considering the unique physiological characteristics of infants, we aimed to determine the feasibility and effect of low TV with PEEP in infants undergoing OLV during thoracoscopy. PATIENTS AND METHODS: We randomized 60 infants to a conventional group (group I: TV, 8-10 ml/kg; RR, 23-45 bpm; PEEP, 0 cmH2O) or a low TV with PEEP group (group II: TV, 5-7 ml/kg; RR, 23-45 bpm; PEEP, 4-6 cmH2O). Arterial blood gas analyses were performed at four time points: 5 min of two-lung ventilation (TLV, T0), and 20 min, 40 min, and 60 min of OLV (T1, T2, T3); hemodynamic parameters (heart rate, mean blood pressure), temperature, as well as gas exchange (SpO2 and PETCO2) and ventilation parameters (FiO2, PEEP, Pmax) were recorded simultaneously. Lung compliance and shunt were also calculated. RESULT: No significant difference was found between both groups at T0. Compared with T0, PETCO2, Pmax, PaCO2, lactic acid, and intrapulmonary shunt volume (Qs/Qt) were increased while PaO2 and respiratory system compliance (Cdyx) were decreased noticeably in both groups at T1, T2, and T3. At T1, T2, and T3, Pmax and Qs/Qt were much lower while PETCO2, PaCO2, and Cdyx were higher in group II than in group I. There was no significant difference in lactic acid and PaO2 measurements between the two groups at T1, T2, and T3. CONCLUSION: Low TV with PEEP could be an effective intraoperative ventilation strategy for infants undergoing OLV during video-assisted thoracoscopic surgery and may reduce the risk of lung injury. However, this strategy, as well as the influence of intraoperative hypercapnia on infants, needs further investigation.
Assuntos
Ventilação Monopulmonar/métodos , Respiração com Pressão Positiva , Testes de Função Respiratória , Volume de Ventilação Pulmonar , Feminino , Hemodinâmica , Humanos , Lactente , Ácido Láctico/sangue , Complacência Pulmonar , Masculino , Consumo de Oxigênio , Troca Gasosa Pulmonar , Doenças Respiratórias/congênito , Doenças Respiratórias/cirurgia , Cirurgia Torácica Vídeoassistida/métodosRESUMO
Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. In the present study, we sought to investigate whether rosuvastatin could alleviate morphine tolerance by attenuating the glia mediated neuroinflammation in the spinal cord. Using a rat model of L5 spinal nerve transection, on day 8 after surgery morphine (10 mg/kg) was injected subcutaneously twice daily for consecutive 10 days. On day 13, with the establishment of morphine tolerance, rosuvastatin (10 mg/kg) was given o.p. for 5 days. On day 18, lumbar spinal cord was collected immediately after last behavioral testing. The analgesic effect of morphine was determined as the percentage of maximal possible effect (%MPE) after a single morphine (4 mg/kg) injection via tail vein on day 8, 13, and 18. The MPE decreased significantly after administration of morphine to rats with neuropathy for 5 days. Rosuvastatin administration for 5 days could restore morphine antinociceptive effect significantly. Additionally, the activation of astrocytes, the phosphorylation of extracellular signal-regulated kinase 42/44 (ERK(42/44)) and the expressions of TNFα and IL-1ß were inhibited significantly by rosuvastatin. Our data suggested that rosuvastatin was a promising choice to treat neuropathic pain in combination with morphine.
Assuntos
Analgésicos Opioides/farmacologia , Fluorbenzenos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Morfina/farmacologia , Neuralgia/metabolismo , Pirimidinas/farmacologia , Traumatismos da Medula Espinal/metabolismo , Sulfonamidas/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Interações Medicamentosas , Tolerância a Medicamentos , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Interleucina-1beta/metabolismo , Masculino , Neuralgia/etiologia , Fosforilação , Ratos Sprague-Dawley , Rosuvastatina Cálcica , Traumatismos da Medula Espinal/etiologia , Nervos Espinhais/lesões , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The present study was conducted to identify the difference of the relationship between lifestyle behaviors with hypertension (HTN) by various body mass index (BMI) categories. A cross-sectional study was conducted among Tianjin urban communities. A total of 26 438 subjects were randomly selected. The authors evaluated associations of lifestyle behaviors with HTN among normal, overweight, and obese adults using a hierarchical logistic model considering the gross domestic product of residence as socioeconomic proxy. A positive association was found between BMI and the risk of HTN among male and female subjects. Current smoking was associated with a higher risk of HTN in overweight (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36) and obese groups (OR = 1.20, 95% CI = 1.03-1.53). There were statistically significant associations of current drinking with risk of HTN in normal weight (OR = 1.18, 95% CI = 1.01-1.31) and overweight groups (OR = 1.22, 95% CI = 1.07-1.40). The prevention of overweight and obesity is important in preventing HTN. Additionally, adherence to healthy lifestyle is associated with less risk of HTN in various BMI categories.