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1.
Arch Esp Urol ; 77(7): 766-771, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39238301

RESUMO

OBJECTIVE: Benign prostatic hyperplasia (BPH) is a common chronic disease affecting the health of the urinary system and the quality of life in older adults. Plasmakinetic resection of the prostate (PKRP) is one of the important surgical procedures for treating BPH; However, older adults may experience anesthesia complications and postoperative pain. This retrospective study aimed to assess the effects of preoperative oral gabapentin on anesthesia outcomes in older adults with BPH undergoing PKRP and to provide detailed clinical evidence for improving the impact of surgical treatment. METHODS: The medical records of 178 older adults with BPH who underwent PKRP in Tianjin Hospital from March 2021 to March 2023 were retrospectively analyzed. After excluding 18 patients who did not meet the inclusion criteria, 160 patients were finally included in the study. According to preoperative use of gabapentin, patients were divided into the observation group (n = 75, received gabapentin) and the control group (n = 85, did not receive gabapentin). The baseline data, visual analog scale (VAS) scores, postoperative Ramsay Sedation Scale (RSS) scores, and incidence of adverse reactions were collected. RESULTS: There were no significant differences observed between the two groups in terms of age, body mass index, prostate volume, surgery duration, International Prostate Symptom Score (IPSS), American Society of Anesthesiologists (ASA) classification, history of hypertension and diabetes mellitus, VAS scores at postoperative 36 hours and 48 hours, and RSS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours (p > 0.05). Compared to the control group, the observation group had significantly lower VAS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours (p < 0.001), and the incidence of adverse reactions was significantly lower within 24 hours after surgery (p < 0.05). CONCLUSIONS: Preoperative administration of gabapentin before PKRP could reduce pain severity and the incidence of adverse reactions and improve anesthetic effects in older adults with BPH, which is conducive to postoperative recovery.


Assuntos
Gabapentina , Hiperplasia Prostática , Humanos , Masculino , Gabapentina/administração & dosagem , Gabapentina/uso terapêutico , Estudos Retrospectivos , Hiperplasia Prostática/cirurgia , Idoso , Administração Oral , Cuidados Pré-Operatórios , Anestesia/métodos , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle
2.
Ann Ital Chir ; 95(4): 669-677, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39186347

RESUMO

AIM: Acute appendicitis is a common disease in the elderly. Exploring a suitable anesthesia method is crucial in promoting postoperative recovery in elderly patients. Therefore, this study aimed to investigate the clinical effect of intraspinal anesthesia in elderly patients with appendicitis. METHODS: This study included the clinical data of 217 elderly patients with acute appendicitis who underwent laparoscopic appendectomy (LA) at Tianjin Hospital of Tianjin University from January 2022 to January 2023. After excluding 8 patients who did not meet the inclusion criteria, the data from 209 patients were retrospectively analyzed. Based on the different anesthesia methods, the study participants were divided into a reference group (n = 106) and a study group (n = 103). We compared the heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), diastolic blood pressure (DBP), blood oxygen saturation (SaO2), operation duration, hospitalization costs, discharge time, postoperative adverse reactions, inflammatory factor levels, Visual Analogue Scale (VAS) score, recovery time of intestinal peristalsis, anal exsufflation time, out-of-bed time, and incidence of postoperative complications between the two experimental groups. RESULTS: We observed that the study group exhibited higher levels of HR, RR, SBP, DBP, and SaO2 compared to the reference group (p < 0.001). However, there was no difference in operation time between the two groups (p > 0.05). The study group showed lower hospitalization cost and shorter discharge time than the reference group (p < 0.001). Similarly, the study group had lower incidence of postoperative adverse reactions than reference group (p < 0.05). There were no significant differences in the levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α between the two groups before and after surgery (p > 0.05). Furthermore, the study group had a lower VAS score compared to the reference group at 3 h, 6 h and 12 h after surgery (p < 0.001). The recovery time of intestinal peristalsis, anal exsufflation time, and out-of-bed time in the study group were substantially shorter than the reference group (p < 0.001). Additionally, there was no difference in the incidence of postoperative complications between the two groups within 1 year after surgery (p < 0.001). CONCLUSIONS: Intraspinal anesthesia, as a safe anesthesia method, can reduce the discharge time of elderly patients with acute appendicitis who underwent LA, and reduce the occurrence of adverse reactions, and is beneficial for postoperative recovery.


Assuntos
Apendicectomia , Apendicite , Humanos , Estudos Retrospectivos , Apendicite/cirurgia , Idoso , Feminino , Masculino , Apendicectomia/métodos , Raquianestesia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Doença Aguda , Laparoscopia/métodos , Pessoa de Meia-Idade , Frequência Cardíaca
3.
Arch Esp Urol ; 76(10): 780-786, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38186071

RESUMO

BACKGROUND: The reasonable selection of anaesthesia methods and drugs is the key to ensuring the perioperative safety of patients with the transurethral resection of the prostate (TURP). The effect of intravenous remazolam injection on stress response and analgesic effect in patients with transurethral prostate cancer electrotomy were explored. METHODS: The medical records of 160 patients with prostatic hyperplasia who underwent TURP in Tianjin hospital from November 2020 to November 2022 were selected for retrospective analysis. Five patients who did not meet the study conditions were excluded, and 155 patients were finally included. According to anaesthesia schemes, the patients were divided into the observation group (OBG, n = 76, routine surgical anaesthesia and intravenous remazolam injection) and control group (COG, n = 79, routine surgical anaesthesia). Postoperative eye-opening times were recorded for both groups. The groups were compared in terms of anaesthetic effects, stress indexes, haemodynamic indexes, and use of postoperative analgesic drugs at different times, and adverse reactions were observed. RESULTS: The anaesthesia onset time and eye-opening time in the OBG were shorter than those in the COG (p < 0.001). The heart rate and mean arterial pressure of the OBG during anaesthesia induction were higher than those in the COG (p < 0.001). The OBG showed significantly lower noradrenaline and cortisol levels than the COG 1, 12 and 24 h after surgery (p < 0.001). The time of first pressing in the analgesic pump in the OBG was later than that in the COG, and the total consumption of sufentanil was less than that in the COG (p < 0.001). The total incidence of adverse reactions in the OBG was lower than that in the COG (p < 0.05). CONCLUSIONS: Intravenous remazolam injection provides safe and effective sedation and analgesia for patients on TURP and reduces the occurrence of stress responses and adverse reactions. However, cases involved in this study were all from a single centre, and multi-centre research and verification are needed.


Assuntos
Ressecção Transuretral da Próstata , Masculino , Humanos , Injeções Intravenosas , Estudos Retrospectivos , Próstata/cirurgia , Procedimentos Cirúrgicos Urológicos
4.
Dis Markers ; 2022: 8692966, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990245

RESUMO

Objective: To investigate the effects of lumbar plexus block combined with infiltration anesthesia on anesthesia comfort scores and stress responses in elderly patients undergoing hip replacement. Methods: The materials of 100 elderly patients undergoing hip replacement who were treated in our hospital (January 2020-January 2021) were retrospectively analyzed, and they were equalized into the experimental group (n = 50) and control group (n = 50) according to the anesthesia methods. The experimental group received lumbar plexus block combined with infiltration anesthesia, and the control group received combined spinal-epidural anesthesia combined with infiltration anesthesia. The patients' anesthesia comfort scores, stress responses, and postoperative pain indexes were compared between the two groups. Results: Compared with the control group, the experimental group achieved much lower scores of mood change, shivering response, and traction reaction (P < 0.001), indicating that the anesthesia comfort in the experimental group was higher. Compared with the control group, the experimental group had much better perioperative stress response indexes (P < 0.05) and eminently lower pain scores at 12 and 24 hours after surgery (P < 0.05). Conclusion: Lumbar plexus block combined with infiltration anesthesia can relieve the stress responses and postoperative pain of elderly patients undergoing hip replacement and increase their anesthesia comfort. Therefore, this anesthesia method is translational in clinic.


Assuntos
Anestesia Local , Bloqueio Nervoso , Idoso , Humanos , Plexo Lombossacral , Bloqueio Nervoso/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/etiologia , Estudos Retrospectivos
5.
Sci Rep ; 12(1): 14269, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35995967

RESUMO

The embryo transfer depth may affect the chance of pregnancy. However, embryo dislodging caused by uterine contraction may occur after the transfer. The aim of the retrospective study was to investigate whether the factors associated with uterine contractilities, such as endometrial thickness and progesterone elevation, affect the association between transfer depth and implantation. A total of 7849 fresh transfer cycles on conventional stimulation in a single in vitro fertilization (IVF) center during the period 2013-2015 was reviewed. Patients were categorized according to quartiles of embryo transfer depth (≤ 9 mm, n = 1735, 9.1-11 mm, n = 2557, 11.1-14 mm, n = 1933, ≥ 1.4 mm, n = 1624, respectively). Adjusted for confounding factors, the adjusted odds ratio (aOR) (95% confidence interval, CI) for clinical pregnancy was 0.90 (0.79-1.02), 0.86 (0.74-0.99), and 0.70 (0.60-0.82) respectively in quartiles 2 through 4, comparing with quartile 1. However, the aORs were significantly increased when the endometrial thickness was < 8 mm. In comparison with that in the cycles with a normal endometrial thickness (8-11 mm), the aORs comparing quartiles 2 through 4 with quartile 1 in the cycles with an endometrial thickness < 8 mm increased from 0.78 (95% CI 0.65-0.93), 0.79 (95% CI 0.65-0.97), and 0.64 (95% CI 0.51-0.81) to 1.73 (95% CI 1.21-2.47), 1.04 (95% CI 0.69-1.56), and 1.45 (95% CI 0.91-2.31), respectively. In the cycles with elevated progesterone and blastocyst stage transfer, the aORs comparing quartiles 4 with quartile 1 decreased from 0.73 (95% CI 0.62-0.87) and 0.74 (95% CI 0.63-0.87) to 0.58 (95% CI 0.40-0.84) and 0.42 (95% CI 0.25-0.73) than those in the cycles without. However, only blastocyst transfer showed a significant interaction with transfer depth (p = 0.043). Our data suggested that endometrial thickness and blastocyst transfer significantly affect the association between embryo transfer depth and clinical pregnancy.


Assuntos
Transferência Embrionária , Progesterona , Blastocisto , Feminino , Fertilização in vitro , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
6.
Contrast Media Mol Imaging ; 2022: 6064007, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35815058

RESUMO

To assess the preventive role of dexamethasone (Dex) in the development of neuroinflammation and concomitant neurocognitive disorders following acute inflammation. C57BL6 mice were fallen into the sham group, ischemia-reperfusion (I/R) group, and I/R + Dex group randomly. In the end, behavioral alterations were assessed with the Morris water maze (MWM) test, passive avoidance test (PAT), and open field test (OFT). The serum levels of IL-1ß and TNF-α were detected by ELISA. Immunofluorescence was adopted to observe the NF-kB expression in the hippocampus. In addition, TLR4, NF-kB, CD68, and CD206 were examined by Western blot. The cognitive ability of mice can be impaired by tourniquet-induced acute inflammation, and these changes were prevented by Dex. Compared to the I/R group, Dex pretreatment could decrease levels of IL-1ß and TNF-α proteins in serum. Besides, Dex preconditioning significantly decreased the utterance of NF-kB immunoreactive cells and TLR4, NF-kB, and CD68 overexpression in the hippocampus. Dex partly through inhibiting microglia transformation to the M1 polarization state and inactivating the TLR4/NF-kB pathway attenuates the cognitive disorders in mice.


Assuntos
Disfunção Cognitiva , Dexametasona , Inflamação , Animais , Disfunção Cognitiva/prevenção & controle , Dexametasona/uso terapêutico , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
Cell Mol Biol (Noisy-le-grand) ; 68(2): 103-108, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35869732

RESUMO

The study aimed to investigate the effects of different anesthesia methods on the analgesia, inflammation and oxidative stress levels and cognitive function in elderly patients undergoing hip replacement. 100 elderly patients requiring hip replacement and admitted to Tianjin Hospital from March 2017 to March 2019 were enrolled and divided into group A (n=35, general anesthesia with endotracheal intubation), group B (n=35, epidural anesthesia) and group C (n=30, general anesthesia with endotracheal intubation + epidural anesthesia). The basic vital signs, inflammatory factors, stress response indicators and cognitive function changes were compared among three groups. Additionally, the effects of three different anesthesia methods were analyzed based on the differences in postoperative analgesic effect, extubation time and recovery time. The vital signs [systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR)] were lower in group C than those in group A and group B after surgery (p<0.05). The VAS score at 12 h and 24 h after surgery was lower than that at 3 h after surgery (p<0.05). Group A and B had increased levels of these inflammatory factors after surgery compared with those before surgery. Postoperative extubation time, eye-opening time upon calling and recovery time were significantly shorter in group C than those in groups A and B (p<0.05). The oxidative stress indexes in group C were remarkably lower than those in groups A and B (p<0.05). The MMSE score was decreased in groups A and B after surgery compared with that before surgery (p<0.05). General anesthesia combined with epidural anesthesia applied in elderly patients undergoing hip replacement achieves a good anesthetic effect and is able to stabilize the vital signs and stress levels of patients and improve postoperative analgesic effect and cognitive function, which is worthy of popularization in clinical practice.


Assuntos
Analgesia , Anestesia Geral , Idoso , Analgésicos , Cognição , Humanos , Inflamação , Estresse Oxidativo
8.
Comput Intell Neurosci ; 2022: 8039358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392043

RESUMO

Objective: To explore the clinical application effect of perioperative anesthesia management based on enhanced recovery after surgery (ERAS) concept to elderly patients undergoing total knee replacement (TKR). Methods: By means of retrospective analysis, the medical data of elderly patients undergoing TKR treated in our hospital (02, 2019-02, 2020) were analyzed, and 100 patients were selected as the study objects according to the inclusion and exclusion criteria and divided into the study group (SG) and reference group (RG) according to their admission order, with 50 cases each. Patients in SG received perioperative anesthesia management based on ERAS concept, and those in RG accepted routine perioperative anesthesia management, so as to compare the perioperative inflammatory factors levels, postoperative recovery indicators, and postoperative Numeric Rating Scale (NRS) scores between the two groups. Results: Compared with RG after surgery, SG obtained significantly lower inflammatory factors levels (P < 0.001) and significantly better recovery indicators (P < 0.05), and the pain scores at postoperative 12 h and 24 h of SG were, respectively (1.46 ± 0.67) points and (2.00 ± 0.45) points, which were significantly lower than those of RG (P < 0.05). Conclusion: Perioperative anesthesia management based on EARS concept can improve the perioperative indicators of elderly patients undergoing TKR, result in less postoperative pain, and obtain a more desirable recovery.


Assuntos
Anestesia , Artroplastia do Joelho , Recuperação Pós-Cirúrgica Melhorada , Idoso , Artroplastia do Joelho/efeitos adversos , Humanos , Dor Pós-Operatória , Estudos Retrospectivos
9.
J Healthc Eng ; 2021: 3080098, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950440

RESUMO

Objective: To explore the application of different doses of dexmedetomidine combined with general anesthesia in patients with traumatic tibiofibular fractures. Methods: A total of 120 patients with traumatic tibiofibular fractures treated in our hospital (January 2018-January 2021) were selected as the research subjects and equally grouped into group A, group B, group C, and group D according to the dosage of dexmedetomidine. Group B, group C, and group D were pumped with 0.3 µg/kg, 0.5 µg/kg, and 0.8 µg/kg load doses of dexmedetomidine before anesthesia induction, with the same doses for maintenance during surgery. Group A was intravenously pumped with the same amount of normal saline and received tracheal intubation after anesthesia induction, with propofol and remifentanil to maintain general anesthesia during surgery. Results: No notable differences in general data were observed among the groups (P > 0.05). Ramsay sedation scores of all groups showed a downward trend after drug withdrawal. At 10 min, 30 min, and 60 min, the scores of groups C and D were markedly higher than those of groups A and B (P < 0.05), and the scores were higher in group D than those in group C (P < 0.05). The HR changes at each period were close between groups A and B (P > 0.05). The HRs at T1 and T2 in group C were slightly lower than those in group D (P > 0.05), and the HRs at T1 in groups A and B were remarkably higher than those in groups C and D, and were higher than those at T0 and T2 (P < 0.05). The SBP levels of all groups began to rise at T0, peaked at T1, and decreased to a lower level at T2 than that at T0. Moreover, the SBP levels of groups C and D at T1 and T2 were notably lower compared with groups A and B (P < 0.05). With a lower DBP level in group C than the other three groups at T1, the DBP levels were notably lower in groups C and D than those in groups A and B at T2 (P < 0.05). With no statistical difference in the MAP levels at T0 among the four groups (P > 0.05), the MAP levels in group A at T1 and T2 were obviously higher compared with groups C and D (P < 0.05). The extubation time in group A was notably longer than that that in groups B, C, and D (P < 0.05), with longer extubation time in group B than that in groups C and D (P < 0.05). The orientation recovery time in group D was markedly shorter than that in groups A, B, and C (P < 0.05). The incidence of cognitive dysfunction, chills, and restlessness in groups C and D was notably lower compared with groups A and B (P < 0.05), with a higher incidence of chills, intraoperative hypotension, and delayed awakening in group D than in group C (P < 0.05). Conclusion: Dexmedetomidine at doses of 0.5 µg/kg and 0.8 µg/kg has a better effect in the maintenance of general anesthesia for patients with traumatic tibiofibular fractures, with faster orientation recovery, better recovery of postoperative cognitive function, and a lower incidence of adverse reactions. Dexmedetomidine at 0.5 µg/kg is recommended in view of the increased risk of excessive sedation, chills, restlessness, and intraoperative hypotension in patients at 0.8 µg/kg.


Assuntos
Anestesia Geral , Dexmedetomidina , Fraturas Ósseas , Anestesia Geral/efeitos adversos , Cognição , Dexmedetomidina/administração & dosagem , Humanos , Incidência , Propofol/efeitos adversos , Remifentanil/efeitos adversos
10.
Cost Eff Resour Alloc ; 19(1): 53, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404418

RESUMO

BACKGROUND: Lung cancer is the most prevalent cancer, and the leading cause of cancer-related deaths in China. The aim of this study was to estimate the direct medical expenditure incurred for lung cancer care and analyze the trend therein for the period 2002-2011 using nationally representative data in China METHODS: This study was based on 10-year, multicenter retrospective expenditure data collected from hospital records, covering 15,437 lung cancer patients from 13 provinces diagnosed during the period 2002-2011. All expenditure data were adjusted to 2011 to eliminate the effects of inflation using China's annual consumer price index. RESULTS: The direct medical expenditure for lung cancer care (in 2011) was 39,015 CNY (US$6,041) per case, with an annual growth rate of 7.55% from 2002 to 2011. Drug costs were the highest proportionally in the total medical expenditure (54.27%), followed by treatment expenditure (14.32%) and surgical expenditure (8.10%). Medical expenditures for the disease varied based on region, hospital level, type, and stage. CONCLUSION: The medical expenditure for lung cancer care is substantial in China. Drug costs and laboratory test are the main factors increasing medical costs.

11.
J Gastroenterol Hepatol ; 36(5): 1197-1207, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32875595

RESUMO

BACKGROUND AND AIM: This study aimed to clarify health-related quality of life (HRQoL) of patients with colorectal precancer and colorectal cancer (CRC) in China and to better understand related utility scores. METHODS: A hospital-based cross-sectional survey was conducted in precancer and CRC patients from 2012 to 2014, covering 12 provinces in China. HRQoL was assessed with EuroQol 5-Dimensions 3-Levels. Utility scores were derived using Chinese value set. A multivariate regression model was established to explore potential predictors of utility scores. RESULTS: A total of 376 precancer (mean age 58.7 years, 61.2% men) and 2470 CRC patients (mean age 58.6 years, 57.6% men) were included. In five dimensions, there was a certain percentage of problem reported among precancer (range: 12.0% to 36.7%) and CRC (range: 32.4% to 50.3%) patients, with pain/discomfort being the most serious dimension. Utility scores of precancer and CRC patients were 0.870 (95% confidence interval [CI], 0.855-0.886) and 0.751 (95% CI, 0.742-0.759), both of which were lower than those of general Chinese population (0.960 [95% CI, 0.960-0.960]). Utilities for patients at stage I to stage IV were 0.742 (95% CI, 0.715-0.769), 0.722 (95% CI, 0.705-0.740), 0.756 (95% CI, 0.741-0.772), and 0.745 (95% CI, 0.742-0.767), respectively. Multivariate analysis showed that therapeutic regimen, time point of the interview, education, occupation, annual household income, and geographic region were associated with utilities of CRC patients. CONCLUSION: Health-related quality of life of both precancer and CRC patients in China declined considerably. Utility scores differed by sociodemographic and clinical characteristics, and findings of these utilities may facilitate implementation of further cost-utility evaluations.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Neoplasias Colorretais/patologia , Neoplasias Colorretais/psicologia , Neoplasias Colorretais/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Análise de Regressão , Adulto Jovem
12.
J Recept Signal Transduct Res ; 41(5): 511-519, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32981413

RESUMO

The treatment of ccRCC by targeting hypoxia-inducible factor HIF-2α is currently a direct and effective method. Studies have shown that HIF-2α and c-Myc cooperate to promote ccRCC tumor progression, and the overexpression of c-Myc is related to the progress and drug resistance of most human cancers. Although HIF-2α and c-Myc are important drug targets, their dual inhibitors are still lacking. We used virtual screening tools (mainly including molecular docking and MM-GBSA technology) to obtain some well-listed compounds that can potentially target HIF-2α and c-Myc and used molecular dynamics simulations to study their binding with these protein systems. Using a structure-based screening scheme, a batch of top-ranking compounds were selected, and their binding affinities were predicted of these compounds were performed. Representative compound C93106, C43257, and C41580 all showed good comprehensive binding score. Our results indicate that the target compounds can all form key interactions with the active site of the protein, and 30 ns molecular dynamic simulation of the complex system indicates a stable binding conformation. This research laid the foundation for the development of more effective and specific HIF-2α and c-Myc dual-target inhibitors.


Assuntos
Antineoplásicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Simulação de Acoplamento Molecular , Preparações Farmacêuticas/metabolismo , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Antineoplásicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Humanos , Preparações Farmacêuticas/química , Ligação Proteica , Conformação Proteica , Proteínas Proto-Oncogênicas c-myc/química , Proteínas Proto-Oncogênicas c-myc/metabolismo
13.
J Biomol Struct Dyn ; 39(15): 5358-5367, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32627678

RESUMO

Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates integrin and growth factor signaling pathways, which is a promising therapeutic target because of involving in the migration, proliferation and survival of cancer cell. Overexpression and amplification of cyclin-dependent kinase 4/6 (CDK4/6) occur in many cancers and may be the cause of resistance to CDK4/6 inhibitors in preclinical models. The latest research shows that the combination of FAK and CDK4/6 can be dually targeted to enhance the antitumor effects. In this study, FAK and CDK4/6 dual target inhibitors were designed by computer-aided drug design. Seven million molecules were screened by the pharmacophore model and molecular docking. Finally, 6 compounds were obtained. Molecular dynamics simulation of compound 1, 2 and 3 showed that it has good binding stability to both receptors. According to the binding modes of compound 1 with two receptors, corresponding modifications were made, and 7 novel designed compounds were obtained. The docking energy of these novel designed compounds were lower than that of compound 1, and they can be tested in future.Communicated by Ramaswamy H. Sarma.


Assuntos
Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases , Desenho de Fármacos , Proteína-Tirosina Quinases de Adesão Focal , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/farmacologia , Relação Quantitativa Estrutura-Atividade
14.
Ann Palliat Med ; 9(6): 3810-3817, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33183027

RESUMO

BACKGROUND: Evidence on the effect of cooking oil fumes exposure on fatty liver disease (FLD) is limited. Our study aimed to investigate the association between exposure to the fumes of cooking oil and the risk of FLD. METHODS: A total of 55,959 participants aged 40-75 years old participated in a community-based survey in Ningbo, China. Information on exposure to cooking oil fumes and FLD were collected by face-to-face interviews. Stratified analysis was performed, and participants were divided into 2 groups according to gender. Multiple logistic regression analyses were conducted to investigate the association between exposure to cooking oil fumes and the risk of FDL. Furthermore, ordered logistic regression analysis was conducted to investigate the association between cooking oil fume exposure and the severity of FLD. RESULTS: The prevalence of FLD was 8.79% in the no oil fume exposure group, 10.52% in the light oil fume exposure group, 23.47% in the moderate oil fume exposure group, and 41.45% in the heavy oil fume exposure group. After adjusting for confounding factors, participants in the light, moderate, and heavy cooking oil fume exposure groups all had significantly higher odds ratios (ORs) as compared with participants in the no oil fume exposure group. In addition, an interaction effect between cooking oil fume exposure and gender on the prevalence and severity of FLD was observed. Females with heavy oil fume exposure had the highest ORs of FLD and extent of disease severity. In the stratified analysis, compared to participants in the fumeless group, males and females in the light, moderate, and heavy cooking oil fume exposure groups all had significantly higher risks of FLD and more severe extent of disease, while participants with heavier cooking oil fume exposure tended to have higher risk of FLD and more severe extent of disease. CONCLUSIONS: Exposure to the fumes of cooking oil is associated with the incidence and severity of FLD in 40-75 year old Chinese people. The associations might be dose-responsive. In addition, heavy exposure to oil fumes and the female gender might have a synergistic effect on the incidence and severity of FLD.


Assuntos
Culinária , Hepatopatias , Adulto , Idoso , China/epidemiologia , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
15.
J Extracell Vesicles ; 9(1): 1809765, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32944195

RESUMO

Circulating extracellular vesicles (EVs) were recognized as a promising source of diagnostic biomarker. However, there are limited studies published in this area, partly due to the limited number of detection platforms capable of detecting extracellular vesicles. In this study, extracellular vesicle immunoassays were developed using the Single Molecule array technology (SiMoa) and their clinical applications to cancer diagnosis were evaluated. Two extracellular vesicle detection assays, CD9-CD63 and Epcam-CD63, were designed to detect universal extracellular vesicles and tumour-derived extracellular vesicles, respectively. Our results show that CD9-CD63 and Epcam-CD63 SiMoa assays specifically detect extracellular vesicles but not free proteins with high sensitivities. The Epcam-CD63 levels detected in cancer cell culture media were consistent with levels of Epcam-expressing EVs isolated from the same cancer cell lines and detected by Western blot. Furthermore, the assays distinguish cancerous from non-cancerous plasma samples. The highest CD9-CD63 and Epcam-CD63 signals were observed in colorectal cancer patients comparing to healthy and benign controls. Both assays showed superior diagnostic performance for colorectal cancer. In addition, our results show that CD9-CD63 detection is an independent prognosis factor for both progression free survival and overall survival, while Epcam-CD63 detectionis an independent prognosis factor for OS.

16.
J Clin Lab Anal ; 34(9): e23422, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32715506

RESUMO

BACKGROUND: Estradiol (E2 ) is an important hormone in women. Changes of serum E2 levels may affect the endometrial receptivity for embryo implantation and thus affect pregnancy outcomes. This study was to assess the association between serum E2 levels on the day of human chorionic gonadotrophin (HCG) administration and live-birth rates in patients with frozen embryo transfer (FET). METHODS: Totally 2071 women receiving long protocols of long-acting gonadotropin-releasing hormone (GnRH) agonists were enrolled. According to the E2 levels on the day of HCG administration, these patients were divided into four groups: 676 cases of E2  ≤ 3051 pg/mL in Q1 group, 676 cases of 3051 pg/mL < E2  ≤ 4558 pg/mL in Q2 group, 675 cases of 4558 pg/mL < E2  ≤ 6718 pg/mL in Q3 group, and 674 cases of E2  > 6718 pg/mL in Q4 group. The clinical indicators including female age, body mass index (BMI), duration of infertility, infertility styles, treatment protocols, hormone levels, total antral follicle count, endometrial thickness, top-level embryos, and live-birth rates were analyzed, and multivariable logistic model was conducted to select significant variables. RESULTS: Significant differences were observed for the female age (OR = 0.965, 95% CI: 0.946-0.985, P < .001), total antral follicle counts (OR = 1.025, 95% CI: 1.008-1.043, P = .004), transferring what day of embryos (OR = 1.242, 95% CI: 1.137-1.356, P < .001), endometrial thickness (OR = 1.058, 95% CI: 1.004-1.115, P = .035), top-level embryos (OR = 1.416, 95% CI: 1.157-1.731, P = .001), and E2 levels on HCG day >6781 pg/mL (OR = 1.344, 95% CI: 1.069-1.690, P = .011) between live-birth and non-live-birth groups. The area under the curve (AUC) for E2 levels on HCG day was 0.558, the sensitivity was 54.75%, and the specificity was 55.10%. CONCLUSION: Serum E2 level on HCG day was an independent predictor of live-birth achievement in patients with FET.


Assuntos
Coeficiente de Natalidade , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária/métodos , Estradiol/sangue , Nascido Vivo/epidemiologia , Adulto , China/epidemiologia , Criopreservação , Feminino , Humanos , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Resultado do Tratamento
17.
Thorac Cancer ; 11(4): 1076-1089, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130756

RESUMO

BACKGROUND: We aimed to obtain a set of health state utility scores of patients with esophageal cancer (EC) and precancerous lesions in China, and to explore the influencing factors of health-related quality of life (HRQoL). METHODS: A hospital-based multicenter cross-sectional study was conducted. From 2013 to 2014, patients with EC or precancerous lesions were enrolled. HRQoL was assessed using a European quality of life-5 dimension (EQ-5D-3L) instrument. Multivariable linear regression analysis was performed to explore the influencing factors of the EQ-5D utility scores. RESULTS: A total of 2090 EC patients and 156 precancer patients were included in the study. The dimension of pain/discomfort had the highest rate of self-reported problems, 60.5% in EC and 51.3% in precancer patients. The mean visual analog scale (VAS) score for EC and precancer patients were 68.4 ± 0.7 and 64.5 ± 3.1, respectively. The EQ-5D utility scores for EC and precancer patients were estimated as 0.748 ± 0.009 and 0.852 ± 0.022, and the scores of EC at stage I, stage II, stage III, and stage IV were 0.693 ± 0.031, 0.747 ± 0.014, 0.762 ± 0.015, and 0.750 ± 0.023, respectively. According to the multivariable analyses, the factors of region, occupation, household income in 2012, health care insurance type, pathological type, type of therapy, and time points of the survey were statistically associated with the EQ-5D utility scores of EC patients. CONCLUSIONS: There were remarkable decrements of utility scores among esophageal cancer patients, compared with precancer patients. The specific utility scores of EC would support further cost-utility analysis in populations in China.


Assuntos
Neoplasias Esofágicas/psicologia , Inquéritos Epidemiológicos/estatística & dados numéricos , Lesões Pré-Cancerosas/psicologia , Psicometria/instrumentação , Qualidade de Vida , Fatores Socioeconômicos , Adulto , Idoso , Estudos Transversais , Neoplasias Esofágicas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/terapia , Prognóstico
18.
BMC Cancer ; 20(1): 138, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085736

RESUMO

BACKGROUND: To study the kinetic profile and clinicopathological implications of squamous cell carcinoma antigen (SCC-Ag) in cervical cancer patients who underwent surgery by a self-developed SCC-Ag single molecule assay (Simoa) prototype immunoassay. METHODS: Participants were prospectively enrolled between 04/2016 and 06/2017. Consecutive serum samples were collected at five points: day 0 (the day before surgery), postoperative day 4, weeks 2-4, months 2-4 and months 5-7. In total, 92 patients and 352 samples were included. The kinetic change in SCC-Ag levels and their associations with clinicopathological characteristics were studied. RESULTS: Simoa SCC-Ag was validated by comparison with the Architect assay. SCC-Ag levels measured by the Simoa assay were highly correlated with the Architect assay's levels (Pearson's correlation coefficient = 0.979, Passing-Bablok regression slope 0.894 (0.847 to 0.949), intercept - 0.009 (- 0.047 to 0.027)). The median values for each time-point detected by the Simoa assay were 2.49, 0.66, 0.61, 0.72, and 0.71 ng/mL, respectively. The SCC-Ag levels decreased dramatically after surgery and then stabilized and fluctuated to some extent within 6 months. Patients with certain risk factors had significantly higher SCC-Ag values than their negative counterparts before surgery and at earlier time points after surgery, while no difference existed at the end of observation. Furthermore, although patients with positive lymph nodes had sustained higher SCC-Ag levels compared to those with negative lymph nodes, similar kinetic patterns of SCC-Ag levels were observed after surgery. Patients who received postoperative treatment had significantly higher SCC-Ag values than those with surgery only at diagnosis, while no difference existed after treatment. CONCLUSIONS: The Simoa SCC-Ag prototype was established for clinical settings. The SCC-Ag levels were higher in patients with risk factors, whereas the kinetic trend of SCC-Ag might be mainly affected by postoperative adjuvant therapy. These data indicate that the SCC-Ag level might be a good predictor for the status of cervical cancer, including disease aggressiveness and treatment response.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Histerectomia/métodos , Serpinas/sangue , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Estudos Longitudinais , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Risco , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/cirurgia
19.
J Mol Cell Biol ; 12(2): 125-137, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31065671

RESUMO

Histone methylation is a context-dependent modification that regulates gene expression, and the trimethylation of histone H3 lysine 27 (H3K27me3) usually induces gene silencing. Overcoming colorectal cancer (CRC) chemoresistance is currently a huge challenge, but the relationship between H3K27me3 modification and chemoresistance remains largely unclear. Here, we found that H3K27me3 levels positively correlated with the metastasis-free survival of CRC patients and a low H3K27me3 level predicted a poor outcome upon chemotherapeutic drug treatment. Oxaliplatin stimulation significantly induced the expression of H3K27 lysine demethylase 6A/6B (KDM6A/6B), thus decreasing the level of H3K27me3 in CRC cells. Elevation of H3K27me3 level through KDM6A/6B depletion or GSK-J4 (a KDM6A/6B inhibitor) treatment significantly enhanced oxaliplatin-induced apoptosis. Conversely, when inhibiting the expression of H3K27me3 by EPZ-6438, an inhibitor of the histone methyltransferase EZH2, the proportion of apoptotic cells remarkably decreased. In addition, the combination of GSK-J4 and oxaliplatin significantly inhibited tumor growth in an oxaliplatin-resistant patient-derived xenograft model. Importantly, we revealed that oxaliplatin treatment dramatically induced NOTCH2 expression, which was caused by downregulation of H3K27me3 level on the NOTCH2 transcription initiation site. Thus, the activated NOTCH signaling promoted the expression of stemness-related genes, which resulted in oxaliplatin resistance. Furthermore, oxaliplatin-induced NOTCH signaling could be interrupted by GSK-J4 treatment. Collectively, our findings suggest that elevating H3K27me3 level can improve drug sensitivity in CRC patients.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Histonas/metabolismo , Oxaliplatina/administração & dosagem , Regulação para Cima/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Benzazepinas/administração & dosagem , Benzazepinas/farmacologia , Compostos de Bifenilo , Neoplasias Colorretais/patologia , Quimioterapia Combinada , Feminino , Células HCT116 , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Morfolinas , Oxaliplatina/farmacologia , Prognóstico , Piridonas/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Receptor Notch2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Exp Ther Med ; 18(5): 3905-3912, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31656539

RESUMO

A large number of menopausal women report sleep disturbances along with psychological, somatic and urogenital menopausal symptoms. The aim of this study was to evaluate the efficacy of menopausal hormonal therapy (MHT) in improving subjective sleep quality and the severity of menopausal symptoms. An institutional ethics committee approved this retrospective chart review of 342 women treated with MHT for menopausal symptoms. Standard 28-day MHT consisted of the oral administration of 2 mg estradiol daily for 14 days, followed by 2 mg estradiol and 10 mg dydrogesterone daily for the remaining 14 days. A subgroup of 14 participants with a family history of cancer and mammography scores of 3 and above, received only tibolone 2.5 mg daily. Perceived sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI), while the assessment of menopausal symptoms was performed using the Kupperman Menopause Index (KMI) and menopause rating scale (MRS). Of the 342 patients, 79 were followed-up for 3 years. Compared to the baseline scores, the mean decrease in PSQI scores was 1.53±0.29 points (P<0.0001) at 1 month, 2.21±0.187 points (P<0.0001) at 2 months and 2.26±0.6 points (P<0.0001) after 3 years of MHT. The KMI scores also decreased by a mean of 6.37±1.59 points (P<0.0001) at 1 month and by 8.73±1.92 points after 3 years (P<0.0001). The MRS scores decreased by a mean of 3.56±1.05 points (P<0.0001) at 1 month and by 4.28±2.01 points (P<0.0001) after 3 years, as compared to the baseline scores. Patients receiving tibolone MHT did not report any improvement in sleep quality (P=0.956). On the whole, the findings of this study indicate that conventional MHT has a rapid and prolonged beneficial effect on self-reported sleep quality and menopausal symptoms in women. However, further clinical studies are warranted to compare the effects of different MHT regimens.

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