RESUMO
The application of Sevoflurane (Sev) in neurological diseases has been documented. We herein clarified the role of Sev in intracerebral hemorrhage (ICH). Through bioinformatics analysis, ICH-related microRNA (miRNA) was collected with microRNA-133b (miR-133b) chosen for the study subject. Then, the related downstream gene Forkhead box O4 (FOXO4) was identified. For in vivo assays, an ICH mouse model was established by autologous blood injection. For in vitro assays, hippocampal neurons were extracted from mouse brain tissues, and erythrocyte lysates were employed to simulate in vitro hemorrhage. Interaction between miR-133b and FOXO4 as well as between FOXO4 and BCL2 were assayed. We found decreased miR-133b in the brain tissue of ICH mice and erythrocyte lysate-treated hippocampal neurons. Sev treatment attenuated ICH and hippocampal neuronal apoptosis in mice by upregulating miR-133b. miR-133b targeted FOXO4 expression, and inhibition of FOXO4 attenuated hippocampal neuronal apoptosis by increasing BCL2 expression. Sev attenuated ICH in mice by increasing BCL2 expression through regulation of miR-133b-mediated FOXO4 expression. The findings highlighted the protective effect of Sev on ICH mice through the regulation of miR-133b-mediated FOXO4 expression.
Assuntos
MicroRNAs , Camundongos , Animais , Sevoflurano/farmacologia , Sevoflurano/uso terapêutico , MicroRNAs/genética , MicroRNAs/metabolismo , Hemorragia Cerebral/metabolismo , Encéfalo/metabolismo , Apoptose/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Fatores de Transcrição Forkhead/metabolismoRESUMO
BACKGROUND: The majority of patients may experience atelectasis under general anesthesia, and the Trendelenburg position and pneumoperitoneum can aggravate atelectasis during laparoscopic surgery, which promotes postoperative pulmonary complications. Lung recruitment manoeuvres have been proven to reduce perioperative atelectasis, but it remains controversial which method is optimal. Ultrasonic imaging can be conducive to confirming the effect of lung recruitment manoeuvres. The purpose of our study was to assess the effects of ultrasound-guided alveolar recruitment manoeuvres by ultrasonography on reducing perioperative atelectasis and to check whether the effects of recruitment manoeuvres under ultrasound guidance (visual and semiquantitative) on atelectasis are superior to sustained inflation recruitment manoeuvres (classical and widely used) in laparoscopic gynaecological surgery. METHODS: In this randomized, controlled, double-blinded study, women undergoing laparoscopic gynecological surgery were enrolled. Patients were randomly assigned to receive either lung ultrasound-guided alveolar recruitment manoeuvres (UD group), sustained inflation alveolar recruitment manoeuvres (SI group), or no RMs (C group) using a computer-generated table of random numbers. Lung ultrasonography was performed at four predefined time points. The primary outcome was the difference in lung ultrasound score (LUS) among groups at the end of surgery. RESULTS: Lung ultrasound scores in the UD group were significantly lower than those in both the SI group and the C group immediately after the end of surgery (7.67 ± 1.15 versus 9.70 ± 102, difference, -2.03 [95% confidence interval, -2.77 to -1.29], P < 0.001; 7.67 ± 1.15 versus 11.73 ± 1.96, difference, -4.07 [95% confidence interval, -4.81 to -3.33], P < 0.001;, respectively). The intergroup differences were sustained until 30 min after tracheal extubation (9.33 ± 0.96 versus 11.13 ± 0.97, difference, -1.80 [95% confidence interval, -2.42 to -1.18], P < 0.001; 9.33 ± 0.96 versus 10.77 ± 1.57, difference, -1.43 [95% confidence interval, -2.05 to -0.82], P < 0.001;, respectively). The SI group had a significantly lower LUS than the C group at the end of surgery (9.70 ± 1.02 versus 11.73 ± 1.96, difference, -2.03 [95% confidence interval, -2.77 to -1.29] P < 0.001), but the benefit did not persist 30 min after tracheal extubation. CONCLUSIONS: During general anesthesia, ultrasound-guided recruitment manoeuvres can reduce perioperative aeration loss and improve oxygenation. Furthermore, these effects of ultrasound-guided recruitment manoeuvres on atelectasis are superior to sustained inflation recruitment manoeuvres. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100042731, Registered 27 January 2021, www.chictr.org.cn .
Assuntos
Laparoscopia , Atelectasia Pulmonar , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Pulmão/diagnóstico por imagem , Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias , Atelectasia Pulmonar/diagnóstico por imagem , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/prevenção & controle , Ultrassonografia , Ultrassonografia de IntervençãoRESUMO
Background: Possible influences of statin therapy on the risk of cardiovascular events, cancer, and all-cause mortality in people living with HIV (PLWH) remain unclear. We performed a meta-analysis to systematically evaluate the efficacy of statin in PLWH. Methods: Relevant cohort studies were retrieved via a search of the Medline, the Embase, and the Web of Science databases until June 14, 2021. The data were combined with a random-effects model by incorporating the between-study heterogeneity. Results: A total of 12 multivariate cohort studies with 162,252 participants were eligible for the meta-analysis and 36,253 (22.3%) of them were statin users. Pooled results showed that statin use was independently related to a reduced mortality risk in PLWH [adjusted risk ratio (RR): 0.56, 95% CI: 0.44 to 0.72, p < 0.001, I 2 = 41%]. In addition, results of the meta-analysis showed that statin use was not significantly associated with a reduced risk of cardiovascular events in PLWH compared to the statin non-users (RR: 1.14, 95% CI: 0.80 to 1.63, p = 0.48, I 2 = 42%). However, statin use was significantly related to a reduced risk of cancer in PLWH (RR: 0.73, 95% CI: 0.58 to 0.93, p = 0.009, I 2 = 49%). Sensitivity analyses by excluding one study at a time showed consistent results. No significant publication biases were observed. Conclusion: Statin use is associated with reduced all-cause mortality in PLWH. In addition, statin use is related to a reduced risk of cancer, although the risk of cardiovascular events seems not significantly affected.
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Postoperative cognitive dysfunction (POCD) is a complication of the central nervous system (CNS) often occurred after surgery or anesthesia in the elder patients. Mind bomb-2 (MIB2) has been reported to modulate neuronal functions. Here, we aimed to study whether MIB2 exerts roles in the effects of sevoflurane anesthesia on mice hippocampal neurons and function, and how. Aging male C57BL/6 mice were subjected to sevoflurane administration, and primary hippocampal neurons were adopted to study sevoflurane effects in vitro. Western blotting and immunohistochemistry assay were used to study the protein expression of MIB2. CCK-8 assay and propidium iodide (PI) staining were performed to evaluate cell viability and cell death, respectively. Ferroptosis-related indicators malondialdehyde (MDA), glutathione (GSH), and iron levels were checked through indicated ELISA kits. Co-immunoprecipitation was adopted to study the binding effects of MIB2 to GPX4. We found that sevoflurane anesthesia increased MIB2 expression in mice hippocampus tissues and neurons. Knockdown of MIB2 alleviated neuron death and ferroptosis induced by sevoflurane exposure. Downregulated MIB2 enhanced GPX4 stability and reduced its ubiquitination. MIB2 was verified to bind to GPX4. The effects of MIB2 knockdown on the neuron death and ferroptosis can be reversed by further siGPX4 transfection. In vivo results also showed that MIB2 knockdown reduced hippocampal neuron death, ferroptosis, and cognitive impairments in the sevoflurane-exposed mice. Taking all together, downregulation of MIB2 could alleviate the sevoflurane-anesthesia-induced cognitive dysfunction and neuron injury through reducing ferroptosis via GPX4. Our results also provide novel directions for POCD treatment using anti-MIB2-related drugs or strategies.
Assuntos
Anestesia , Disfunção Cognitiva , Ferroptose , Idoso , Animais , Disfunção Cognitiva/induzido quimicamente , Hipocampo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sevoflurano/toxicidade , Ubiquitina-Proteína LigasesRESUMO
OBJECTIVE: To compare the prognosis of papillary and clear cell renal cell carcinoma (RCC) in order to determine the optimal follow-up and therapy for patients with RCC. METHODS: A systematic search of Web of Science, EMBASE, Cochrane Library, and PubMed databases was conducted for articles published through July 30, 2018, reporting on a comparison of the prognosis of papillary RCC and clear cell RCC using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Of 1896 studies, 11 were considered for the evidence synthesis. A total of 35,832 patients were included. Of these patients, 6907 patients were diagnosed with papillary renal cell carcinoma, and 28,925 patients were diagnosed with clear cell renal cell carcinoma. The prognosis of papillary RCC was better than that of clear cell RCC (hazard ratio (HR) = 0.50; 95% confidence interval (CI) 0.45 to 0.56; Pâ<â.001; I = 91.9%). A subgroup analysis indicated that papillary RCC was associated with better outcomes (HR = 0.76, 95% CI 0.50-1.16), and a trend toward a higher risk of mortality was observed in patients with metastatic RCC presenting with papillary histology, but the difference was not statistically significant (HR = 1.12, 95% CI 0.71-1.76, Pâ=â.085). Pooled data suggested a lack of a significant difference between papillary RCC (p-RCC) type 1 and clear cell RCC (cc-RCC) (HR = 0.30, 95% CI 0.12-0.73, Pâ=â.085). The pooled HR for the prognosis of p-RCC type 2 compared to cc-RCC was 1.69 (95% CI 0.93-3.08; Pâ=â.032). CONCLUSION: Papillary RCC is associated with better outcomes than clear cell RCC in patients without metastases, but not in patients with metastases. Optimal follow-up or therapy for patients with RCC should be assigned according to the tumor stage and subtype.
Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/terapia , PrognósticoRESUMO
The aim of the present study was to determine the role of androgen receptor in the effect of dexamethasone on cell proliferation and migration of multiple prostate cancer cells. The prostate cancer cell lines LNCaP, 22Rv1, C42 and PC3 were cultured in vitro. For glucocorticoidinduced experiments, the cells were transferred and cultured in RPMI1640 medium with 10% charcoalstripped serum from RPMI1640 medium with 10% fetal bovine serum for at least 24 h. The effects of dexamethasone on the proliferation and migration of various cell lines were analyzed by MTT and migration assays. Dexamethasone exhibited no effect on LNCaP, C42 and 22Rv1 cell lines, but suppressed proliferation of glucocorticoid receptor (GR)+ androgen receptor (AR) PC3 cell line. Dexamethasone suppressed PC3 cell migration, and did not affect migration of PC3AR9 cells. Dexamethasone positively or negatively regulated proliferation of various prostate cancer cells based on AR and GR expression profiles. The data presented in the present study indicates that androgen receptor reverts the dexamethasoneinduced inhibition of prostate cancer cell proliferation and migration.