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1.
BMC Anesthesiol ; 24(1): 99, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475699

RESUMO

BACKGROUND: The use of nonintubated video-assisted thoracoscopic surgery (NI-VATS) has been increasingly reported to yield favourable outcomes. However, this technology has not been routinely used because its advantages and safety have not been fully confirmed. The aim of this study was to assess the safety and feasibility of nonintubated spontaneous ventilation (NI-SV) anesthesia compared to intubated mechanical ventilation (I-MV) anesthesia in VATS by evaluating of perioperative complications and practitioners' workloads. METHODS: Patients who underwent uniportal VATS were randomly assigned at a 1:1 ratio to receive NI-SV or I-MV anesthesia. The primary outcome was the occurrence of intraoperative airway intervention events, including transient MV, conversion to intubation and repositioning of the double-lumen tube. The secondary outcomes included perioperative complications and modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) scores from anesthesiologists and surgeons. RESULTS: Thirty-five patients in each group were enrolled in the intention-to-treat analysis. The incidence of intraoperative airway intervention events was greater in the NI-SV group than in the I-MV group (12 [34.3%] vs. 3 [8.6%]; OR = 0.180; 95% CI = 0.045-0.710; p = 0.009). No significant difference was found in the postoperative pulmonary complications between the groups (p > 0.05). The median of the anesthesiologists' overall NASA-TLX score was 37.5 (29-52) when administering the NI-SV, which was greater than the 25 (19-34.5) when the I-MV was administered (p < 0.001). The surgeons' overall NASA-TLX score was comparable between the two ventilation strategies (28 [21-38.5] vs. 27 [20.5-38.5], p = 0.814). CONCLUSION: The NI-SV anesthesia was feasible for VATS in the selected patients, with a greater incidence of intraoperative airway intervention events than I-MV anesthesia, and with more surgical effort required by anesthesiologists. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055427. https://www.chictr.org.cn/showproj.html?proj=147872 was registered on January 09, 2022.


Assuntos
Anestesia , Cirurgia Torácica Vídeoassistida , Humanos , Respiração Artificial/efeitos adversos , Carga de Trabalho , Projetos Piloto , Anestesia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia
2.
Curr Med Imaging ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38343050

RESUMO

OBJECTIVE: To investigate the influence of improved exposure parameters on the image quality of multi-slice spiral computed tomography in nasal bone fracture imaging. METHODS: Fifty patients with optimised parameters combined with coronal scanning were allocated to the modified group and 50 patients with routine scanning parameters to the routine group. The image quality and nasal bone display of the two groups were assessed and statistically analysed, and the quality of scanned images before and after parameter optimisation was compared. RESULTS: The optimised image quality was better than that of conventional scanning parameters. The parameters used were 120 kv, 180 mA, a layer thickness of 0.625 mm, a layer spacing of 0.312 mm, a pitch of 0.516:1, a frame speed of 1 s, a scanning field of 12 cm and a reconstructed layer thickness for scanning of 0.625 mm; the scanned image was clear, and the parameter optimisation was achieved. This ensures that the annotation data in ITK labelling is more accurate. CONCLUSION: The optimised parameters and scanned coronal plane show the nasal bone and its surrounding structures more comprehensively, which is of high diagnostic value for nasal bone fractures. The three-dimensional annotation data based on ITK is more standardised, laying a foundation for the subsequent research of artificial intelligence modelling.

3.
World Neurosurg ; 178: e777-e790, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562682

RESUMO

OBJECTIVE: The anterior clinoid process (ACP) is surrounded by nerves and vessels that, together, constitute an intricate anatomical structure with variations that challenges the performance of individualized anterior clinoidectomy in treating lesions with different extents of invasion. In the present study, we established a 6-surface system for the ACP based on anatomical landmarks and analyzed its value in guiding ACP drilling and resection of paraclinoid meningiomas. METHODS: Using the anatomical characteristics of 10 dry skull specimens, we set 9 anatomical landmarks to delineate the ACP into 6 surfaces. Guided by our 6-surface system and eggshell technique, 5 colored silicone-injected anatomical specimens were dissected via a frontotemporal craniotomy to perform anterior clinoidectomy. Next, 3 typical cases of paraclinoid meningioma were selected to determine the value of using our 6-surface system in tumor resection. RESULTS: Nine points (A-H and T) were proposed to delineate the ACP surface into frontal, temporal, optic nerve, internal carotid artery, cranial nerve III, and optic strut surfaces according to the adjacent tissues. Either intradurally or extradurally, the frontal and temporal surfaces could be identified and drilled into depth, followed by skeletonization of the optic nerve, cranial nerve III, internal carotid artery, and optic strut surfaces. After the residual bone was removed, the ACP was drilled off. In surgery of paraclinoid meningiomas, our 6-surface system provided great benefit in locating the dura, nerves, and vessels, thus, increasing the safety of opening the optic canal and relaxing the oculomotor or optic nerves and allowing for individualized ACP drilling for meningioma removal. CONCLUSIONS: Our 6-surface system adds much anatomical information to the classic Dolenc triangle and can help neurosurgeons, especially junior ones, to increase their understanding of the paraclinoid spatial structure and accomplish individualized surgical procedures with high safety and minimal invasiveness.


Assuntos
Aneurisma Intracraniano , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Aneurisma Intracraniano/cirurgia , Base do Crânio/cirurgia , Osso Esfenoide/cirurgia , Osso Esfenoide/anatomia & histologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia
4.
Oxid Med Cell Longev ; 2023: 7857760, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36819779

RESUMO

Intracerebral hemorrhage (ICH) is lethal but lacks effective therapies. Nicotinamide adenine dinucleotide (NAD+) is a central metabolite indispensable for a broader range of fundamental intracellular biological functions. Reduction of NAD+ usually occurs after acute brain insults, and supplementation of NAD+ has been proven neuroprotective. P7C3-A20 is a novel compound featuring its ability to facilitate the flux of NAD+. In this study, we sought to determine the potential therapeutic value of P7C3-A20 in ICH. In collagenase-induced ICH mouse models, we found that P7C3-A20 treatment could diminish lesion volume, reduce blood-brain barrier (BBB) damage, mitigate brain edema, attenuate neural apoptosis, and improve neurological outcomes after ICH. Further, RNA sequencing and subsequent experiments revealed that ICH-induced neuroinflammation and microglial proinflammatory activities were significantly suppressed following P7C3-A20 treatment. Mitochondrial damage is an important trigger of inflammatory response. We examined mitochondrial morphology and function and found that P7C3-A20 could attenuate OxyHb-induced impairment of mitochondrial dynamics and functions in vitro. Mechanistically, Sirt3, an NAD+-dependent deacetylase located in mitochondria, was then found to play a vital role in the protection of P7C3-A20 against mitochondrial damage and inflammatory response. In rescue experiments, P7C3-A20 failed to exert those protective effects in microglia-specific Sirt3 conditional knockout (CKO) mice. Finally, preclinical research revealed a correlation between the plasma NAD+ level and the neurological outcome in ICH patients. These results demonstrate that P7C3-A20 is a promising therapeutic agent for neuroinflammatory injury after ICH and exerts protective actions, at least partly, in a Sirt3-dependent manner.


Assuntos
Lesões Encefálicas , Sirtuína 3 , Animais , Camundongos , Lesões Encefálicas/metabolismo , Hemorragia Cerebral/patologia , Inflamação , Microglia/metabolismo , NAD/metabolismo
5.
Technol Health Care ; 31(3): 1017-1025, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36442167

RESUMO

BACKGROUND: Artificial intelligence (AI) technology is a promising diagnostic adjunct in fracture detection. However, few studies describe the improvement of clinicians' diagnostic accuracy for nasal bone fractures with the aid of AI technology. OBJECTIVE: This study aims to determine the value of the AI model in improving the diagnostic accuracy for nasal bone fractures compared with manual reading. METHODS: A total of 252 consecutive patients who had undergone facial computed tomography (CT) between January 2020 and January 2021 were enrolled in this study. The presence or absence of a nasal bone fracture was determined by two experienced radiologists. An AI algorithm based on the deep-learning algorithm was engineered, trained and validated to detect fractures on CT images. Twenty readers with various experience were invited to read CT images with or without AI. The accuracy, sensitivity and specificity with the aid of the AI model were calculated by the readers. RESULTS: The deep-learning AI model had 84.78% sensitivity, 86.67% specificity, 0.857 area under the curve (AUC) and a 0.714 Youden index in identifying nasal bone fractures. For all readers, regardless of experience, AI-aided reading had higher sensitivity ([94.00 ± 3.17]% vs [83.52 ± 10.16]%, P< 0.001), specificity ([89.75 ± 6.15]% vs [77.55 ± 11.38]%, P< 0.001) and AUC (0.92 ± 0.04 vs 0.81 ± 0.10, P< 0.001) compared with reading without AI. With the aid of AI, the sensitivity, specificity and AUC were significantly improved in readers with 1-5 years or 6-10 years of experience (all P< 0.05, Table 4). For readers with 11-15 years of experience, no evidence suggested that AI could improve sensitivity and AUC (P= 0.124 and 0.152, respectively). CONCLUSION: The AI model might aid less experienced physicians and radiologists in improving their diagnostic performance for the localisation of nasal bone fractures on CT images.


Assuntos
Inteligência Artificial , Fraturas Ósseas , Humanos , Leitura , Fraturas Ósseas/diagnóstico por imagem , Algoritmos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos
6.
Medicine (Baltimore) ; 101(47): e31717, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451510

RESUMO

BACKGROUND: Self-gravitation traction is 1 of the most popular treatments for lumbar disc herniation (LDH). This study aims to evaluate the effectiveness and safety of the self-gravitation traction device in the treatment of LDH and to confirm its positive treatment effect. METHODOLOGY: This trial is designed as a pragmatic double-center, single-blind, and 3-arm (1:1:1 ratio) randomized controlled trial. The recruited patients with LDH will be randomly allocated to the intervention (traction weight is 40% or 60% of its body weight) or control (traction weight is 20% of its body weight) group. Traction will be completed within 6 consecutive weeks (3 times a week), with 10 minutes of traction for the first 3 weeks, 20 minutes of traction for the next 3 weeks. After the experiment is completed, we will establish an experiment-related database. The software of SPSS, version 21 (SPSS Inc. Chicago, IL) will be used for statistical analysis, and measurement data will be expressed via mean and standard deviation (mean ±â€…SD). DISCUSSION: Once the trial is completed, we will publish the study in journals in both Chinese and English to promote the dissemination and use of the results. In addition, we also plan to promote the research results at various academic conferences both domestically and internationally.


Assuntos
Deslocamento do Disco Intervertebral , Tração , Humanos , Deslocamento do Disco Intervertebral/terapia , Método Simples-Cego , Gravitação , Peso Corporal , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Medicine (Baltimore) ; 101(45): e31562, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397389

RESUMO

RATIONALE: Gout in the spine and adnexa is rare in clinical practice and can also be easily misdiagnosed, we reported a patient with nerve root compression due to lumbar gout stones in the lumbar spinal canal. PATIENT CONCERNS: A 51-year-old male was admitted to the hospital with lumbar pain with numbness in the left lower limb for more than 6 months. The physical examination showed that tenderness and percussion pain were present at L4-S1 spinous process. Straight leg raise test: 50° on the left side were positive. Laboratory tests showed that the sUA was 669 µmol/L, MRI of the lumbar spine showed that cystic T1WI low signal and T2WI mixed high signal shadows were seen in the spinal canal at the level of L4-L5. DIAGNOSES: Combining with lab examinations, imaging examinations, and histopathological results, the patient was diagnosed with lumbar spinal canal tophi. INTERVENTIONS: After active improvement of all examinations, the patient underwent surgical treatment with decompression and internal fixation of the L4-L5 segment. OUTCOMES: After surgery, the patient's symptoms improved and muscle strength returned to normal. Among the 95 previously reported patients with lumbar gout, the ratio of men to women was 2.96:1, and the peak age group of incidence was 56 to 65 years. The onset of the disease was mainly in a single segment of the lumbar spine, with 34.41% of all cases occurring at the L4-L5 level. 61.05% of the patients had a history of gout attacks or hyperuricemia, and the most frequently involved site was the foot and ankle, followed by the wrist. Sixty-seven patients underwent surgical treatment, and 22 chose conservative treatment, with overall satisfactory results. LESSONS SUBSECTIONS: The incidence of lumbar gout is low and relatively rare in the clinic and pathological biopsy is still the gold standard. Vertebral plate incision and decompression are often selected for surgical treatment, and whether to perform fusion should be comprehensively considered for the destruction of vertebral bone by gout and the reasonable selection of the extent of surgical resection. Whether choosing surgical treatment or conservative therapy, the control of uric acid levels should be emphasized.


Assuntos
Artrite Gotosa , Gota , Radiculopatia , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Radiculopatia/etiologia , Radiculopatia/cirurgia , Canal Medular/diagnóstico por imagem , Região Lombossacral , Artrite Gotosa/complicações , Gota/complicações , Gota/diagnóstico , Dor/complicações
8.
Front Oncol ; 12: 860257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686112

RESUMO

Objective: To design a multidisciplinary enhanced recovery after surgery (ERAS) protocol for glioma patients undergoing elective craniotomy and evaluate its clinical efficacy and safety after implementation in a tertiary neurosurgical center in China. Methods: ERAS protocol for glioma patients was developed and modified based on the best available evidence. Patients undergoing elective craniotomy for treatment of glioma between September 2019 to May 2021 were enrolled in a randomized clinical trial comparing a conventional neurosurgical perioperative care (control group) to an ERAS protocol (ERAS group). The primary outcome was postoperative hospital length of stay (LOS). Secondary outcomes were 30-day readmission rate, postoperative complications, duration of the drainage tube, time to first oral fluid intake, time to ambulation and functional recovery status. Results: A total of 151 patients were enrolled (ERAS group: n = 80; control group: n = 71). Compared with the control group, postoperative LOS was significantly shorter in the ERAS group (median: 5 days vs. 7 days, p<0.0001). No 30-day readmission or reoperation occurred in either group. The time of first oral intake, urinary catheter removal within 24 h and early ambulation on postoperative day (POD) 1 were earlier and shorter in the ERAS group compared with the control group (p<0.001). No statistical difference was observed between the two groups in terms of surgical- and nonsurgical-related complications. Functional recovery in terms of Karnofsky Performance Status (KPS) scores both at discharge and 30-day follow-up was similar in the two groups. Moreover, no significant difference was found between the two groups in the Hospital Anxiety and Depression Scale (HADS) scores. Conclusion: The implementation of the ERAS protocol for glioma patients offers significant benefits over conventional neurosurgical perioperative management, as it is associated with enhancing postoperative recovery, without additional perioperative complications and risks. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=42016), identifier ChiCTR1900025108.

9.
Arch Gynecol Obstet ; 304(3): 671-677, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33987686

RESUMO

PURPOSE: Endometriosis is a common chronic gynecological disease greatly affecting women health. Prior studies have implicated that dysferlin (DYSF) aberration might be involved in the pathogenesis of ovarian endometriosis. In the present study, we explore the potential presence of DYSF mutations in a total of 152 Han Chinese samples with ovarian endometriosis. METHODS: We analyze the potential presence of DYSF mutations by direct DNA sequencing. RESULTS: A total of seven rare variants/mutations in the DYSF gene in 10 out of 152 samples (6.6%) were identified, including 5 rare variants and 2 novel mutations. For the 5 rare variants, p.R334W and p.G941S existed in 2 samples, p.R865W, p.R1173H and p.G1531S existed in single sample, respectively; for the two novel mutations, p.W352* and p.I1642F, they were identified in three patients. These rare variants/mutations were absent or existed at extremely low frequency either in our 1006 local control women without endometriosis, or in the China Metabolic Analytics Project (ChinaMAP) and Genome Aggregation Database (gnomAD) databases. Evolutionary conservation analysis results suggested that all of these rare variants/mutations were evolutionarily conserved among 11 vertebrate species from Human to Fox. Furthermore, in silico analysis results suggested these rare variants/mutations were disease-causing. Nevertheless, we find no significant association between DYSF rare variants/mutations and the clinical features in our patients. To our knowledge, this is the first report revealing frequent DYSF mutations in ovarian endometriosis. CONCLUSION: We identified a high frequency of DYSF rare variants/mutations in ovarian endometriosis for the first time. This study suggests a new correlation between DYSF rare variants/mutations and ovarian endometriosis, implicating DYSF rare variants/mutations might be positively involved in the pathogenesis of ovarian endometriosis.


Assuntos
Disferlina/genética , Endometriose/genética , Doenças Ovarianas/genética , Adulto , Povo Asiático/genética , China/epidemiologia , Endometriose/etnologia , Feminino , Humanos , Mutação , Doenças Ovarianas/etnologia
10.
Chin Neurosurg J ; 7(1): 18, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33597027

RESUMO

BACKGROUND: Cerebral fat embolism (CFE) syndrome at high altitude was rare complicated with paroxysmal sympathetic hyperactivity (PSH) syndrome and septic shock. It is a challenge to differential diagnosis and treatment at high altitude. CASE PRESENTATION: This case presents a CFE with PSH and septic shock of a 23-year-old man occurred at high altitude of 3800 m above sea level, transferred by airplane successfully and cured in the department of neurosurgery, Xi'an Tangdu Hospital. CONCLUSIONS: It is key that CFE with PSH can be rapid diagnosed and treatment bundles of septic shock should be initiated as soon as possible. Early neurological rehabilitation played an important role for good outcome.

11.
Cancer Med ; 9(17): 6399-6410, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32691991

RESUMO

Puerarin 6″-O-xyloside is a tumor suppressive derivate of Puerarin that is recently characterized as a lysine-specific demethylase 6B inhibitor. Here we investigated the effects of Puerarin 6″-O-xyloside in hepatocellular carcinoma (HCC) cell lines SMMC-7721 and HepG2. Cell viability, proliferation, stemness, protein expression, and autophagy were tested by CCK-8, colony formation, sphere formation, western blotting, and LC3B GFP puncta per cell, respectively. Apoptosis, CD133-positive cells, and JC-1-labeled mitochondrial membrane potential were measured by flow cytometry. The effects of Puerarin 6″-O-xyloside in vivo were explored in HepG2 xenograft mice. Puerarin 6″-O-xyloside inhibited cell viability, proliferation, and stemness, and promoted apoptosis in both SMMC-7721 and HepG2 cells. Further experiments showed promoted autophagy and decreased mitochondrial membrane potential, and decreased expression of p-PI3K, p-AKT, and p-mTOR in HepG2 cells. Co-administration of 3-MA with Puerarin 6″-O-xyloside obviously augmented these effects including inhibited protein expression of p-PI3K, p-AKT, and p-mTOR, and inhibited proliferation, promoted apoptosis, and decreased stemness. In HepG2 xenograft mice, 100 mg/kg/d Puerarin 6″-O-xyloside significantly suppressed tumor growth, stemness, and apoptosis. In conclusion, our study indicated that Puerarin 6″-O-xyloside decreased cell viability, proliferation, and stemness, and promoted autophagy and mitochondria-dependent apoptosis of HCC, at least partly through inhibiting PI3K/AKT/mTOR. These results highlighted Puerarin 6″-O-xyloside as a promising prodrug that could inhibit both PI3K/AKT/mTOR and epigenetic demethylation.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/efeitos dos fármacos , Glicosídeos/farmacologia , Isoflavonas/farmacologia , Neoplasias Hepáticas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Antígeno AC133 , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Autofagia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Glicosídeos/administração & dosagem , Células Hep G2 , Humanos , Isoflavonas/administração & dosagem , Neoplasias Hepáticas/patologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ensaio Tumoral de Célula-Tronco
12.
J Otol ; 15(1): 33-35, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32110238

RESUMO

BACKGROUND: Tympanomastoid paragangliomas are usually benign, slowly growing, painless tumors. The common presenting symptoms of this tumor are pulsatile tinnitus and conductive hearing loss. Vertigo as the cardinal or initial symptom is extremely are, especially in the early stages of the disease. CASE PRESENTATION: A 53-year-old female patient presented only with intermittent recurrent vertigo and was later found to have a tympanomastoid paraganglioma. Her symptoms disappeared completely after resection of the tumor. This is the first report in literature of a case of tympanomastoid paraganglioma with vertigo as the single symptom. CONCLUSION: The tympanomastoid paraganglioma is rare and its clinical symptoms are nonspecific, so it is easy to be misdiagnosed or missed. It is worth noting that although clinically uncommon, vertigo can also be the first or sole symptom of tympanomastoid paraganglioma. Detailed physical examination and imaging examination of the ear are necessary and should be carried out meticulously.

13.
Front Oncol ; 10: 602553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33659209

RESUMO

PURPOSE: Diffuse midline gliomas (DMG) with H3K27M mutations have been identified as a rare distinctive entity with unique genetic features, varied molecular alterations, and poor prognosis. The current study aimed to evaluate the clinical characteristics and profile of molecular markers on patients with a DMG harboring H3K27M mutations, and explore the impact of this genetic makeup on overall survival. METHODS: We retrospectively analyzed 43 consecutive patients diagnosed with a DMG harboring H3K27M mutations (age range 3 to 75 years) and treated in a tertiary institution within China between January 2017 to December 2019. Various clinical and molecular factors were evaluated to assess their prognostic value in this unique patient cohort. RESULTS: The median overall survival (OS) was 12.83 months. Preoperative Karnofsky Performance Score (KPS) and adjuvant radiotherapy were found to be independent clinical parameters influencing the OS by multivariate analysis (p = 0.027 and p < 0.001 respectively). Whereas extent of tumor resection failed to demonstrate statistical significance. For molecular markers, P53 overexpression was identified as a negative prognostic factor for overall survival by multivariate analysis (p = 0.030). CONCLUSION: Low preoperative KPS, absence of radiotherapy and P53 overexpression were identified as predictors of a dismal overall survival in patients with DMG and H3K27M mutations.

14.
Front Mol Neurosci ; 12: 121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213978

RESUMO

The small GTPases from the Ras superfamily play crucial roles in basic cellular processes during practically the entire process of neurodevelopment, including neurogenesis, differentiation, gene expression, membrane and protein traffic, vesicular trafficking, and synaptic plasticity. Small GTPases are key signal transducing enzymes that link extracellular cues to the neuronal responses required for the construction of neuronal networks, as well as for synaptic function and plasticity. Different subfamilies of small GTPases have been linked to a number of non-neoplastic cerebral diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), intellectual disability, epilepsy, drug addiction, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and a large number of idiopathic cerebral diseases. Here, we attempted to make a clearer illustration of the relationship between Ras superfamily GTPases and non-neoplastic cerebral diseases, as well as their roles in the neural system. In future studies, potential treatments for non-neoplastic cerebral diseases which are based on small GTPase related signaling pathways should be explored further. In this paper, we review all the available literature in support of this possibility.

15.
Front Psychiatry ; 10: 240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031665

RESUMO

Drug addiction can be viewed as a chronic psychiatric disorder that is related to dysfunction of neural circuits, including reward deficits, stress surfeits, craving changes, and compromised executive function. The nucleus accumbens (NAc) plays a crucial role in regulating craving and relapse, while the medial prefrontal cortex (mPFC) represents a higher cortex projecting into the NAc that is active in the management of executive function. In this study, we investigated the role of the small conductance calcium-activated potassium channels (SK channels) in NAc and mPFC after morphine withdrawal. Action potential (AP) firing of neurons in the NAc shell was enhanced via the downregulations of the SK channels after morphine withdrawal. Furthermore, the expression of SK2 and SK3 subunits in the NAc was significantly reduced after 3 weeks of morphine withdrawal, but was not altered in the dorsal striatum. In mPFC, the SK channel subunits were differentially expressed. To be specific, the expression of SK3 was upregulated, while the expression of SK2 was unchanged. Furthermore, the AP firing in layer 5 pyramidal neurons of the infralimbic (IL) cortex was decreased via the upregulations of the SK channel-related tail current after 3 weeks of morphine withdrawal. These results suggest that the SK channel plays a specific role in reward circuits following morphine exposure and a period of drug withdrawal, making it a potential target for the prevention of relapse.

16.
Medicine (Baltimore) ; 97(44): e12847, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30383637

RESUMO

BACKGROUND: As a well-known cancer with high mortality, lung cancer has been implied to be closely associated with brain metastasis. Despite notable advances, effective treatment methods are still in urgent need. This study aims to investigate the value of serum microRNA-let-7a (miR-let-7a) expression in predicting efficacy and prognosis of radiotherapy in patients with lung cancer brain metastasis. METHODS: To begin with, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed for better understand of the correlation between miR-let-7a and lung cancer. Afterwards, the relationship between serum miR-let-7a expression and radiotherapy efficacy was analyzed by receiver operating characteristic curve analysis. Following successful transfection, RT-qPCR and Western blot assay were utilized for evaluating the involvement of miR-let-7a in regulation of DICER1 expression in lung cancer cell line. Then, whether miR-let-7a was implicated in proliferation and cell cycle distribution of lung cancer cells were confirmed by cell counting kit-8 assay and flow cytometry respectively. RESULTS: Initially, it was revealed that serum miR-let-7a expression was decreased in lung cancer. Later, we found that decreased miR-let-7a displayed an unfavorable role in radiotherapy efficacy and overall survival rate of patients with lung cancer brain metastasis. After the successful transfection, the inverse relationship between miR-let-7a and DICER1 expression was uncovered. Meanwhile, biological behaviors of lung cancer cells were presented to be limited after transfection of overexpressed miR-let-7a. CONCLUSION: Our findings demonstrated that the lower expression of miR-let-7a in patients with lung cancer brain metastasis was closely related to unfavorable efficacy and prognosis of radiotherapy, and it may be an important predictive biomarker by regulation of DICER1.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Adulto , Idoso , Western Blotting , Encéfalo/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Estudos de Casos e Controles , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células , RNA Helicases DEAD-box/metabolismo , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Ribonuclease III/metabolismo , Taxa de Sobrevida
17.
Mol Neurobiol ; 55(3): 2696-2711, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28421542

RESUMO

Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 µl NSCs (5.0 × 105/µl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-ß were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/terapia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/transplante , Plasticidade Neuronal/fisiologia , Transplante de Células-Tronco/métodos , Animais , Fator Neurotrófico Derivado do Encéfalo/deficiência , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia
18.
Int J Biol Markers ; 32(4): e409-e414, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-28799624

RESUMO

BACKGROUND: This study aimed to evaluate the correlation between neutrophil to lymphocyte ratio (NLR) with overall survival (OS) of esophageal squamous cell carcinoma (ESCC) patients. METHOD: Records of patients with diagnosed ESCC were reviewed. Leukocyte counts and patients' characteristics were extracted from their clinical records to calculate NLR. Correlation between NLR and baseline characteristics with overall survival (OS) was then analyzed using Cox regression. The patients were then separated into higher and lower NLR groups according to median NLR. OS was further compared between the 2 groups. RESULTS: A total of 1281 patients were included in the study. Cox regression analysis showed a significant correlation of NLR with OS of ESCC patients. The median pretreatment NLR was identified as 2.86. Higher NLR was associated with worse prognosis in terms of OS. CONCLUSIONS: Pretreatment NLR is independently associated with OS of ESCC patients. Therefore, NLR may be used as a predictive indicator for pretreatment evaluation and adjustment of treatment regimen.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Linfócitos/patologia , Neutrófilos/patologia , Prognóstico , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Intervalo Livre de Doença , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
19.
Front Neurol ; 8: 256, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28649223

RESUMO

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

20.
World Neurosurg ; 90: 701.e7-701.e10, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26915699

RESUMO

BACKGROUND: Symptomatic cavernous malformations involving the brainstem are difficult to access by conventional approaches, which often require dramatic brain retraction to gain adequate operative corridor. Here, we present a successful endoscopic endonasal transclival approach for resection of a hemorrhagic, symptomatic mesencephalic cavernous malformation. CASE DESCRIPTION: A 20-year-old woman presented with acute onset of headache, nausea, and vomiting. Computed tomography scan revealed a ventral midbrain hemorrhage. On day 3 of admission, the patient developed left-sided hemiparesis, restriction of medial and lateral left-eye movements, and loss of left pupillary light reflex. Subsequent magnetic resonance imaging demonstrated an increase of the midbrain lesion to 1.2 cm × 1.7 cm. Diffusion tensor imaging showed compression and lateral displacement of the right corticospinal tract near the thalamus and cerebral peduncle. Given the patient's clinical presentation and the findings on imaging, we suspected a mesencephalic cavernous malformation. CONCLUSIONS: The patient underwent an endoscopic endonasal transclival resection of a ventral midline mesencephalon cavernous malformation. A dark red lesion was directly visualized under the endoscope. After a small cortiectomy, the pial and perforator vessels were dissected, and dark-brown blood was drained from the cavernoma cavity. Using a biopsy forceps and with careful attention to the cavernoma borders, the lesion was removed and hemostasis was achieved. Pathologic examination confirmed cavernous malformation. One week after the operation, magnetic resonance imaging demonstrated total resection of the lesion. A 3-month follow-up revealed improved neurologic symptoms with minimal surgical morbidity.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Mesencéfalo/cirurgia , Cirurgia Endoscópica Transanal/métodos , Feminino , Humanos , Mesencéfalo/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neuroendoscopia/métodos , Resultado do Tratamento , Adulto Jovem
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