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Objective: To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy. Methods: This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group,a 1︰2 match was performed using the propensity score matching method,and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fishier's exact test were used to compare the data between the two groups,respectively. Results: After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant (t=-3.800,P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml;U=1 026.500,P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28)in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups(P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the groups(P=0.532,P=0.927). Conclusion: The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.
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OBJECTIVE: The aim of this study was to investigate the effects of transcranial direct current stimulation (TDCS) combined with tinnitus retraining therapy (TRT) on clinical efficacy and sleep disorder in patients with chronic tinnitus. PATIENTS AND METHODS: 126 patients with chronic tinnitus treated in our hospital from May 2020 to June 2022 were retrospectively analyzed. These subjects were randomly divided into two groups: the electrical stimulation group and the combined group, in line with the random table method, with 63 patients in each group. Patients in the electrical stimulation group received TDCS treatment, and patients in the combined group were given TDCS combined with TRT. The clinical effects, tinnitus severity [Tinnitus Evaluation Questionnaire (TEQ) score and Tinnitus handicap inventory (THI) score], sleep status [Sleep Status Rating Scale (SRSS) score and Pittsburgh Sleep Quality Index (PSQI) score], psychological status [Hamilton Anxiety Scale (HAMA) score and Self Rating Depression Scale (SDS) score] and the quality of life (Quality of Life Scale) of these subjects in two groups were analyzed. RESULTS: The clinical effect of simple TDCS was 82.53%, which was sharply lower compared to 95.24% in the combined group (p<0.05). After the treatment, TEQ score, THI score, SRSS score, PSQI score, HAMA score, and SDS score were decreased in both groups (p<0.05), and the combined group was much lower than the TDCS group (p<0.01). Compared with the pre-treatment period, the scores of restrictions in daily living, medical resource utilization, somatic symptoms, and emotional disturbance were elevated in both groups after treatment, and the combined group had markedly higher scores than the TDCS group (p<0.05). CONCLUSIONS: TDCS combined with TRT had obvious effects in treating chronic tinnitus, which largely reduced the severity of tinnitus, improved patients' sleep quality and psychological status, and improved the quality of life, indicating a certain worthy of clinical application and promotion.
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Transtornos do Sono-Vigília , Zumbido , Estimulação Transcraniana por Corrente Contínua , Humanos , Qualidade de Vida , Estudos Retrospectivos , Zumbido/terapia , Transtornos do Sono-Vigília/terapiaRESUMO
OBJECTIVE: The aim of this study was to analyze the tendency of myocarditis mortality in 204 countries and areas during the last three decades and its connection with age, epoch, and birth cohort. MATERIALS AND METHODS: The Global Burden of Disease 2019 Study acquired a cause-specific myocarditis mortality estimate. The net drift, as well as the influence caused by age, period, and birth cohort, were evaluated by the age-period-cohort model. Additionally, we analyzed the tendency in research intensity and international collaboration across countries using 3,983 myocarditis-related publications from four periods during 1990-2019. RESULTS: During the last three decades, 101 of 204 countries and areas experienced an increase (net drifts ≥0.0%) or stagnant declines (≥-0.5%) in the death rate. In particular, increasing death rate was generally discovered in most countries whose Socio-demographic indexes (SDIs) are high and middle-high, such as the United States [net drift=2.11% (95% CI 1.71-2.51)] and Italy [2.65% (1.24-4.08)]. Countries with a higher number of deaths were more active in this field of study, such as the United States (237 publications), China (120), and Italy (73). The United States and Italy, whose total link strengths were 209 and 135, respectively, were more active in international collaborative studies. CONCLUSIONS: Despite the global decrease in myocarditis death rate during the last three decades, negative period and cohort effects and elevated mortality were discovered in numerous countries, especially in those whose SDIs were high, and the age distribution of deaths shifted from adolescent to middle-aged and older populations. We also observed a decline in myocarditis research in some countries with increased mortality.
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Miocardite , Pessoa de Meia-Idade , Adolescente , Humanos , Idoso , Carga Global da Doença , Distribuição por Idade , Estudos de Coortes , Saúde Global , MortalidadeRESUMO
Objective: To compare the intraoperative neurophysiological monitoring (IONM) results between patients with arthrogryposis multiplex congenita (AMC) and adolescent idiopathic scoliosis (AIS) and to analyze the influence of congenital spinal deformity on IONM in AMC patients, thus to evaluate the efficiency of IONM in AMC patients. Methods: A cross-sectional study. The clinical data of 19 AMC patients underwent correction surgery from July 2013 to January 2022 in Nanjing Drum Tower Hospital were retrospectively reviewed. There were 13 males and 6 females with a mean age of (15.2±5.6) years, and the average Cobb angle of main curve was 60.8°±27.7°. And 57 female AIS patients of similar age and curve type with the AMC patients during the same period were selected as the control group, with an average age of (14.6±4.4) years and a mean Cobb angle of 55.2°±14.2°. The latency and amplitude of samatosensory evoked potentials (SSEPs) and transcranial electric motor evoked potentials (TCeMEPs) were compared between the two groups. The difference in IONM data between AMC patients with and without congenital spinal deformity was also evaluated. Results: The success rates of SSEPs and TCeMEPs were 100% and 14/19 for AMC patients, 100% and 100% for AIS patients. The SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency, TCeMEPs-amplitude showed no significant difference between AMC patients and AIS patients (P>0.05 for all). The side-difference of TCeMEPs-amplitude showed an increasing trend in AMC patients when compared with that in AIS patients, but there was no statistical difference between the two groups [(147.0±185.6) µV vs (68.1±311.4) µV, P=0.198]. The SSEPs-amplitude value was (1.4±1.1) µV on concave side in AMC patients with congenital spinal deformity, and it was (2.6±1.2) µV on concave side in AMC patients without congenital spinal deformity (P=0.041). The SSEPs-amplitude value was (1.4±0.8) µV on convex side in AMC patients with congenital spinal deformity, and it was (2.6±1.3) µV on convex side in AMC patients without congenital spinal deformity (P=0.028). Conclusions: The values of SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency and TCeMEPs-amplitude are similar in AMC and AIS patients. The SSEPs-amplitude of AMC patients with congenital spinal deformity is lower than that of AMC patients without congenital spinal deformity.
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Artrogripose , Monitorização Neurofisiológica Intraoperatória , Cifose , Escoliose , Masculino , Humanos , Adolescente , Feminino , Criança , Adulto Jovem , Adulto , Escoliose/cirurgia , Estudos Transversais , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the preparation of decellularized small intestinal submucosa (dSIS) sponge scaffolds with chelated strontium (Sr) ions at different pH values, and to select the appropriate pH values for synthesizing Sr/dSIS scaffolds using the physicochemical properties and biocompatibility of the scaffolds as evaluation indexes. METHODS: (1) Sr/dSIS scaffolds preparation and grouping: After mixing dSIS solution and strontium chloride solution in equal volumes, adjusting pH of the solution to 3, 5, 7, and 9 respectively, porous scaffolds were prepared by freeze-drying method after full reaction at 37â, which were named Sr/dSIS-3, -5, -7, and -9 respectively, and the dSIS scaffolds were used as the control group. (2) Physicochemical property evaluation: The bulk morphology of the scaffolds was observed in each group, the microscopic morphology analyzed by scanning electron microscopy, and the porosity and pore size determined, the surface elements analyzed by energy spectroscopy, the structure of functional groups analyzed by infrared spectroscopy, the chelation rate determined by atomic spectrophotometry, the water absorption rate detected by using specific gravity method, and the compression strength evaluated by universal mechanical testing machine.(3) Biocompatibility evaluation: The cytotoxicity and proliferative effect to bone mesenchymal stem cells (BMSCs) of each group were evaluated by Calcein-AM/PI double staining method. RESULTS: Scanning electron microscopy showed that the scaffolds of each group had an interconnected three-dimensional porous structure with no statistical difference in pore size and porosity. Energy spectrum analysis showed that strontium could be detected in Sr/dSIS-5, -7 and -9 groups, and strontium was uniformly distributed in the scaffolds. Functional group analysis further supported the formation of chelates in the Sr/dSIS-5, -7 and -9 groups. Chelation rate analysis showed that the Sr/dSIS-7 group had the highest strontium chelation rate, which was statistically different from the other groups (P < 0.05). The scaffolds in all the groups had good water absorption. The scaffolds in Sr/dSIS-5, -7 and -9 groups showed significantly improved mechanical properties compared with the control group (P < 0.05). The scaffolds in all the groups had good biocompatibility, and the Sr/dSIS-7 group showed the best proliferation of BMSCs. CONCLUSION: When pH was 7, the Sr/dSIS scaffolds showed the highest strontium chelation rate and the best proliferation effect of BMSCs, which was the ideal pH value for the preparation of the Sr/dSIS scaffolds.
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Materiais Biocompatíveis , Alicerces Teciduais , Alicerces Teciduais/química , Estrôncio/química , Estrôncio/farmacologia , Íons , Concentração de Íons de Hidrogênio , Engenharia Tecidual/métodos , PorosidadeRESUMO
BACKGROUND: Lateral spinous process deviation (LSPD) is a commonly used morphological parameter in the anatomical study of the cervical spinous process. However, quantitative studies on this issue are still lacking. In this study we aimed to establish reference intervals of C2-C7 LSPD in the adult Chinese population and provide decision-making information for clinical practitioners. MATERIALS AND METHODS: This was a retrospective study of 92 adult patients who received neck computed tomography scans, including 42 females and 50 males meeting the inclusion criteria. Three-dimensional reconstruction and anatomical measurements were performed using Mimics Research 19.0 and 3-Matic Research 11.0. RESULTS: The inter-observer reliability of LSPD measurement in this study was excellent (intraclass correlation coefficient value > 0.93). Only 2 cases of LSPD angles of 90 degrees were found, which means most cervical spinous process exist deviation. The reference interval for the C2-C7 LSPD angle was (85.11, 94.75) degrees. The C2 LSPD showed the different directions to C5 and C7 (p < 0.05). In the C4 vertebrae, the male tends to have greater LSPD angles than the female (T = -2.013, p = 0.047). In the C2 vertebrae, there was a statistically significant but weak correlation between age and LSPD angles (r = 0.24, p = 0.029). There was no statistically significant effect of sex or age on other levels of cervical vertebrae. CONCLUSIONS: Cervical spinous process deviation of less than 5 degrees on either side is a common morphological manifestation in Chinese adults. Thus, LSPD may not be an indicator for clinical care. Moreover, the vertebrae may have opposite directions of LSPD in the upper levels (C2-C4) and lower levels (C5-C7).
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Vértebras Cervicais , População do Leste Asiático , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos , Masculino , Vértebras Cervicais/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Valores de ReferênciaRESUMO
BACKGROUND: This study aimed to investigate the incidence, topographical distribution, morphology, and interrelationship of the metopism and Wormian bones (WBs) in dry adult-Chinese skulls. MATERIALS AND METHODS: In this study, 285 dried adult-Chinese skull specimens from the Department of Anatomy at the Southern Medical University were examined. The incidence of different types of metopism and WBs were recorded. The length of the metopic suture was measured using a flexible ruler. Additionally, the lengths and widths of the WBs were measured using a vernier calliper. RESULTS: The incidence of metopism and WBs in Chinese adults were estimated at 10.18% (29/285) and 63.86% (182/285), respectively. The metopism always accompanied WBs (26/29, 89.66%), but the WBs did not necessarily accompany metopism (26/182, 14.29%). The locations of the WBs in the order of decreasing incidence were the lambdoid suture (78.57%, 143/182), pterion (34.62%, 63/182), asterion (12.09%, 22/182), lambda (8.24%, 15/182), sagittal suture (4.95%, 9/182), and Inca bone (3.85%, 7/182). These locations differed in topographical distribution and morphological patterns. CONCLUSIONS: Chinese adults differ in incidence of metopism and WBs from adults of other races, indicating racial differences. The characteristics of WBs vary depending on the cranial site of occurrence. The metopism always accompanies WBs, but the WBs do not necessarily accompany metopism.
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População do Leste Asiático , Crânio , Adulto , Humanos , Crânio/anatomia & histologia , Suturas Cranianas/anatomia & histologia , Povo Asiático , IncidênciaRESUMO
OBJECTIVE: The stability of fractures of the middle and lower 1/3 of the displaced humeral shaft is poor, and surgery is currently the main treatment. The posterolateral approach to the upper arm has many advantages but it is not widely used in clinical applications. The aim of the study was to investigate the clinical effect of open reduction and internal fixation with a steel plate through the triceps approach in the treatment of fractures of the middle and lower 1/3 of the humerus. PATIENTS AND METHODS: A retrospective analysis was performed on 26 patients with fractures of the middle and lower 1/3 of the humerus who were admitted to our hospital from January 2018 to December 2021. According to the AO ASIF classification, 12 patients had type A, 8 patients had type B, and 6 patients had type C fractures. The posterior transtriceps approach was used for open reduction and internal fixation with a steel plate to evaluate its clinical efficacy. RESULTS: All patients were followed completely, and the follow-up time was 6.0-18.0 months. Fracture nonunion occurred in 1 patient after the operation, and the other 25 patients healed well; 2 patients showed symptoms of radial nerve injury and numbness in the tiger's mouth area, which improved after 2 weeks. The average healing time of the fracture was 12.3 weeks. There were no infections or complications such as plate fractures. Elbow joint function according to Mayo scoring standards was as follows: 19 cases were excellent, 3 cases were good, 2 cases were fair, and 2 cases were poor. The excellent and good rate was 84.6%. CONCLUSIONS: Open reduction through the triceps approach and internal fixation with a steel plate for the treatment of the middle and lower 1/3 of the humerus can directly expose and protect the radial nerve and its branches and reduce radial nerve damage, and plate fixation on the tension side is biomechanical and worthy of clinical application.
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Fraturas do Úmero , Humanos , Fraturas do Úmero/cirurgia , Braço , Estudos Retrospectivos , Aço , Placas Ósseas , Fixação Interna de Fraturas , Úmero/cirurgia , Resultado do TratamentoRESUMO
Objective: To evaluate the related factors of postoperative recurrence intrigeminal neuralgia (TN) patients treated with fully neuroendoscopic microvascular decompression (MVD). Methods: The clinical baseline data and preoperative MRI imaging data of 112 patients with TN treated by neuroendoscopic MVD from December 2008 to December 2020 in the Department of Neurosurgery, Beijing Shijitan Hospital Affiliated to Capital Medical University were retrospectively analyzed, including: area ratio of cerebellopontine area (CPA)(healthy side/affected side), trigeminal nerve(TGN)length ratio(healthy side/affected side), TGN angle ratio(healthy side/affected side), and criminal vessel type. Multivariate Cox proportional hazards model was used to analyze the factors affecting postoperative recurrence. Results: Among the 112 patients in this group, there were 49 males and 63 females. The age ranged from 20 to 82 (59±9) years, and the course of disease was 0.05 to 30.00 (5.60±5.15) years. Pain was located on the left side in 43 cases (38.39%) and on the right side in 69 cases (61.61%), respectively. All patients were followed up for more than 1 year, with an average follow-up time of 21.5 months, and 11 cases recurred. Multivariate Cox regression analysis revealed that disease duration≥3 years(HR=9.34, 95%CI:1.12-39.07), CPA area ratio(healthy side/affected side)>1 (HR=27.47, 95%CI:1.69-44.20), criminal vessel type with vein(HR=35.39, 95%CI:1.26-18.60) and criminal vessel type with arteriovenous (HR=46.07, 95%CI: 2.74-27.75) were the main factors influencing recurrence of MVD surgery (all P<0.05). Conclusion: The disease duration≥3 years, CPA area ratio(healthy side/affected side)>1, and criminal vessel type with vein/arteriovenous are the relevant factors that affect the recurrence rate after the fully neuroendoscopic MVD treatment for trigeminal neuralgia.
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Cirurgia de Descompressão Microvascular , Complicações Pós-Operatórias , Neuralgia do Trigêmeo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Cirurgia de Descompressão Microvascular/efeitos adversos , Pessoa de Meia-Idade , Dor/etiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Nervo Trigêmeo/cirurgia , Neuralgia do Trigêmeo/cirurgia , Adulto JovemRESUMO
BACKGROUND: This study aimed to investigate the incidence, number, diameter, and relative location of the parietal foramen (PF) as well as communication of intracranial and extracranial orifices and their direction, and sagittal suture morphology and length. MATERIALS AND METHODS: A total of 280 dry Chinese adult skull specimens from the Department of Anatomy, Southern Medical University, were observed and measured. The occurrence rate and quantity of the PF near the sagittal suture were recorded. The aperture of the PF, the vertical distance between PF and sagittal suture, and the linear distance between PF and lambda were measured using a Vernier calliper. The length of the sagittal suture was measured by a flexible ruler; the direction and communication of intracranial and extracranial orifices were detected using a probe. RESULTS: The total incidence of the PF was 82.86%, slightly higher on the right side than on the left side. The single-foramen type was the most prevalent. The mean diameter of the PF on the left and right sides were 1.02 ± 0.72 mm and 1.07 ± 0.67 mm, respectively, and the diameter of the PF on the sagittal suture was 1.77 ± 0.44 mm. The mean vertical distance between the PF and the sagittal suture was 5.90 ± 2.78 mm and 5.85 ± 2.75 mm on the left and right sides, respectively. The shape of the sagittal suture in the PF area was primarily dentate shaped, with an average arc length of χ = 124.36 ± 7.76 mm, of which the majority were completely healed type. The intracranial and extracranial communication was 39.97%, and the majority of the PF were anteromedial direction. CONCLUSIONS: The current study provided an anatomical basis for imaging diagnosis and neurosurgery by investigating the incidence, diameter, and relative location of the PF and intracranial and extracranial communication and direction.
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População do Leste Asiático , Osso Esfenoide , Adulto , Humanos , Suturas Cranianas/anatomia & histologiaRESUMO
Objective: The purpose of this study is to use the next-generation sequencing (NGS) technology platform to detect the methylation rate of phosphatase and tensin homolog deleted on chromosome ten (PTEN) promoter region in hepatocellular carcinoma (HCC) tissue samples, and to analyze the clinical significance of its correlation with the prognosis of patients receiving sorafenib treatment. Methods: The 52 pairs of tumor tissue and para-cancerous tissue samples from HCC patients treated with sorafenib alone, which were collected and preserved in the Liver Tumor Diagnosis and Research Center of the former 302 Hospital of the People's Liberation Army by the National Natural Science Foundation of China Youth Project with the project batch number 81702986 in 2018, were extracted total DNA from the samples. Then the DNA samples were treated with bisulfite and specific primers were designed to amplify the PTEN promoter region. Finally, the amplified products were analyzed by second-generation sequencing. In the analysis of clinical significance of PTEN methylation, log-rank statistical analysis was used to calculate whether there was a statistical difference in survival between the patient groups. Results: The methylation rate of PTEN promoter region in tumor tissues (29.17%±9.58%) was significantly higher than that in paracancer tissues (4.17%±2.86%)(t=19.970,P<0.05). At the same time, in HCC tissues, the methylation rate of the PTEN promoter region is negatively correlated with its expression (F=47.270,P<0.000 1;Y=-1 800×X+38.03), and the PTEN methylation rate is negatively correlated with the prognosis of patients receiving the molecularly targeted drug Sorafenib (χ²=4.313,P<0.05). Conclusion: This study successfully established a new method for detecting methylation in the promoter region of PTEN, and the methylation rate of PTEN can be used as one of the targets of HCC diagnosis and targeted therapy.
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Carcinoma Hepatocelular , Metilação de DNA , Neoplasias Hepáticas , PTEN Fosfo-Hidrolase/genética , Carcinoma Hepatocelular/genética , Cromossomos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/genética , Regiões Promotoras GenéticasRESUMO
A common clinical problem encountered by colorectal surgeons is the secondary tumors of the ovary (STO), particularly in young female patients. Most STO are from the digestive tract, and the known possible metastatic mechanisms include lymphatic, hematogenous, and intraperitoneal spreading. The molecular and histopathological characteristics of STO from different sites are diverse. It is particularly important to correctly identify the origin and feature of STO, which should be clarified by combining medical history, histopathology, immunohistochemistry, molecular biology, imaging and other means. The prognosis of patients with STO is poor in general. Comprehensive therapies based on surgical resection can benefit some patients. There is no specific treatment for STO at present, but not giving up easily on these patients is the right choice that every surgeon should understand.
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Neoplasias Colorretais , Tumor de Krukenberg , Neoplasias Ovarianas , Cirurgiões , Neoplasias Colorretais/terapia , Feminino , Humanos , Neoplasias Ovarianas/cirurgia , PrognósticoRESUMO
OBJECTIVE: This study aims to investigate whether liraglutide can affect proliferation, osteogenic differentiation and serum deprivation-induced apoptosis of preosteoblast cell line MC3T3-E1 through the Notch, Wnt/ß-catenin, and Hedgehog (Hh) signaling pathways. MATERIALS AND METHODS: MC3T3-E1 cells were exposed to different treatments (via Notch inhibitor DAPT, an Hh inhibitor cyclopamine, or serum deprivation) or transfections of different siRNAs (targeting glucagon-like peptide-1 receptor (GLP-1R), ß-catenin, or Gli1) in the presence or absence of 100 nM liraglutide. Cell proliferation, mRNA levels of osteogenic differentiation-related genes, mRNA and protein levels of the Notch and Hh signaling pathway proteins, and apoptosis-related proteins were assessed. RESULTS: Liraglutide significantly increased proliferation of MC3T3-E1 cells, expression levels of the Notch and Hh signaling pathway proteins and ß-catenin, and mRNA levels of osteogenic differentiation-related genes and TCF7L2. Moreover, liraglutide promoted a translocation of ß-catenin, increased a ratio of Bcl-2/Bax proteins, reduced serum deprivation-induced apoptosis of MC3T3-E1 cells, and a ratio of caspase-3/procaspase-3. However, a cotreatment with liraglutide and DAPT reversed the alterations. A cyclopamine treatment and knockdowns of GLP-1R, Gli1, and ß-catenin significantly reduced the expression of Notch proteins. Furthermore, the knockdown of GLP-1R, ß-catenin, or Gli1 significantly increased apoptosis, which could be inhibited by liraglutide. CONCLUSIONS: In summary, liraglutide can promote proliferation and differentiation of MC3T3-E1 cells, and inhibit their serum deprivation-induced apoptosis by activating both the Notch and Hh signaling pathways involving ß-catenin and Gli1. These results provide a therapeutic foundation that patients with diabetes and osteoporosis may be cured with treatments of liraglutide.
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Apoptose/efeitos dos fármacos , Liraglutida/farmacologia , Osteogênese/efeitos dos fármacos , Células 3T3 , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas Hedgehog/metabolismo , Camundongos , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismoRESUMO
OBJECTIVE: The aim of this study was to explore the effect of long non-coding ribonucleic acid (lncRNA) AK125437 on rats with postmenopausal osteoporosis via the mitogen-activated protein kinase (MAPK) pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including normal group, model group, and an inhibitor group, with 12 rats in each group. Only ovaries were exposed in normal group. The postmenopausal osteoporosis model was established in model group. Meanwhile, the intervention was performed with inhibitor for 3 months after modeling in inhibitor group, followed by sampling. The expression of receptor activator of nuclear factor kappa-B ligand (RANKL) was detected via immunohistochemistry. The protein expression level of phosphorylated p38 (p-p38) MAPK was determined via Western blotting (WB). Furthermore, the expression level of lncRNA AK125437 and the content of serum estradiol were determined via quantitative Polymerase Chain Reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. In addition, bone mineral density was measured using dual-energy X-ray bone mineral absorptiometer. RESULTS: Immunohistochemistry results indicated that model group and inhibitor group had notably up-regulated positive expression level of RANKL than normal group (p<0.05), which was remarkably lower in inhibitor group than model group (p<0.05). Western blot results showed that compared with normal group, the protein expression level of p-p38 MAPK was substantially elevated in model and inhibitor groups (p<0.05). Meanwhile, the protein expression level of p-p38 MAPK was markedly lower in inhibitor group than that in model group (p<0.05). According to qPCR results, the expression level of lncRNA AK125437 was significantly up-regulated in both model group and inhibitor group compared with normal group, showing statistically significant differences (p<0.05). However, no significant differences were observed between model group and inhibitor group (p>0.05). ELISA results revealed that model group and inhibitor group had markedly lower estradiol content than normal group (p<0.05). There was no statistically significant difference in the content of estradiol between the two groups (p>0.05). According to the measurement results of bone mineral density, compared with normal group, bone mineral density was notably lower in model group and inhibitor group (p<0.05). Furthermore, it was markedly higher in inhibitor group than that of model group (p<0.05). CONCLUSIONS: LncRNA AK125437 affects the bone mineral density of rats with postmenopausal osteoporosis by activating the MAPK pathway.
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Sistema de Sinalização das MAP Quinases , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Feminino , Humanos , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/patologia , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effect of long non-coding ribonucleic acid (lncRNA) AK023948 (AK0) on rats with postmenopausal osteoporosis via the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. MATERIALS AND METHODS: Firstly, postmenopausal osteoporosis rat models were established to obtain osteoblasts. The phosphorylation level of AKT was analyzed by controlling the expression of AK0 gene in osteoblasts. Finally, XTT was used to analyze the proliferation of osteoblasts and the messenger ribonucleic acid (mRNA) expression level of caspase in AK0 gene knockout (KO) rat model. RESULTS: In the bone tissue of postmenopausal osteoporosis rats, the levels of phospho-PI3K (p-PI3K), p-Akt, and p-phosphoinositide-dependent kinase-1(PDK1) were significantly decreased (p<0.05). In rat model osteoblasts, the overexpression of AK0 gene upregulated the phosphorylation level of AKT, while the interference with small interfering RNA (siRNA) in AK0 gene decreased that of AKT. Knocking out AK0 gene led to the down-regulation of phosphorylation level of AKT in cells. Moreover, if the AK0 gene was re-expressed in the KO rat model cells, the phosphorylation level of AKT was restored to a certain extent, but still lower than that after the overexpression of AK0 gene. Although the proliferation rate of osteoblasts in estrogen deficiency-related osteoporosis rats was low, the growth rate of osteoblasts with AK0 KO was remarkably lower than that in blank control group (p<0.05). It was also found that there was a certain correlation between AK0 gene and osteoblast apoptosis. CONCLUSIONS: LncRNA AK0 can regulate the phosphorylation level of AKT in osteoblasts of rats with estrogen deficiency-related osteoporosis through the PI3K/AKT signaling pathway, thus regulating the proliferation of osteoblasts. It is speculated that lncRNA AK0 may be an important factor in regulating the PI3K/AKT signaling pathway.
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Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Animais , Células Cultivadas , Feminino , Humanos , Osteoporose Pós-Menopausa/patologia , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-DawleyRESUMO
Objective: To detect the spatial clustering and high risk areas of pulmonary tuberculosis (PTB) in Sichuan province in 2018 and, to compare the effects of application on both SaTScan 9.4.1 software and FleXScan 3.1.2 software to detect the PTB spatial clusters. Methods: Geographic information database was established by using the incidence data of PTB and demographic data reported in the 'China disease prevention of infectious disease reporting information management system' in Sichuan province in 2018. Spatial clustering analysis was conducted using the Poisson model in software SaTScan 9.4.1 and FleXScan 3.1.2 to detect the high risk areas of PTB by software ArcGIS 10.5. Differences of clusters locations and scopes in the two scanning methods were compared. Results: The reported incidence rate of PTB was 57.34/100 000 (47 601 cases) in Sichuan province in 2018, presenting an obvious clustering distribution. SaTScan and FleXScan scanned 8 and 10 clusters showed statistically significant differences (P<0.05), with log-likelihood ratio (LLR) as 24.62-2 416.05 and 1.48-2 618.96, respectively. Results from scanning of the two methods showed that the most likely clusters appeared in the Daliangshan and Xiaoliangshan of Liangshan Yi ethnic aggregation areas. The other clustering areas would include some minority areas in the western Sichuan plateau, detected by both two methods differences in the shape and scope of the clustering were detected by both methods. The clustering scopes detected by SaTScan covered some counties, in which the actual incidence was not high. FleXScan could distinguish the clusters and detect more irregular shaped clusters. Conclusions: Obvious spatial clusters of PTB distribution were found in Sichuan in 2018. Areas of Daliangshan, Xiaoliangshan and the minority areas in Western Sichuan plateau appeared at high risk, suggesting these were the key areas for prevention and control. FleXScan seemed more conducive in accurately distinguishing the "cold spot" areas in the highly aggregated areas, and more suitable for the application of spatial clustering detection for TB, in Sichuan province.
Assuntos
Software , Tuberculose Pulmonar/epidemiologia , China/epidemiologia , Análise por Conglomerados , Humanos , Incidência , Reprodutibilidade dos Testes , Análise EspacialRESUMO
Objective: To observe ascitic interleukin-7 expression level in cirrhotic patients complicated with spontaneous bacterial peritonitis, and to detect the effect of recombinant human IL-7 on CD4(+) and CD8(+)T lymphocyte function. Methods: A total of 84 patients with liver cirrhosis who were hospitalized from August 2017 to April 2018 were selected. Among them, 51 cases were complicated with cirrhosis and untainted ascites, and 33 cases were cirrhosis complicated with spontaneous bacterial peritonitis. Peripheral blood and ascites were collected routinely. The levels of IL-7 in peripheral blood and ascites were measured by enzyme-linked immunosorbent assay. CD4(+)T cells and CD8(+)T cells were purified from ascites, and were stimulated with recombinant IL-7. Cellular proliferation, key transcription factors for mRNA, and cytokines production by CD4(+)T cells in response to IL-7 stimulation was measured. mRNA expression corresponding to perforin, granzyme B, and granulysin as well as cytokines production by CD8(+)T cells was also measured in response to IL-7 stimulation. Cytolytic and non-cytolytic activity of CD8(+)T cells in response to IL-7 stimulation was also investigated in both direct and indirect contact co-culture system. Measurement data of the normal distribution were compared between the two groups by Student's t-test and the data before and after stimulation were compared by paired t-test. Measurements that did not conform to normal distribution were compared between the two groups using Mann-Whitney U test, and data before and after stimulation were compared using Wilcoxon paired test. Results: There was no significant statistical difference in serum IL-7 levels between the two groups [(5 001 ± 1 458) pg/ml vs. (4 768 ± 1 128) pg/ml, P = 0.41]. The level of ascitic IL-7 in cirrhotic patients complicated with SBP was significantly lower than cirrhosis patients with untainted ascites [(966.4 + 155.8) pg/ml vs. (792.1 + 126.4) pg/ml, P < 0.01]. Recombinant IL-7 stimulation promoted the proliferation of CD4(+) and CD8(+)T cells from ascites in patients with liver cirrhosis complicated by SBP. T-bet mRNA relative expression and IFN-γ secretion in CD4(+)T cells was also elevated in response to IL-7 stimulation in vitro. Moreover, IL-7 stimulation also increased the mRNA expressions of perforin, granzyme B, and granulysin as well as productions of IFN-γ and TNF-α by CD8(+)T cells. Recombinant IL-7 stimulation elevated cytolytic and non-cytolytic activity of CD8(+)T cells from ascites in patients with liver cirrohosis complicated by SBP, which manifested as increased target cell death and IFN-γ production in both direct and indirect contact co-culture system. Conclusion: Ascitic IL-7 promotes T lymphocyte function in patients with liver cirrhosis complicated with SBP.
Assuntos
Ascite/diagnóstico , Líquido Ascítico/metabolismo , Interleucina-7/análise , Cirrose Hepática/metabolismo , Peritonite/metabolismo , Ascite/microbiologia , Biomarcadores/análise , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/microbiologia , Peritonite/complicações , Peritonite/microbiologiaRESUMO
Objective: To investigate the relationships between serum cystatin C (Cys C), chemerin levels and subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Methods: A cross-sectional study was carried out between January 2016 and January 2018, and T2DM patients with carotid intima-media thickness (IMT) less than 1.1 mm were selected as subjects (100 males and 80 females, aged 40-60 years). The brachial-ankle pulse wave velocity (baPWV) ≥ 1 700 cm/s was set as the observation group (subclinical atherosclerosis) and baPWV<1 700 cm/s as the control group (non-subclinical atherosclerosis). Physical and blood examination were performed in both groups. Serum Cys C and chemerin levels were measured and their relationship with subclinical atherosclerosis was analyzed. Results: There was a statistically significant correlation between serum creatinine (r=0.167, P=0.011) and baPWV in the observation group, but not in the control group (r=0.105, P=0.070). Multiple linear regression analysis showed that age, duration of diabetes, serum creatinine, estimated glomerular filtration rate (eGFR), Cys C and chemerin were independently associated with baPWV, while high sensitive C reactive protein (hsCRP) and glycosylated hemoglobin (HbA1c) were not associated with baPWV. The elevation of serum Cys C (ß'=0.393, P=0.003) and chemokine (ß'=0.340, P=0.007) were correlative factors for atherosclerosis. Conclusion: The level of serum Cys C and chemerin is possibly related to the occurrence and development of subclinical atherosclerosis in T2DM patients.
Assuntos
Aterosclerose/complicações , Diabetes Mellitus Tipo 2 , Adulto , Índice Tornozelo-Braço , Biomarcadores , Espessura Intima-Media Carotídea , Quimiocinas , Estudos Transversais , Cistatina C , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de RiscoRESUMO
Ketamine and phencyclidine are well-known drugs of abuse of the arylcyclohexylamine class, the backbone of which is used for the synthesis of new psychoactive substances (NPS). In October 2017, a cluster of acute intoxications was encountered where patients presented with ketamine-like toxidrome. Upon initial toxicology screening, however, neither ketamine nor other causative agents were detected in the patients' urine. Instead, an unidentified substance was consistently detected. Further investigations using gas- and liquid-chromatography mass spectrometry led to the identification of an arylcyclohexylamine analogue, 2-oxo-PCE. The present study reports the analytical and toxicological profile of this emerging NPS. Chart review found, in total, 56 cases of 2-oxo-PCE associated acute poisoning between October and November 2017. Laboratory analysis confirmed the presence of 2-oxo-PCE in the urine of all patients; nasal swab samples from three patients revealed the lone presence of 2-oxo-PCE. Urine bedside immunoassay for ketamine was found not to cross-react with 2-oxo-PCE. In 55% of the cases, other drugs of abuse were detected on toxicology analysis; whilst in the remainder, 2-oxo-PCE was used alone. The main clinical symptoms associated with sole 2-oxo-PCE use include impaired consciousness (84%), confusion (60%), abnormal behaviour (44%), hypertension (80%) and tachycardia (40%). Convulsion (16%) was also observed relatively frequently. Management was mainly supportive, whilst three patients required intensive care. All patients recovered uneventfully. In conclusion, frontline clinical and laboratory personnel should be highly vigilant in the lookout for 2-oxo-PCE, a dangerous emerging arylcyclohexylamine analogue.