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@#The cardiac conduction system (CCS) is a set of specialized myocardial pathways that spontaneously generate and conduct impulses transmitting throughout the heart, and causing the coordinated contractions of all parts of the heart. A comprehensive understanding of the anatomical characteristics of the CCS in the heart is the basis of studying cardiac electrophysiology and treating conduction-related diseases. It is also the key of avoiding damage to the CCS during open heart surgery. How to identify and locate the CCS has always been a hot topic in researches. Here, we review the histological imaging methods of the CCS and the specific molecular markers, as well as the exploration for localization and visualization of the CCS. We especially put emphasis on the clinical application prospects and the future development directions of non-destructive imaging technology and real-time localization methods of the CCS that have emerged in recent years.
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OBJECTIVE@#To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.@*METHODS@#Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).@*RESULTS@#DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.@*CONCLUSION@#CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
Subject(s)
Female , Humans , Cell Line, Tumor , HeLa Cells , Neoplastic Stem Cells/metabolism , RNA, Small Interfering/metabolism , Uterine Cervical Neoplasms/metabolismABSTRACT
OBJECTIVE@#To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.@*METHODS@#The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.@*RESULTS@#Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).@*CONCLUSIONS@#The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.
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Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
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Humans , Brain Neoplasms/pathology , Neoplasm Recurrence, Local/metabolism , Glioma/pathology , Neural Stem Cells/pathology , Oligodendrocyte Precursor Cells/pathology , Tumor MicroenvironmentABSTRACT
Type II innate lymphoid cell (ILC2) is a newly identified innate immunological cell that belongs to the lymphocyte lineage in cell morphology, resides in the body's mucosal tissues, and has the dual functions of innate and adaptive immunity to promote tissue remodeling and repair after injury. Additionally, it is involved in the occurrence and development of a variety of liver diseases and plays an important role in maintaining the immunological homeostasis of the liver region. This article reviews the differentiation, development, and biological functions of ILC2, with particular attention to the research progress in liver diseases.
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Humans , Immunity, Innate , Lymphocytes , Cell Differentiation , Liver DiseasesABSTRACT
Objective: To explore the characteristics of pulmonary blood flow perfusion imaging of single photo emission computer tomography/computer tomography (SPECT/CT) in chronic pulmonary vascular Stenosis (CPVS) caused by different etiological factors. Methods: This is a retropective study. Present study screened 50 consecutive cases diagnosed with chronic pulmonary vascular stenosis from January 2019 to January 2020 in the department of cardiology of Gansu Provincial Hospital and underwent SPECT/CT pulmonary blood flow perfusion examination. Thirteen patients were excluded because of pulmonary vascular lesions with a disease course of less than 3 months and poor image quality. According to the etiology, patients were divided into fibrosing mediastinitis (FM) group, Takyasu's arteritis (PTA) group, and chronic thromboembolic pulmonary hypertension/chronic thromboembolic pulmonary disease (CTEPH/CTED) group. The severity of pulmonary blood flow perfusion was evaluated in accordance with the Begic scoring principle in the three groups. The overall Begic score, lung lobe scores among three groups were compared. CT signs of lung SPECT/CT, such as enlargement of hilar lymph node, atelectasis, bronchial stenosis, were also analyzed in three groups. Results: A total of 37 patients with chronic pulmonary vascular stenosis were finally enrolled (18 in the FM group, 5 in the PTA group, and 14 in the CTEPH/CTED group). The total Begic score of pulmonary perfusions was similar among the three groups (F=0.657,P>0.05). There was a statistically significant difference in the left upper lobe Begic score among the three groups (H=4.081, P<0.05). The left upper lobe Begic score was higher in the FM group than in the PTA group (3.44±2.50 vs. 1.60±0.55, P<0.05). As compared to other two groups, patients in FM group were featured with CT signs of higher percent of hilar enlargement (FM group vs. PTA group: 16/18 vs. 1/5, P=0.008; FM group vs. CTEPH/CTED group: 16/18 vs. 3/14, P=0.000 2), enlargement of the pulmonary hilum lymph nodes (FM group vs. PTA group: 14/18 vs. 1/5, P=0.033; FM group vs. CTEPH/CTED group: 14/18 vs. 2/14, P=0.001), and calcification of mediastinal soft tissue (FM group vs. PTA group: 11/18 to 0/5, P=0.037; FM group vs. CTEPH/CTED group: 11/18 vs. 1/14, P=0.003). The proportion of CT signs of bronchial stenosis (9/18 vs. 0/14, P=0.002) and atelectasis (9/18 vs. 1/14, P=0.002) was also higher in the FM group than in the CTEPH/CTED group. In case of abnormal pulmonary blood flow perfusion, the diagnostic accuracy of CT signs hilar enlargement, hilar lymph node enlargement, mediastinal soft tissue calcification, bronchial stenosis, and atelectasis for the diagnosis of FM were 81.1%, 83.8%, 78.4%, 75.7%, and 73.0%, respectively. Conclusion: There is no significant difference in the Begic score of SPECT/CT pulmonary blood flow perfusion imagines among the three groups of patients. Impaired pulmonary blood flow perfusion combined with typical CT signs is useful for identifying patients with FM.
Subject(s)
Humans , Constriction, Pathologic/diagnostic imaging , Perfusion , Pulmonary Atelectasis , Mediastinitis , Calcinosis , Lung/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
Objective: To explore the characteristics of pulmonary blood flow perfusion imaging of single photo emission computer tomography/computer tomography (SPECT/CT) in chronic pulmonary vascular Stenosis (CPVS) caused by different etiological factors. Methods: This is a retropective study. Present study screened 50 consecutive cases diagnosed with chronic pulmonary vascular stenosis from January 2019 to January 2020 in the department of cardiology of Gansu Provincial Hospital and underwent SPECT/CT pulmonary blood flow perfusion examination. Thirteen patients were excluded because of pulmonary vascular lesions with a disease course of less than 3 months and poor image quality. According to the etiology, patients were divided into fibrosing mediastinitis (FM) group, Takyasu's arteritis (PTA) group, and chronic thromboembolic pulmonary hypertension/chronic thromboembolic pulmonary disease (CTEPH/CTED) group. The severity of pulmonary blood flow perfusion was evaluated in accordance with the Begic scoring principle in the three groups. The overall Begic score, lung lobe scores among three groups were compared. CT signs of lung SPECT/CT, such as enlargement of hilar lymph node, atelectasis, bronchial stenosis, were also analyzed in three groups. Results: A total of 37 patients with chronic pulmonary vascular stenosis were finally enrolled (18 in the FM group, 5 in the PTA group, and 14 in the CTEPH/CTED group). The total Begic score of pulmonary perfusions was similar among the three groups (F=0.657,P>0.05). There was a statistically significant difference in the left upper lobe Begic score among the three groups (H=4.081, P<0.05). The left upper lobe Begic score was higher in the FM group than in the PTA group (3.44±2.50 vs. 1.60±0.55, P<0.05). As compared to other two groups, patients in FM group were featured with CT signs of higher percent of hilar enlargement (FM group vs. PTA group: 16/18 vs. 1/5, P=0.008; FM group vs. CTEPH/CTED group: 16/18 vs. 3/14, P=0.000 2), enlargement of the pulmonary hilum lymph nodes (FM group vs. PTA group: 14/18 vs. 1/5, P=0.033; FM group vs. CTEPH/CTED group: 14/18 vs. 2/14, P=0.001), and calcification of mediastinal soft tissue (FM group vs. PTA group: 11/18 to 0/5, P=0.037; FM group vs. CTEPH/CTED group: 11/18 vs. 1/14, P=0.003). The proportion of CT signs of bronchial stenosis (9/18 vs. 0/14, P=0.002) and atelectasis (9/18 vs. 1/14, P=0.002) was also higher in the FM group than in the CTEPH/CTED group. In case of abnormal pulmonary blood flow perfusion, the diagnostic accuracy of CT signs hilar enlargement, hilar lymph node enlargement, mediastinal soft tissue calcification, bronchial stenosis, and atelectasis for the diagnosis of FM were 81.1%, 83.8%, 78.4%, 75.7%, and 73.0%, respectively. Conclusion: There is no significant difference in the Begic score of SPECT/CT pulmonary blood flow perfusion imagines among the three groups of patients. Impaired pulmonary blood flow perfusion combined with typical CT signs is useful for identifying patients with FM.
Subject(s)
Humans , Constriction, Pathologic/diagnostic imaging , Perfusion , Pulmonary Atelectasis , Mediastinitis , Calcinosis , Lung/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
Objective:To investigate the related factors of cerebral collateral circulation in patients with acute cerebral infarction (ACI).Methods:A retrospective study was conducted on 4 483 inpatients with ACI admitted to the Renqiu Kangji Xintu Hospital from January 2014 to November 2018 were selected as the research subjects. According to transcranial Doppler (TCD) and CT angiography(CTA) examination results, they were divided into the group with collateral circulation (154 cases) and the group without collateral circulation (4 329 cases) according to the presence of collateral circulation. The related factors affecting the formation of cerebral collateral circulation in the two groups were statistically analyzed. According to the Modified Rankin Scale (mRS) score, 0 - 1 score was defined as good discharge outcome, and mRS ≥ 3 scores was defined as bad discharge outcome. The relationship between collateral circulation opening and poor discharge outcome was analyzed.Results:Compared with the group without collateral circulation, age: 67.00 (61.00, 73.00) years vs. 65.00 (57.00, 72.00) years, history of stroke: 52.59% (81/154) vs. 32.08% (1 389/4 329), carotid artery stenosis: 85.71% (132/154) vs. 20.23%(876/4 329), homocysteine (Hcy): 16.85 (13.00, 28.03) μmol/L vs. 15.00 (11.00, 21.00) μmol/L, significantly promoted the formation of collateral circulation, and the differences were statistically significant ( P<0.05). After adjusting for confounding factors, age ( OR = 0.97, 95% CI 0.95 - 0.99), stroke history ( OR = 1.60, 95% CI 1.11 - 2.32), carotid artery stenosis ( OR = 23.63, 95% CI 14.64 -38.11) and Hcy ( OR = 1.01, 95% CI 1.00 -1.02) were independent factors promoting the formation of cerebral collateral circulation in ACI patients ( P<0.05), carotid artery stenosis was a significant promoting factor, OR value was 23.63. Receiver operating characteristic (ROC) curve analysis showed that the model predicted the area under the curve value of cerebral collateral circulation opening reached 0.869. Among 4 483 ACI patients, 798 cases (17.80%) had poor discharge outcome, including 18 cases (11.68%) with collateral circulation and 780 cases (18.01%) without collateral circulation, suggesting that the incidence of adverse discharge outcome was lower in the group with collateral circulation ( P<0.05), OR = 0.60, 95% CI 0.36 - 0.99, suggesting that the formation of cerebral collateral circulation was a factor promoting the good prognosis of ACI patients. Conclusions:Age, history of stroke, carotid artery stenosis and Hcy are correlated with the formation of cerebral collateral circulation in ACI patients. Existing model can effectively predict the formation of cerebral collateral circulation in ACI patients, and the formation of cerebral collateral circulation is closely related to the discharge outcome of ACI patients.
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Objective: To evaluate the short-term efficacy and perioperative safety of catheter-based intervention in patients with pulmonary vein stenosis caused by fibrosing mediastinitis (FM). Methods: It was a case series study. Consecutive patients with pulmonary vein stenosis caused by FM, who underwent percutaneous pulmonary vein angioplasty in Gansu Provincial Hospital from January 2018 to June 2020, were retrospective enrolled. The baseline characteristics, comorbidities, exercise capacity and hemodynamic data before and after treatment were compared, and the procedural related complications were evaluated. Results: A total of 30 patients ((64.3±7.1) years, 15 males) were included. Sixty-three pulmonary vein stenosis were treated by 32 percutaneous pulmonary vein angioplasty procedures. Forty-four stents were implanted in 41 pulmonary veins after balloon angioplasty, and the diameter of implanted stents was (8.3±1.2)mm. Balloon angioplasty was performed on 22 pulmonary vein stenosis, the mean balloon diameter was (4.2±2.1)mm. The pulmonary vein diameter increased from (2.6±1.3) to (6.6±2.6) mm (P<0.001) and the pressure gradient across the pulmonary vein stenotic segment reduced from 19 (12, 29) to 2 (0, 4) mmHg (1 mmHg=0.133 kPa) (P<0.001) immediately post procedure. The pulmonary vein flow grade was significantly improved compared with baseline (P<0.001). The most common operation related complications were lung injury (44.0% (11/25)) and hemoptysis (18.8% (6/32)), which did not need special treatment. During the 2.0 (1.3, 3.2) months follow-up, the WHO functional class was significantly improved (P<0.05), the 6-minute walking distance increased from (254.8±114.5) m to (342.8±72.4)m (P<0.05), the mean pulmonary arterial pressure decreased from (40.9±8.3) mmHg to (35.4±7.7) mmHg (P<0.01), 17 out of 19 patients with refractory pleural effusion experienced total remission during the follow-up period (P<0.001). CT pulmonary venography was repeated in 17 patients. The incidence of in-stent restenosis of pulmonary vein was 24.0% (6/25). Conclusions: Percutaneous pulmonary vein angioplasty is effective for the treatment of pulmonary vein stenosis caused by fibrosing mediastinitis. However, it's not so safe, procedural related complication should be paid attention to and the rate of in-stent restenosis is relative high during the short-term follow-up.
Subject(s)
Humans , Male , Angioplasty, Balloon , Catheters , Mediastinitis , Retrospective Studies , Sclerosis , Stenosis, Pulmonary Vein , Stents , Treatment OutcomeABSTRACT
Objective: To explore the clinical application value of two longitudes three transverses method in the location of the perforator of thoracodorsal artery perforator and deep wound repair. Methods: The retrospectively observational study was conducted. From December 2018 to June 2020, 17 patients with deep wounds who were admitted to the Affiliated Hospital of Zunyi Medical University met the inclusion criteria and were included in this study, including 7 males and 10 females, aged 12 to 72 years. The wound areas of patients after debridement were 7 cm×3 cm to 11 cm×7 cm. Two longitudinal lines were located through the midpoint of the armpit, the posterior superior iliac spine, and the protruding point of the sacroiliac joint, and three transverse lines were located 5, 10, and 15 cm below the midpoint of the armpit between the two longitudinal lines, i.e. two longitudes three transverses method, resulting in two trapezoidal areas. And then the thoracodorsal artery perforators in two trapezoidal areas were explored by the portable Doppler blood flow detector. On this account, a single or lobulated free thoracodorsal artery perforator flap or flap that carrying partial latissimus dorsi muscle, with an area of 7 cm×4 cm to 12 cm×8 cm was designed and harvested to repair the wound. The donor sites were all closed by suturing directly. The number and location of thoracodorsal artery perforators, and the distance from the position where the first perforator (the perforator closest to the axillary apex) exits the muscle to the lateral border of the latissimus dorsi in preoperative localization and intraoperative exploration, the diameter of thoracodorsal artery perforator measured during operation, and the flap types were recorded. The survivals of flaps and appearances of donor sites were followed up. Results: The number and location of thoracodorsal artery perforators located before operation in each patient were consistent with the results of intraoperative exploration. A total of 42 perforators were found in two trapezoidal areas, with 2 or 3 perforators each patient. The perforators were all located in two trapezoid areas, and a stable perforator (the first perforator) was located and detected in the first trapezoidal area. There were averagely 1.47 perforators in the second trapezoidal area. The position where the first perforator exits the muscle was 2.1-3.1 cm away from the lateral border of the latissimus dorsi. The diameters of thoracodorsal artery perforators were 0.4-0.6 mm. In this group, 12 cases were repaired with single thoracodorsal artery perforator flap, 3 cases with lobulated thoracodorsal artery perforator flap, and 2 cases with thoracodorsal artery perforator flap carrying partial latissimus dorsi muscle. The patients were followed up for 6 to 16 months. All the 17 flaps survived with good elasticity, blood circulation, and soft texture. Only linear scar was left in the donor area. Conclusions: The two longitudes three transverses method is helpful to locate the perforator of thoracodorsal artery perforator flap. The method is simple and reliable. The thoracodorsal artery perforator flap designed and harvested based on this method has good clinical effects in repairing deep wound, with minimal donor site damage.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Arteries , Perforator Flap , Plastic Surgery Procedures/methods , Retrospective Studies , Skin Transplantation , Soft Tissue Injuries/surgery , Treatment OutcomeABSTRACT
ObjectiveTo study the virulence and biofilm inhibition effect of Fufang Huangbai Fluid Paint (FFHBFP) on methicillin-resistant Staphylococcus aureus (MRSA), and to explore the antibacterial effect of FFHBFP on MRSA, which provides a theoretical basis and reference for clinical medication. MethodFirstly, the microdilution method and time–growth curve were used to determine the minimum inhibitory concentration (MIC) of FFHBFP and vancomycin (VAN) against MRSA and the effect on bacterial growth. The effects of FFHBFP and VAN on the inhibition of MRSA virulence factor lipase and restoration of hydrogen peroxide (H2O2) sensitivity were detected under sub-minimum inhibitory concentration (sub-MIC). The inhibitory effect of FFHBFP and VAN on MRSA biofilm formation and maturation was detected by the microplate method. The morphological changes of mature biofilms before and after administration were observed under a scanning electron microscope (SEM). Real-time polymerase chain reaction (Real-time PCR) was utilized to detect the effect of 50.600 g·L-1 concentration of FFHBFP on the expression of MRSA virulence gene crtM and biofilm-forming genes fnbA and icaA. Finally, molecular docking technology was used to predict the mechanism of potential antibacterial active ingredients of FFHBFP in inhibiting the virulence and biofilm of MRSA. ResultThe MIC of VAN was 2 mg·L-1, and VAN below 1 mg·L-1 exerted no effect on MRSA growth. The MIC of FFHBFP was not determined, while the 101.200-202.400 g·L-1 original solution inhibited MRSA growth. Compared with the blank group and the VAN group, sub-MIC (25.300-50.600 g·L-1 original solution) inhibited lipase and recovered MRSA sensitivity to H2O2 (P<0.01). The results of the microplate method showed that FFHBFP (25.300-202.400 g·L-1 original solution) inhibited biofilm formation and maturation (P<0.05, P<0.01). The SEM exhibited that FFHBFP made the structure of biofilm loose and the size of the bacteria varied. FFHBFP at 50.600 g·L-1 concentration can inhibit the expression of related virulence genes and biofilm-forming genes (P<0.05, P<0.01), and molecular docking results also showed that the main antibacterial active ingredients in FFHBFP have good binding ability to the target. ConclusionFFHBFP that cannot directly kill MRSA exerts clinical efficacy by impairing virulence expression, biofilm formation, and other pathogenic properties.
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OBJECTIVE@#To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats.@*METHODS@#Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA.@*RESULTS@#The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05).@*CONCLUSION@#Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.
Subject(s)
Animals , Rats , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Autophagy , Beclin-1 , Caspase 3/metabolism , Cerebral Hemorrhage/therapy , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats, Sprague-Dawley , bcl-2-Associated X Protein/metabolismABSTRACT
Aim To observe the inhibitory effect of neferine(Nef)on the migration and invasion of non-small cell lung cancer(NSCLC)H1299 cells by blocking ROCK pathway.Methods H1299 cells were taken for in vitro culture, and treated with different concentrations of Nef.H1299 cell viability was measured by CCK-8 method to determine the dose of the experimental group.The migration and invasion abilities of H1299 cells were detected by cell scratch test and Transwell chamber test.The expression of matrix metalloproteinases MMP-2 and MMP-9 secreted from lung cancer cells was detected by enzyme linked immunosorbent assay(ELISA).The protein level of ROCK1 in H1299 cells was tested by real-time fluorescent quantitative PCR and Western blot; the binding mode and affinity between Nef and ROCK1 were stimulated by AutoDock semi flexible docking method.Results The doses of Nef in the experimental group were determined as 4, 6 and 10 μmol·L-1.These three concentrations of Nef could inhibit the migration and invasion of H1299 lung cancer cells to a certain degree in a dose-dependent manner.At the same time, Nef reduced the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.In addition, the affinity of Nef to ROCK1 was significantly higher than that of fasudil, an inhibitor of ROCK, and the binding force was stronger to A-chain of ROCK1.Conclusions As a potential natural anticancer compound, Nef can inhibit the migration and invasion of NSCLC by reducing the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.
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Objective:To explores the clinical efficacy and safety of carotid endarterectomy in patients with high bifurcation carotid artery stenosis.Methods:A total of 169 patients with carotid artery stenosis (147 patients with non-high bifurcation carotid artery stenosis and 22 patients with high bifurcation carotid artery stenosis), underwent carotid endarterectomy under surgical microscope in our hospital from January 2017 to January 2020, were included in the study. Patients with high bifurcation carotid artery stenosis were operated by cutting off the posterior abdomen of the digastric muscle to assist in exposing the distal end of the internal carotid artery plaque. Cervical CTA/DSA examination was performed within one week of surgery to confirm whether carotid artery stenosis was relieved; ultrasound examination of cervical vessels was performed 6 months and 1 year after surgery to determine whether restenosis was appeared in the carotid artery. The surgical efficacy, perioperative complications and re-examination results were compared between the two groups.Results:Postoperative carotid artery stenosis was relieved in both groups. The proportions of new cerebral infarction and temporary neurological impairment between the two groups (4.5% vs. 2.0%; 9.1% vs. 3.4%) showed no significant differences ( P>0.05). Carotid artery restenosis was not found in both groups. There was no obvious functional abnormality in the digastric muscles of patients with high bifurcation carotid stenosis. Conclusion:Cutting off the posterior abdomen of the digastric muscle during carotid endarterectomy can better expose the distal end of the internal carotid plaque in patients with high bifurcation carotid stenosis, and provide convenience for effective relief of carotid artery stenosis with high safety.
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Objective:To explore the influences of times of venous thromboembolism (VTE) drug prophylaxis in formation of deep vein thrombosis (DVT) in patients with severe craniocerebral injury after surgical treatment.Methods:Ninety patients with severe craniocerebral injury, admitted to our hospital from February 2021 to December 2021, were chosen in our study; they were divided into early group ( n=47, less than 48 h from the time of admission) and late group ( n=43, more than 48 h from the time of admission) according to the times of initiation for VTE drug prophylaxis (low molecular weight heparin calcium injection [LMWH] 100 IU/Kg was injected subcutaneously once a d). One week after injection, the DVT formation in the lower limbs, intracranial rebleeding, gastrointestinal bleeding and death were compared in the two groups. Results:The times of initiation for drug prophylaxis in the early group and late group were (28.91±4.50) h and (71.56±8.89) h. The DVT formation in the early group was significantly lower than that in the late group (12.8% vs. 34.9%, P<0.05). There was no difference in the incidence of intracranial rebleeding, mortality or gastrointestinal bleeding between the two groups ( P>0.05). Conclusion:Early initiation of VTE drug prophylaxis can significantly reduce the incidence of DVT in patients with severe craniocerebral injury after surgical treatment, enjoying high safety.
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Objective:To investigate the predictive value of pressure ulcer score and fall score and NIHSS scale for discharge outcome in patients with acute ischemic stroke (AIS).Methods:From January 2014 and November 2018, 4 468 patients with AIS who were treated in Hebei Province Renqiu Kangjixintu Hospital were selected as the research object. According to the modified Rankin scale (mRS) score standard discharge, mRS score in 0 to 2 scores was defined as good discharge outcome, and mRS score ≥3 scores defined as bad discharge outcome. Predictive value of pressure ulcer score, fall score and NIHSS score for the discharge outcome of AIS was analyzed.Results:The score of pressure ulcer in the group with bad discharge outcome was significantly lower than that in the group with good discharge outcome: (16.96 ± 2.89) scores vs. (19.91 ± 1.71) scores, the score of fall and NIHSS in the group with bad discharge outcome were higher than that in the group with good discharge outcome, with statistical significance: (6.66 ± 1.77) scores vs. (5.21 ± 1.64) scores, (7.34 ± 5.08) scores vs. (3.15 ± 2.21) scores ( P<0.01). The cutoff values of pressure sore score, fall score and NIHSS score for predicting adverse discharge outcome were 18.5, 5.5 and 3.5 scores, respectively. The area under the curve (AUC) was 0.809, 0.731 and 0.863, respectively. The sensitivity was 86.00%, 76.200% and 78.30%, and the specificity was 64.00%, 59.50% and 80.60%. The pressure ulcer score, fall score and NIHSS score had statistical difference in predicting the adverse outcome of discharge ( P<0.01). Conclusions:The pressure ulcer score, fall score and NIHSS score have good predictive value for the discharge outcome of AIS. The lower the pressure ulcer score and the higher fall score and NIHSS score are, the higher the risk of poor discharge outcome of AIS is. Actively controlling the occurrence of pressure ulcers and falls can effectively reduce the risk of poor discharge outcome of AIS.
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Objective:To investigate the characteristics of postoperative internal fixation failures of femoral intertrochanteric fractures and analyze the related reasons using the leverage-balance-reconstruction theory.Methods:A retrospective case series study was performed for 40 patients suffering from implant failure after internal fixation of femoral intertrochanteric fractures admitted to Peking University People's Hospital from January 1999 to December 2019. There were 20 males and 20 females, aged from 43 to 92 years [(74.1±11.5)years]. The patients were assigned to extramedullary fixation (extramedullary fixation group, 17 patients) and intramedullary fixation (intramedullary fixation group, 23 patients). Complications associated with internal fixation were recorded, including internal fixation cutout, coxa vara deformity of hip joint, internal fixation withdrawal, femoral heck shortening and internal fixation breakage. Based on the lever-balance-reconstruction theory, the failure reasons of internal fixation were analyzed in combination with the change of arm length and outward shift of fulcrum measured before operation, after internal fixation and after fixation failure.Results:Among 40 patients, internal fixation cutout occurred in 18 patients, coxa vara deformity of hip joint in 37, internal fixation withdrawal in 29, femoral neck shortening in 37 and internal fixation breakage in 3. In extramedullary fixation group, the lengths of primary power arm and resistance arm were (8.0±1.0)mm and (59.4±10.9)mm, the lengths of power arm and resistance arm after fixation were (72.7±21.7)mm and (8.9±7.4)mm, the lengths of power arm and resistance arm after fixation failure were (50.3±14.9)mm and (33.6±17.6)mm. In intramedullary fixation group, the lengths of primary power arm and resistance arm were (6.7±0.6)mm and (49.8±9.9)mm, the lengths of power arm and resistance arm after fixation were (51.5±7.0)mm and (19.8±5.9)mm, the lengths of power arm and resistance arm after fixation failure were (41.6±9.6)mm and (32.4±7.7)mm. In each group, the lengths of power arm and resistance arm after internal fixation showed significant differences from that of normal ones and from that after fixation failure ( P<0.05). The length of power arm in extramedullary fixation group was larger than that in intramedullary fixation group ( P<0.05). The shortening of power arm in extramedullary fixation group was larger than that in intramedullary fixation group after fixation failure ( P<0.05). Conclusions:The extramedullary and intramedullary fixation of femoral intertrochanteric fractures result in the displacement of reconstruction fulcrum. The shortening of power arm is observed after fixation failure. The leverage-balance-reconstruction theory is helpful to analyze the cause of complications. The power arm after extramedullary fixation is longer than that after intramedullary fixation and is therefore more prone to fixation failure. The primary cause of postoperative internal fixation complications is to achieve a new balance of leverage.
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Objective:To compare the biomechanical properties of traditional surface hip prosthesis and bionic surface hip prosthesis.Methods:The Sawbone digital model (#3908, Left, Medium) was selected as the research object. Mimics 21.0 software was used to reconstruct the physical model of femur. Solidworks 16.0 software was used to build the model of prostheses, including the traditional and bionic (type 1-4) protheses and their assembly. The distances from the screw cross position to the top of pressure screw of type 1 to type 4 protheses were 20.22 mm, 30.12 mm, 32.17 mm and 37.76 mm, respectively. The mechanical distribution characteristics of the whole model were measured and the stress distribution cloud map was obtained.Results:The peak stresses at bone-stem junction of traditional prosthesis and type 1-4 hip prostheses were 32.18 MPa, 13.80 MPa, 15.01 MPa, 23.46 MPa and 34.51 MPa, respectively. With the fulcrums away from the top of the femur, the peak stresses at the fulcrums of type 1-4 hip protheses were 37.98 MPa, 48.60 MPa, 54.80 MPa, and 53.87 MPa, respectively. The maximum stress above femoral neck of traditional prosthesis and type 1-4 hip prostheses were 8.00 MPa, 7.80 MPa, 7.04 MPa, 7.03 MPa and 7.51 MPa, respectively. The maximum stresses under femoral neck was 15.38 MPa, 14.20 MPa, 11.11 MPa, 13.10 MPa and 12.18 MPa, respectively. The maximum stresses in the greater trochanter region of femur were 13.08 MPa, 11.61 MPa, 13.09 MPa, 11.02 MPa and 39.51 MPa, respectively.Conclusion:Compared with the traditional surface hip prosthesis, the type I bionic surface hip prosthesis is designed based on the lever balance reconstruction theory. With the bionic reconstruction of the tension trabeculae and compression trabeculae through reasonable screw placement angles and the inward movement of the fulcrum closer to the center of the femoral head, the new type prothesis make up for the design defects of the traditional surface hip prosthesis, optimize the stress distribution in the proximal femur, and improve the stability of the prosthesis after replacement, which help reduce the risk of femoral neck fracture and prosthesis loosening, and extend the service life of the prosthesis.
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Objective@#Nutrition is closely related to the health of the elderly population. This study aimed to provide a comprehensive picture of the nutrition status of elderly Chinese and its related dietary, geographical, and socioeconomic factors.@*Methods@#A total of 13,987 ≥ 60-year-old persons from the 2010-2013 Chinese National Nutrition and Health Survey were included to evaluate various aspects of malnutrition, including underweight, overweight or obesity, and micronutrient inadequacy.@*Results@#Overall, the prevalence of obesity, overweight, and underweight was 12.4%, 34.8%, and 5.7%, respectively, with disparities both geographically and socioeconomically. The prevalence of underweight was higher among the older old (≥ 75 years), rural residents and those with low income, with low education status, and residing in undeveloped West areas. More than 75% of the elderly do not meet the Dietary Reference Intakes for vitamins A, B @*Conclusions@#Obesity epidemic, inadequacy of micronutrient intake, and high prevalence of underweight and anemia in susceptible older people are the major nutrition challenges for the rapidly aging population in China.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Age Factors , China/epidemiology , Cross-Sectional Studies , Diet/statistics & numerical data , Health Surveys , Malnutrition/etiology , Micronutrients/deficiency , Nutritional Status , Overweight/etiology , Risk Factors , Socioeconomic Factors , Thinness/etiologyABSTRACT
Objective:To analyze the causes and risk factors for failure of internal fixation with proximal femoral nail antirotation (PFNA) in the treatment of femoral intertrochanteric fractures.Methods:A retrospective analysis was conducted of the 568 patients with femoral intertrochanteric fracture who had been treated with PFNA fixation at Department of Orthopaedic Surgery, The Fifth Central Hospital of Tianjin from March 2013 to March 2018. They were 348 males and 220 females, aged from 44 to 93 years (average, 74.6 years). According to the fracture stability classification, the patients were divided into a stable group of 424 cases and an unstable group of 144 cases. According to the AO classification, the stable group had type 31-A1 and type 31-A2.1 while the unstable group type 31-A2.2, type 31-A2.3 and type 31-A3. The 2 groups were compared in terms of reduction quality, rate of internal fixation failure, and function of the affected hip. Single factor and multi-factor binary logistic regression analyses were conducted to determine the risk factors responsible for failure of PFNA fixation of femoral intertrochanteric fracture.Results:There were no significant differences in the preoperative general data between the 2 groups, showing comparability between groups ( P> 0.05). Internal fixation failure occurred in 19 cases, which was caused by spiral blade withdrawal in 13 cases, femoral neck shortening in 17 cases, hip varus in 14 cases, and spiral blade cut-out in 14 cases. The failure rate for the stable group was 1.2% (5/424), significantly lower than that for the unstable group [9.7%,(14/144)] ( P<0.05). The Harris hip score at the last follow-up for the stable group [98(95,100)] was significantly higher than that for the unstable group [84 (82, 87)] ( P<0.05). There was no significant difference in reduction quality between the 2 groups ( P>0.05). The multivariate analysis showed that osteoporosis ( OR=7.283, 95% CI: 1.626 to 32.623, P=0.009) and unstable fracture ( OR=11.607, 95% CI: 4.039 to 33.355, P<0.001) were risk factors responsible for the failure of PFNA fixation of femoral intertrochanteric fracture. Conclusions:PFNA fixation for unstable intertrochanteric fracture can lead to a high failure rate. It forms a lever like structure so that the main stress is shifted to the internal fixation. Its lever fulcrum is located at the angle of intramedullary fixation so that a long arm forms at the load-bearing side, leading to a high failure rate. The weight-free time should be longer for patients with osteoporosis and unstable fracture after operation.