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Cuproptosis plays an important role in cancer, but its role in lung cancer remains unknown. Transcriptional profiles, clinical details and mutation data were acquired from the Cancer Genome Atlas database through a variety of methods. The analysis of this publicly available data was comprehensively performed using R software along with its relevant packages, ensuring a thorough examination of the information. In this study, we conducted a detailed analysis of cuproptosis-related genes and lncRNA co-expression, identifying 129 relevant lncRNAs and establishing a prognostic model with four key lncRNAs (LINC00996, RPARP-AS1, SND1-IT1, TMPO-AS1). Utilizing data from TCGA and GEO databases, the model effectively categorized patients into high- and low-risk groups, showing significant survival differences. Correlation analysis highlighted specific relationships between individual lncRNAs and cuproptosis genes. Our survival analysis indicated a higher survival rate in the low-risk group across various cohorts. Additionally, the model's predictive accuracy was confirmed through independent prognostic analysis and ROC curve evaluations. Functional enrichment analysis revealed distinct biological pathways and immune functions between risk groups. Tumour mutation load analysis differentiated high- and low-risk groups by their mutation profiles. Drug sensitivity analysis and immune infiltration studies using the CIBERSORT algorithm further elucidated the potential treatment responses in different risk groups. This comprehensive evaluation underscores the significance of lncRNAs in cuproptosis and their potential as biomarkers for lung cancer prognosis and immune microenvironment.
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Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , RNA Longo não Codificante , Microambiente Tumoral , Humanos , RNA Longo não Codificante/genética , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Mutação , Perfilação da Expressão Gênica , Bases de Dados Genéticas , Curva ROCRESUMO
BACKGROUND: Ketone ß-hydroxybutyrate (BHB) has been reported to prevent tumor cell proliferation and improve drug resistance. However, the effectiveness of BHB in oxaliplatin (Oxa)-resistant colorectal cancer (CRC) and the underlying mechanism still require further proof. METHODS: CRC-Oxa-resistant strains were established by increasing concentrations of CRC cells to Oxa. CRC-Oxa cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) were checked following BHB intervention in vitro. The subcutaneous and metastasis models were established to assess the effects of BHB on the growth and metastasis of CRC-Oxa in vivo. Eight Oxa responders and seven nonresponders with CRC were enrolled in the study. Then, the serum BHB level and H3K79me, H3K27ac, H3K14ac, and H3K9me levels in tissues were detected. DOT1L (H3K79me methyltransferase) gene knockdown or GNE-049 (H3K27ac inhibitor) use was applied to analyze further whether BHB reversed CRC-Oxa resistance via H3K79 demethylation and/or H3K27 deacetylation in vivo and in vitro. RESULTS: Following BHB intervention based on Oxa, the proliferation, migration, invasion, and EMT of CRC-Oxa cells and the growth and metastasis of transplanted tumors in mice were suppressed. Clinical analysis revealed that the differential change in BHB level was associated with drug resistance and was decreased in drug-resistant patient serum. The H3K79me, H3K27ac, and H3K14ac expressions in CRC were negatively correlated with BHB. Furthermore, results indicated that H3K79me inhibition may lead to BHB target deletion, resulting in its inability to function. CONCLUSIONS: ß-hydroxybutyrate resensitized CRC cells to Oxa by suppressing H3K79 methylation in vitro and in vivo.
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Ácido 3-Hidroxibutírico , Proliferação de Células , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Histonas , Oxaliplatina , Oxaliplatina/farmacologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Ácido 3-Hidroxibutírico/farmacologia , Animais , Camundongos , Histonas/metabolismo , Metilação , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos NusRESUMO
Peroxisome proliferator-activated receptors (PPARs) are essential for cellular physiological processes. However, there is less research on the PPAR-related genes in lung adenocarcinoma (LUAD). Open-access data were get from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. All the analysis were conducted in the R software based on different R packages. In this study, we gauged the PPAR score employing a set of 72 PPAR-associated genes and probed the biological impact of this score on lung adenocarcinoma (LUAD). Subsequently, we established a unique signature composed of eight PPAR-related genes (ANGPTL4, ACSL3, ADIPOQ, FABP1, SLC27A1, ACOX2, PPARD and OLR1) to forecast the prognosis of LUAD. The signature's effectiveness in predicting survival was validated through the receiver operating characteristic curve in the TCGA-LUAD cohort. As per the pathway enrichment analysis, several crucial oncogenic pathways and metabolic processes were enriched in high-risk individuals. Further, we observed that these high-risk patients exhibited heightened genomic instability. Additionally, compared to the low-risk cohort, high-risk patients demonstrated diminished immune components and function. Intriguingly, high-risk patients exhibited a potential heightened sensitivity to immunotherapy and certain drugs, including Gefitinib, Afatinib, Erlotinib, IAP_5620, Sapitinib, LCL161, Lapatinib and AZD3759. The prognosis model based on eight PPAR-related genes has satisfactory prognosis prediction efficiency. Meanwhile, our results can provide direction for future studies in the relevant aspects.
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Numerous metabolic reactions and pathways use adenosine 5'-triphosphate (ATP) as an energy source and as a phosphorous or pyrophosphorous donor. Based on three-dimensional (3D)-printing, enzyme immobilization can be used to improve ATP regeneration and operability and reduce cost. However, due to the relatively large mesh size of 3D-bioprinted hydrogels soaked in a reaction solution, the lower-molecular-weight enzymes cannot avoid leaking out of the hydrogels readily. Here, a chimeric adenylate-kinase-spidroin (ADK-RC) is created, with ADK serving as the N-terminal domain. The chimera is capable of self-assembling to form micellar nanoparticles at a higher molecular scale. Although fused to spidroin (RC), ADK-RC remains relatively consistent and exhibits high activity, thermostability, pH stability, and organic solvent tolerance. Considering different surface-to-volume ratios, three shapes of enzyme hydrogels are designed, 3D bioprinted, and measured. In addition, a continuous enzymatic reaction demonstrates that ADK-RC hydrogels have higher specific activity and substrate affinity but a lower reaction rate and catalytic power compared to free enzymes in solution. With ATP regeneration, the ADK and ADK-RC hydrogels significantly increase the production of d-glucose-6-phosphate and obtain an efficient usage frequency. In conclusion, enzymes fused to spidroin might be an efficient strategy for maintaining activity and reducing leakage in 3D-bioprinted hydrogels under mild conditions.
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Adenilato Quinase , Fibroínas , Adenilato Quinase/química , Adenilato Quinase/metabolismo , Hidrogéis , Trifosfato de Adenosina/química , CatáliseRESUMO
Due to their advantages in structural stability and versatility, cysteine-rich peptides, which are secreted from the venom glands of venomous animals, constitute a naturally occurring pharmaceutical arsenal. However, the correct folding of disulfide bonds is a challenging task in the prokaryotic expression system like Escherichia coli due to the reducing environment. Here, a secretory expression plasmid pSE-G1M5-SUMO-HWTX-I for the spider neurotoxin huwentoxin-I (HWTX-I) with three disulfides as a model of cysteine-rich peptides was constructed. By utilizing the signal peptide G1M5, the fusion protein 6 × His-SUMO-HWTX-I was successfully secreted into extracellular medium of BL21(DE3). After enrichment using cation-exchange chromatography and purification utilizing the Ni-NTA column, 6 × His-SUMO-HWTX-I was digested via Ulp1 kinase to release recombinant HWTX-I (rHWTX-I), which was further purified utilizing RP-HPLC. Finally, both impurities with low and high molecular weights were completely removed. The molecular mass of rHWTX-I was identified as being 3750.8 Da, which was identical to natural HWTX-I with three disulfide bridges. Furthermore, by utilizing whole-cell patch clamp, the sodium currents of hNav1.7 could be inhibited by rHWTX-I and the IC50 value was 419 nmol/L.
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Venenos de Aranha , Aranhas , Animais , Neurotoxinas/química , Neurotoxinas/farmacologia , Cisteína/metabolismo , Aranhas/química , Aranhas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Venenos de Aranha/genética , Venenos de Aranha/química , Venenos de Aranha/metabolismo , Peptídeos/metabolismo , Dissulfetos/metabolismoRESUMO
OBJECTIVES: Nrf2/BACH1/HO-1 proteins have been implicated in the development and progression of tumors. However, their clinical relevance in breast cancer remains unclear and understudied. This study evaluated Nrf2/BACH1/HO-1 protein expression and its relationship with age, tumor grade, tumor stage, TNM, ER, PR, HER2, and histologic type. METHODS: 114 female breast cancer and 30 noncancerous tissues were evaluated for Nrf2/BACH1/HO-1 protein expression using immunohistochemistry and Western blot. The relationships between the expression and clinicopathologic factors were assessed using the χ2 test. RESULTS: 74% of the cancerous samples had high Nrf2 protein expression, and 26% of them had low Nrf2 protein expression. Regarding the non-cancer samples, 43% had high Nrf2 protein expression and 57% had low Nrf2 protein expression (p < 0.002). 39% of the cancerous samples had high BACH1 protein expression, and 61% had low BACH1 protein expression. For the non-cancer samples, 80% had high BACH1 protein expression and 20% had low BACH1 protein expression (p < 0.031). 67% of the cancerous samples had high HO-1 protein expression, and 33% had low HO-1 protein expression. However, for the non-cancer samples, 17% of them had high HO-1 protein expression and 83% had low HO-1 protein expression (p < 0.001). The expression of Nrf2 and HO-1 significantly correlated with tumor grade, while BACH1 was significantly associated with tumor stage (p < 0.05). CONCLUSION: Nrf2, BACH1, and HO-1 could be explored as a biomarker for cancer stage, progression, and prognosis.
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Fatores de Transcrição de Zíper de Leucina Básica , Biomarcadores Tumorais , Neoplasias da Mama , Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Humanos , Feminino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Valor Preditivo dos Testes , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
Acute pulmonary embolism (PE) remains a significant cause of cardiovascular morbidity and mortality worldwide. Brain natriuretic peptide (BNP) combined with catheter-directed therapy (CDT) may improve right ventricular (RV) dysfunction and stabilize hemodynamics in acute PE.We retrospectively studied 159 patients with confirmed acute PE who were treated with CDT and admitted to the intensive care unit of our department between September 2016 and May 2020. The patients were divided into the control group and the rhBNP group based on whether to receive recombinant human BNP treatment (rhBNP) or not. The basic characteristics of the patients between the control group and the rhBNP group was systematically compared during admission and follow-up. Risk factors for all-cause mortality within 30 days were determined using multivariate logistic regression analysis.Respiratory rate was found to be significantly lower in the rhBNP group than in the control group. Patients in the rhBNP group had significantly lower levels of white blood cell, C-reactive protein (CRP), D-dimers, troponin I, creatinine, and N-terminal (NT) -proBNP compared with those in the control group. Levels of tricuspid annular plane systolic excursion were significantly higher in the rhBNP group than in the control group. The percentage of patients with rehospitalization readmission due to PE differed significantly between the control group and the rhBNP group. On the basis of the multivariate regression analysis, CRP, creatinine, troponin I, and NT-proBNP were independent factors of all-cause mortality in 30 days.rhBNP is effective in the treatment of patients with RV dysfunction caused by acute PE who underwent CDT, which may be an alternative treatment option for improving clinical prognosis.
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Cateterismo de Swan-Ganz , Natriuréticos/uso terapêutico , Peptídeo Natriurético Encefálico/uso terapêutico , Embolia Pulmonar/terapia , Disfunção Ventricular Direita/tratamento farmacológico , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Trombólise Mecânica , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Proteínas Recombinantes , Estudos Retrospectivos , Terapia Trombolítica , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/etiologiaRESUMO
PURPOSE: Previous clinical studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest, but the results are conflicting and there is no uniform agreement regarding gender differences in survival and prognosis. The present study was aimed to investigate the interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest. METHODS: Asphyxia was induced by blocking the endotracheal tube in 120 adult Sprague-Dawley rats (60 males and 60 females) at the same age. Cardiopulmonary resuscitation (CPR) was started after 5 min of untreated cardiac arrest. Animals were randomized into one of the three post resuscitation care intervention groups (n = 40, 20 males) immediately after resuscitation: (1) normothermic control (NC): ventilated with 2% N2/98% O2 for 1 h under normothermia; (2) targeted temperature management (TTM): ventilated with 2% N2/98% O2 for 1 h under hypothermia; (3) hydrogen inhalation (HI): ventilated with 2% H2/98% O2 for 1 h under normothermia. Physiological variables were recorded during the 5 h post resuscitation monitoring period. Neurological deficit score (NDS) and accumulative survival were used to assess 96 h outcomes. Mutual independence analysis and Mantel-Haenszel stratified analysis were used to explore the associations among gender, intervention and survival. RESULTS: The body weights of female rats were significantly lighter than males, but CPR characteristics did not differ between genders. Compared with male rats, females had significantly lower mean arterial pressure, longer onset time of the electroencephalogram (EEG) burst and time to normal EEG trace (TTNT) in the NC group; relatively longer TTNT in the TTM group; and substantially longer TTNT, lower NDSs, and higher survival in the HI group. Mutual independence analysis revealed that both gender and intervention were associated with neurological outcome. Mantel-Haenszel stratified analysis demonstrated that female rats had significantly higher survival rate than males when adjusted for the confounder intervention. CONCLUSION: In this rat model cardiac arrest and CPR, gender did not affect resuscitation but associated with neurological outcome. The superiority of female rats in neurological recovery was affected by post resuscitation interventions and female rats were more likely to benefit from hydrogen therapy.
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Ondas Encefálicas , Encéfalo/fisiopatologia , Reanimação Cardiopulmonar , Parada Cardíaca/terapia , Animais , Asfixia/complicações , Modelos Animais de Doenças , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Hemodinâmica , Masculino , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Fatores Sexuais , Fatores de TempoRESUMO
Dysfunction of neural stem cells (NSCs) has been linked to fetal neuropathy, one of the most devastating complications of gestational diabetes. Several studies have demonstrated that melatonin (Mel) exerted neuroprotective actions in various stresses. However, the role of autophagy and the involvement of Mel in NSCs in hyperglycemia (HG) have not yet been fully established. Here, we found that HG increased autophagy and autophagic flux of NSCs as evidenced by increasing LC3B II/I ratio, Beclin-1 expression, and autophagosomes. Moreover, Mel enhanced NSCs proliferation and self-renewal in HG with decreasing autophagy and activated mTOR signaling. Consistently, inhibition of autophagy by 3-Methyladenine (3-Ma) could assist Mel effects above, and induction of autophagy by Rapamycin (Rapa) could diminish Mel effects. Remarkably, HG induced premature differentiation of NSCs into neurons (Map2 positive cells) and astrocytes (GFAP positive cells). Furthermore, Mel diminished HG-induced premature differentiation and assisted NSCs in HG differentiation as that in normal condition. Coincidentally, inhibiting of NSCs autophagy by 3-Ma assisted Mel to modulate differentiation. However, increasing NSCs autophagy by Rapa disturbed the Mel effects and retarded NSCs differentiation. These findings suggested that Mel supplementation could contribute to mimicking normal NSCs proliferation and differentiation in fetal central nervous system by inhibiting autophagy in the context of gestational diabetes. Stem Cells 2019;37:504-515.
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Autofagia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Células-Tronco Neurais/metabolismo , Melatonina , Células-Tronco Neurais/citologia , Transdução de SinaisRESUMO
The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01-2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30-2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.
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Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Adolescente , Adulto , Idoso , Bioestatística , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto JovemRESUMO
KEY POINTS: Endothelial dysfunction is an early hallmark of multiple disease states that also display sex differences with respect to age of onset, frequency and severity. Results of in vivo studies of basal and stimulated microvascular barrier function revealed sex differences that are difficult to ascribe to specific cells or environmental factors. The present study evaluated endothelial cells (EC) isolated from macro- and/or microvessels of reproductively mature rats under the controlled conditions of low-passage culture aiming to test the assumption that EC phenotype would be sex independent. The primary finding was that EC, regardless of where they are derived, retain a sex-bias in low-passage culture, independent of varying levels of reproductive hormones. The implications of the present study include the fallacy of expecting a universal set of mechanisms derived from study of EC from one sex and/or one vascular origin to apply uniformly to all EC under unstimulated conditions, and no less in disease. ABSTRACT: Vascular endothelial cells (EC) are heterogeneous with respect to phenotype, reflecting at least the organ of origin, location within the vascular network and physical forces. As an independent influence on EC functions in health or aetiology, susceptibility, and progression of dysfunction in numerous disease states, sex has been largely ignored. The present study focussed on EC isolated from aorta (macrovascular) and skeletal muscle vessels (microvascular) of age-matched male and female rats under identical conditions of short-term (passage 4) culture. We tested the hypothesis that genomic sex would not influence endothelial growth, wound healing, morphology, lactate production, or messenger RNA and protein expression of key proteins (sex hormone receptors for androgen and oestrogens α and ß; platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin mediating barrier function; αv ß3 and N-cadherin influencing matrix interactions; intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 mediating EC/white cell adhesion). The hypothesis was rejected because the EC origin (macro- vs. microvessel) and sex influenced multiple phenotypic characteristics. Statistical model analysis of EC growth demonstrated an hierarchy of variable importance, recapitulated for other phenotypic characteristics, with predictions assuming EC homogeneity < sex < vessel origin < sex and vessel origin. Furthermore, patterns of EC mRNA expression by vessel origin and by sex did not predict protein expression. Overall, the present study demonstrated that accurate assessment of sex-linked EC dysfunction first requires an understanding of EC function by position in the vascular tree and by sex. The results from a single EC tissue source/species/sex cannot provide universal insight into the mechanisms regulating in vivo endothelial function in health, and no less in disease.
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Adesão Celular , Endotélio Vascular/fisiologia , Microvasos/fisiologia , Fenótipo , Caracteres Sexuais , Cicatrização , Animais , Células Cultivadas , Endotélio Vascular/citologia , Feminino , Hormônios Esteroides Gonadais/metabolismo , Técnicas In Vitro , Masculino , Microvasos/citologia , Ratos , Ratos Sprague-Dawley , Receptores de Esteroides/metabolismoRESUMO
OBJECTIVE: To evaluate the clinical effectiveness of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in single-level lumbar degeneration disease treatment. METHODS: We retrospectively analyzed the clinical data of 32 patients who underwent the MIS-TLIF surgery from Nov. 2013 to Oct. 2014 in Shanghai Tongji Hospital.Clinical and radiological outcomes including operation time, X-ray exposure, surgical blood loss, drainage blood loss, complications, visual analogue scores (VAS), Oswestry disability index (ODI) scores, average intervertebral space and fusion rate. VAS scores of low back and leg pain, ODI scores were recorded before and after surgery to evaluate the functional recovery, average intervertebral space height, lumbar and surgical Cobb angle were measured by X-rays before and after surgery to assess recovery of intervertebral space height and the change of lumbar kyphosis. The Bridwell criterion was used for evaluating the interbody fusion and the MacNab criterion was used for assessment after surgery. RESULTS: All the patients received successful surgery. The mean operative time was (171.9±31.1) min with (36.7±16.4) seconds radiation exposure, and mean blood loss was (153.3±64.8) ml, drainage blood loss was (58.9±49.2) ml. All cases were followed up for (11.6±3.3) months. Compared with preoperation, VAS score of low back and leg pain, ODI score and average intervertebral space showed significant improvements after surgery. There were 26 (81.3%) cases were grade I and II 3 months after surgery according to the Bridwell criteria while the number was 31 (96.9%) at the last follow-up. The clinical results were excellent in 22 cases, good in 8 cases and fair in 2 cases according to the MacNab criteria at the final follow-up. CONCLUSION: MIS-TLIF under Spotlight work channel system is a safe and effective procedure for single segment lumbar degenerative disease and it may offer patients additional advantages in less trauma and reduction of hospital stay.
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Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Fusão Vertebral/métodos , Perda Sanguínea Cirúrgica , China , Drenagem , Humanos , Tempo de Internação , Região Lombossacral , Dor , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
ABSTRACT: Background: The high mortality rates of patients who are resuscitated from cardiac arrest (CA) are attributed to post cardiac arrest syndrome (PCAS). This study evaluated the effect of hyperoxygenation and targeted temperature management (TTM) on PCAS in rats with different causes of CA. Methods and Results: One hundred sixty-eight Sprague-Dawley rats were equally divided into asphyxial and dysrhythmic groups. Animals were further randomized into four subgroups immediately after resuscitation: normoxia-normothermia (NO-NT), ventilated with 21% oxygen under normothermia; hyperoxia-normothermia (HO-NT), ventilated with 100% oxygen for 3 hours under normothermia; normoxia-hypothermia (NO-HT), ventilated with 21% oxygen for 3 hours under hypothermia; and hyperoxia-hypothermia (HO-HT), ventilated with 100% oxygen for 3 hours under hypothermia. Post resuscitation cardiac dysfunction, neurological recovery, and pathological analysis were assessed. For asphyxial CA, HO-NT and HO-HT (68.8% and 75.0%) had significantly higher survival than NO-NT and NO-HT (31.3% and 31.3%). For dysrhythmic CA, NO-HT and HO-HT (81.3% and 87.5%) had significantly higher survival than NO-NT and HO-NT (44.0% and 50.0%). When all of the rats were considered, the survival rate was much higher in HO-HT (81.3%). Compared with NO-NT (57.7% ± 14.9% and 40.3% ± 7.8%), the collagen volume fraction and the proportion of fluoro-jade B-positive area in HO-HT (14.0% ± 5.7% and 28.0% ± 13.3%) were significantly reduced. Conclusion: The beneficial effects of hyperoxygenation and TTM are dependent on the cause of arrest: hyperoxygenation benefits asphyxial, whereas TTM benefits dysrhythmic CA. The combination of hyperoxygenation and TTM could effectively improve the functional outcome of PCAS regardless of the cause of CA.
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Hipotermia Induzida , Ratos Sprague-Dawley , Animais , Ratos , Hipotermia Induzida/métodos , Masculino , Síndrome Pós-Parada Cardíaca/terapia , Reanimação Cardiopulmonar/métodos , Oxigenoterapia/métodos , Parada Cardíaca/terapiaRESUMO
Interleukin (IL)-32 is induced by pro-inflammatory cytokines and promotes the release of inflammatory cytokines. Therefore, it can promote inflammatory responses. The present review article summarized the role of the receptors required for IL-32 action, the biological function of IL-32 and its mechanism of action in tumors. Moreover, it assessed the significance of aberrant IL-32 expression in associated diseases and analyzed the effects of IL-32 on four key types of cancer: Colorectal, gastric, breast and lung. However, the mechanism of action of IL-32 needs to be further demonstrated by assessing the role of this cytokine in cancer to elucidate novel and reliable targets for future cancer treatments.
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Complex and stubborn bacterial biofilm infections significantly hinder diabetic wound healing and threaten public health. Therefore, a dressing material that effectively clears biofilms and promotes wound healing is urgently required. Herein, we introduce a novel strategy for simultaneously dispersing extracellular polymeric substances and eradicating drug-resistant bacteria. We prepared an ultrabroad-spectrum and injectable quaternized chitosan (QCS) hydrogel loaded with trypsin, which degrades biofilm extracellular proteins. Increased temperature initiated QCS gelation to form the hydrogel, enabling the sustained release of trypsin and effective adherence of the hydrogel to irregularly shaped wounds. To reproduce clinical scenarios, biofilms formed by a mixture of Staphylococcus aureus (S. aureus), Methicillin-resistant S. aureus, and Pseudomonas aeruginosa were administered to the wounds of rats with streptozotocin-induced diabetes. Under these severe infection conditions, the hydrogel efficiently suppressed inflammation, promoted angiogenesis, and enhanced collagen deposition, resulting in accelerated healing of diabetic wounds. Notably, the hydrogel demonstrates excellent biocompatibility without cytotoxicity. In summary, we present a trypsin-loaded QCS hydrogel with tremendous clinical applications potential for the treatment of chronic infected wounds.
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Background: Exploration of the benefits and timing of surgical decompression in spinal cord injury (SCI) has been a research hotspot. However, despite the higher volume and increasing emphasis on quality there remains no bibliometric view on SCI and surgical decompression. In this study, we aimed to perform bibliometric analysis to reveal the core countries, affiliations, journals, authors, and developmental trends in SCI and surgical decompression across the past 50 years. Methods: Articles and reviews were retrieved from web of science core collection between 1975 and 2024. The bibliometrix package in R was used for data analysis and visualizing. Results: A total of 8,688 documents were investigated, indicating an ascending trend in annual publications. The USA and China played as the leaders in scientific productivity. The University of Toronto led in institutional productions. Core authors, such as Michael G. Fehlings, showed high productivity, and occasional authors showed widespread interests. Core journals like Spine and Spinal Cord served as beacons in this field. The interaction of core authors and international collaboration accentuated the cross-disciplinary feature of the field. Prominent documents emphasized the clinical significance of early decompression in 24 h post SCI. Conclusion: Based on comprehensive bibliometric analysis and literature review, we identified the hotspots and future directions of this field: (1) further investigation into the molecular and cellular mechanisms to provide pre-clinical evidence for biological effects of early surgical decompression in SCI animal models; (2) further evaluation and validation of the optimal time window of surgical decompression based on large cohort, considering the inherent heterogeneity of subpopulations in complicated immune responses post SCI; (3) further exploration on the benefits of early decompression on the neurological, functional, and clinical outcomes in acute SCI; (4) evaluation of the optimal surgical methods and related outcomes; (5) applications of artificial intelligence-based technologies in spinal surgical decompression.
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Background: Wuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic. Objective: This study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017-2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools. Methods: This study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis. Results: From 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools. Conclusion: We successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.
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Instituições Acadêmicas , Tuberculose , Humanos , China/epidemiologia , Masculino , Feminino , Instituições Acadêmicas/estatística & dados numéricos , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Adolescente , Inquéritos e Questionários , Estudantes/estatística & dados numéricos , Fatores de Risco , CriançaRESUMO
OBJECTIVE: To evaluate the efficacies of unilateral versus bilateral pedicle screw fixation through the pedicle of fractured vertebra plus short-segment pedicle instrumentation (SSPI) in the treatment of thoracolumbar fractures. METHODS: Between June 2008 and September 2010, a total of 46 patients with fractures of thoracolumbar junction, whose scores of load sharing classification (LSC) ranging from 5 to 7, underwent the combined treatment of SSPI and fracture level pedicle screw at our department. They were divided into 2 groups. Group I included 25 patients undergoing SSPI plus unilateral pedicle screw fixation through the pedicle of fractured vertebra (5 screws) while Group II included 21 patients had SSPI plus bilateral pedicle screw fixation through the pedicle of fractured vertebra (6 screws). The data of anterior body height compression (AVHC), sagittal Cobb's angle, internal fixation failure, restoration of nervous function, visual analogue score (VAS) and Oswestry disability index (ODI) were analyzed. RESULTS: The groups were similar with regards to age, gender, LSC, AVHC and sagittal Cobb's angle preoperatively. Blood loss volume and operative duration were less in the Group I (109.2 ± 30.68 vs 110.0 ± 32.06 min, t = -0.086, P > 0.05 and 376.0 ± 303.1 vs 409.5 ± 361.1 ml, t = -0.342, P > 0.05). They were followed up for a minimum period of 12 months. In follow-up period was 17.48 ± 4.14 months in Group I versus 18.33 ± 4.31 months in Group II (t = -0.683, P > 0.05). All patients with initial partial neurologic deficits improved at the final follow-up. Radiographic parameters and clinical outcomes were similar in both groups. CONCLUSIONS: Pedicle screw fixation through the pedicle of fractured vertebra plus SSPI is an excellent surgical therapeutic choice for patients with a LSC range of 5-7 thoraclumbar fractures. The efficacies of unilateral and bilateral pedicle screw fixation at fracture level are the same.
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Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Fraturas da Coluna Vertebral/cirurgia , Adulto , Parafusos Ósseos , Feminino , Humanos , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas/lesões , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the clinical efficacies of intermediate screws plus injectable calcium sulfate MIIGX3 for thoracolumbar fracture in postmenopausal patients. METHODS: A total of 21 postmenopausal patients with vertebral compression fractures reconstructed with posterior internal fixation of intermediate screws technique and anterior vertebral augmentation of MIIGX3 technique in three dimension were retrospectively analyzed. The changes of fracture vertebral height and Cobb's angle were compared.Visual analogue scale (VAS) was performed to evaluate their symptoms. All patients were followed up. RESULTS: Intermediate screws surgical technique plus MIIGX3 was successfully performed. The average injection dose was 4.6 ml.Leakage occurred intraoperatively in two cases. The average follow-up period was 15 (6-36) months. The VAS system demonstrated that pain decreased significantly (preoperative:7.8, postoperative:2.2). The height and Cobb's angle of fractured vertebra improved greatly. The preoperative values were 45.0 ± 6.4% and 19.4 ± 4.5° and postoperative ones 15.4 ± 3.9% and 8.64 ± 3.18° respectively. There was no occurrence of severe complications related with treatment.Except for 2 patients with a loss of 15% of vertebral height, the average heights of fractured vertebra in other 19 patients recovered to 85% of normal ones. CONCLUSION: Thoracolumbar fracture in postmenopausal patients may be managed satisfactorily by intermediate screws and injectable calcium sulfate technique.Such a technique is both safe and effective. And its stable and durable reduction offers significant improvement.