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IL1RL2 has been reported to be highly expressed in a variety of tumor types whereas its role in bladder cancer (BLCA) remains unclear. The aim of the present study was to explore the prognostic value of Il1RL2 in BLCA and its relationship with clinical pathological features. The Cancer Genome Atlas (TCGA) database was used to assess the levels of IL1RL2 expression in BLCA tissues and cells, which were validated by reverse transcription-quantitative polymerase chain reaction and western blotting. Immunohistochemistry was employed to analyze expression of the IL1RL2 gene in 17 pairs of tumor and normal specimens, as well as 112 samples with different stages and grades of tumors. To investigate the biological functions of Il1RL2 in BLCA, co-expression networks and functional enrichment analyses were conducted. A protein-protein interaction network was constructed using interaction gene search tools. IL1RL2 was revealed to be clearly expressed in BLCA cells and tissues. The area under the curve for amplification of IL1RL2 distinguishing between tumor and normal tissues was 0.700 (95% CI: 0.579-0.821) in the TCGA database and 0.647 (95% CI: 0.497-0.797) in Miyun chart database, respectively. Furthermore, in our database, both univariate and multivariate analyses indicated that IL1RL2 expression was an independent risk factor for overall survival (OS). Kaplan-Meier survival analysis revealed an association between high IL1RL2 expression and low OS. Pathway enrichment analysis suggested that IL1RL2 is involved in the regulation of tumor progression through the MAPK signaling pathway. The expression level of IL1RL2 was associated with the stage, grade, lymph node album and prognosis of BLCA.
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Background: The number of prediction models for diabetic foot ulcer (DFU) risk is increasing, but their methodological quality and clinical applicability are uncertain. We conducted a systematic review to assess their performance. Methods: We searched PubMed, Cochrane Library, and Embase databases up to 10 February 2024 and extracted relevant information from selected prediction models. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) checklist was used to assess bias risk and applicability. All statistical analyses were conducted in Stata 14.0. Results: Initially, 13,562 studies were retrieved, leading to the inclusion of five development and five validation models from eight studies. DFU incidence ranged from 6% to 16.8%, with age and hemoglobin A1C (HbA1c) commonly used as predictive factors. All included studies had a high risk of bias, mainly due to disparities in population characteristics and methodology. In the meta-analysis, we observed area under the curve (AUC) values of 0.78 (95% CI [0.69-0.89]) for development models and 0.84 (95% CI [0.79-0.90]) for validation models. Conclusion: DFU risk prediction models show good overall accuracy, but there is a risk of bias. Adherence to the PROBAST checklist is crucial for improving their clinical applicability.
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Pé Diabético , Pé Diabético/epidemiologia , Pé Diabético/diagnóstico , Humanos , Medição de Risco/métodos , Fatores de Risco , Hemoglobinas Glicadas/análise , Modelos EstatísticosRESUMO
Skeletal muscle can undergo detrimental changes in various diseases, leading to muscle dysfunction and atrophy, thus severely affecting people's lives. Along with exercise, there is a growing interest in the potential of nutritional support against muscle atrophy. This review provides a brief overview of the molecular mechanisms driving skeletal muscle atrophy and summarizes recent advances in nutritional interventions for preventing and treating muscle atrophy. The nutritional supplements include amino acids and their derivatives (such as leucine, ß-hydroxy, ß-methylbutyrate, and creatine), various antioxidant supplements (like Coenzyme Q10 and mitoquinone, resveratrol, curcumin, quercetin, Omega 3 fatty acids), minerals (such as magnesium and selenium), and vitamins (such as vitamin B, vitamin C, vitamin D, and vitamin E), as well as probiotics and prebiotics (like Lactobacillus, Bifidobacterium, and 1-kestose). Furthermore, the study discusses the impact of a combined approach involving nutritional support and physical therapy to prevent muscle atrophy, suggests appropriate multi-nutritional and multi-modal interventions based on individual conditions to optimize treatment outcomes, and enhances the recovery of muscle function for patients. By understanding the molecular mechanisms behind skeletal muscle atrophy and implementing appropriate interventions, it is possible to enhance the recovery of muscle function and improve patients' quality of life.
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Suplementos Nutricionais , Músculo Esquelético , Atrofia Muscular , Humanos , Atrofia Muscular/prevenção & controle , Atrofia Muscular/dietoterapia , Músculo Esquelético/efeitos dos fármacos , Probióticos/administração & dosagem , Antioxidantes , Prebióticos , Vitaminas , AnimaisRESUMO
BACKGROUND: Endoscopic surgery has shown promise in treating Spontaneous Intracerebral Hemorrhage (sICH), but its adoption in county-level hospitals has been hindered by the high level of surgical expertise required. METHODS: In this retrospective study at a county hospital, we utilized a Cumulative Sum (CUSUM) control chart to visualize the learning curve for two neurosurgeons. We compared patient outcomes in the learning and proficient phases, and compared them with expected outcomes based on ICH score and ICH functional outcome score, respectively. RESULTS: The learning curve peaked at the 12th case for NS1 and the 8th case for NS2, signifying the transition to the proficient stage. This stage saw reductions in operation time, blood loss, rates of evacuation < 90 %, rebleeding rates, intensive care unit stay, hospital stay, and overall costs for both neurosurgeons. In the learning stage, 6 deaths occurred within 30 days, less than the 10.66 predicted by the ICH score. In the proficient stage, 3 deaths occurred, less than the 15.88 predicted. In intermediate and high-risk patients by the ICH functional outcome score, the proficient stage had fewer patients with an mRS ≥ 3 at three months than the learning stage (23.8 % vs. 69.2 %, P = 0.024; 40 % vs. 80 %, P = 0.360). Micromanipulating bipolar precision hemostasis and aspiration devices in the endoport's channels sped up the transition from learning to proficient. CONCLUSION: The data shows a learning curve, with better surgical outcomes as surgeons gain proficiency. This suggests cost benefits of surgical proficiency and the need for ongoing surgical education and training in county hospitals.
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Hemorragia Cerebral , Curva de Aprendizado , Neuroendoscopia , Humanos , Estudos Retrospectivos , Hemorragia Cerebral/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neuroendoscopia/métodos , Neuroendoscopia/educação , Hospitais de Condado , Resultado do Tratamento , Neurocirurgiões/educação , Competência ClínicaRESUMO
Improving inflammation may serve as useful therapeutic interventions for the hindlimb unloading-induced disuse muscle atrophy. Celecoxib is a selective non-steroidal anti-inflammatory drug. We aimed to determine the role and mechanism of celecoxib in hindlimb unloading-induced disuse muscle atrophy. Celecoxib significantly attenuated the decrease in soleus muscle mass, hindlimb muscle function and the shift from slow- to fast-twitch muscle fibers caused by hindlimb unloading in rats. Importantly, celecoxib inhibited the increased expression of inflammatory factors, macrophage infiltration in damaged soleus muscle. Mechanistically, Celecoxib could significantly reduce oxidative stress and endoplasmic reticulum stress in soleus muscle of unloaded rats. Furthermore, celecoxib inhibited muscle proteolysis by reducing the levels of MAFbx, MuRF1, and autophagy related proteins maybe by inhibiting the activation of pro-inflammatory STAT3 pathway in vivo and in vitro. This study is the first to demonstrate that celecoxib can attenuate disuse muscle atrophy caused by hindlimb unloading via suppressing inflammation, oxidative stress and endoplasmic reticulum stress probably, improving target muscle function and reversing the shift of muscle fiber types by inhibiting STAT3 pathways-mediated inflammatory cascade. This study not only enriches the potential molecular regulatory mechanisms, but also provides new potential therapeutic targets for disuse muscle atrophy.
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Elevação dos Membros Posteriores , Atrofia Muscular , Animais , Ratos , Celecoxib/farmacologia , Celecoxib/uso terapêutico , Elevação dos Membros Posteriores/efeitos adversos , Elevação dos Membros Posteriores/fisiologia , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Estresse OxidativoRESUMO
Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease, accompanied by the gradual loss of motor neuron, even life-threatening. However, the pathogenesis, early diagnosis, and effective strategies of ALS are not yet completely understood. In this study, the function of differentially expressed genes (DEGs) in non-neuronal cells of the primary motor cortex of ALS patients (DATA1), the brainstem of SOD1 mutant ALS mice (DATA2), and the whole blood tissue of ALS patients (DATA3) were explored. The results showed that the functions of DEGs in non-neuronal cells were mainly related to energy metabolism (such as oxidative phosphorylation) and protein synthesis. In non-neuronal cells, six upregulated DEGs (HSPA8, SOD1, CALM1, CALM2, NEFL, COX6C) and three downregulated DEGs (SNRNP70, HSPA1A, HSPA1B) might be key factors in regulating ALS. Microglia played a key role in the development of ALS. The expression of SOD1 and TUBA4A in microglia in DATA1 was significantly increased. The integration analysis of DEGs in DATA1 and DATA2 showed that SOD1 and CALM1 might be potential biomarkers. The integration analysis of DEGs in DATA1 and DATA3 showed that CALM2 and HSPA1A might be potential biomarkers. Cell interaction showed that the interaction between microglia and other cells was reduced in high oxidative phosphorylation states, which might be a risk factor in ALS. Our research provided evidence for the pathogenesis, early diagnosis, and potential targeted therapy for ALS.
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Esclerose Lateral Amiotrófica , Biomarcadores , Metabolismo Energético , Microglia , Análise de Célula Única , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Microglia/metabolismo , Microglia/patologia , Animais , Metabolismo Energético/genética , Humanos , Biomarcadores/metabolismo , Análise de Sequência de RNA/métodos , Camundongos , Camundongos Transgênicos , Masculino , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , FemininoRESUMO
Supratentorial spontaneous intracerebral hemorrhage (SICH) can be treated with endoscopic surgery, but the optimal timing remains uncertain. We retrospectively analyzed data from 46 patients who underwent endoscopic surgery for supratentorial SICH. We examined the relationship between time to evacuation and functional outcome at 3 months, adjusting for prognostic factors. Surgical outcomes and complications were compared between patients with early (≤ 12 h) or late (> 12 h) evacuation. Median time to evacuation was 12 h, and the rate of unfavorable outcome (modified Rankin Scale > 3 at 3 months) was 32.6%. Longer time to evacuation was independently associated with unfavorable outcome (odds ratio per hour delay: 1.26). Late evacuation carried a 7.25-fold higher risk of unfavorable outcome compared to early evacuation. This association held across subgroups based on hematoma volume, location, and intraventricular extension (P for interaction > 0.05). Patients with late evacuation had fewer spot signs (24% vs. 4.8%, P = 0.035) and markers of hemorrhagic expansion (36% vs. 9.5%, P = 0.018), longer neurosurgical intensive care unit (NSICU) stay (3.2 vs. 1.9 days, P = 0.011) and hospital stay (15.7 vs. 11.9 days, P = 0.014), and higher 30-day mortality (28.6 vs. 4%, P = 0.036) and complication rates (57.1% vs. 28.0%, P = 0.023). This study suggests a potential association between early endoscopic evacuation of supratentorial SICH and improved functional outcomes, lower 30-day mortality and reduced complications. The need for timely intervention in managing supratentorial SICH is highlighted, yet further validation through multi-center prospective studies is essential to substantiate these findings and provide a higher level of evidence.
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Hemorragia Cerebral , Endoscopia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Estudos Prospectivos , Hemorragia Cerebral/complicações , Hematoma/cirurgia , Hematoma/diagnósticoRESUMO
This study aimed to explore the risk factors for infection and bleeding after lateral decubitus percutaneous nephrolithotomy procedures to prevent their occurrence and improve surgical outcomes. A retrospective analysis was conducted on 356 patients who underwent lateral decubitus percutaneous nephrolithotomy for the treatment of kidney stones and upper ureteral stones from January 2015 to August 2022. Among them, 290 patients had complete clinical data. General clinical data, perioperative data, and stone characteristics were collected for each patient. Univariate and multivariate logistic regression analyses were performed to identify risk factors for infection and bleeding after lateral decubitus percutaneous nephrolithotomy. The postoperative infection rate after lateral decubitus percutaneous nephrolithotomy was 19.31%, and the postoperative bleeding rate was 12.07%. Independent risk factors for postoperative infection were multiple stones (P < .001), stone size (P < .001), and stone co-infection (P = .012). Independent risk factors for postoperative bleeding were multiple stones (P = .008) and stone size (P = .014). Multiple stones, stone size, and stone co-infection are independent risk factors for postoperative infection after lateral decubitus percutaneous nephrolithotomy. Multiple stones and stone size are independent risk factors for postoperative bleeding after lateral decubitus percutaneous nephrolithotomy.
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Coinfecção , Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Cálculos Ureterais , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/métodos , Estudos Retrospectivos , Coinfecção/etiologia , Cálculos Renais/cirurgia , Fatores de Risco , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Cálculos Ureterais/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Nefrostomia Percutânea/efeitos adversos , Nefrostomia Percutânea/métodosRESUMO
BACKGROUND: Denervation-induced muscle atrophy is complex disease involving multiple biological processes with unknown mechanisms. N6-methyladenosine (m6A) participates in skeletal muscle physiology by regulating multiple levels of RNA metabolism, but its impact on denervation-induced muscle atrophy is still unclear. Here, we aimed to explore the changes, functions, and molecular mechanisms of m6A RNA methylation during denervation-induced muscle atrophy. METHODS: During denervation-induced muscle atrophy, the m6A immunoprecipitation sequencing (MeRIP-seq) as well as enzyme-linked immunosorbent assay analysis were used to detect the changes of m6A modified RNAs and the involved biological processes. 3-deazidenosine (Daa) and R-2-hydroxyglutarate (R-2HG) were used to verify the roles of m6A RNA methylation. Through bioinformatics analysis combined with experimental verification, the regulatory roles and mechanisms of m6A RNA methylation had been explored. RESULTS: There were many m6A modified RNAs with differences during denervation-induced muscle atrophy, and overall, they were mainly downregulated. After 72 h of denervation, the biological processes involved in the altered mRNA with m6A modification were mainly related to zinc ion binding, ubiquitin protein ligase activity, ATP binding and sequence-specific DNA binding and transcription coactivator activity. Daa reduced overall m6A levels in healthy skeletal muscles, which reduced skeletal muscle mass. On the contrary, the increase in m6A levels mediated by R-2HG alleviated denervation induced muscle atrophy. The m6A RNA methylation regulated skeletal muscle mass through ubiquitin-proteasome pathway. CONCLUSION: This study indicated that decrease in m6A RNA methylation was a new symptom of denervation-induced muscle atrophy, and confirmed that targeting m6A alleviated denervation-induced muscle atrophy.
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Atrofia Muscular , Complexo de Endopeptidases do Proteassoma , Humanos , Metilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , RNA/metabolismo , Denervação , Ubiquitinas/metabolismoRESUMO
Myasthenia gravis (MG) is a type of autoimmune disease caused by the blockage of neuromuscular junction transmission owing to the attack of autoantibodies on transmission-related proteins. Related antibodies, such as anti-AChR, anti-MuSK and anti-LRP4 antibodies, can be detected in most patients with MG. Although traditional therapies can control most symptoms, several challenges remain to be addressed, necessitating the development of more effective and safe treatment strategies for MG. With the in-depth exploration on the mechanism and immune targets of MG, effective therapies, especially therapies using biologicals, have been reported recently. Given the important roles of immune cells, cytokines and intercellular interactions in the pathological process of MG, B-cell targeted therapy, T-cell targeted therapy, proteasome inhibitors targeting plasma cell, complement inhibitors, FcRn inhibitors have been developed for the treatment of MG. Although these novel therapies exert good therapeutic effects, they may weaken the immunity and increase the risk of infection in MG patients. This review elaborates on the pathogenesis of MG and discusses the advantages and disadvantages of the strategies of traditional treatment and biologicals. In addition, this review emphasises that combined therapy may have better therapeutic effects and reducing the risk of side effects of treatments, which has great prospects for the treatment of MG. With the deepening of research on immunotherapy targets in MG, novel opportunities and challenges in the treatment of MG will be introduced.
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Miastenia Gravis , Receptores Proteína Tirosina Quinases , Humanos , Receptores Proteína Tirosina Quinases/metabolismo , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/diagnóstico , Junção Neuromuscular/metabolismo , Autoanticorpos/metabolismo , ImunoterapiaRESUMO
BACKGROUND: There is no clear evidence on the indication and surgical approaches on evacuating basal ganglia hemorrhage caused by hypertensive bleeding. Some studies have shown that minimally invasive approaches have therapeutic potentials, but its benefits remain inconclusive. We describe an endoport assisted endoscopic transsylvian approach for basal ganglia hemorrhage evacuation. We evaluate the safety and efficacy of this approach in a cohort study. METHODS: We included 19 patients (mean age 57 years) who underwent the surgery at a single county-level hospital in Yunan Province, China. The majority had a Glasgow coma scale between 9 and 12 on admission. The midline shift ranged from 16-29 mm (mean 19 mm). Hematoma volume ranged from 46 to 106 ml (mean 67 ml). Six patients (31.6%) presented with intraventricular hemorrhage. RESULTS: All patients achieved greater than 90% decrease in hematoma volume at postoperative computed tomography scan. The average operative time was 115 minutes and average blood loss of 44 ml. The most common postoperative complication was pulmonary infection (63.2%). No rebleeding, seizure, infectious meningitis, or postoperative mortality was observed. A total of 17 patients (89.5%) achieved good functional recovery at follow up within 90 days after surgery (Glasgow outcome scale 4-5) and 2 patients had severe disability (Glasgow outcome scale 3). CONCLUSIONS: Endoport assisted endoscopic surgery through transsylvian approach is safe and effective treatment for hypertensive basal ganglia hemorrhage. The majority of patients have good functional recovery and the rate of severe complications is low.
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Hemorragia dos Gânglios da Base , Hipertensão , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Hemorragia dos Gânglios da Base/diagnóstico por imagem , Hemorragia dos Gânglios da Base/cirurgia , Endoscopia/métodos , Hemorragia Cerebral/cirurgia , Resultado do Tratamento , Escala de Coma de Glasgow , Hematoma/cirurgia , Estudos RetrospectivosRESUMO
Due to the long-term and irrational use of antibiotics for the prevention and control of bacterial diseases in aquaculture, antibiotic resistance genes have become a new source of pollution in aquatic products. Factors such as the spread of drug-resistant strains and the horizontal transfer of drug-resistant genes have led to multi-drug resistance in fish-infecting bacteria, which seriously affects the quality and safety of aquatic products. In this study, 50 samples of horse mackerel and puffer fish sold in Dalian aquatic products market and seafood supermarket were collected, and the phenotypic characteristics of the bacteria carried by the fish for drugs such as sulfonamides, amide alcohols, quinolones, aminoglycosides and tetracyclines were tested and analyzed, and the resistance genes carried by fish samples were detected by SYBG qPCR. Our statistical analyses demonstrated that the drug resistance phenotypes and genotypes of bacteria carried by mariculture horse mackerel and puffer fish in the Dalian area of China were complex, and the multi-drug resistance rate reached 80%. Among the examined antibiotics, the resistance rates to cotrimoxazole, tetracycline, chloramphenicol, ciprofloxacin, norfloxacin, levofloxacin, kanamycin, and florfenicol exceeded 50%, whereas the resistance rates to gentamicin and tobramycin were 26 and 16%, respectively. The detection rate of the drug resistance genes tetA, sul1, sul2, qnrA, qnrS, and floR exceeded 70% and all samples carried more than three drug resistance genes. The correlation analysis of drug resistance genes and drug resistance phenotypes showed that the detection of the drug resistance genes sul1, sul2, floR, and qnrD was correlated with the detection of drug resistance phenotypes (p < 0.01). However, the correlation between the resistance genes cmlA, cfr, tetA, qnrA, qnrS, and aac(6')-Ib-cr and the corresponding resistance phenotype was not significant (p > 0.05). In general, our findings indicated that the multi-drug resistance of bacteria carried by marine horse mackerel and puffer fish in the Dalian area was serious. From the perspective of drug resistance rate and drug resistance gene detection rate, the aminoglycosides gentamicin and tobramycin are still considered effective in controlling bacterial infection in marine fish in the study area. Collectively, our findings provide a scientific basis for the management of drug use in mariculture, which can prevent the transmission of drug resistance through the food chain and minimize the associated human health risks.
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The development of an exceptionally sensitive diagnostic technique for early identification of aquaculture diseases, specifically Aeromonas hydrophila, is essential for efficient management of disease outbreaks at aquaculture locations. In this research, a swift and sensitive diagnostic assay employing Loop-mediated isothermal amplification (LAMP) of Aeromonas hydrophila was devised and compared to the conventional qPCR method documented by Rong Wang. Validation of the diagnostic assay was carried out using actual samples obtained from aquaculture fish. The findings revealed that based on the rapid detection of crude bacterial genomic DNA, the fluorescent LAMP assay possessed a lower limit of detection (LOD) of 0.559 ng/µL (0.315-1.693, 95% CI), while the LOD for qPCR stood at 4.301 ng/µL (2.084-8.876, 95% CI). Both techniques demonstrated outstanding specificity, exhibiting no cross-reactivity with bacteria from the same or closely related genera. A total of 74 fish samples suspected to be infected with the fish disease were gathered, with 26 and 23 samples testing positive for Aeromonas hydrophila via LAMP and qPCR, respectively. The concordance analysis for LAMP and qPCR methods generated a Kappa value of 0.909 (0.778-1.000, 95% CI), signifying a high degree of diagnostic consensus. This study highlights that the LAMP assay eliminates the thermal cycle temperature change process of qPCR, uses lysate to crudely extract bacterial genomic DNA, and can complete the detection within 40 min, rendering it a practical and efficient alternative for monitoring disease outbreaks at aquaculture sites.
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Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-ß-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.
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Atrofia Muscular , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Músculo Esquelético/metabolismo , Mitocôndrias/metabolismo , Transdução de Sinais , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
In recent years, the world has encountered many epidemic impacts caused by various viruses, COVID-19 has spread and mutated globally since its outbreak in 2019, causing global impact. Nucleic acid detection is an important means for the prevention and control of infectious diseases. Aiming at people who are susceptible to sudden and infectious diseases, considering the control of viral nucleic acid detection cost and completion time, a probabilistic group test optimization method based on the cost and time value is proposed. Firstly, different cost functions to express the pooling and testing costs are used, a probability group test optimization model that considers the pooling and testing costs is established, the optimal combination number of samples for nucleic acid testing is obtained, and the positive probability and the cost functions of the group testing on the optimization result are explored. Secondly, considering the impact of the detection completion time on epidemic control, the sampling ability and detection ability were incorporated into the optimization objective function, then a probability group testing optimization model based on time value is established. Finally, taking COVID-19 nucleic acid detection as an example, the applicability of the model is verified, and the Pareto optimal curve under the minimum cost and shortest detection completion time is obtained. The results show that under normal circumstances, the optimal combination number of samples for nucleic acid detection is about 10. Generally, 10 is used to calculate for the convenience of organization, arrangement and statistics, except for cases where there are special requirements for testing cost and detection completion time.
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Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting disease, characterized by progressive deterioration of skeletal muscle that causes rapid loss of mobility. The failure in respiratory and cardiac muscles is the underlying cause of premature death in most patients with DMD. Mutations in the gene encoding dystrophin result in dystrophin deficiency, which is the underlying pathogenesis of DMD. Dystrophin-deficient myocytes are dysfunctional and vulnerable to injury, triggering a series of subsequent pathological changes. In this review, we detail the molecular mechanism of DMD, dystrophin deficiency-induced muscle cell damage (oxidative stress injury, dysregulated calcium homeostasis, and sarcolemma instability) and other cell damage and dysfunction (neuromuscular junction impairment and abnormal differentiation of muscle satellite). We also describe aberrant function of other cells and impaired muscle regeneration due to deterioration of the muscle microenvironment, and dystrophin deficiency-induced multiple organ dysfunction, while summarizing the recent advances in the treatment of DMD.
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Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Distrofina/genética , Músculo Esquelético , Mutação , Junção Neuromuscular/patologiaRESUMO
On the basis of the classical light scattering models, the light extinction model is the first to establish as [Formula: see text] (Ï, N and γ - average diameter in µm, number and relative refractive index of the suspending particles, λ, A and δ - incident light wavelength in µm, absorbance and optical path in cm of the suspension liquid) by spectrometric characterization of ten standard suspension liquids. It has been used to determine the suspending particles in the calcium oxalate, Formazine, soil, milk and sewage suspension water samples. As the result, the light extinction model method brought out less than 12% error of Ï and 18% error of the suspending particles' quality by comparing with the conventional methods. It provides a simple and reliable spectroptometric determination of a suspension liquid. Also, it is very potential to in-situ monitor the growth and working state of the suspending particles using in synthesis of materials, culture of cells, treatment of wastewater and safety of drinking water and foods.
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Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are great obstacles for drug delivery. As an important part of cell information transmission and behavior regulation, cell membrane can be used as drug coating material which represents a promising strategy and can overcome these limitations. Mesenchymal stem cell (MSC) membrane, as a new carrier, has the characteristics of active targeting and immune escape of MSC, and has broad application potential in tumor treatment, inflammatory disease, tissue regeneration and other fields. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for therapy and drug delivery, aiming to provide guidance for the design and clinical application of membrane carrier in the future.
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Células-Tronco Mesenquimais , Nanopartículas , Membranas , Sistemas de Liberação de Medicamentos , Membrana Celular/metabolismo , ExcipientesRESUMO
Conversion anode materials such as Mn3O4 draw much attention due to their considerable theoretical capacity for lithium-ion batteries (LIBs). However, poor conductivity, slow solid-state Li-ion diffusion, and huge volume expansion of the active materials during charge/discharge lead to unsatisfied electrochemical performance. Despite several strategies like nanocrystallization, fabricating hierarchical nanostructures, and introducing a matrix are valid to address these crucial issues, the achieved electrochemical performance still needs to be further enhanced. What is worse, the matrix with less or no Li-ion storage activity may lower the achieved capacity of the electrodes. Herein, ultra-thin CuMnO2 nanosheets with the thickness of 5-8 nm were evaluated for LIBs. The ultra-thin sheet-like nanostructure offers sufficient contact areas with electrolyte and shortens the Li-ion diffusion distance. Moreover, the in-situ generated Mn and Cu along with their oxides could play the role of matrix and conductive agent in turn at different stages, relieving the stress brought by volume expansion. Therefore, the as-prepared ultra-thin CuMnO2 nanosheets electrode displays a remarkable reversible capacity, long cycling stability, and outstanding rate capability (a reversible capacity of 1160.5 mAh g-1 at 0.1A g-1 was retained after 100 cycles with a capacity retention of 95.1 %, and 717.8 mAh g-1 at 2.0 A g-1 after 400 cycles).
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There has been no evidence on the effects of birth season and birth month on mortality in China. We aimed to explore the association between birth season, birth month and all-cause and cardiovascular disease (CVD) death. A population-based sample of 21,338 Chinese rural participants aged ≥35 years at baseline was included in our analysis. Age and multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the relationship between astronomical birth season (autumn as the reference), birth month (November as the reference), and all-cause and CVD mortality. During a median follow-up period of 11.9 years, 2,207 people died from all-cause and 1,214 people were attributed to CVD death. In multivariable adjusted analyses, for all-cause death, spring and winter had HRs (95% CIs) of 1.134 (1.005-1.280) and 1.162 (1.038-1.301), respectively; January, March, May, and August had HRs (95% CIs) of 1.249 (1.027-1.518), 1.234 (1.008-1.512), 1.276 (1.037-1.571), and 1.232 (1.003-1.513), respectively. For CVD death, spring and winter with HRs (95% CIs) of mortality were 1.232 (1.048-1.449) and 1.174 (1.007-1.369), respectively; March with HR (95% CI) of mortality were 1.343 (1.030-1.750) (all P < 0.05). Our study indicated that people born in the winter or spring were significantly associated with all-cause and cardiovascular disease mortality in rural areas of China.