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This corrects the article DOI: 10.1103/PhysRevLett.132.162502.
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The nuclear charge radius of ^{32}Si was determined using collinear laser spectroscopy. The experimental result was confronted with ab initio nuclear lattice effective field theory, valence-space in-medium similarity renormalization group, and mean field calculations, highlighting important achievements and challenges of modern many-body methods. The charge radius of ^{32}Si completes the radii of the mirror pair ^{32}Ar-^{32}Si, whose difference was correlated to the slope L of the symmetry energy in the nuclear equation of state. Our result suggests L≤60 MeV, which agrees with complementary observables.
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Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.
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Parafusos Ósseos , Análise de Elementos Finitos , Vértebras Lombares , Fusão Vertebral , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Humanos , Vértebras Lombares/cirurgiaRESUMO
Objective: This study aims to explore the efficacy of multi-slice spiral computed tomography (MSCT) and rapid on-site evaluation (ROSE) in diagnosing pulmonary nodules, thereby providing more diagnostic information for clinical diagnosis, and improving the diagnostic efficiency of pulmonary nodules. Methods: With the means of a retrospective study, 103 patients with pulmonary nodules in our hospital from January 2019 to December 2021 were analyzed. The included patients had no history of lung surgery, and had no cognitive, audio-visual, language communication and physical activity disorders, with visual lesions in bronchoscopy. All patients underwent MSCT scans and ROSE. In the process of cell puncture or tissue biopsy, cell fluid smears or tissue prints were directly used to make cytological specimens. In the operation site, real-time production, staining and real-time cell analysis were carried out to determine whether the material was qualified. The diagnostic efficacy of MSCT, ROSE, and the combination of the two for pulmonary nodules was analyzed. Results: Of the 103 patients, there were finally 68 cases diagnosed with solitary nodules (66.02%) and 35 cases with multiple nodules (33.98%), with 196 pulmonary nodules in total; 25 of them were peripheral lung cancer (24.27%) and 78 were benign nodules (75.73%); and based on the results of clinical diagnosis, they were divided into the malignant group and the benign group separately. Diagnosis of MSCT showed that the probabilities of calcification, spicular sign, lobulation sign, vacuolar sign, and spinous process in the malignant group were significantly higher than those in the benign group (P = .000). 30 positive cases and 73 negative cases were detected by MSCT, including 13 false positives and 8 false negatives. ROSE detected 29 positive cases and 74 negative cases, of which 5 positives were diagnosed as negatives, and the 9 negatives were diagnosed as positives. There were 28 positive cases and 75 negative cases detected by the combination of MSCT and ROSE, including 5 false positives and 2 false negatives. The combined diagnosis of MSCT and ROSE demonstrated an accuracy of 93.20%, sensitivity of 92.00%, specificity of 93.59%, positive predictive value of 82.14%, and negative predictive value of 97.33%. The accuracy, sensitivity, specificity, positive and negative predictive values of MSCT diagnosis were 79.61%, 68.00%, 83.33%, 56.67% and 89.04%, respectively. In ROSE diagnosis, the accuracy, sensitivity, specificity, positive and negative predictive values were 86.41%, 80.00%, 88.46%, 68.97% and 93.24%. The combined diagnosis of MSCT and ROSE had a significantly higher diagnosis rate than the single diagnosis of MSCT and ROSE (P = .000). Through ROC analysis, the area under the curve (AUC) of combined diagnosis was overtly larger than that of single diagnosis of MSCT and ROSE (P = .000). The AUC of MSCT diagnosis and ROSE diagnosis were 0.757 (95%CI: 0.639-0.875) and 0.842 (95%CI: 0.742-0.943) respectively, and the AUC of the combined diagnosis of MSCT and ROSE was 0.928 (95%CI: 0.859-0.997). Conclusion: The combination of MSCT and ROSE contributes to the advances in the diagnostic efficacy for pulmonary nodules in order to reduce the damage caused by ineffective biopsy, which is of great clinically instructional value to the early diagnosis of this disease. This method is convenient to provide reasonable reference materials for the formulation of scientific clinical treatment plan and accurate judgment of prognosis, thereby promoting the good prognosis of patients.
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The pandemic caused by severe acute respiratory syndrome coronavirus 2 is sweeping the world, threatening millions of lives and drastically altering our ways of living. According to current studies, failure to either activate or eliminate inflammatory responses timely and properly at certain stages could result in the progression of the disease. In other words, robust immune responses to coronavirus disease 2019 (COVID-19) are critical. However, they do not theoretically present in some special groups of people, including the young, the aged, patients with autoimmunity or cancer. Differences also do occur between men and women. Our immune system evolves to ensure delicate coordination at different stages of life. The innate immune cells mainly consisted of myeloid lineage cells, including neutrophils, basophils, eosinophils, dendritic cells and mast cells; they possess phagocytic capacity to different degrees at different stages of life. They are firstly recruited upon infection and may activate the adaptive immunity when needed. The adaptive immune cells, on the other way, are comprised mainly of lymphoid lineages. As one grows up, the adaptive immunity matures and expands its memory repertoire, accompanied by an adjustment in quantity and quality. In this review, we would summarise and analyse the immunological characteristics of these groups from the perspective of the immune system 'evolution' as well as 'revolution' that has been studied and speculated so far, which would aid the comprehensive understanding of COVID-19 and personalised-treatment strategy.
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COVID-19 , Imunidade Adaptativa , Idoso , Feminino , Humanos , Sistema Imunitário , Imunidade Inata , SARS-CoV-2RESUMO
Background and Purpose- tPA (tissue-type plasminogen activator) is the only recommended intravenous thrombolytic agent for ischemic stroke. However, its application is limited because of increased risk of hemorrhagic transformation beyond the time window. T541 is a Chinese compound medicine with potential to attenuate ischemia and reperfusion injury. This study was to explore whether T541-benefited subjects underwent tPA thrombolysis extending the time window. Methods- Male C57BL/6 N mice were subjected to carotid artery thrombosis by stimulation with 10% FeCl3 followed by 10 mg/kg tPA with/without 20 mg/kg T541 intervention at 4.5 hours. Thrombolysis and cerebral blood flow were observed dynamically until 24 hours after drug treatment. Neurological deficit scores, brain edema and hemorrhage, cerebral microvascular junctions and basement membrane proteins, and energy metabolism in cortex were assessed then. An in vitro hypoxia/reoxygenation model using human cerebral microvascular endothelial cells was used to evaluate effect of T541 on tight junctions and F-actin in the presence of tPA. Results- tPA administered at 4.5 hours after carotid thrombosis resulted in a decrease in thrombus area and survival rate, whereas no benefit on cerebral blood flow. Study at 24 hours after tPA administration revealed a significant angioedema and hemorrhage in the ischemia hemisphere, a decreased expression of junction proteins claudin-5, zonula occludens-1, occludin, junctional adhesion molecule-1 and vascular endothelial cadherin, and collagen IV and laminin. Meanwhile, ADP/ATP, AMP/ATP, and ATP5D (ATP synthase subunit) expression and activities of mitochondria complex I, II, and IV declined, whereas malondialdehyde and 8-Oxo-2'-deoxyguanosine increased and F-actin arrangement disordered. All the insults after tPA treatment were attenuated by addition of T541 dose dependently. Conclusions- The results suggest T541 as a potential remedy to attenuate delayed tPA-related angioedema and hemorrhage and extend time window for tPA treatment. The potential of T541 to upregulate energy metabolism and protect blood-brain barrier is likely attributable to its effects observed.
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Alcenos/farmacologia , Edema Encefálico , Trombose das Artérias Carótidas , Circulação Cerebrovascular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hemorragias Intracranianas , Polifenóis/farmacologia , Traumatismo por Reperfusão , Saponinas/farmacologia , Animais , Antígenos CD/efeitos dos fármacos , Antígenos CD/metabolismo , Astrágalo , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Caderinas/efeitos dos fármacos , Caderinas/metabolismo , Moléculas de Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Claudina-5/efeitos dos fármacos , Claudina-5/metabolismo , Colágeno Tipo IV/efeitos dos fármacos , Colágeno Tipo IV/metabolismo , Modelos Animais de Doenças , Combinação de Medicamentos , Complexo I de Transporte de Elétrons , Complexo II de Transporte de Elétrons , Complexo IV da Cadeia de Transporte de Elétrons , Laminina/efeitos dos fármacos , Laminina/metabolismo , Masculino , Camundongos , Ocludina/efeitos dos fármacos , Ocludina/metabolismo , Panax notoginseng , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/metabolismo , Ativador de Plasminogênio Tecidual/farmacologia , Proteína da Zônula de Oclusão-1/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
The safety of occupational exposure to inhaled anesthetics remains a concern among the medical staff in hospitals. Few reports are seen about the impact of inhaled anesthetics on the reproductive system, particularly that of males. Several clinical and basic studies on isoflurane and others suggest that inhaled anesthetics affect the reproductive system of rodents by decreasing the sperm count, inducing sperm morphological abnormality, reducing sperm motility, and changing the levels of reproductive hormones, the underlying mechanisms of which are mainly associated with the alteration of the hypothalamic-pituitary-gonadal axis and DNA damage and apoptosis of reproductive cells. This article reviews the main impacts of inhaled anesthetics on the male reproductive system and the possible mechanisms.
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Anestésicos Inalatórios/farmacologia , Genitália Masculina/efeitos dos fármacos , Exposição Ocupacional , Espermatozoides/efeitos dos fármacos , Apoptose , Dano ao DNA , Humanos , Isoflurano/farmacologia , Masculino , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacosRESUMO
LPS-induced microvascular hyperpermeability and hemorrhage play a key role in the development of sepsis, the attenuation of which might be an important strategy to prevent sepsis. However, the current clinical therapies have proven to be inefficient in improving the prognosis for patients with sepsis. Catalpol, an iridoid glycoside extracted from the roots of Rehmannia, has been reported to protect against LPS-induced acute lung injury through a Toll-like receptor-4 (TLR-4)-mediated NF-κB signaling pathway. However, it is still unknown whether catalpol can be an effective treatment to ameliorate the LPS-induced microvascular disorder. The present study aimed to investigate the impact of catalpol on LPS-induced mesenteric microvascular disorder and its underlying mechanism. Male Wistar rats were challenged by infusion of LPS (10 mg·kg-1·h-1) through the left femoral vein for 120 min. Post-treatment with catalpol (10 mg/kg) alleviated the LPS-induced microvascular hyperpermeability and hemorrhage; reduced mortality; ameliorated the alteration in the distribution of claudin-5 and the junctional adhesion molecule-1, as well as the degradation of collagen IV and laminin; and attenuated the increase of TLR-4 level, phosphorylations of Src tyrosine kinase, phosphatidyl inositol 3-kinase, focal adhesion kinase, and cathepsin B activation. In vitro study in human umbilical vein endothelial cells verified these results and further revealed that inhibition of TLR-4 and Src each simulated some, but not all, of the effects that catalpol exerted. Besides, surface plasmon resonance showed that catalpol could directly bind to TLR-4 and Src. These results demonstrated that catalpol was able to ameliorate the LPS-induced microvascular barrier damage and hemorrhage by targeting both TLR-4 and Src, thus attenuating the phosphorylation of Src kinase, phosphatidyl inositol 3-kinase, and focal adhesion kinase, as well as cathepsin B activation.
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Permeabilidade Capilar/efeitos dos fármacos , Hemorragia/metabolismo , Glucosídeos Iridoides/farmacologia , Receptor 4 Toll-Like/metabolismo , Quinases da Família src/metabolismo , Animais , Catepsina B/metabolismo , Claudina-5/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Mesentério/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Ligação Proteica , Ratos , Ratos Wistar , Transdução de Sinais , Receptor 4 Toll-Like/antagonistas & inibidores , Quinases da Família src/antagonistas & inibidoresRESUMO
Lipopolysaccharide (LPS) is one of the common pathogens that causes mesentery hyperpermeability- and intestinal edema-related diseases. This study evaluated whether ginsenoside Rb1 (Rb1), an ingredient of a Chinese medicine Panax ginseng, has beneficial effects on mesentery microvascular hyperpermeability induced by LPS and the underlying mechanisms. Male Wistar rats were continuously infused with LPS (5 mg · kg(-1) · h(-1)) via the left jugular vein for 90 min. In some rats, Rb1 (5 mg · kg(-1) · h(-1)) was administrated through the left jugular vein 30 min after LPS infusion. The dynamics of fluorescein isothiocynate-labeled albumin leakage from mesentery venules was assessed by intravital microscopy. Intestinal tissue edema was evaluated by hematoxylin and eosin staining. The number of caveolae in endothelial cells of microvessels was examined by electron microscopy. Confocal microscopy and Western blotting were applied to detect caveolin-1 (Cav-1) expression and phosphorylation, junction-related proteins, and concerning signaling proteins in intestinal tissues and human umbilical vein endothelial cells. LPS infusion evoked an increased albumin leakage from mesentery venules that was significantly ameliorated by Rb1 posttreatment. Mortality and intestinal edema around microvessels were also reduced by Rb1. Rb1 decreased caveolae number in endothelial cells of microvessels. Cav-1 expression and phosphorylation, VE-Cadherin phosphorylation, ZO-1 degradation, nuclear factor-κB (NF-κB) activation, and Src kinase phosphorylation were inhibited by Rb1. Rb1 ameliorated microvascular hyperpermeability after the onset of endotoxemia and improved intestinal edema through inhibiting caveolae formation and junction disruption, which was correlated to suppression of NF-κB and Src activation.
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Permeabilidade Capilar/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Endotoxemia/tratamento farmacológico , Ginsenosídeos/farmacologia , Lipopolissacarídeos , Mesentério/irrigação sanguínea , Albumina Sérica/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Caveolina 1/metabolismo , Modelos Animais de Doenças , Esquema de Medicação , Edema/induzido quimicamente , Edema/metabolismo , Edema/prevenção & controle , Células Endoteliais/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/metabolismo , Endotoxemia/patologia , Ginsenosídeos/administração & dosagem , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Infusões Intravenosas , Interleucina-6/sangue , Masculino , NF-kappa B/metabolismo , Fosforilação , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Vênulas/efeitos dos fármacos , Vênulas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Quinases da Família src/metabolismoRESUMO
Cardiac ischemia-reperfusion (I/R) injury remains a challenge for clinicians, which initiates with energy metabolism disorder. The present study was designed to investigate the protective effect of notoginsenoside R1 (NR1) on I/R-induced cardiac injury and underlying mechanism. Male Sprague-Dawley rats were subjected to 30-min occlusion of the left coronary anterior descending artery followed by reperfusion with or without NR1 pretreatment (5 mg·kg(-1)·h(-1)). In vitro, H9c2 cells were cultured under oxygen and glucose deprivation/reoxygenation conditions after NR1 (0.1 mM), Rho kinase (ROCK) inhibitor Y-27632 (10 µM), or RhoA/ROCK activator U-46619 (10 nM) administration. Myocardial infarct size, myocardial histology, and cardiac function were evaluated. Myofibril and mitochondria morphology were observed by transmission electron microscopy. F-actin and apoptosis were determined by immunofluorescence and TUNEL staining. ATP and AMP content were assessed by ELISA. Phosphorylated-AMP-activated protein kinase, ATP synthase subunits, apoptosis-related molecules, and the level and activity of ROCK were determined by Western blot analysis. We found that NR1 pretreatment ameliorated myocardial infarction, histological injury, and cardiac function induced by I/R. Furthermore, similar to the effect of Y-27632, NR1 improved H9c2 cell viability, maintained actin skeleton and mitochondria morphology, and attenuated apoptosis induced by oxygen and glucose deprivation/reoxygenation. Importantly, NR1 prevented energy abnormity, inhibited the expression and activation of ROCK, and restored the expression of the mitochondrial ATP synthase δ-subunit both in vivo and in vitro, whereas U-46619 suppressed the effect of NR1. These results prove NR1 as an agent able to prevent I/R-induced energy metabolism disorder via inhibiting ROCK and enhancing mitochondrial ATP synthase δ-subunits, which at least partially contributes to its protection against cardiac I/R injury.
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Cardiotônicos/farmacologia , Ginsenosídeos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Actinas/metabolismo , Trifosfato de Adenosina/metabolismo , Amidas/farmacologia , Animais , Apoptose , Cardiotônicos/uso terapêutico , Técnicas de Cultura de Células , Hipóxia Celular , Inibidores Enzimáticos/farmacologia , Ginsenosídeos/uso terapêutico , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/ultraestrutura , Miofibrilas/efeitos dos fármacos , Miofibrilas/metabolismo , Miofibrilas/ultraestrutura , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate kinase, (MVK) a gene know to play an important role in regulation of calcium-induced keratinocyte differentiation and proliferation, has recently been suggested as the disease-causing gene for DSAP. Here we report a direct sequencing analysis of this gene in 3 DSAP families, 6 sporadic cases, and 100 unrelated healthy controls. We detected a heterozygous T to A transition at nucleotide 205 in exon 3 of MVK gene in one familial case. This mutation will result in an amino acid change at codon 69 (P.Ser69Thr), which is from a serine codon (TCA) to a threonine codon (ACA). No such mutation was detected in the unaffected family members or the 100 unrelated healthy controls. Our results demonstrated a novel missense mutation in MVK gene. This will be valuable for the diagnosis of DSAP as well as for genetic counseling and prenatal diagnosis of affected families.
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Povo Asiático/genética , Mutação de Sentido Incorreto/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Poroceratose/genética , Sequência de Aminoácidos , Sequência de Bases , China , Biologia Computacional , Família , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
OBJECTIVE: To analyze potential mutations of NOTCH3 gene in a Chinese family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL) in order to facilitate genetic counseling and prenatal diagnosis. METHODS: The proband and related family members and 100 healthy controls were recruited. The NOTCH3 gene was screened for mutations by polymerase chain reaction and direct DNA sequencing. PolyPhen-2 and SIFT software were used to predict the protein function. RESULTS: The proband and two affected individuals from the family were adult-onset, with main clinical manifestations including recurrent transient ischemic attacks and(or) strokes, cognitive impairment, memory decline, and depression. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A novel heterozygous missense mutation c.3043T> A (p.Cys1015Ser) located in exon 19 of NOTCH3 gene was identified not only in the proband and two patients, but also in an asymptomatic relative from the family. The same mutation was detected in none of the 100 unrelated healthy controls. Function analysis suggested that this mutation can severely affect the functions of this protein. Multiple sequence alignment revealed that the mutation site was extremely conserved in various species. CONCLUSION: A novel heterozygous Cys1015Ser mutations in exon 19 of the NOTCH3 gene probably underlies the CADASIL in this family.
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CADASIL/genética , Éxons/genética , Mutação de Sentido Incorreto , Receptores Notch/genética , Adulto , Idoso , Sequência de Aminoácidos , Sequência de Bases , CADASIL/complicações , Análise Mutacional de DNA , Saúde da Família , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , Receptor Notch3 , Homologia de Sequência de AminoácidosRESUMO
Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells (RGCs) and axons. Currently, there is no effective method to address the cause of RGCs degeneration. However, studies on neuroprotective strategies for optic neuropathy have increased in recent years. Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy. Regenerative medicine research into the repair of optic nerve damage using stem cells has received considerable attention. Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGC-friendly microenvironments through paracrine effects. This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury, raising the controversies and unresolved issues surrounding the future of stem cells.
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The emergence of spatial multi-omics has helped address the limitations of single-cell sequencing, which often leads to the loss of spatial context among cell populations. Integrated analysis of the genome, transcriptome, proteome, metabolome, and epigenome has enhanced our understanding of cell biology and the molecular basis of human diseases. Moreover, this approach offers profound insights into the interactions between intracellular and intercellular molecular mechanisms involved in the development, physiology, and pathogenesis of human diseases. In this comprehensive review, we examine current advancements in multi-omics technologies, focusing on their evolution and refinement over the past decade, including improvements in throughput and resolution, modality integration, and accuracy. We also discuss the pivotal contributions of spatial multi-omics in revealing spatial heterogeneity, constructing detailed spatial atlases, deciphering spatial crosstalk in tumor immunology, and advancing translational research and cancer therapy through precise spatial mapping.
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Genômica , Neoplasias , Humanos , Genômica/métodos , Neoplasias/genética , Proteômica/métodos , Metabolômica/métodos , Animais , MultiômicaRESUMO
The lack of human-derived in vitro models that recapitulate cervical pre-cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection-associated pre-cancerous lesions and cancers for a long time. Here, a long-term 3D organoid culture protocol for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human-derived samples, a small biobank of cervical pre-tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre-tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus-specific T-cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre-cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre-cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV-related cervical diseases.
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Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Animais , Camundongos , Neoplasias do Colo do Útero/patologia , Papillomaviridae/genética , Perfilação da Expressão GênicaRESUMO
Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients' prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas/metabolismo , Prognóstico , Adenocarcinoma/genética , Microambiente Tumoral/genéticaRESUMO
OBJECTIVE: The present study was designed to evaluate whether CP was beneficial in alleviating myocardial fibrosis following I/R injury. METHODS: Sprague-Dawley rats were subjected to 30 minutes occlusion of the LADCA, followed by reperfusion. CP (0.4 or 0.8 g/kg) was daily administered starting from three hour after reperfusion until day 6. Coronary venular diameter, RBC velocity, albumin leakage, MBF, heart function, myocardial infarction and fibrosis size, myocardium ultrastructure, MPO activity, and MDA level were evaluated. The expression of MCP-1, RP S19, TGF-ß1, P-Smad3, Smad4, MMP-9 and α-SMA, and the infiltration of leukocytes were examined. RESULTS: CP post-treatment ameliorated I/R-induced myocardial RBC velocity reduction, MBF decrease, cardiac dysfunction, and albumin leakage increase. Moreover, myocardial infarction and fibrosis size, MPO activity, MDA level, the expression of RP S19, TGF-ß1, P-Smad3, Smad4, MMP-9 and α-SMA, the number of CD68-positive cells increased significantly after I/R, and myocardium collagen deposition was observed on day 6 after reperfusion. All the alterations after I/R were significantly ameliorated by CP. CONCLUSIONS: Post-treatment with CP ameliorates I/R-induced myocardial fibrosis, suggesting that CP may be applied as an option for preventing cardiac remodeling after I/R injury.
Assuntos
Cardiotônicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Fitoterapia , Actinas/metabolismo , Animais , Canfanos/administração & dosagem , Cardiotônicos/administração & dosagem , Quimiocina CCL2/metabolismo , Circulação Coronária/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Fibrose , Hemodinâmica/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Microcirculação/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Monócitos/patologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Panax notoginseng , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Salvia miltiorrhiza , Fator de Crescimento Transformador beta1/metabolismo , Remodelação Ventricular/efeitos dos fármacosRESUMO
Background: Resection of a giant retroperitoneal liposarcoma is difficult and technically demanding, especially for large retroperitoneal tumors accompanied by a diaphragmatic hernia. Technically, the open abdominal approach can be time-consuming and difficult to perform, with possible intraoperative complications and other factors bringing psychological and physical difficulties to the patient. This study reports a safe and feasible approach for the complete resection of a large retroperitoneal tumor complicated by a diaphragmatic hernia. Methods: A 58-year-old male patient with persistent upper abdominal pain and distension was treated at a local hospital on 4 July 2022. Computed tomography showed a mixed-density mass on the right retroperitoneum, and liposarcoma was considered. On 6 July 2022, the patient was transferred to our hospital for further treatment. Computed tomography showed a mass with low-density fatty shadow in the right adrenal region. The boundary with the right adrenal gland was unclear. The mass was 102 mm × 74 mm, and the right lobe of the liver was compressed. Insufficiency of the right middle lobe of the liver was seen due to a right diaphragmatic hernia and left mediastinal deviation. We considered the traditional approach for tumor resection via laparotomy, but we opted to perform a comprehensive evaluation first. The tumor was close to the back of the right kidney and liver, causing the diaphragm to rise because of its proximity to these organs. Exposing the tumor through laparotomy would be difficult, making it challenging to remove. The patient had a diaphragmatic hernia and moderate pulmonary dysfunction; therefore, we decided to enter the abdomen through a thoracotomy of the ninth rib. Results: Using our technique, the tumor was easily visualized and completely removed in approximately 30 min. The intraoperative blood loss was 100 ml, and no postoperative bleeding, pneumothorax, intestinal fistula, infection, or other complications occurred. Conclusion: The transthoracic approach may be a safer and more feasible resection method than the traditional open approach for patients with giant retroperitoneal liposarcoma with a diaphragmatic hernia.
RESUMO
OBJECTIVE: To investigate the clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the Interlaminar Endoscopic Surgical System(iLESSYS) Delta for the treatment of lumbar spinal stenosis (LSS) in the elderly. METHODS: Total of 29 patients with LSS treated with the iLESSYS Delta from December 2018 to January 2021 were retrospectively analyzed, including 12 males and 17 females with an average age of (71.52±10.82) years old ranging from 63 to 83 years old. All patients had definite intermittent claudication, mainly neurogenic symptoms of both lower limbs. All patients had single-level spinal stenosis, including L3,4 5 cases, L4,5 21 cases, and L5S1 3 cases. Visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified Macnab assessment criteria were used to evaluate pain, low back pain dysfunction index and clinical efficacy, respectively. RESULTS: All 29 cases were successfully completed. The operation time was (73.45±5.89) min, the intraoperative blood loss was (9.93±0.83) ml, the hospital stay was (4.03±0.41) days, and the follow-up was more than 12 months. The VAS scores of low back pain before surgery and 1 day, 1 month, 3 months, 1 year after surgery were 2.31±0.88, 1.45±0.62, 1.21±0.61, 1.10±0.55, 1.03±0.49;VAS of leg pain were 6.48±0.49 0.56, 1.97±0.61, 1.31±0.59, 1.17±0.59, 1.10±0.55;ODI scores were 38.41±2.74, 18.14±1.17, 5.17±0.53, 5.07±0.45, 4.90±0.48;low back and leg pain VAS score and ODI score have statistically significant differences between preoperative and postoperative follow-up time points (P<0.05). The MacNab efficacy evaluation at 1-year follow-up:excellent in 22 cases, good in 5 cases and fair in 2 cases. CONCLUSION: The clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly is satisfactory, with the advantages of less trauma and less bleeding, large microscopic operation space, sufficient decompression, and ideal post-operative recovery, and at the same time, it can minimize the damage to the stable structure of the lumbar spine, which is an ideal surgical method for the treatment of elderly lumbar spinal stenosis.
Assuntos
Dor Lombar , Estenose Espinal , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estenose Espinal/cirurgia , Estudos Retrospectivos , Canal Medular/cirurgia , Descompressão Cirúrgica/métodos , Resultado do Tratamento , Endoscopia/métodos , Vértebras Lombares/cirurgiaRESUMO
Damage to the nervous system can lead to functional impairment, including sensory and motor functions. Importantly, neuropathic pain (NPP) can be induced after nerve injury, which seriously affects the quality of life of patients. Therefore, the repair of nerve damage and the treatment of pain are particularly important. However, the current treatment of NPP is very weak, which promotes researchers to find new methods and directions for treatment. Recently, cell transplantation technology has received great attention and has become a hot spot for the treatment of nerve injury and pain. Olfactory ensheathing cells (OECs) are a kind of glial cells with the characteristics of lifelong survival in the nervous system and continuous division and renewal. They also secrete a variety of neurotrophic factors, bridge the fibers at both ends of the injured nerve, change the local injury microenvironment, and promote axon regeneration and other biological functions. Different studies have revealed that the transplantation of OECs can repair damaged nerves and exert analgesic effect. Some progress has been made in the effect of OECs transplantation in inhibiting NPP. Therefore, in this paper, we provided a comprehensive overview of the biology of OECs, described the possible pathogenesis of NPP. Moreover, we discussed on the therapeutic effect of OECs transplantation on central nervous system injury and NPP, and prospected some possible problems of OECs transplantation as pain treatment. To provide some valuable information for the treatment of pain by OECs transplantation in the future.