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Viral infections usually induce the rearrangement of cellular cytoskeletal proteins and organelle membrane structures, thus creating independent compartments [termed replication organelles (ROs)] to facilitate viral genome replication. Within the ROs, viral replicases, including polymerases, helicases, and ligases, play functional roles during viral replication. These viral replicases are pivotal in the virus life cycle, and numerous studies have demonstrated that the viral replicases could be the potential targets for drugs development. Here, we summarize primarily the key replicases within viral ROs and emphasize the advancements of antiviral drugs targeting crucial viral replicases, providing novel insights into the future development of antiviral strategies.
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The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSSs) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92-169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.
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Vírus da Febre Suína Africana , Processamento Alternativo , Regulação Viral da Expressão Gênica , Regiões Promotoras Genéticas , Sítio de Iniciação de Transcrição , Transcrição Gênica , Vírus da Febre Suína Africana/genética , Animais , Humanos , Suínos , Células HEK293 , Proteínas Virais/genética , Proteínas Virais/metabolismo , Febre Suína Africana/virologia , Replicação ViralRESUMO
Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.
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Aminoácido Oxirredutases , Vesículas Extracelulares , Células Estreladas do Fígado , Cirrose Hepática , Células-Tronco Mesenquimais , MicroRNAs , Animais , Humanos , Masculino , Camundongos , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Vesículas Extracelulares/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/terapia , Cirrose Hepática/metabolismo , Cirrose Hepática/genética , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), results in significant economic losses to the swine industry in many countries. Vaccination represents the primary strategy to control CSF and the CSFV E2 protein is known as the major protective antigen. However, the E2 protein expressed or presented by different systems elicits distinct immune responses. In this study, we established a stable CHO cell line to express the E2 protein and delivered it using self-assembled ferritin nanoparticles (NPs). Subsequently, we compared the adaptive immune responses induced by the E2-ferritin NPs and the monomeric E2 protein produced by the CHO cells or a baculovirus expression system. The results revealed that the NP-delivered E2 protein elicited higher titers of neutralizing antibodies than did the monomeric E2 protein in pigs. Importantly, only the NP-delivered E2 protein significantly induced CSFV-specific IFN-γ-secreting cells. Furthermore, all the pigs inoculated with the E2-ferritin NPs were completely protected from a lethal CSFV challenge infection. These findings demonstrate the ability of the E2-ferritin NPs to protect pigs against the lethal CSFV challenge by eliciting robust humoral and cellular immune responses.
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BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the liver illnesses that may be affected by mitophagy, which is the selective removal of damaged mitochondria. RNF31, an E3 ubiquitin ligase, is carcinogenic in many malignancies. However, the influence of RNF31 on mitochondrial homeostasis and NAFLD development remains unknown. METHODS: Oleic-palmitic acid treated hepatocytes and high-fat diet (HFD)-fed mice were established to observe the effect of RNF31 on hepatocyte mitophagy and steatosis. Mitophagy processes were comprehensively assessed by mt-Keima fluorescence imaging, while global changes in hepatic gene expression were measured by RNA-seq. RESULTS: The present study discovered a reduction in RNF31 expression in lipotoxic hepatocytes with mitochondrial dysfunction. The observed decrease in RNF31 expression was associated with reduced mitochondrial membrane potential, disturbed mitophagy, and increased steatosis. Additionally, the findings indicated that RNF31 is a pivotal factor in the initiation of mitophagy and the facilitation of mitochondrial homeostasis, resulting in a decrease in steatosis in lipotoxic hepatocytes. Mechanistically, RNF31 enhanced p53 ubiquitination and subsequent proteasomal degradation. Down-regulation of p53 led to increased expression of the mitophagy receptor protein BCL2 and adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), thereby promoting mitophagy in hepatocytes. Furthermore, it was demonstrated that the transportation of RNF31 via small extracellular vesicles derived from mesenchymal stem cells (referred to as sEV) had a substantial influence on reducing hepatic steatosis and restoring liver function in HFD-fed mice. CONCLUSIONS: The findings highlight RNF31's essential role in the regulation of mitochondrial homeostasis in hepatocytes, emphasizing its potential as a therapeutic target for NAFLD.
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Dieta Hiperlipídica , Hepatócitos , Proteínas de Membrana , Mitofagia , Hepatopatia Gordurosa não Alcoólica , Proteína Supressora de Tumor p53 , Ubiquitina-Proteína Ligases , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Hepatócitos/metabolismo , Hepatócitos/patologia , Potencial da Membrana Mitocondrial , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Mitofagia/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , UbiquitinaçãoRESUMO
We have recently demonstrated that Jumonji domain-containing protein D3 (JMJD3), a histone demethylase of histone H3 on lysine 27 (H3K27me3), is protective against renal fibrosis, but its role in acute kidney injury (AKI) remains unexplored. Here, we report that JMJD3 activity is required for renal protection and regeneration in murine models of AKI induced by ischemia/reperfusion (I/R) and folic acid (FA). Injury to the kidney upregulated JMJD3 expression and induced expression of H3K27me3, which was coincident with renal dysfunction, renal tubular cell injury/apoptosis, and proliferation. Blocking JMJD3 activity by GSKJ4 led to worsening renal dysfunction and pathological changes by aggravating tubular epithelial cell injury and apoptosis in both murine models of AKI. JMJD3 inhibition by GSKJ4 also reduced renal tubular cell proliferation and suppressed expression of cyclin E and phosphorylation of CDK2, but increased p21 expression in the injured kidney. Furthermore, inactivation of JMJD3 enhanced I/R- or FA-induced expression of TGF-ß1, vimentin, and Snail, phosphorylation of Smad3, STAT3, and NF-κB, and increased renal infiltration by F4/80 (+) macrophages. Finally, GSKJ4 treatment caused further downregulation of Klotho, BMP-7, Smad7, and E-cadherin, all of which are associated with renal protection and have anti-fibrotic effects. Therefore, these data provide strong evidence that JMJD3 activation contributes to renal tubular epithelial cell survival and regeneration after AKI.
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Injúria Renal Aguda , Histonas , Animais , Camundongos , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Proliferação de Células , Histonas/metabolismo , Rim/metabolismo , FosforilaçãoRESUMO
Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898-0.973) and prognosis (AUC = 0.840, 95%CI: 0.751-0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.
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Síndrome do Nevo Basocelular , Cistos Odontogênicos , Tumores Odontogênicos , Humanos , Inteligência Artificial , Diagnóstico Diferencial , Cistos Odontogênicos/diagnóstico por imagem , Tumores Odontogênicos/patologia , PrognósticoRESUMO
Ferroptosis, a form of regulated cell death that is driven by iron-dependent phospholipid peroxidation, has been implicated in multiple diseases, including cancer1-3, degenerative disorders4 and organ ischaemia-reperfusion injury (IRI)5,6. Here, using genome-wide CRISPR-Cas9 screening, we identified that the enzymes involved in distal cholesterol biosynthesis have pivotal yet opposing roles in regulating ferroptosis through dictating the level of 7-dehydrocholesterol (7-DHC)-an intermediate metabolite of distal cholesterol biosynthesis that is synthesized by sterol C5-desaturase (SC5D) and metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis. We found that the pathway components, including MSMO1, CYP51A1, EBP and SC5D, function as potential suppressors of ferroptosis, whereas DHCR7 functions as a pro-ferroptotic gene. Mechanistically, 7-DHC dictates ferroptosis surveillance by using the conjugated diene to exert its anti-phospholipid autoxidation function and shields plasma and mitochondria membranes from phospholipid autoxidation. Importantly, blocking the biosynthesis of endogenous 7-DHC by pharmacological targeting of EBP induces ferroptosis and inhibits tumour growth, whereas increasing the 7-DHC level by inhibiting DHCR7 effectively promotes cancer metastasis and attenuates the progression of kidney IRI, supporting a critical function of this axis in vivo. In conclusion, our data reveal a role of 7-DHC as a natural anti-ferroptotic metabolite and suggest that pharmacological manipulation of 7-DHC levels is a promising therapeutic strategy for cancer and IRI.
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Desidrocolesteróis , Ferroptose , Humanos , Membrana Celular/metabolismo , Colesterol/biossíntese , Colesterol/metabolismo , Sistemas CRISPR-Cas/genética , Desidrocolesteróis/metabolismo , Genoma Humano , Nefropatias/metabolismo , Membranas Mitocondriais/metabolismo , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Fosfolipídeos/metabolismo , Traumatismo por Reperfusão/metabolismoRESUMO
IMPORTANCE: Sliding clamp is a highly conserved protein in the evolution of prokaryotic and eukaryotic cells. The sliding clamp is required for genomic replication as a critical co-factor of DNA polymerases. However, the sliding clamp analogs in viruses remain largely unknown. We found that the ASFV E301R protein (pE301R) exhibited a sliding clamp-like structure and similar functions during ASFV replication. Interestingly, pE301R is assembled into a unique ring-shaped homotetramer distinct from sliding clamps or proliferating cell nuclear antigens (PCNAs) from other species. Notably, the E301R gene is required for viral life cycle, but the pE301R function can be partially restored by the porcine PCNA. This study not only highlights the functional role of the ASFV pE301R as a viral sliding clamp analog, but also facilitates the dissection of the complex replication mechanism of ASFV, which provides novel clues for developing antivirals against ASF.
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Vírus da Febre Suína Africana , Suínos , Animais , Vírus da Febre Suína Africana/genética , Replicação Viral , DNA Polimerase Dirigida por DNA , Células EucarióticasRESUMO
IMPORTANCE: African swine fever (ASF) is an acute, hemorrhagic, and severe porcine infectious disease caused by African swine fever virus (ASFV). ASF outbreaks severely threaten the global pig industries and result in serious economic losses. No safe and efficacious commercial vaccine is currently available except in Vietnam. To date, large gaps in the knowledge concerning viral biological characteristics and immunoevasion strategies have hindered the ASF vaccine design. In this study, we demonstrate that pD129L negatively regulates the type I interferon (IFN) signaling pathway by interfering with the interaction of the transcriptional coactivator p300 and IRF3, thereby inhibiting the induction of type I IFNs. This study reveals a novel immunoevasion strategy employed by ASFV, shedding new light on the intricate mechanisms for ASFV to evade the host immune responses.
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Vírus da Febre Suína Africana , Febre Suína Africana , Proteína p300 Associada a E1A , Fator Regulador 3 de Interferon , Interferon Tipo I , Animais , Febre Suína Africana/virologia , Interferon Tipo I/metabolismo , Interferon beta/metabolismo , Suínos , Fatores de Transcrição/metabolismo , Vacinas/metabolismo , Proteína p300 Associada a E1A/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Evasão da Resposta ImuneRESUMO
Cellular metabolism plays a central role in the regulation of both innate and adaptive immunity. Immune cells utilize metabolic pathways to modulate the cellular differentiation or death. The intricate interplay between metabolism and immune response is critical for maintaining homeostasis and effective antiviral activities. In recent years, immunometabolism induced by viral infections has been extensively investigated, and accumulating evidence has indicated that cellular metabolism can be hijacked to facilitate viral replication. Generally, virus-induced changes in cellular metabolism lead to the reprogramming of metabolites and metabolic enzymes in different pathways (glucose, lipid, and amino acid metabolism). Metabolic reprogramming affects the function of immune cells, regulates the expression of immune molecules and determines cell fate. Therefore, it is important to explore the effector molecules with immunomodulatory properties, including metabolites, metabolic enzymes, and other immunometabolism-related molecules as the antivirals. This review summarizes the relevant advances in the field of metabolic reprogramming induced by viral infections, providing novel insights for the development of antivirals.
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Viroses , Vírus , Humanos , Antivirais/farmacologia , Redes e Vias Metabólicas , ImunidadeRESUMO
Lysyl oxidase-like 2 (LOXL2) is an extracellular copper-dependent enzyme that plays a central role in fibrosis by catalyzing the crosslinking and deposition of collagen. Therapeutic LOXL2 inhibition has been shown to suppress liver fibrosis progression and promote its reversal. This study investigates the efficacy and underlying mechanisms of human umbilical cord-derived exosomes (MSC-ex) in LOXL2 inhibition of liver fibrosis. MSC-ex, nonselective LOX inhibitor ß-aminopropionitrile (BAPN), or PBS were administered into carbon tetrachloride (CCl4)-induced fibrotic livers. Serum LOXL2 and collagen crosslinking were assessed histologically and biochemically. MSC-ex's mechanisms on LOXL2 regulation were investigated in human hepatic stellate cell line LX-2. We found that systemic administration of MSC-ex significantly reduced LOXL2 expression and collagen crosslinking, delaying the progression of CCl4-induced liver fibrosis. Mechanically, RNA-sequencing and fluorescence in situ hybridization (FISH) indicated that miR-27b-3p was enriched in MSC-ex and exosomal miR-27b-3p repressed Yes-associated protein (YAP) expression by targeting its 3' untranslated region in LX-2. LOXL2 was identified as a novel downstream target gene of YAP, and YAP bound to the LOXL2 promoter to positively regulate transcription. Additionally, the miR-27b-3p inhibitor abrogated the anti-LOXL2 abilities of MSC-ex and diminished the antifibrotic efficacy. miR-27b-3p overexpression promoted MSC-ex mediated YAP/LOXL2 inhibition. Thus, MSC-ex may suppress LOXL2 expression through exosomal miR-27b-3p mediated YAP down-regulation. The findings here may improve our understanding of MSC-ex in liver fibrosis alleviation and provide new opportunities for clinical treatment.
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Células-Tronco Mesenquimais , MicroRNAs , Humanos , Colágeno/metabolismo , Hibridização in Situ Fluorescente , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismoRESUMO
Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with ferroptosis inducer (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and cytosolic reactive oxygen species (ROS). In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the phosphatidylinositol 3 kinase (PI3K)-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.
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Carcinoma de Células Renais , Ferroptose , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Renais/tratamento farmacológicoRESUMO
Cancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells, has revolutionized the oncology landscape as it utilizes patients' own immune systems in combating the cancer cells. Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes. Phagocytosis checkpoints, such as CD47, CD24, MHC-I, PD-L1, STC-1 and GD2, have emerged as essential checkpoints for cancer immunotherapy by functioning as "don't eat me" signals or interacting with "eat me" signals to suppress immune responses. Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy. Genetic ablation of these phagocytosis checkpoints, as well as blockade of their signaling pathways, robustly augments phagocytosis and reduces tumor size. Among all phagocytosis checkpoints, CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment. CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials. However, anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes. Here, we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy, highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.
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Antígeno CD47 , Neoplasias , Humanos , Antígeno CD47/genética , Imunoterapia , Fagocitose/genética , Imunidade Inata/genética , Imunidade Adaptativa , Neoplasias/genética , Neoplasias/terapiaRESUMO
A novel circovirus called porcine circovirus type 4 (PCV4) was recently detected in pigs suffering from severe clinical diseases in Hunan province, China. There are few reports on the origin and evolution of PCV4, although some researchers have conducted epidemiological investigations of PCV4 and found that PCV4 is widespread in pigs. Based on the previous study, we detected PCV2 in farmed foxes and raccoon dogs with reproductive failure. To explore whether the PCV4 genome also exists in fur animals, we detected 137 cases admitted from fur animal farms in Hebei China between 2015 and 2020, which were characterized by inappetence, lethargy, depression, abortion, and sterility. The overall infection rate of PCV4 was 23.36% (32/137), including 20.37% (22/108) for raccoon dogs, 18.75% (3/16) for foxes, and 53.85% (7/13) for minks. Finally, five raccoon dog-origin PCV4 strains and one fox-origin PCV4 strain were sequenced in our study, whose nucleotide identities with other representative PCV4 strains varied from 96.5% to 100%. Phylogenetic analysis based on the complete genomes of PCV4 strains indicated a close relationship with those of PCV4 strains identified from pigs. To our knowledge, this is the first study to detect PCV4 in fur animals. Interestingly, we also identified PCV4 in a mixed farm (feeding pigs and raccoon dogs at the same time). In summary, our findings extend the understanding of the molecular epidemiology of PCV4 and provide new evidence for its cross-species transmission.
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BACKGROUND: Cup-shaped ear is a common congenital auricle deformity. There are many specific surgical methods, such as V-Y method, Barsky method, Musgrave method, etc., but there is no unified treatment method. The authors used the outer helix reconstruction method for cup-shaped ear and achieved remarkable therapeutic effects. MATERIALS AND METHODS: The authors performed the outer helix reconstruction on 30 patients with cup-shaped ear. The authors followed up the patients after the stage II operation. The authors used the SPSAU data science analysis platform (https://spssau.com/) for statistical analysis of the data. RESULT: The mean follow-up time was 14.43±4.5 months. The mean preoperative perimeter of auricle was 8.19±0.56 cm. The mean postoperative perimeter of auricle was 10.82±0.49 cm. The mean perimeter of the healthy auricle was 10.89±0.44 cm. Through data analysis, the authors found that the comparison between preoperative and postoperative auricle perimeters was statistically significant (P<0.05). The comparison between postoperative auricle perimeter and the perimeter of the healthy auricle was not statistically significant (P>0.05). In terms of postoperative satisfaction of patients and their families, the satisfaction rate was 100%. In terms of postoperative complications, there were 1 case of incision dehiscence, 0 cases of incision infection, 2 cases of incision hematoma, and 0 cases of postoperative skin flap ischemia and necrosis. CONCLUSION: The outer helix reconstruction method is suitable for most cup-shaped ears, and the operation is simple and the effect is remarkable. It is worthy of promotion and application in plastic surgery clinical.
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Pavilhão Auricular , Projetos de Pesquisa , Humanos , Orelha Externa/cirurgia , Pavilhão Auricular/cirurgia , Período Pós-Operatório , Deiscência da Ferida OperatóriaRESUMO
Objective: To compare the effectiveness between three-dimensional (3D) printed porous titanium alloy cage (3D Cage) and poly-ether-ether-ketone cage (PEEK Cage) in the posterior lumbar interbody fusion (PLIF). Methods: A total of 66 patients who were scheduled to undergo PLIF between January 2018 and June 2019 were selected as the research subjects, and were divided into the trial group (implantation of 3D Cage, n=33) and the control group (implantation of PEEK Cage, n=33) according to the random number table method. Among them, 1 case in the trial group did not complete the follow-up exclusion study, and finally 32 cases in the trial group and 33 cases in the control group were included in the statistical analysis. There was no significant difference in gender, age, etiology, disease duration, surgical segment, and preoperative Japanese Orthopaedic Association (JOA) score between the two groups (P>0.05). The operation time, intraoperative blood loss, complications, JOA score, intervertebral height loss, and interbody fusion were recorded and compared between the two groups. Results: The operations of two groups were completed successfully. There was 1 case of dural rupture complicated with cerebrospinal fluid leakage during operation in the trial group, and no complication occurred in the other patients of the two groups. All incisions healed by first intention. There was no significant difference in operation time and intraoperative blood loss between groups (P>0.05). All patients were followed up 12-24 months (mean, 16.7 months). The JOA scores at 1 year after operation in both groups significantly improved when compared with those before operation (P<0.05); there was no significant difference between groups (P>0.05) in the difference between pre- and post-operation and the improvement rate of JOA score at 1 year after operation. X-ray film reexamination showed that there was no screw loosening, screw rod fracture, Cage collapse, or immune rejection in the two groups during follow-up. At 3 months and 1 year after operation, the rate of intervertebral height loss was significantly lower in the trial group than in the control group (P<0.05). At 3 and 6 months after operation, the interbody fusion rating of trial group was significantly better in the trial group than in the control group (P<0.05); and at 1 year after operation, there was no significant difference between groups (P>0.05). Conclusion: There is no significant difference between 3D Cage and PEEK Cage in PLIF, in terms of operation time, intraoperative blood loss, complications, postoperative neurological recovery, and final intervertebral fusion. But the former can effectively reduce vertebral body subsidence and accelerate intervertebral fusion.
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Cetonas , Fusão Vertebral , Ligas , Benzofenonas , Perda Sanguínea Cirúrgica , Parafusos Ósseos , Éter , Éteres , Etil-Éteres , Humanos , Vértebras Lombares/cirurgia , Polímeros , Porosidade , Fusão Vertebral/métodos , Titânio , Resultado do TratamentoRESUMO
BACKGROUND: In the context of the novel coronavirus disease 2019 (COVID-19) pandemic, people have had to stay at home more and make fewer trips to the hospital. Furthermore, hospitals give priority to the treatment of COVID-19 patients. These factors are not conducive to the treatment of diabetic foot, and even increase the risk of amputation. Therefore, how to better treat patients with diabetic foot during the COVID-19 epidemic, prevent further aggravation of the disease and reduce the risk of amputation in patients with diabetic foot has become an urgent problem for doctors around the world. METHODS: The researchers searched PubMed, the Cochrane Library, and the Embase database. The retrieval time was set from the database establishment to October 2021. All studies on treatment of diabetic foot in the COVID-19 pandemic were included in our study. RESULTS: A total of 6 studies were included in this study. In the 6 protocols for treating patients with diabetic foot, the researchers classified patients according to the condition of their diabetic foot. Diabetic foot patients with general conditions received treatment at home, and doctors can guide the wound dressing change and medication treatment of patients through telemedicine. Patients with severe conditions of diabetic foot were admitted to hospital for treatment. Patients were screened for COVID-19 before hospitalization, those infected or suspected of COVID-19 were treated in isolation, and those not infected with COVID-19 were treated in a general ward. CONCLUSION: Through this systematic review, we proposed a new protocol for the treatment of patients with diabetic foot in the context of the COVID-19 pandemic. It provided reference for the treatment of diabetic foot in the context of COVID-19 epidemic. However, the global applicability of the treatment protocol for diabetic foot in the context of COVID-19 epidemic proposed in this study needs further clinical testing.
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COVID-19 , Diabetes Mellitus , Pé Diabético , Telemedicina , Amputação Cirúrgica , Diabetes Mellitus/epidemiologia , Pé Diabético/epidemiologia , Pé Diabético/terapia , Humanos , PandemiasRESUMO
Under normal circumstances, wound healing can be summarized as three processes. These include inflammation, proliferation, and remodeling. The vast majority of wounds heal rapidly; however, a large percentage of nonhealing wounds have still not been studied significantly. The factors affecting wound nonhealing are complex and diverse, and identifying an effective solution from nature becomes a key goal of research. This study aimed to highlight and review the mechanisms and targets of natural products (NPs) for treating nonhealing wounds. The results of relevant studies have shown that the effects of NPs are associated with PI3K-AKT, P38MAPK, fibroblast growth factor, MAPK, and ERK signaling pathways and involve tumor growth factor (TNF), vascular endothelial growth factor, TNF-α, interleukin-1ß, and expression of other cytokines and proteins. The 25 NPs that contribute to wound healing were systematically summarized by an inductive collation of the six major classes of compounds, including saponins, polyphenols, flavonoids, anthraquinones, polysaccharides, and others, which will further direct the attention to the active components of NPs and provide research ideas for further development of new products for wound healing.