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1.
Gut ; 73(7): 1169-1182, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38395437

RESUMO

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Integração Viral , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/patologia , Vírus da Hepatite B/genética , Humanos , Integração Viral/genética , Animais , Camundongos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Sequenciamento Completo do Genoma , Variações do Número de Cópias de DNA , Idoso
2.
Cancer Immunol Immunother ; 73(2): 31, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38279998

RESUMO

The small, heavily glycosylated protein CD24 is primarily expressed by many immune cells and is highly expressed mostly in cancer cells. As one of the most crucial biomarkers of cancers, CD24 is frequently highly expressed in solid tumors, while tumor-associated macrophages express Siglec-10 at high levels, Siglec-10 and CD24 can interact on innate immune cells to lessen inflammatory responses to a variety of disorders. Inhibiting inflammation brought on by SHP-1 and/or SHP-2 phosphatases as well as cell phagocytosis by macrophages, the binding of CD24 to Siglec-10 can prevent toll-like receptor-mediated inflammation. Targeted immunotherapy with immune checkpoint inhibitors (ICI) has lately gained popularity as one of the best ways to treat different tumors. CD24 is a prominent innate immune checkpoint that may be a useful target for cancer immunotherapy. In recent years, numerous CD24/Siglec-10-related research studies have made tremendous progress. This study discusses the characteristics and workings of CD24/Siglec-10-targeted immunotherapy and offers a summary of current advances in CD24/Siglec-10-related immunotherapy research for cancer. We then suggested potential directions for CD24-targeted immunotherapy, basing our speculation mostly on the results of recent preclinical and clinical trials.


Assuntos
Macrófagos , Neoplasias , Humanos , Transdução de Sinais , Inflamação , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Imunoterapia/métodos , Antígeno CD24/metabolismo
3.
J Transl Med ; 22(1): 127, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308352

RESUMO

BACKGROUND: Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. METHODS: We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. RESULTS: Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828-0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). CONCLUSION: We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Feminino , Humanos , Hiperplasia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Endométrio/tratamento farmacológico , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , China
4.
Appl Microbiol Biotechnol ; 108(1): 360, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836914

RESUMO

In the fight against hospital-acquired infections, the challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) necessitates the development of novel treatment methods. This study focused on undermining the virulence of S. aureus, especially by targeting surface proteins crucial for bacterial adherence and evasion of the immune system. A primary aspect of our approach involves inhibiting sortase A (SrtA), a vital enzyme for attaching microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) to the bacterial cell wall, thereby reducing the pathogenicity of S. aureus. Verbascoside, a phenylethanoid glycoside, was found to be an effective SrtA inhibitor in our research. Advanced fluorescence quenching and molecular docking studies revealed a specific interaction between verbascoside and SrtA, pinpointing the critical active sites involved in this interaction. This molecular interaction significantly impedes the SrtA-mediated attachment of MSCRAMMs, resulting in a substantial reduction in bacterial adhesion, invasion, and biofilm formation. The effectiveness of verbascoside has also been demonstrated in vivo, as shown by its considerable protective effects on pneumonia and Galleria mellonella (wax moth) infection models. These findings underscore the potential of verbascoside as a promising component in new antivirulence therapies for S. aureus infections. By targeting crucial virulence factors such as SrtA, agents such as verbascoside constitute a strategic and potent approach for tackling antibiotic resistance worldwide. KEY POINTS: • Verbascoside inhibits SrtA, reducing S. aureus adhesion and biofilm formation. • In vivo studies demonstrated the efficacy of verbascoside against S. aureus infections. • Targeting virulence factors such as SrtA offers new avenues against antibiotic resistance.


Assuntos
Aminoaciltransferases , Antibacterianos , Aderência Bacteriana , Proteínas de Bactérias , Biofilmes , Cisteína Endopeptidases , Glucosídeos , Staphylococcus aureus Resistente à Meticilina , Simulação de Acoplamento Molecular , Fenóis , Infecções Estafilocócicas , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Cisteína Endopeptidases/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Glucosídeos/farmacologia , Animais , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fenóis/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Mariposas/microbiologia , Virulência/efeitos dos fármacos , Modelos Animais de Doenças , Fatores de Virulência/metabolismo , Inibidores Enzimáticos/farmacologia , Polifenóis
5.
Arch Orthop Trauma Surg ; 144(1): 229-237, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37838982

RESUMO

PURPOSE: To evaluate the outcomes of patients with supination-adduction (SAD) type II (OTA/AO 44A2) fractures who had a lateral ankle ligament rupture repaired compared with patients who did not have a lateral ankle ligament repaired using patients who underwent fibula fracture fixation as a control group. METHODS: A retrospective analysis of all 104 patients diagnosed with SAD type II fractures from January 2011 to December 2020 and managed operatively was performed. The patients were divided into three groups: 32 patients with ruptures of the lateral ligaments that were not repaired (group A), 34 patients with ruptures of the lateral ligaments that were repaired (group B), and 38 patients with fibula fracture fixation acting as the control group (group C). The objective outcomes including radiographic findings, the ankle range of motion, the manual ankle stress tests, and complications were gained from the record of the last time in outpatient clinics. The functional outcomes including the identification of functional ankle instability (IdFAI) scores were collected postoperatively at 12-month intervals to assess clinical outcomes. The Manchester Oxford Foot Questionnaire (MOXFQ) and Karlsson scoring scale were also recorded at the last follow-up. RESULTS: The mean follow-up of the objective and subjective functional outcomes was 23.4 (range, 13-42) and 76.9 (range, 25-134) months, respectively. There was no significant difference in the radiographic findings, the ankle range of motion and complications between the three groups. All ankles were found to be stable using the manual ankle stress test in both group A and group B. The IdFAI scores showed a significant difference between group A and group B (1.12 ± 1.3 vs 0.35 ± 0.69; p < 0.001) in the first year of follow-up and no significant difference after the first year. No differences were noted in MOXFQ scores or Karlsson scores among the groups. CONCLUSION: Directly repairing the lateral ligament could minimize the proportion of the first year of postoperative functional ankle instability, although the final stability of the ankle and clinical outcomes were not significantly different in SAD type II fractures. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.


Assuntos
Fraturas do Tornozelo , Ligamentos Laterais do Tornozelo , Humanos , Fraturas do Tornozelo/cirurgia , Tornozelo , Estudos Retrospectivos , Supinação , Fixação Interna de Fraturas , Resultado do Tratamento , Articulação do Tornozelo/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia
6.
Small ; 19(17): e2207211, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36651038

RESUMO

Paracrine is an important mechanism in mesenchymal stem cells (MSCs) that promotes tissue regeneration. However, anoikis is attributed to unsuitable adhesion microenvironment hindered this paracrine effect. In this study, a living and injectable porous hydrogel microsphere with long-term paracrine activity is constructed via the freeze-drying microfluidic technology and the incorporation of platelet-derived growth factor-BB (PDGF-BB) and exogenous MSCs. Benefiting from the porous structure and superior mechanical property of methacrylate gelatin (GelMA) hydrogel microspheres (GMs), exogenous stem cells are able to adhere and proliferate on GMs, thereby facilitating cell-to-extracellular matrix (ECM) and cell-to-cell interactions and enhancing paracrine effect. Furthermore, the sustained release of PDGF-BB can recruit endogenous MSCs to prolong the paracrine activity of the living GMs. In vitro and in vivo experiments validated that the living GMs exhibit superior secretion properties and anti-inflammatory efficacy and can attenuate osteoarthritis (OA) progression by favoring the adherent microenvironment and utilizing the synergistic effect of exogenous and endogenous MSCs. Overall, a living injectable porous hydrogel microsphere that can enhance the paracrine activity of stem cells is fabricated and anticipated to hold the potential of future clinical translation in OA and other diseases.


Assuntos
Materiais Biocompatíveis , Cartilagem , Microesferas , Becaplermina , Porosidade , Materiais Biocompatíveis/química , Hidrogéis/química
7.
Acta Neurochir (Wien) ; 165(8): 2131-2137, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37166509

RESUMO

BACKGROUND: Previous studies have demonstrated satisfactory outcomes of percutaneous endoscopic thoracic decompression (PETD) for single-segment thoracic ossification of the ligamentum flavum (TOLF). However, the clinical outcomes of PETD in patients with multi-segment TOLF (mTOLF) remain unclear. The aim of the present study was to evaluate the efficacy and safety of PETD for patients with multi-segment mTOLF. METHODS: Eighteen consecutive patients (41 segments) with mTOLF were treated with PETD between January 2020 and December 2021. The clinical outcomes were evaluated using the modified Japanese Orthopaedic Association (mJOA) score and Visual Analog Scale (VAS), whereas radiographic parameters were measured by cross-section area of the spinal canal and anteroposterior diameter of the spinal cord. RESULTS: The follow-up period ranged from 14 to 34 months. The mean operation time and blood loss were 154.06 ± 32.14 min and 61.72 ± 12.72 ml, respectively. Hospital stay after first-stage operation was 10.89 ± 2.42 days. The mJOA score and VAS score significantly improved at the final follow-up, with a mean mJOA recovery rate of 63.3 ± 21.90%. The incidence of complications was 12.2% per level. The radiographic outcomes showed adequate decompression of the spinal cord. CONCLUSIONS: The present study demonstrates that PETD is effective and safe as a minimally invasive procedure to treat patients with mTOLF. All patients showed relief of their symptoms and improvement in neurological function.


Assuntos
Ligamento Amarelo , Ossificação Heterotópica , Doenças da Medula Espinal , Humanos , Osteogênese , Descompressão Cirúrgica/métodos , Ligamento Amarelo/diagnóstico por imagem , Ligamento Amarelo/cirurgia , Resultado do Tratamento , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Estudos Retrospectivos , Doenças da Medula Espinal/cirurgia
8.
Arch Orthop Trauma Surg ; 143(1): 71-79, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34128117

RESUMO

INTRODUCTION: Studies have reported various effects of autologous chondrocyte implantation (ACI) on osteochondral defects of the talus. Therefore, to assess the effectiveness of ACI for osteochondral defects of the talus, we used the meta-analytic approach. MATERIALS AND METHODS: Electronic databases PubMed, Embase, and the Cochrane Library were systematically searched to identify eligible studies from their inception until November 2020. The random-effects model was used to calculate the incidence of success rate and American Orthopaedic Foot and Ankle Society (AOFAS) score for patients after ACI treatment. Subgroup analyses were also conducted based on age, technique, indication, size, and follow-up duration. RESULTS: For the final meta-analysis, we selected 23 case series studies with a total of 458 patients with osteochondral defects of the talus. Overall, after ACI for patients with osteochondral defects of the talus, we noted that the incidence of success rate was 89% (95% confidence interval (95% CI) 85%-92%; P < 0.001). Moreover, after ACI for patients with osteochondral defects of the talus, the AOFAS score was 86.33 (95% CI 83.33-89.33; P < 0.001). Subgroup analysis showed that the AOFAS score after ACI is significantly different when stratified by the mean age of the patients (P = 0.006). CONCLUSIONS: This study revealed that the use of ACI could provide a relatively high success rate and improve the AOFAS score for patients with osteochondral defects of the talus, which should be recommended in clinical practice.


Assuntos
Cartilagem Articular , Procedimentos Ortopédicos , Tálus , Humanos , Condrócitos , Tálus/cirurgia , Transplante Autólogo , Extremidade Inferior , Resultado do Tratamento , Cartilagem Articular/cirurgia
9.
Foot Ankle Surg ; 29(1): 79-85, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36270884

RESUMO

BACKGROUND: Most of modified posteromedial approaches require prone position for the treatment of pilon fractures. We describe the technique of modified posteromedial approach under supine position. The goal of the study was to compare the radiographic and clinical outcomes of prone-supine versus supine position for the treatment of pilon fractures via modified posteromedial approach combined with anterolateral approach. METHODS: A total of 50 retrospectively consecutive pilon fractures that underwent open reduction internal fixation via modified posteromedial approach combined with anterolateral approach from 2016 to 2019 were reviewed at least a two-year follow up. The positions of patients were divided into two groups: prone-supine versus supine position (26 vs 24, respectively). The operation time, radiographic outcomes including bone union time and ratio of congruent articular reduction were evaluated. The post-operative function was evaluated using the Manchester Oxford score (MOXFQ) and the visual analogue score (VAS). The motion of ankle joint and complications and were also compared. RESULTS: The mean follow-up was 42.2(24.7-73.0) months in the prone-supine group and 42.7(37.3-56.5) months in the supine group (P = .87). The mean operation time was 141.9 ± 10.1 min in the prone-supine group and 107.5 ± 18.9 min in the supine group (P = .00). There was no significant difference in the bone union time and ratio of congruent articular reduction between the two groups. There was no significant difference in the final MOXFQ score, VAS score, and the mean range of ankle motion between the two groups (P > .05). The total incidence of complications was 11.5% in the prone-supine group and 16.6% in the supine group (P = .66). CONCLUSION: The patient in the prone-supine position versus supine position for pilon fractures via modified posteromedial approach combined with anterolateral approach contributed comparable quality of reduction, bone union time functional outcomes and complications. The supine technique was significantly shorter in terms of operation time.


Assuntos
Fraturas do Tornozelo , Fraturas da Tíbia , Humanos , Estudos Retrospectivos , Decúbito Ventral , Decúbito Dorsal , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia
10.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5419-5437, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114136

RESUMO

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.


Assuntos
Curcuma , Anti-Inflamatórios , Curcuma/química , Fígado
11.
Small ; 18(40): e2202156, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36056898

RESUMO

The localization and accumulation of drugs in the body determine their therapeutic effects; however, the specific microstructure of damaged tissues hinders drug delivery. Currently, there is a shortage of effective drug carriers to breach these barriers and achieve efficient tissue and cellular delivery of drugs. In this study, an injectable double positively charged functional hydrogel microsphere with "targeting cartilage extracellular matrix", "cartilage penetration", and "cellular phagocytosis" is designed for matching the structural characteristics of joints, addressing the difficulties of drug delivery in joints. The microspheres could be adsorbed on the negatively charged cartilage surface because of their positively charged poly-lysine surface. Furthermore, the internally loaded positively charged polyamidoamine contained kartogenin, which helped further the penetration of the cartilage under the guidance of electrical charge. The microspheres could release kartogenin for more than 21 days. In in vivo experiments, the microspheres effectively improve the efficiency of drug delivery, inhibit the degradation of cartilage matrix and subchondral bone, and delay the development of osteoarthritis. As a double positively charged drug delivery system, the versatile microsphere has great potential for treating osteoarthritis and other diseases.


Assuntos
Hidrogéis , Osteoartrite , Anilidas , Portadores de Fármacos/química , Humanos , Hidrogéis/química , Lisina , Microesferas , Osteoartrite/tratamento farmacológico , Fagocitose , Ácidos Ftálicos
12.
Reprod Biol Endocrinol ; 20(1): 134, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064542

RESUMO

OBJECTIVE: Fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients has recently emerged important social health topic. This study is designed to explore the risk factors for time to complete remission (CR) of fertility-sparing treatment in woman with AEH and early EC. METHODS: A retrospective study was designed with clinical data from 106 patients admitted between January 2012 to December 2019. Univariate and multivariate logistic analysis were used to explore independent risk factors for time to CR. These factors were employed in receiver operator characteristic (ROC) curve and the decision curve analysis (DCA) to evaluate predictive accuracy of time to CR. Stratified analysis and interactive analysis was also performed for more in-depth perspective. RESULTS: Univariate analysis showed that fasting blood glucose levels (FBG, OR = 1.6, 95%CI: 0.6-2.5, P = 0.020), metabolic syndrome (MetS, OR = 3.0, 95%CI: 1.1-5.0, P = 0.003), and polycystic ovary syndrome (PCOS, OR = 2.0, 95%CI: 0.5-3.4, P = 0.009) were associated with time to CR. Among these factors, multivariate analysis confirmed MetS (OR = 3.1, 95%CI: 1.0-5.2, P = 0.005) was an independent risk factor. The area under the ROC curve (AUC) of MetS was higher than FBG and PCOS (AUC = 0.723 vs 0.612 and 0.692). The AUC of FBG combined with PCOS was 0.779, and it was improved to 0.840 when MetS was included (P < 0.05). Additionally, MetS played different roles in time to CR in various groups. Moreover, we found high-density lipoprotein (HDL) and MetS had an interactive effect for time to CR. CONCLUSION: MetS is an independent risk factor for time to CR and should be taken seriously in fertility-sparing management of AEH and early EC patients.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Síndrome Metabólica , Síndrome do Ovário Policístico , Hiperplasia Endometrial/complicações , Hiperplasia Endometrial/tratamento farmacológico , Feminino , Humanos , Síndrome Metabólica/complicações , Síndrome do Ovário Policístico/metabolismo , Estudos Retrospectivos , Fatores de Risco
13.
Macromol Rapid Commun ; 43(10): e2200034, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35332623

RESUMO

Cancer remains a formidable global problem with a high mortality rate. There are many effective anti-cancer drugs in clinical use, among which paclitaxel (PTX) has good effects on non-small cell lung cancer, ovarian cancer, and breast cancer. However, when applied to the clinic, PTX still has many limitations, such as poor water solubility, drug resistance, and side effects on healthy tissues. A gold nanodots-paclitaxel-polylysine (AuNDs-PTX-PLL) core-shell nano-system of integrated diagnosis and treatment is constructed to achieve intelligent responsive drug delivery. On the one hand, the problem of poor water-solubility and drug resistance of PTX are solved. On the other hand, the nano-system has an excellent intelligent response effect. Drugs can only be released in the weakly acidic environment of the tumor, which reduces the damage and side effects to normal tissues. Moreover, the nano-system can be used for real-time tracking and auxiliary diagnosis for the tumor through the multi-mode imaging mode, such as fluorescence, photoacoustic, and computed tomography to achieve accurate visualization. The photothermal effect of AuNDs is beneficial to promote the release of drugs. The nano-system integrates multi-mode imaging, chemotherapy, intelligent drug release in tumor weakly acidic environment, and has excellent practical application prospects in tumor diagnosis and treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Ouro , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Água
14.
BMC Musculoskelet Disord ; 23(1): 835, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057592

RESUMO

BACKGROUND: A symptomatic postoperative pseudocyst (PP) is a cystic lesion that is formed in the operation area of the intervertebral disc, leading to worse symptoms. Some minority patients who developed PP experienced rapidly aggravating symptoms and could not be treated by any kind of conservative treatment. However, no clinical studies have evaluated the clinical characteristics and surgical strategies of symptomatic PP requiring a revision surgery after full-endoscopic lumbar discectomy (FELD). This study aimed to demonstrate the clinical characteristics and surgical strategies of symptomatic PP requiring a revision surgery after FELD. METHODS: We retrospectively analyzed the data of patients who received FELD revision surgeries due to symptomatic PP formation between January 2016 and December 2021. Common characteristics, time intervals of symptom recurrence and revision surgery, strategies for conservative treatment and revision surgery, operative time, imaging characteristics, numeric rating scale (NRS) score, Oswestry disability index (ODI) and overall outcome rating based on modified MacNab criteria were analyzed. RESULTS: Fourteen patients (males = 10, females = 4), with a mean age of 24.4 years, were enrolled. The mean time intervals of symptom recurrence and revision surgery were 43.5 and 18.9 days respectively. While the patients were conservatively managed with analgesics and physical therapy, pain persisted or progressively worsened. In comparison to the initial herniated disc, the PP was larger in 11 cases, and up- or down-migrated in four cases. The PP location included the lateral recess (n = 12), foraminal (n = 1), and centrolateral (n = 1) zones. One of the two cases treated by percutaneous aspiration (PA) was eventually treated by FELD as pain was not relieved. Follow-ups revealed an improved mean NRS score from 7.1 to 1.4, mean ODI from 68.6 to 7.9% and promising overall surgical outcomes. CONCLUSIONS: The progressively severe pain experienced due to PP might be a result of its enlargement or migration to the lateral recess and foraminal zones. As complete removal of capsule is the goal, we recommend FELD instead of PA.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Adulto , Discotomia/efeitos adversos , Discotomia/métodos , Discotomia Percutânea/efeitos adversos , Discotomia Percutânea/métodos , Endoscopia/efeitos adversos , Endoscopia/métodos , Feminino , Humanos , Deslocamento do Disco Intervertebral/etiologia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Dor/etiologia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Genomics ; 113(4): 2032-2044, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33915245

RESUMO

Endometrial cancer (EC) is a common female reproductive tumor worldwide. Nonetheless, the pathogenesis of EC still remains ambiguous and associated epigenetic mechanism still to be explored. The goal of this study is to investigate whether gene methylation signature is associated with overall survival (OS) for EC patients. In this study, a 10-gene methylation risk model was built and the OS in high- and low-risk groups was significant different. The area under the ROC curve (AUC) of this model was 0.856 at 5 years survival. The nomogram could accurately predict the OS in EC patients, with concordance index and AUC at 5 year survival reached 0.796 and 0.792, respectively. Furthermore, we verified the nomogram with 24 patients in our center and the Kaplan-Meier survival curve also proved to be significantly different (p < 0.01). WGCNA revealed a key gene group for the model and further bioinformatics analysis indicated 6 genes as the hub genes in the module. Knockdown of MMP12 inhibited the proliferation, invasion and metastasis of EC cells. After all, a methylation signature and a nomogram based on this signature were constructed, and they could both predict survival in patients with EC. Moreover, WGCNA model identified MMP12 as a potential target for the treatment of EC.


Assuntos
Biomarcadores Tumorais , Neoplasias do Endométrio , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metilação , Prognóstico
16.
Int Orthop ; 46(8): 1767-1774, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35513549

RESUMO

PURPOSE: Hallux valgus is a common disease which causes pain and dysfunction of the foot. Although numerous methods of procedures have been introduced, a single procedure cannot correct all deformities of hallux valgus. The study aims to evaluate the radiographic and clinical effectiveness of a new minimally invasive surgery (MIS) versus open Chevron-Akin procedures. METHODS: This was a retrospective comparative study. Data were collected from May 2018 to January 2020. A total of 27 patients (31 feet) undergoing MIS for hallux valgus were included in this study. The average age of patients underwent MIS was 59.9 years. The mean follow-up was 25.1 months. Open osteotomies were performed in 30 patients (31 feet) during the same period. The mean age of these patients at the time of surgery was 59.1 years. The mean follow-up was 26.1 months. Pre-operative and post-operative radiographic outcome measures included HVA, IMA, DMAA, the Sgarlato's angle and the length of the first metatarsal, and distance between the dorsal cortex of first and second metatarsal necks. The AOFAS and VAS were used to assess foot function. RESULTS: The preoperative HVA in MIS group and open group were 34.8° and 33.1° respectively. The post-operative HVA were 20.4° and 13.7°. The pre-operative IMA in MIS group and open group were 13.0° and 12.1°. The post-operative IMA were 11.4° and 5.5° respectively. The pre-operative DMAA were 14.8° and 15.1° respectively. The post-operative DMAA were 6.3° and 8.7°. The AOFAS increased from 44.0 to 90.2 in MIS group and from 47.6 to 89.5 in open group. The VAS decreased from 7.3 to 1.3 in MIS group and from 7.1 to 1.2 in open group. CONCLUSION: Although open osteotomies were superior than MIS in HVA and IMA, MIS showed advantages in correcting DMAA. MIS provided equivalent functional outcomes compared to open surgery.


Assuntos
Hallux Valgus , Ossos do Metatarso , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Osteotomia/efeitos adversos , Osteotomia/métodos , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
17.
J Environ Manage ; 306: 114495, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35038670

RESUMO

Accelerating the development of renewable energy is seen as an effective way for achieving the goals of carbon peak and carbon neutrality. The polices of Renewable Electricity Standard (RES) and Renewable Energy Certificates (REC) play increasing and important roles in developing renewable energy. In this paper, we develop an analytical model to analyze the impacts of the interaction of RES and REC polices on the renewable energy investment levels of an electricity generation firm and the carbon emissions. Our analysis reveals several interesting insights. First, we find that the green tags price under REC policy has a non-monotonic effect on the renewable energy investment, which highly depends on the quota (i.e., the required percentage of renewable electricity consumption on total electricity consumption) under the RES policy. Specifically, when the quota in RES policy is set too high, an increase in the green tags price will increase renewable energy investment; otherwise it will reduce the electricity generation firm's incentive to invest in renewable energy. Second, we show that the green tags price also has a non-monotonic effect on the carbon emissions. Specifically, when the quota in RES policy is set small enough, an increase in the green tags price will decrease the carbon emission. However, when the quota in RES policy is high enough, an increase in the green tags price will increase the carbon emission.


Assuntos
Dióxido de Carbono , Carbono , Desenvolvimento Econômico , Eletricidade , Investimentos em Saúde , Energia Renovável
18.
Aesthet Surg J ; 42(10): 1175-1184, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-35468182

RESUMO

BACKGROUND: Historically, standard evaluations for photoaging have involved subjective analysis; recently, however, investigators have turned to noninvasive systems for more objective evaluation of facial aging. OBJECTIVES: The aim of this study was to establish a clinical correlation between the Glogau Photoaging Scale and the VISIA-CR Complexion Analysis System (Canfield Imaging Systems, Fairfield, NJ), and thereby reduce intra- and interobserver variability when assessing photodamage. METHODS: In total, 117 subjects aged between 18 and 89 years were included. Two-dimensional facial photographs were analyzed by 3 independent reviewers and assigned Glogau scores. Images were also captured and analyzed with VISIA software. Data were grouped by median Glogau score and compared between groups. RESULTS: All groups were statistically different (P < 0.05) for Spots, Wrinkles, and Remasked Wrinkles, except for Glogau 1 and 2 for Spots and Remasked Wrinkles. Scores for Wrinkles were plotted against age, and an exponential regression model was noted to be a better fit (R2 = 0.5) than a linear model (R2 = 0.47). The same was true for Spots with an exponential model (R2 = 0.36) compared with a linear model (R2 = 0.33). Scores were also evaluated based on sun exposure history, but no significant differences were observed. CONCLUSIONS: The results illustrate that an imaging system can be used to reliably determine objective scores correlating to Glogau photoaging evaluations, and indicate that aging appears to be an exponential process. Collectively, these findings will assist future investigations of facial aging and the therapeutic options available for facial skin rejuvenation, and enable objective assessment of treatment outcomes.


Assuntos
Envelhecimento da Pele , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Face , Humanos , Pessoa de Meia-Idade , Rejuvenescimento , Pele , Resultado do Tratamento , Adulto Jovem
19.
Reprod Biol Endocrinol ; 19(1): 118, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344384

RESUMO

BACKGROUND: Fertility-sparing therapy is an alternative conservative treatment for patients with early stage endometrioid cancer or atypical endometrial hyperplasia. In this study, we investigated pregnancy outcomes and pregnancy-associated factors in young patients receiving hormonal therapy. METHODS: We retrospectively analyzed 68 patients who attempted to conceive after fertility-sparing therapy and achieving complete remission (CR). They were divided into a pregnancy group and a non-pregnancy group. A Cox proportional hazard regression model was applied for univariate and multivariate analysis to determine factors associated with pregnancy. Kaplan-Meier analysis, combined with the log-rank test, was used to calculate a patient's pregnancy probability and the distribution of recurrence-free survival (RFS). RESULTS: A total of 36 patients became pregnant with 47 pregnancies. Univariate and multivariate Cox analysis revealed that several factors were associated with pregnancy, including BMI at the time of pregnancy permission, the time to CR, prolonged treatment time, the number of hysteroscopy procedures, the endometrium thickness after CR, and relapse before pregnancy. The mean RFS of patients who achieved pregnancy, and those who did not, was 27.6 months and 14.8 months, respectively (P = 0.002). No significant difference was detected in terms of cumulative RFS when compared between assisted reproductive technology (ART) cases and those involving natural conception (NC) (P = 0.707). CONCLUSIONS: Normal BMI, a shorter time to CR, a prolonged three-month treatment, fewer hysteroscopy procedures, and a thicker endometrium may be positive indicators for successful pregnancies, while relapse before pregnancy may have a negative effect on conception. Moreover, a successful pregnancy protects the endometrium while ART does not increase the risk of recurrence.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Taxa de Gravidez , Progestinas/uso terapêutico , Adulto , Índice de Massa Corporal , Carcinoma Endometrioide/patologia , Intervalo Livre de Doença , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Preservação da Fertilidade , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Gravidez , Resultado da Gravidez , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Técnicas de Reprodução Assistida/estatística & dados numéricos , Estudos Retrospectivos , Útero
20.
Macromol Rapid Commun ; 42(20): e2100362, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34435714

RESUMO

The treatment of large segmental bone defects and complex types of fractures caused by trauma, inflammation, or tumor resection is still a challenge in the field of orthopedics. Various natural or synthetic biological materials used in clinical applications cannot fully replicate the structure and performance of raw bone. This highlights how to endow materials with multiple functions and biological properties, which is a problem that needs to be solved in practical applications. Hydrogels with outstanding biocompatibility, for their casting into any shape, size, or form, are suitable for different forms of bone defects. Therefore, they have been used in regenerative medicine more widely. In this review, versatile hydrogels are compounded with nanoparticles of different dimensions, and many desirable features of these materials in bone regeneration are introduced, including drug delivery, cell factor vehicle, cell scaffolds, which have potential in bone regeneration applications. The combination of hydrogels and nanoparticles of different dimensions encourages better filling of bone defect areas and has higher adaptability. This is due to the minimally invasive properties of the material and ability to match irregular defects. These biological characteristics make composite hydrogels with different dimensional nanoparticles become one of the most attractive options for bone regeneration materials.


Assuntos
Hidrogéis , Nanopartículas , Materiais Biocompatíveis , Regeneração Óssea , Engenharia Tecidual
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