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Introduction: Salt stress is a major environmental factor that constrains soybean growth, development, and productivity. Flavonoids are key secondary metabolites that play a crucial role in enhancing plant resistance to both biotic and abiotic stress. However, a comprehensive understanding of the regulatory mechanisms underlying flavonoid biosynthesis under salt stress in soybean is lacking. Methods: In this study, an integrative analysis of soybean metabolome and transcriptome was conducted using two soybean lines, FQ03 (salt-sensitive, SS) and FQ07 (salt-tolerant, ST). Results: A total of 650 significantly changed metabolites were identified in SS and ST after salt stress treatment. Among them, 151 flavonoids were categorized into nine classes, with flavones and flavonols being the predominant flavonoid types in soybean. Heatmap analysis showed higher contents of most flavonoid metabolites in ST than in SS under salt stress, and the total flavonoid content in ST was significantly higher than that in SS. In addition, transcriptome analysis revealed a higher number of differentially expressed genes (DEGs) in ST than in SS under salt stress. KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways related to phenylpropanoid biosynthesis, isoflavonoid biosynthesis, flavonoid biosynthesis, as well as flavone and flavonol biosynthesis. Notably, 55 DEGs that were mapped to the flavonoid biosynthetic pathway were identified, with most showing higher expression levels in ST than in SS. Weighted gene correlation network analysis identified eight structural genes and six transcription factor genes as key regulators of flavonoid biosynthesis within the blue module. Furthermore, qRT-PCR results confirmed the accuracy of the transcriptomic data and reliability of the identified candidate genes. Discussion: This study provides insights into the regulatory mechanisms underlying salt stress responses in soybean and highlights hub genes as potential targets for developing salt-tolerant soybean varieties.
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BACKGROUND: One popular and well-established marker for the immune checkpoint blockade (ICB) response is tumor mutation burden (TMB). Persistent TMB (pTMB), a subset of TMB, provides a better indicator to predict patient ICB therapy outcomes, as shown by some studies. Immune checkpoint drugs have significantly changed how melanoma is treated in recent years. METHODS: In this study, we integrated the TCGA-SKCM database and data of pTMB of TCGA from the paper that first mentioned pTMB and analyzed mutational and Immune characteristics associated with pTMB level in SKCM. Next, the predictive DEGs were identified the subgroups of pTMB by Cox regression and LASSO analyses to construct a pTMB-related signature. Finally, the expression and Biological functions of signature genes was detected, and further validated in vitro assay. RESULTS: In the current research, we explored the mutational and immunological features related to the level of TMB in cutaneous melanoma (CM). The high-pTMB subgroup exhibited an increasing incidence of gene changes and higher levels of immune cell infiltration. Subsequently, we established a pTMB-related signature based on the predictive DEGs and found the biological features and immune-associated variables between two distinct risk groups. Lastly, the results of the clinical sample validation demonstrated that the expression of IL17REL was down-regulated in the collected samples of individuals with CM. The in vitro assay results indicated that IL17REL effectively suppressed the proliferation, clonality, and migration of CM cells. CONCLUSION: In conclusion, we have developed a prediction model associated with TMB and subsequently validated the potential influence of IL17REL on Overall Survival (OS) in patients diagnosed with melanoma.
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Melanoma , Mutación , Neoplasias Cutáneas , Humanos , Melanoma/genética , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/inmunología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inmunología , Pronóstico , Biomarcadores de Tumor/genética , Femenino , Melanoma Cutáneo Maligno , Masculino , Interleucina-17/genética , Persona de Mediana EdadRESUMEN
Purpose: The large resection area of perianal tumor makes the skin defect hard to reconstruct. The keystone flap has demonstrated a growing application in skin defects. Herein, we aimed to explore the efficacy of keystone flap in the repair of skin defect after perianal tumor resection. Methods: This study is a retrospective review of patients diagnosed with perianal tumor from January 2010 to November 2021. A standardized data collection template was used to collect variables. The detailed process of the reconstructive surgery is carefully described in this article. After surgery, the healing process was closely observed. Results: Twenty patients underwent keystone flap repair. The average wound size before closure measured 3.5 × 4.9 cm2. Primary wound healing was achieved, and the flap survived during the follow up period, which ranged from 6 to 24 months. No severe complications occurred; slight edema was noticed in one patient. Conclusion: The application of keystone flap is a promising way to repair skin defect after tumor removal, and the complications rate was low after surgery. It can be concluded that this method is an effective and reliable way to repair perianal skin defect.
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BACKGROUND: As a key regulatory enzyme in the glycolysis pathway, pyruvate kinase (PK) plays crucial roles in multiple physiological processes during plant growth and is also involved in the abiotic stress response. However, little information is known about PKs in soybean. RESULTS: In this study, we identified 27 PK family genes against the genome of soybean cultivar Zhonghuang13. They were classified into 2 subfamilies including PKc and PKp. 22 segmental duplicated gene pairs and 1 tandem duplicated gene pair were identified and all of them experienced a strong purifying selective pressure during evolution. Furthermore, the abiotic stresses (especially salt stress) and hormone responsive cis-elements were present in the promoters of GmPK genes, suggesting their potential roles in abiotic stress tolerance. By performing the qRT-PCR, 6 GmPK genes that continuously respond to both NaCl and ABA were identified. Subsequently, GmPK21, which represented the most significant change under NaCl treatment was chosen for further study. Its encoded protein GmPK21 was localized in the cytoplasm and plasma membrane. The transgenic Arabidopsis overexpressing GmPK21 exhibited weakened salinity tolerance. CONCLUSIONS: This study provides genomic information of soybean PK genes and a molecular basis for mining salt tolerance function of PKs in the future.
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Arabidopsis , Piruvato Quinasa , Glycine max/genética , Cloruro de Sodio , Genes Duplicados , Arabidopsis/genéticaRESUMEN
BACKGROUND: Pilonidal sinus disease (PSD), a chronic inflammatory disease, affects the sacrococcygeal soft tissue, especially in young adults. The ideal treatment for PSD remains divergence. This study evaluated the application of a simplified modified Limberg flap combined with vacuum-assisted closure for treating PSD. METHODS: This prospective study was conducted from 1 June 2017 to 31 March 2022 in Changhai Hospital, Naval Military Medical University, Shanghai, China. The study included 88 male patients (91.7%) and 8 female patients (8.3%). The 96 patients ranged in age from 15 to 34 years (mean ± SD, 23 ± 4.4). Under general anaesthesia, all patients underwent simplified modified Limberg flap reconstruction with vacuum-assisted closure. The patient's weight, surgical time, extubation time, hospital stay, time to return to normal life or work, wound infection, wound dehiscence and recurrence rate were recorded. The visual analogue scale (VAS) score and the Vancouver scar score were used to score patients' pain and scars in the surgical area. RESULTS: The volume of resected diseased tissue was 13.5-120 (mean ± SD, 34.993 ± 24.406) cm2 . The average surgical time during the treatment period was 97.68 ± 18.72 min, and the average extubation time was (6.36 ± 1.55) days, the mean hospital stay was 19.4 days; no patients were lost to follow-up. None of the patients experienced post-operative recurrence, wound infection, seroma or hematoma. Six patients (6.3%) experienced wound dehiscence at the flap tip around the natal cleft. The mean time to the resumption of daily activities was 26.3 days. The average VAS pain score was (6.00 ± 1.53) points, and the average Vancouver scar score was (5.96 ± 1.51) points, 12 patients (12.5%) were dissatisfied with their aesthetic results, and the average beauty satisfaction score is (6.64 ± 1.28) points. CONCLUSIONS: Simplified modified Limberg flap reconstruction with vacuum-assisted closure surgery is an effective and innovative method for the treatment of PSD, with a low recurrence rate and rapid recovery.
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Terapia de Presión Negativa para Heridas , Seno Pilonidal , Enfermedades de la Piel , Infección de Heridas , Adulto Joven , Humanos , Masculino , Femenino , Adolescente , Adulto , Cicatriz , Seno Pilonidal/cirugía , Estudios Prospectivos , China , Recurrencia Local de Neoplasia , Complicaciones Posoperatorias , Dolor , Recurrencia , Resultado del TratamientoRESUMEN
PURPOSE: Cancer vaccine (CV) has thrived as a promising tool for cancer prevention and treatment. However, how to maintain the integrity and diversity of individualized vaccine antigens and activate the adaptive immune system is still challenging. METHODS: Herein, a preventive and therapeutic vaccine platform for in situ effective multi-model synergistic therapy is developed. In our study, we process B16F10 cells by liquid nitrogen frozen (LNF) to obtain LNF cells, the characterization of LNF cells were conducted. Moreover, the anti-tumor effect and immune activation ability were studied, and the role as a CV were investigated. RESULTS: The LNF cells preserve intact cellular structure and tumor-associated self-antigen gp100. Moreover, LNF cells have the ability of loading and releasing doxorubicin (DOX). Except for the anti-tumor effect of chemotherapy brought by DOX, the LNF cells can promote the maturation of dendritic cells (DCs) and induce immune response by activating CD4+ and CD8+ T cells, particularly with the existence of adjuvant, R848. Specifically, the CD8+ T cells of mice in LNF-DOX/R848 group are 6 times of that in PBS group in tumor microenvironment, and twice in spleen. Therefore, LNF cells can also be utilized as a CV. Vaccination with LNF/R848 cells effectively suppress the tumor growth in mice by fivefold as compared to the control group. CONCLUSION: In this work, we obtain the LNF cells with a simple procedure. The LNF cells not only provides a tumor cells-based multi-modal system for cancer therapy but inspires new insights into future development of individualized CVs strategies. This study processes live B16F10 cells by liquid nitrogen frozen to obtain LNF cells, which preserve cell integrity and homologous targeting ability. The LNF cells can load and deliver drug and can serve as tumor vaccine. Results demonstrated the LNF cells have effective prophylactic ability, and ideal anti-tumor ability with the loaded drug and adjuvant.
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OBJECTIVE: We aimed to introduce and evaluate the safety of double-layer-vacuum-assisted closure (DL-VAC) therapy with flap repair of the wound near the eyes or ears. METHODS: This study is case reports of 2 patients who underwent DL-VAC therapy for tissue defects near the eyes or ears. The detailed process of the DL-VAC therapy is carefully described in this study. The postoperative wound healing process was closely observed. The biggest concern was the treatment outcome of DL-VAC therapy on the eyes and ears. RESULTS: Two patients underwent DL-VAC therapy due to their soft tissue defects close to the eyes or ears. Both patients achieved primary wound healing and the flaps survived during the follow-up period, which ranged from 1 to 24 months. Patients did not receive any dressing change until the VAC device was removed on the 5th to 7th postoperative day. No severe complications appeared and the patients were satisfied with both appearance and function. CONCLUSIONS: Double-layer-vacuum-assisted closure therapy is an effective and safe option for the treatment of wounds near the eyes and ears.
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Terapia de Presión Negativa para Heridas , Humanos , Cicatrización de Heridas , Colgajos Quirúrgicos , Resultado del Tratamiento , Infección de la Herida Quirúrgica/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: This study sought to analyse the impact of elderly age on long-term prognosis of superficial spreading melanoma (SSM) after surgery. METHODS: A population-based cohort of patients undergoing resection for SSM from 2004 to 2015 was collected, using data from National Cancer Institute' Surveillance, Epidemiology, and End Results (SEER)* Stat software. Patients were divided into the non-elderly group (≤70 years) and elderly group (>70 years). Baseline characteristics and long-term survivals were compared between the two groups. A 1:1 propensity score matching (PSM) was used to reduce the risk of bias. The impact of the elderly age on overall survival (OS) and cause-specific mortality (CSM) was estimated by Cox-regression and competing-risk regression models. RESULTS: Among 12 536 patients with SSM after resection included into the cohort, 8664 patients were ≤70 years, and 3872 were >70 years. Patients in the elderly group had higher incidences of multiple tumours, worse tumour stage and infiltration degree, lymphatic metastasis, and larger size of primary lesions. Using PSM, 3581 pairs of patients were created. On matched analysis, the elderly group was associated with worse OS and CSM. On multivariable Cox-regression and competing-risk regression analyses, elderly age was identified as an independent risk factor of OS and CSM after adjusting for other prognostic variables. CONCLUSIONS: The elderly age of patients was independently associated with worse OS and CSM after resection of SSM when baseline and tumour characteristics were balanced. Adjuvant therapy and individualized strategy on follow-up should be made for elderly patients after resection of SSM.
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Melanoma , Neoplasias Cutáneas , Humanos , Persona de Mediana Edad , Pronóstico , Neoplasias Cutáneas/patología , Melanoma/patología , Terapia Combinada , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Vaginal agenesis is a rare condition worldwide. Most reported cases were accompanied by the absence of uterus or uterine hypoplasia; for patients with functional endometrium, hysterectomy was most likely to be conducted to lower postoperative complications. OBJECTIVE: Based on our successful experience in vaginoplasty with autologous buccal mucosal, the purpose of this article is to discuss the surgical strategies in the reconstruction of neovaginal for vaginal agenesis patients with functional uterus and cervical hypoplasia. METHODS: The uterus was preserved in our procedure, and the cervicoplasty was performed to connect the uterine cavity with the neovagina. After the vaginal cavity was formed, the cervix was confirmed and fixed. With the assistance of laparoscope, the direction and angle of the cervix and the uterine body were observed and confirmed. An incision was made in cervix to connect the uterine cavity, and a Foley's catheter was inserted. The newly formed opening of cervix and neovagina was covered by autologous buccal mucosal. RESULTS: The connection between neovagina and cervix uteri was successfully conducted in patient with functional uterus. Unimpeded and regular menstrual was achieved, and the cyclic abdominal pain was disappeared. No complications were observed. CONCLUSION: For patients without functional uterus, vaginoplasty with autologous buccal mucosal can be conducted. However, fertility-preserving surgery should be the primary choice in patients with functional endometrium. It can be concluded from our experience that the utero-vaginal connection with the assistance of laparoscope and the use of autologous buccal mucosa is a promising way to achieve ideal outcomes.
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Procedimientos de Cirugía Plástica , Vagina , Cuello del Útero/anomalías , Cuello del Útero/cirugía , Anomalías Congénitas , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Procedimientos de Cirugía Plástica/métodos , Útero/anomalías , Útero/cirugía , Vagina/anomalías , Vagina/cirugíaRESUMEN
It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).
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Angina Estable/tratamiento farmacológico , Fármacos Cardiovasculares/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Adolescente , Adulto , Anciano , Angina Estable/genética , Angina Estable/patología , Método Doble Ciego , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Ovarian carcinoma (OC) is considered among the most prevalent triggers of cancer-related deaths in women. Many studies have demonstrated that human epididymis protein 4 (HE-4) as well as cancer antigen 125 (CA-125) are over-expressed in various malignant tumors, such as lung, liver, endometrial, gastric, breast, as well as ovarian cancers. Nonetheless, the overall diagnostic value of serum HE-4, in addition to CA-125 n patients experiencing OC, is still largely undetermined. Therefore, the current study intends to investigate the general diagnostic significance of HE-4 along with CA-125 in patients with OC. METHODS: We aim to systematically search retrospective or prospective study for potential eligible studies from electronic databases, such as MEDLINE, EMBASE, Cochrane Library, Web of Science, as well as Chinese National Knowledge Infrastructure. We will relevant articles evaluating the general diagnostic significance of HE-4 and CA-125 in patients with OC from these databases. We will define our search in English and Chinese. Likewise, we will use 2 independent authors to extract the required data, using the Quality Assessment of Diagnostic Accuracy Studies-2 tool to evaluate he procedural quality of all included literature. We will use the appropriate statistical method to complete data analyses. RESULTS: The present study aims to investigate the general diagnostic significance of HE-4 and CA-125 in patients suffering from OC. CONCLUSION: The present study will systematically summarise current evidence of HE-4 in combination with CA-125 in relation to diagnosing OC. ETHICS AND DISSEMINATION: Ethical approval will not be required. PROTOCOL REGISTRATION NUMBER: DOI 10.17605/OSF.IO/YQPC7 (https://osf.io/yqpc7/).
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Biomarcadores de Tumor/sangre , Antígeno Ca-125/sangre , Carcinoma/diagnóstico , Proteínas de la Membrana/sangre , Neoplasias Ováricas/diagnóstico , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/análisis , Carcinoma/sangre , Femenino , Humanos , Metaanálisis como Asunto , Neoplasias Ováricas/sangre , Estudios Prospectivos , Estudios Retrospectivos , Revisiones Sistemáticas como AsuntoRESUMEN
MiR-206 is abnormally expressed in infant hemangioma endothelial cells (HemECs), but the mechanism is not clear. We explored the intervention of miR-206 in HemECs in relation to extracellular matrix (ECM) metabolism. We selected 48 cases of infantile hemangioma (IH) from volunteer organizations. After the isolated and extracted HemECs were interfered with overexpressed or silenced miR-206, the effects of miR-206 on the proliferation, migration and invasion of HemECs were examined through basic cell function experiments. The expression differences of miR-206, DNA Methyltransferase 3A (DNMT3A) and ECM-related genes were analyzed as needed by qRT-PCR or Western blot. TargetScan and dual-luciferase experiments were applied to predict and confirm the binding relationship between miR-206 and DNMT3A. The correlation between miR-206 and DNMT3A was analyzed in IH tissues by Pearson correlation coefficient, and further confirmed in HemECs by conducting rescue experiments. A nude mouse model of xenograft tumor was constructed to verify the results of in vitro experiments. MiR-206, which was downregulated in proliferative hemangioma, suppressed the malignant development of HemECs by regulating ECM-related genes. As the target gene of miR-206, DNMT3A was high-expressed in IH tissues and was negatively correlated with miR-206. Overexpressed DNMT3A counteracted the inhibitory effect of miR-206 mimic on HemECs and its regulatory effect on ECM. The results of in vivo experiments were consistent with those from cell experiments. Thus, miR-206 could promote ECM accumulation through targeted inhibition of DNMT3A, further inhibiting the malignant development of HemECs and relieving IH.
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ADN Metiltransferasa 3A/metabolismo , Matriz Extracelular/metabolismo , Hemangioma/enzimología , Hemangioma/genética , MicroARNs/metabolismo , Animales , Secuencia de Bases , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Regulación hacia Abajo/genética , Xenoinjertos , Humanos , Lactante , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: We aimed at evaluating the effects of hydrosurgery and traditional surgical approach with two parallel incisions in the treatment of osmidrosis. METHODS: This prospective study enrolled patients with axillary osmidrosis between January 2015 and November 2016. For hydrosurgery, a 1-cm-long incision was made in the middle of the posterior long axis. The hand piece was turned upside down and processed in a 'W-O' way. For traditional method, two 3-cm-long parallel incisions were made transversely. Patient demographics, complications, duration of procedures and the outcomes were collected and compared. All patients had a follow-up period of 24-36 months. RESULTS: A total of 93 patients were included: 41 patients in hydrosurgery group and 52 patients in traditional method group. No severe complications occurred in the hydrosurgery group, while necrosis occurred in six sides of axillae of traditional surgical group. No recurrence occurred in both groups. Both groups showed similar odor and hair growth reduction rate. Only one in 82 sides occurred slight scar formation, while in traditional group, 22 sides of axillae formed scars (p < .001). CONCLUSIONS: The application of hydrosurgery in the treatment of osmidrosis is efficient and effective. Moreover, it has less postoperative complications, and high patient satisfaction rates.
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Glándulas Apocrinas/cirugía , Hiperhidrosis/cirugía , Adolescente , Adulto , Cicatriz/complicaciones , Femenino , Hematoma/etiología , Humanos , Masculino , Complicaciones Posoperatorias , Estudios Prospectivos , Adulto JovenRESUMEN
Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its bio-function remains unknown. In this study, we found that miR-200b-3p was down-regulated in melanoma tissues and cell lines compared to benign nevus cells. Overexpression of miR-200b-3p significantly inhibited the proliferation and invasion of melanoma cells. According to bioinformatics analysis and sequencing data, we supposed that SMAD family member 2 (SMAD2) was the target gene and nuclear enriched abundant transcript 1 (NEAT1) was the upstream long non-coding RNA (lncRNA) of miR-200b-3p. These predictions were verified by western blotting and quantitative real-time reverse transcription PCR (RT-qPCR). Luciferase reporter assays revealed that NEAT1 up-regulated SMAD2 by directly sponging miR-200b-3p. In vitro and in vivo, we demonstrated that both NEAT1 and SMAD2 could promote the proliferation and invasion of melanoma cells, and these effects were reversed by up-regulating miR-200b-3p. In addition, NEAT1/miR-200b-3p/SMAD2 axis promoted melanoma progression by activating EMT signaling pathway and immune responses. Taken together, the NEAT1/miR-200b-3p/SMAD2 signaling pathway promotes melanoma via activation of EMT, cell invasion and is related with immune responses, which provides new insights into the molecular mechanisms and therapeutic targets for melanoma.
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Melanoma/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias Cutáneas/metabolismo , Proteína Smad2/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Bases de Datos Genéticas , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Humanos , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , MicroARNs/genética , Invasividad Neoplásica , ARN Largo no Codificante/genética , Transducción de Señal , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Proteína Smad2/genéticaRESUMEN
BACKGROUND: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients. METHODS: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy. RESULTS: A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1-10.2]; P=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1-24.4]). The incidence of adverse events was low in both groups. CONCLUSIONS: The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.
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Anticoagulantes/uso terapéutico , Pueblo Asiatico/genética , Fibrilación Atrial/tratamiento farmacológico , Trombosis de la Vena/tratamiento farmacológico , Warfarina/uso terapéutico , Anciano , Anticoagulantes/efectos adversos , Fibrilación Atrial/genética , China , Citocromo P-450 CYP2C9/genética , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Genotipo , Hemorragia/etiología , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Método Simple Ciego , Resultado del Tratamiento , Trombosis de la Vena/genética , Vitamina K Epóxido Reductasas/genética , Warfarina/efectos adversosRESUMEN
BACKGROUND: Vaginal agenesis, a rare condition, is treated by various surgical techniques to achieve neovaginal reconstruction. The main difference between the approaches lies in the graft material used to cover the newly formed cavity. OBJECTIVES: The purpose of this retrospective study was to describe the surgical procedure and outcomes of autologous buccal mucosal grafting in neovaginal reconstruction. METHODS: Sixteen patients with vaginal agenesis admitted to our department between January 2016 and January 2019 were included in our study. A reconstruction procedure, described in detail here, involving autologous buccal mucosa as graft material was successfully conducted in all of the patients. Long-term anatomic and functional outcomes were evaluated. RESULTS: The blood loss during operation was estimated to be 15 to 20 mL in all cases. No rectal or bladder injury occurred. The buccal mucosal wound completely healed 10 to 14 days after the operation. All patients had a well-formed neovagina 8 to 10 cm in length, with a mean diameter of >3 finger-breadths. CONCLUSIONS: The application of autologous buccal mucosa in neovaginal construction is a simple procedure. Autologous buccal mucosa is an ideal material to achieve excellent cosmetic and functional results in patients with vaginal agenesis.
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Mucosa Bucal , Procedimientos de Cirugía Plástica , Anomalías Congénitas , Femenino , Humanos , Mucosa Bucal/cirugía , Estudios Retrospectivos , Mallas Quirúrgicas , Vagina/anomalías , Vagina/cirugíaRESUMEN
Modulating the surface properties of nanoparticles (NPs) is an important approach to accomplish immune escape, prolonged the blood retention time, and enhance the ability of targeted drug delivery. The camouflage of cancer cell membrane onto nanoparticles has been proved to be an ideal approach to enhance active targeting ability of NPs. Herein, we isolated the membrane of melanoma cells to coat doxorubicin (DOX) and indocyanine green (ICG)-loaded hollow copper sulfide NPs (ID-HCuSNP@B16F10) for targeted photothermal therapy, photoacoustic imaging, and chemotherapy. A remarkable in vitro anticancer effect after irradiation and homologous targeting can be observed in B16F10 cells after the treatment of ID-HCuSNP@B16F10. Moreover, ID-HCuSNP@B16F10 exhibits excellent photothermal effect in melanoma animal models and achieves a high tumor ablation rate. This biomimetic system can realize high drug loading efficiency, enhanced targeting ability, and ideal antitumor efficiency.
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Melanoma Experimental/terapia , Nanopartículas/química , Técnicas Fotoacústicas , Terapia Fototérmica , Animales , Biomimética , Membrana Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cobre/química , Cobre/farmacología , Diagnóstico por Imagen , Quimioterapia , Humanos , Melanoma Experimental/diagnóstico por imagen , Melanoma Experimental/patología , Ratones , Nanopartículas/uso terapéutico , Propiedades de Superficie/efectos de los fármacosRESUMEN
OBJECTIVE: We compared the application of artificial dermis composite tissue flaps and traditional prefabricated flaps in a rat model of exposed bone and tendon injury. METHODS: Sprague Dawley rats were randomly divided into two groups (n = 40 per group). Group A rats received artificial dermis composite tissue flaps and group B rats received traditional prefabricated flaps. Flap appearance, range of motion, degree of swelling, tissue histologic results, and imaging findings were compared between groups at 7, 14, 21, and 28 days. RESULTS: There was no difference in flap appearance, range of motion, or degree of swelling between groups. However, blood perfusion of the artificial dermis composite tissue flap was better than that of the traditional prefabricated flap; the artificial dermis was also found to be thicker than the traditional prefabricated flap. CONCLUSIONS: The artificial dermis composite tissue flap is an ideal method for repairing exposed bone and tendon, and it displays repair effects comparable with those of the traditional prefabricated flap and may be a better alternative.