Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 321
Filtrar
1.
Small ; : e2005752, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544971

RESUMO

Aromatic imides are a class of attractive organic materials with inherently electroactive groups and large π electron-deficient scaffolds, which hold potential as electrode materials for organic secondary batteries (OSBs). However, the undecorated aromatic imides are usually plagued by low capacity, high solubility in electrolyte, and poor electronic/ionic conductivity. Molecular engineering has been demonstrated to be an effective strategy to address unsatisfying characteristics of the aromatic imides, thereby expanding their scope for applications in OSBs. In this review, the recent research progress in modulation of the capacity, dissolution, and electronic/ionic conductivity of aromatic imides for organic lithium batteries, organic sodium batteries, and redox flow batteries are summarized. In addition, the challenge and prospective of aromatic imides in organic secondary battery applications are also discussed.

3.
J Immunol Res ; 2021: 8132569, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506062

RESUMO

Objective: To explore the correlation of indoleamine-2,3-dioxygenase (IDO) and chronic kidney disease (CKD). Methods: A total of 154 CKD patients and 42 non-CKD patients were recruited. Patients were grouped into ACR1~ACR3 (<30 mg/g, 30-300 mg/g, and >300 mg/g). Biomarkers in different groups were compared by ANOVA. Correlation was calculated by Pearson or Spearman analysis and binary logistic regression. The ROC curve was also performed. Results: The levels of albumin, serum creatinine (sCr), and IDO in non-CKD patients were significantly different from those in CKD3-CKD5 stages (p < 0.05). IDO was correlated with age, proteinuria, ACR, and eGFR (p < 0.01). After adjusting for CKD-related indices, ln(IDO) was an independent risk factor for CKD (3.48, p < 0.05). The analysis of ROC curve revealed a best cut-off for IDO was 0.0466 and yielded a sensitivity of 83.8% and a specificity of 75%. Hemoglobin, total protein, and albumin in the ACR1 group were significantly higher than those in the ACR2 and ACR3 groups (p < 0.01), while sCr and IDO levels were significantly lower than those in the ACR2 and ACR3 groups (p < 0.01 or p < 0.05). After adjusting for CKD-related indices, ln(IDO) was still an independent risk factor for ACR (OR = 2.7, p < 0.05). The analysis of ROC curve revealed a best cut-off for IDO was 0.075 and yielded a sensitivity of 71.9% and a specificity of 72.2%. Conclusion: IDO may be a promising biomarker to predict CKD and assess kidney function.

4.
Parkinsonism Relat Disord ; 83: 63-65, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33482438

RESUMO

Mutations in VPS16 have been identified to be responsible for generalized dystonia. We screened VPS16 variants in 53 unrelated subjects with isolated dystonia via whole-exome sequencing. A novel pathogenic frameshift mutation p.R643fs* was found in a patient with early-onset multifocal dystonia with prominent oromandibular and bulbar involvement. Our findings expanded the spectrum of VPS16-related dystonia and suggested that mutations in VPS16 should be considered in patients with progressive early-onset dystonia.

5.
Cell Death Dis ; 12(1): 88, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462182

RESUMO

Inducing autophagy and inhibiting apoptosis may provide a therapeutic treatment for atherosclerosis (AS). For the treatment of progressive AS, arsenic trioxide (ATO) has been used to coat vascular stents. However, the effect of ATO on autophagy of macrophages is still unknown. Therefore, the aims of this study were to characterize the effects and the mechanism of actions of ATO on autophagy in macrophages. Our results showed that ATO-induced activation of autophagy was an earlier event than ATO-induced inhibition of the expression of apoptosis markers in macrophages and foam cells. Nuclear transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy and promoting lysosomal biogenesis. Here, we report that ATO triggered the nuclear translocation of TFEB, which in turn promoted autophagy and autophagosome-lysosome fusion. Both the latter events were prevented by TFEB knockdown. Moreover, ATO decreased the p-AKT and p-mTOR in the PI3K/AKT/mTOR signaling pathway, thus inducing autophagy. Correspondingly, treatment with the autophagy inhibitor 3-methyladenine (3-MA) abolished the autophagy-inducing effects of ATO. Meanwhile, PI3K inhibitor (LY294002) and mTOR inhibitor (rapamycin) cooperated with ATO to induce autophagy. Furthermore, reactive oxygen species (ROS) were generated in macrophages after treatment with ATO. The ROS scavenger N-acetyl-1-cysteine (NAC) abolished ATO-induced nuclear translocation of TFEB, as well as changes in key molecules of the AKT/mTOR signaling pathway and downstream autophagy. More importantly, ATO promoted autophagy in the aorta of ApoE-/- mice and reduced atherosclerotic lesions in early AS, which were reversed by 3-MA treatment. In summary, our data indicated that ATO promoted ROS induction, which resulted in nuclear translocation of TFEB and inhibition of the PI3K/AKT/mTOR pathway. These actions ultimately promoted macrophage autophagy and reduced atherosclerotic lesions at early stages. These findings may provide a new perspective for the clinical treatment of early-stage atherosclerosis and should be further studied.

6.
Neurosci Lett ; 746: 135590, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33388357

RESUMO

INTRODUCTION: Dystonia is a movement disorder with high clinical and genetic heterogeneity. Mutations in Anoctamin-3 (ANO3) gene have been reported to cause dystonia 24 (DYT24). This study aims to clarify the spectrum and frequency of ANO3 rare variants in Chinese populations with primary dystonia and understand the clinical and genetic features of DYT24. METHODS: Sanger sequencing was used to screen all exons and exon-intron boundaries of ANO3 for rare variants in 115 primary dystonia patients. The clinical manifestations of patients with ANO3 variants in our study and previously reported literatures were further characterized. RESULTS: Four distinct variants of ANO3 (c.1127A > G, c.1235 T > A, c.1531-3T > C, c.-11G > T) were identified in six unrelated individuals. Combined with our work and literature review, a total of 35 different rare variants distributed in ANO3 were identified in 62 dystonia patients. The predominant phenotype is cranio-cervical dystonia and more than half of patients develop head/limb tremor. Most of patients presented with isolated dystonia whereas few of them showed combined dystonia. The age of onset ranged from 1 to 69 years and peaked in late adulthood, while for generalized dystonia it peaked in a young age. Half of patients with generalized dystonia experienced deep brain stimulation (DBS). And all of them showed improvement of dystonia by DBS. CONCLUSIONS: This study confirms a relatively high frequency of rare ANO3 variants in Chinese patients with dystonia and indicates that the late adulthood-onset, cranio-cervical dystonia seems to be an important feature of the ANO3 phenotype. Further functional studies are warranted to understand the role of ANO3 in dystonia.

7.
Aging (Albany NY) ; 122020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33293476

RESUMO

Dysfunction of endothelial cells (ECs) and their progenitor cells is an important feature of diabetic vascular disease. MicroRNA (miR)-139-5p is involved in inhibiting the metastasis and progression of diverse malignancies. However, the role of miR-139-5p in ECs still remains unclarified. Here we demonstrated that miR-139-5p expression was elevated in endothelial colony-forming cells (ECFCs) isolated from patients with diabetes, ECs derived from the aorta of diabetic rodents, and human umbilical vein endothelial cells (HUVECs) cultured in high glucose media. MiR-139-5p mimics inhibited tube formation, migration, proliferation, and down-regulated expression of c-jun, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF)-B, in ECFCs and HUVECs, respectively; moreover, miR-139-5p inhibitors reversed the tendency. Further, gain- and-loss function experiments and ChIP assay indicated that miR-139-5p regulate functions of ECFCs by targeting c-jun-VEGF/PDGF-B pathway. In vivo experiments (Matrigel plug assay and hindlimb ischemia model) showed that miR-139-5p downregulation further promoted ECFC-mediated angiogenesis and blood perfusion. In conclusion, diabetes-mediated high miR-139-5p expression inhibits the c-jun-VEGF/PDGF-B pathway, thus decreasing ECFCs migration, tube formation and proliferation, which subsequently reduces ECs survival. Therefore, miR-139-5p might be an important therapeutic target in the treatment of diabetic vasculopathy in the future.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33340714

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) arises in a cirrhotic, pro-angiogenic microenvironment. Inhibiting angiogenesis is a key mode of action of multikinase inhibitors and current non-cirrhotic models are unable to predict treatment response. We present a novel mouse cirrhotic model of xenotransplant that predicts the natural biology of HCC and allows personalized therapy. METHODS: Cirrhosis was induced in NOD Scid gamma mice with 4 months of thioacetamide administration. Patient derived xenografts (PDXs) were created by transplant of human HCC subcutaneously into non-cirrhotic mice and intra-hepatically into both cirrhotic and non-cirrhotic mice. The applicability of cirrhotic PDXs for drug testing was tested with 16 days of either sorafenib or lenvatinib. Treatment response was evaluated by MRI. RESULTS: 8 out of 19 (42%) human HCC engrafted in the cirrhotic model compared with only 3 out of 19 (16%) that engrafted in the subcutaneous non-cirrhotic model. Tumor vasculature was preserved in the cirrhotic model but was diminished in the non-cirrhotic models. Metastasis developed in 3 cirrhotic PDX lines and was associated with early HCC recurrence in all 3 corresponding patients (100%), compared with only 5 out of 16 (31%) of the other PDX lines, P=0.027. The cirrhotic model was able to predict response and non-response to lenvatinib and sorafenib respectively in the corresponding patients. Response to lenvatinib in the cirrhotic PDX was associated with reduction in CD34, VEGFR2 and CLEC4G immunofluorescence area and intensity (all P ≤ .03). CONCLUSIONS: A clinically relevant cirrhotic PDX model preserves tumor angiogenesis and allows prediction of response to multikinase inhibitors for personalized therapy.

9.
Risk Manag Healthc Policy ; 13: 2371-2377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173361

RESUMO

Background: Cardiovascular diseases (CVDs) are the main cause of death in patients with chronic kidney disease (CKD). Interleukin-4 (IL-4) is considered an inflammatory cytokine. However, few studies have investigated the association between serum IL-4 and cardiovascular events in CKD. This study investigated whether serum IL-4 levels were associated with an increased risk of cardiovascular (CV) events in patients with CKD. Patients and Methods: A total of 302 patients with stage 1-5 CKD were followed up for a mean of 32 (range=4-36) months for end points (CV events). Serum IL-4 levels were measured at baseline. The independent relationship between serum IL-4 and the risk of CV events was assessed with multivariate Cox regression analysis. Results: The average age of this cohort (N=302) was 65.4 years. A total of 69.9% of them were male. CV events numbered 41 (13.6%) during the follow-up period. The Kaplan-Meier analysis showed that the rate of CV events was higher in patients with CKD with IL-4 levels above the mean (126.2 pg/mL) than in those with IL-4 levels below the mean. The multivariate Cox proportional hazard analysis revealed that serum IL-4 (HR=1.650, 95% CI 1.266-2.210, P<0.001) was associated with CV events in these patients with CKD. Sensitivity analysis showed that the association between serum IL-4 and CV events was not affected by the use of anti-inflammatory medication. The significant association between higher IL-4 levels and increased risk of CV events existed in patients with CKD3-5 but not in patients with CKD1-2 by using the stratified analysis. Conclusion: Higher serum IL-4 levels were associated with an increased risk of CV events during follow-up. Elevated serum IL-4 levels may help clinicians predict early CV events in patients with CKD.

10.
J Otolaryngol Head Neck Surg ; 49(1): 79, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198806

RESUMO

BACKGROUND: Fourth branchial apparatus anomalies, are rare clinical entities, and present as complex cysts, sinuses and fistulae in the neck that can be difficult to manage. METHODS: This is a retrospective review of a series of consecutive patients with fourth branchial apparatus anomalies treated at Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, from Apr 2014 to Nov 2019. RESULTS: Ten patients with fourth branchial apparatus anomalies were identified, including 8 patients with fourth branchial fistula, and 2 patients with fourth branchial pouch sinus. There were 6 female patients and 4 male patients. Their age was from 6 years old to 39 years old (average age 20.4 years old, median age was 21 years old). All 8 fistulae were on the left side, while 2 pouch sinuses were both on the right side. Pre-operative examination with fiberoptic laryngoscope, barium swallow X-ray, CT or MRI identified internal orifice at pyriform fossa apex in 8 (80%) patients. All patients underwent challenging surgical resection by the senior author. Intra-operative direct laryngoscope confirmed or identified internal orifice in 9 (90%) patients. The tracts were all followed to the vicinity of inferior cornu of the thyroid cartilage and the cricothyroid space. Complete resection of cervical lesions and their attachment to hypopharynx were achieved in 9 cases. No complication occurred. One recurrence was detected, in the only patient whose internal orifice could not be located pre- or intra-operatively, and the hypopharyngeal attachment could not be removed. CONCLUSIONS: Direct laryngoscopy under general anesthesia is a reliable method of diagnosis for the fourth branchial apparatus anomalies. Complete surgical removal of fourth branchial apparatus anomalies, including their hypopharyngeal attachment, is the treatment of choice, and the key to prevent recurrence.

11.
Emerg Microbes Infect ; : 1-29, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232205

RESUMO

In the face of COVID-19 pandemic caused by the newly emerged SARS-CoV-2, an inactivated, Vero cell-based, whole virion vaccine candidate has been developed and entered into phase III clinical trials within six months. Biochemical and immunogenic characterization of structural proteins and their post-translational modifications in virions, the end-products of the vaccine candidate, would be essential for the quality control and process development of vaccine products and for studying the immunogenicity and pathogenesis of SARS-CoV-2. By using a panel of rabbit antisera against virions and five structural proteins together with a convalescent serum, the spike (S) glycoprotein was shown to be N-linked glycosylated, PNGase F-sensitive, endoglycosidase H-resistant and cleaved by Furin-like proteases into S1 and S2 subunits. The full-length S and S1/S2 subunits could form homodimers/trimers. The membrane (M) protein was partially N-linked glycosylated; the accessory protein 3a existed in three different forms, indicative of cleavage and dimerization. Furthermore, analysis of the antigenicity of these proteins and their post-translationally modified forms demonstrated that S protein induced the strongest antibody response in both convalescent and immunized animal sera. Interestingly, immunization with the inactivated vaccine did not elicit antibody response against the S2 subunit, whereas strong antibody response against both S1 and S2 subunits was detected in the convalescent serum. Moreover, vaccination stimulated stronger antibody response against S multimers than did the natural infection. This study revealed that the native S glycoprotein stimulated neutralizing antibodies, while bacterially-expressed S fragments did not. The study on S modifications would facilitate design of S-based anti-SARS-CoV-2 vaccines.

12.
Emerg Microbes Infect ; 9(1): 2606-2618, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33241728

RESUMO

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

13.
Environ Pollut ; 268(Pt A): 115906, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33120333

RESUMO

Fluorescence spectroscopy is a commonly used technique to analyze dissolved organic matter in aquatic environments. Given the high sensitivity and non-destructive analysis, fluorescence has recently been used to study water-soluble organic carbon (WSOC) in atmospheric aerosols, which have substantial abundance, various sources and play an important role in climate change. Yet, current research on WSOC characterization is rather sparse and limited to a few isolated sites, making it challenging to draw fundamental and mechanistic conclusions. Here we presented a review of the fluorescence properties of atmospheric WSOC reported in various field and laboratory studies, to discuss the current advances and limitations of fluorescence applications. We highlighted that photochemical reactions and relevant aging processes have profound impacts on fluorescence properties of atmospheric WSOC, which were previously unnoticed for organic matter in aquatic environments. Furthermore, we discussed the differences in sources and chemical compositions of fluorescent components between the atmosphere and hydrosphere. We concluded that the commonly used fluorescence characteristics derived from aquatic environments may not be applicable as references for atmospheric WSOC. We emphasized that there is a need for more systematic studies on the fluorescence properties of atmospheric WSOC and to establish a more robust reference and dataset for fluorescence studies in atmosphere based on extensive source-specific experiments.

14.
Int J Chron Obstruct Pulmon Dis ; 15: 2289-2295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061346

RESUMO

Background: Vascular cell adhesion molecule-1 (VCAM-1) is associated with vascular-related inflammation and atherosclerosis. This study aimed to evaluate whether VCAM-1 can be used for an indication of increased risk of CV events in patients with COPD. Methods: Serum VCAM-1 levels were measured in 163 COPD patients. All COPD patients were prospectively followed up for a median period of 48 months (range=3-54). Cox proportional hazard analysis was performed to evaluate the prognostic value of serum VCAM-1 for predicting CV events. Results: Serum VCAM-1 levels were higher in COPD patients with CV events than in those without CV events (1174.4±365.3 ng/mL vs 947.8±293.2 ng/mL; P<0.001). The logistic regression analysis revealed that serum VCAM-1 (OR=1.750; 95% CI, 1.324-2.428; P trend =0.0012) was independently associated with CVD (cardiovascular disease) history after adjusting for age, sex, BMI, current smoker, current drinker, admission systolic and diastolic BP, LVEF and laboratory measurements in patients with COPD at baseline. The Kaplan-Meier analysis demonstrated that the rate of CV events was higher in COPD patients with serum VCAM-1 levels above the median (517.3 ng/mL) than in those with VCAM-1 levels below the median. The Cox proportional hazard analysis revealed that serum VCAM-1 (HR=2.617; 95% CI, 1.673-5.328; P trend <0.001) may be an independent prognostic factor for CV events in the COPD patients. Conclusion: Our results suggested that serum VCAM-1 was significantly and independently associated with CV events in COPD patients. The inflammatory marker may help clinicians predict CV complications early.

16.
Chron Respir Dis ; 17: 1479973120940677, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32924598

RESUMO

Hospital-acquired acute kidney injury (HA-AKI) is associated with poor prognosis. In this study, we evaluated whether serum cystatin C on admission could predict AKI in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The retrospective study was conducted using data on adult inpatients with AECOPD from January 2014 to January 2017. A total of 1035 patients were included, among which 79 (7.6%) with HA-AKI were identified. Univariate and multivariate logistic regression analyses were used to investigate predictors of HA-AKI in patients with AECOPD. HA-AKI was associated with poor prognosis, and patients with HA-AKI had higher inpatient mortality (34.2% vs. 2.6%, p < 0.001). Furthermore, after adjusting for confounders, HA-AKI was an independent risk factor for inpatient mortality for patients with AECOPD (odds ratio (OR) 11.02; 95% confidence interval (CI) 4.77-25.45; p < 0.001). Four independent risk factors for HA-AKI (age, levels of urea and cystatin C, and platelet count on admission) were identified in patients with AECOPD. Cystatin C (OR 5.22; 95% CI 2.49-10.95; p < 0.001) was a significant independent predictor of AKI in patients with AECOPD. HA-AKI in patients with AECOPD could be identified with a sensitivity of 73.5% and a specificity of 75.9% (area under the curve (AUC) = 0.803, 95% CI 0.747-0.859) by cystatin C level (cutoff value = 1.3 mg/L) and with a sensitivity of 75.9% and a specificity of 82.0% (AUC = 0.853, 95% CI 0.810-0.896) using a model comprising all significant predictors. Serum cystatin C has the potential for use to predict the risk of HA-AKI in patients with AECOPD.

17.
World J Gastroenterol ; 26(31): 4589-4606, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32884219

RESUMO

BACKGROUND: Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma (ECC). However, current biliary stents that are widely used in clinical practice showed no antitumor effect. Drug-eluting stents (DESs) may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis. AIM: To develop novel DESs coated with gemcitabine (GEM) and cisplatin (CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity. METHODS: Stents coated with different drug-eluting components were prepared by the mixed electrospinning method, with poly-L-lactide-caprolactone (PLCL) as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents. Four different DESs were manufactured with four drug-loading ratios (5%, 10%, 15%, and 20%), including bare-loaded (PLCL-0), single-drug-loaded (PLCL-GEM and PLCL-CIS), and dual-drug-loaded (PLCL-GC) stents. The drug release property, antitumor activity, and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC. RESULTS: The in vitro drug release study showed the stable, continuous release of both GEM and CIS, which was sustained for over 30 d without an obvious initial burst, and a higher drug-loaded content induced a lower release rate. The drug-loading ratio of 10% was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity. All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo; in addition, the dual-loaded nanofilm (PLCL-GC) had a significantly better effect than the single-drug-loaded nanofilms (P < 0.05). No significant differences in the serological analysis (P > 0.05) or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract. CONCLUSION: This novel PLCL-GEM and CIS-eluting stent maintains continuous, stable drug release locally and inhibits tumor growth effectively in vitro and in vivo. It can also be used safely in normal porcine bile ducts. We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.

19.
Acta Otolaryngol ; 140(12): 1036-1042, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32808843

RESUMO

BACKGROUND: This study investigated the effects of reconstruction of hypopharyngeal non-circumferential defects with a submental island flap after ablation of hypopharyngeal carcinoma. OBJECTIVES: The purpose of our study was to identify advantages and limitations of the submental flap for reconstruction of non-circumferential hypopharyngeal defects. METHODS: A total of 27 patients who had stage II-IV hypopharyngeal cancer and underwent pharyngeal reconstruction with a submental flap by the senior author in both Department of Otolaryngology Head Neck Surgery, Chinese PLA General Hospital and Department of Otolaryngology Head Neck Surgery, Beijing Friendship Hospital, Capital Medical University. RESULTS: 96.3% (26/27) cases of submental island flap survived. There were two pharyngocutaneous fistulas, one recovered spontaneously, and the other was associated with flap necrosis, underwent neck debridement and flap removal. All except for one patient had decannulation of their nasogastric tube 2 weeks postoperatively. There was no evidence of a stricture or stenosis of the laryngopharynx, nor any sign of aspiration, except for one with esophageal inlet stricture caused by radiotherapy. There were two cases of obvious paraesthesia pharynges due to beard growth at the submental flap after reconstruction. 63.0% (17/27) patients are alive and 37% (10/27) have died of disease. The 3-year survival rate is 56.3% and the 5-year survival rate is 50.0%. CONCLUSION: The submental flap reconstruction for moderately sized non-circumferential hypopharyngeal defects is a recommended treatment option.

20.
JAMA ; 324(10): 951-960, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32789505

RESUMO

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Imunogenicidade da Vacina , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adolescente , Adulto , Hidróxido de Alumínio/administração & dosagem , Hidróxido de Alumínio/efeitos adversos , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Feminino , Humanos , Injeções Intramusculares , Masculino , Pneumonia Viral/imunologia , Propiolactona , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA