Search

Studies have shown that disulfiram (DSF) can combine with Cu

A porous spherical artificial nanozyme (HF-900) prepared via pyrolysis of a porous organic polymer was used as drug carrier for efficient loading and highly selective pH-responsive delivery of doxorubicin (DOX) for the tumor joint nanotherapy.

BackgroundThe effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut.MethodsSixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa β (NF-κβ), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed.ResultsThe diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κβ, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated.ConclusionChronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.

We aimed to elicit strong blinks among healthy video display terminal (VDT) users by periorbital transcutaneous electric nerve stimulation (TENS) and evaluate its impact on the tear fluid and visual task. Appropriate TENS conditions were evaluated to evoke strong blinks under minimum discomfort. Seventeen healthy VDT users with noninvasive Keratograph first breakup time (NIKf-BUT) 5-15 s and Ocular Surface Disease Index (OSDI) scores15 were recruited in this study. Before the trial, noninvasive Keratograph average breakup time (NIKa-BUT), tear meniscus height (TMH) and OSDI scores were evaluated. Before each TENS session, the volunteers played Tetris while the corresponding blink rate and Tetris scores were recorded. Then, the participants underwent 30 minutes of TENS, which evoked blinking of their right eye 20 times per minute. Tetris scores were evaluated again during TENS. The Tetris scores and corresponding blink rate were assessed after each TENS session while NIKa-BUT, TMH and OSDI scores were recorded after the third and sixth TENS sessions. We found that OSDI scores declined significantly after the sixth TENS (P = .003). The NIKa-BUT of the right eye was promoted after the sixth TENS (P = .02), and the TMH was higher after the third and sixth TENS in both eyes (P = .03, P = .03 for right eyes respectively, P = .01, P = .01 for left eyes respectively). There was no significant difference between the adjusted Tetris scores before and during TENS (P = .12). The blink rate before and after TENS were unaffected after 6 sessions (P = .61). The results indicated that periorbital TENS effectively ameliorated ocular irritation and improved tear secretion and tear film stability by eliciting strong blinks in healthy VDT users without disturbing the visual task.

Shared decision-making (SDM) is a scientific and reasonable decision-making model. However, whether physicians choose SDM is usually influenced by many factors. It is not clear whether the strained doctor–patient relationship will affect physicians' willingness to choose SDM. Through a survey by questionnaire, 304 physicians' evaluations of doctor–patient relationship (DPR) were quantified by the difficult DPR questionnaire-8. Their preferences for SDM and the reasons were also evaluated. The correlation between physicians' evaluations of DPR and their preferences for SDM were analyzed. 84.5% physicians perceived DPR as poor or strained, 53.3% physicians preferred SDM, mainly because of the influences of medical ethics and social desirability bias. Their preferences for SDM were not significantly correlated with their evaluations of DPR (P > 0.05). Physicians with different evaluations of DPR (good, poor, and strained) all had similar preferences for SDM (42.6, 56.4, and 42.9%), with no significant difference (P > 0.05). There was no correlation between physicians' evaluations of DPR and their preferences for SDM. Physicians' evaluations of poor DPR did not affect their preferences for SDM. This may be influenced by the medical ethics and social desirability bias.

The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study.To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis.This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes.A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.

Here, a novel joint chemo/photothermal/chemodynamic therapy was developed using a pH/GSH/photo triple-responsive 2D-covalent organic framework (COF) drug carriers for passive target treatment of tumors with extraordinarily high efficiency. The well-designed COF (DiSe-Por) with simultaneous dynamic diselenium and imine bonds, synthesized by the copolymerization of 4,4'-diselanediyldibenzaldehyde (DiSe) with 5,10,15,20-(tetra-4-aminophenyl)-porphyrin (Por)

Objective. A systematic review was conducted to compare the effectiveness and safety of fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF) for regeneration of the tympanic membrane (TM). Methods. The PubMed database was searched for relevant studies. Experimental and clinical studies reporting acute and chronic TM perforations in relation to two healing outcomes (success rate and closure time) and complications were selected. Results. A total of 47 studies were included. Five experimental studies showed closure rates of 55%–100% with FGF2 compared with 10%–62.5% in controls for acute perforations. Five experimental studies showed closure rates of 30.3%–100% with EGF and 3.6%–41% in controls for chronic perforations. Two experimental studies showed closure rates of 31.6% or 85.7% with FGF2 and 15.8% or 100% with EGF. Nine clinical studies of acute large perforations showed closure rates of 91.4%–100% with FGF2 or EGF. Two clinical studies showed similar closure rates between groups treated with FGF2 and EGF. Seven clinical studies showed closure rates of 88.9%–100% within 3 months and 58%–66% within 12 months using FGF2 in repair of chronic perforations, but only one study showed a significantly higher closure rate in the saline group compared with the FGF2 group (71.4% vs. 57.5%, respectively, P = 0.547 ). In addition, three experimental studies showed no ototoxicity associated with FGF2 or EGF. No middle ear cholesteatoma or epithelial pearls were reported, except in one experimental study and one clinical study, respectively. Conclusions. FGF2 and EGF showed good effects and reliable safety for the regeneration of TM. In addition, EGF was better for the regeneration of acute perforations, while FGF2 combined with biological scaffolds was superior to EGF for chronic perforations, but was associated with high rates of reperforation over time. Further studies are required to determine whether EGF or FGF2 is better for TM regeneration.

Objectives This study was performed to evaluate the efficacy of microwave ablation (MWA) eustachian tuboplasty for the treatment of patients with retracted tympanic membrane (TM) due to eustachian tube dysfunction (ETD). Methods This was a prospective study of 20 patients with ETD (middle ear atelectasis) who underwent MWA eustachian tuboplasty. Outcomes included the ability to perform a Valsalva maneuver, audiometry results, tympanometry results, ETD Questionnaire (ETDQ-7) score, and TM status. Results Eighteen patients (18 ears) were included in this study. There were statistically and clinically significant improvements in the mean ETDQ-7 score at 6 months postoperatively (change in mean score of 16.7 ± 3.6, P P Type A tympanogram was obtained in 27.8% of patients (5/18) at 6 months postoperatively, and in 77.7% at 30 months postoperatively. A Valsalva maneuver was possible in 72.2% of patients at 6 months postoperatively and in 88.9% of patients at 30 months postoperatively. In addition, the ears of 13 patients (72.2%) showed both normal tympanograms and TM at 30 months postoperatively. Interestingly, 38.5% of patients (5/13) exhibited complete sclerosis of the pars tensa. None of the patients experienced severe MWA-related complications during follow-up. Conclusions MWA eustachian tuboplasty is a feasible alternative to conventional tuboplasty, and can improve subjective and objective outcomes in patients with ETD for up to 30 months following treatment. In addition, this study showed that the extent of sclerotic plaque increased over time, whereas the extents of atrophy and tensa retraction decreased following tuboplasty in most patients. Graphical abstract

Aim. To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. Methods. 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. Results. Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. Conclusion. Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.

Interleukin (IL)-1β is a culprit of adipose tissue inflammation, which in turn causes systematic inflammation and insulin resistance in obese individuals. IL-1β is mainly produced in monocytes and macrophages and marginally in adipocytes, through cleavage of the inactive pro-IL-1β precursor by caspase-1, which is activated via the NLRP3 inflammasome complex. The nuclear factor-κB (NF-κB) transcription factor is the master regulator of inflammatory responses. Brindle berry (Garcinia cambogia) has been widely used as health products for treating obesity and related metabolic disorders, but its active principles remain unclear. We previously found a series of polyisoprenylated benzophenones from brindle berry with anti-inflammatory activities. In this study we investigated whether 14-deoxygarcinol (DOG), a major polyisoprenylated benzophenone from brindle berry, alleviated adipose tissue inflammation and insulin sensitivity in high-fat diet fed mice. The mice were administered DOG (2.5, 5 mg · kg

In this work, we study the cosmological consequences of Rényi holographic dark energy model in the framework of the Finsler–Randers cosmology in which the Hubble horizon is considered as the IR cutoff. In this setup, we derive the evolution equation for the Rényi holographic dark energy density parameter, the equation of state (EoS) parameter and deceleration parameter. Our study shows that this model can describe the current accelerating universe in both noninteracting and interacting scenarios, and also a transition occurs from the deceleration phase to the accelerated phase at the late-time. Moreover, we discuss the statefinder diagnosis of this model, meanwhile, plot the curves of r and s versus redshift z and the evolutionary trajectories of [Formula: see text]. We find that statefinder can not only break the degeneracy of different coupling parameter values in this model, but also effectively distinguish the difference between the Rényi holographic dark energy model and the [Formula: see text]CDM model. In addition, we find that the statefinder pair [Formula: see text] performs better than [Formula: see text] and [Formula: see text] in this model.

OBJECTIVE To compare the outcome of endoscopic transtympanic cartilage myringoplasty with and without removal of perforation edges for repairing chronic perforations with mucosal chronic otitis media (COM). STUDY DESIGN Quasi-randomised clinical trial. SETTING Tertiary referral centre. MATERIALS AND METHODS Patients with chronic perforations and mucosal COM undergoing endoscopic transtympanic cartilage myringoplasty were allocated to a control group for whom the perforation edges were preserved (n = 40) and an intervention group for whom the edges were removed (n = 39). Mean operation time, graft success rate, mean scores of graft neovascularisation and epithelialisation, and hearing were compared between the groups at 4 weeks and/or 6 months postoperatively. RESULTS Graft success rate was 95% (38/40) in the control group and 97% (38/39) in the intervention group at 6 months postoperatively; the difference was not significant. Mean graft neovascularisation scores 4 weeks postoperatively were 2.52 ± 0.59 in the control group and 2.58 ± 0.55 in the intervention group; the difference was not significant. Mean graft epithelisation scores 4 weeks postoperatively were 1.48 ± 0.57 in the control group and 1.68 ± 0.51 in the intervention group; the difference was not significant and remained nonsignificant 6 months postoperatively (2.5 ± 0.55 vs. 2.76 ± 0.36). Audiological outcomes at 6 months did not differ between the groups. CONCLUSION Endoscopic, transtympanic cartilage underlay myringoplasty with preservation of the perforation margins did not affect graft neovascularisation, epithelialisation or success. Longer-term outcomes and risk of cholesteatoma require further study.

Long noncoding RNAs (lncRNAs) are closely associated with the initiation, progression, metastasis, and recurrence of hepatocellular carcinoma (HCC). They could therefore serve as markers for the early diagnosis and for the prognosis of HCC patients.This was an observational prospective cohort study. A total of 101 participants were included, comprising patients with HCC (n = 61), liver cirrhosis (LC) (n = 20), or healthy controls (HC) (n = 20). The baseline characteristics of participants in each group were compared. Serum levels of the lncRNAs HOTAIR, BRM and ICR were determined in each group by reverse transcription and quantitative real-time polymerase chain reaction (qRT-PCR). Correlations between the serum levels of the three lncRNAs and multiple clinical parameters were analysed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic potential for HCC of each lncRNA individually, or in combination with AFP. Multivariate Cox regression analysis was used to evaluate the accuracy of these lncRNAs for predicting the outcome and survival of HCC patients.The serum levels of HOTAIR, BRM and ICR were significantly higher in HCC patients compared to LC patients and healthy subjects. The HOTAIR level was positively correlated to tumour-node metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) stage, extrahepatic metastasis, vascular invasion, portal vein tumour thrombus (PVTT), and tumour size. The BRM level was positively associated with TNM stage, BCLC stage, vascular invasion, PVTT, and tumour size, while the ICR level was positively correlated with PVTT. A combination of the three lncRNAs and AFP showed the highest diagnostic accuracy for HCC, with an AUC of 0.998, sensitivity of 98.4%, and specificity of 100.0%. This combination showed a better diagnostic accuracy than the individual lncRNAs or AFP alone. Serum levels of the HOTAIR and ICR lncRNAs decreased significantly following surgery.Serum levels of the HOTAIR, BRM and ICR lncRNAs are potential prognostic markers for HCC. Upregulation of HOTAIR, BRM and ICR may facilitate early diagnosis and indicate poor prognosis for HCC. These lncRNAs could potentially serve as therapeutic targets for HCC. Combination of the three lncRNAs with AFP may increase the diagnostic accuracy for HCC. Further studies in larger cohorts of patients are needed to validate these findings.

Purpose Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. Methods Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. Results PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy—(ANP and BNP), myocardial fibrosis—(collagen I and TGF-β1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. Conclusion PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Graphical abstract Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1β, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.

Using the mass spectrometry analysis of cuticle casts of brown planthopper (BPH, Nilaparvata lugens) and transcriptome analysis of BPH tissues, we identified a gigantic gene (50,922 bp, 16,973 aa) tentatively called Nlegf-like. Multiple transcripts were found. Nlegf-like encodes an integral membrane protein of 16,973 amino acid residues with 260 EGF-like repeats and 16 Ca2+-binding EGF repeats type (cbEGFs) in the extracellular portion. Nlegf-like was highly expressed in the integument and tended to peak at the middle stage or late stage of each nymph instar. Phylogenetic analysis showed this gene is conserved in many other insects. Different double-stranded RNA-mediated RNA interference targeting eight different regions of the Nlegf-like gene resulted in abnormal cuticle formation or molting and lethal phenotypes. Transmission electron microscopy revealed that the newly formed endocuticle was significantly thinner for RNAi-treated BPHs with phenotype of contracted abdomen, or the old cuticle could not be digested sufficiently for those with phenotype of slender body shape or died with molting difficulty when compared with the control group. We suggest that the Nlegf-like is crucial for metabolism of the cuticle in BPH molting.

The brown planthopper (BPH), Nilaparvata lugens, is a major threat to rice production. The eggshell plays an important role in insect reproduction. The constituents and formation process of BPH eggshells remains largely unknown. Here, we report a novel eggshell-associated protein, NlChP38, containing an amelogenin domain, that is essential for normal ovulation in the BPH. NlChP38 is specifically expressed in the follicular cells from egg chambers at both RNA and protein levels. RNA interference of NlChP38 resulted in oocytes with loose and thin eggshell structure and caused ovulation difficulties. Immunofluorescence localization showed NlChP38 is deposited between follicular cells and oocytes during late choriogenesis. These results indicate that NlChP38 plays an important role in eggshell formation and could be a potential target for RNA interference control of the BPH.

Objective To compare the effects of epidermal growth factor (EGF) and observation only on human subacute tympanic membrane perforation (TMP). Methods A total of 44 patients with traumatic TMPs >2 months after trauma were divided into an observation group (n = 18) and EGF group (n = 26). Patients in the EGF group underwent direct application of EGF without stripping of the perforation edge. All patients were followed up for at least 6 months. The TMP closure rate, closure time, and hearing gain were evaluated. Results At 6 months, 25 of 26 (96.2%) perforations achieved complete closure with a mean closure time of 9.1 ± 3.9 days (range, 3–14 days) in the EGF group. However, only 11 of 18 (61.1%) perforations achieved complete closure in the observation group, with a mean closure time of 20.6 ± 10.7 days (range = 9–71 days). The patients in the EGF-treated group had significantly improved closure rates (P = 0.026) and a reduced closure time (P Conclusions Topical application of EGF improved the closure rate and shortened the closure time of human subacute TMPs compared with spontaneous healing, the stripping of the perforation edge was unnecessary. This treatment is simple and convenient and should be recommended pre-myringoplasty.

Background Arterial epistaxis is commonly seen in the rhinology clinic and can have a significant impact on quality of life. Previous studies have explored various therapies to address epistaxis. Methods Patients were treated in the outpatient clinic or operating room by microwave ablation (MWA) with a 2450-MHz cooled-shaft antenna to treat an epistaxis bleeding point. Results Of the 481 patients with arterial epistaxis, bleeding was controlled within 1 to 2 minutes and only 2 patients with recurrent bleeding required re-ablation. The shape of the thermal lesion was elliptical and it was approximately 2 mm in length, 1 mm in width, and 0.5 to 1 mm in penetration depth. Of the 481 patients, 167 (34.7%) complained of minor nasal pain on the same day of ablation. No patients complained of nasal pain or obstruction during the follow-up period. In addition, 139 (28.9%) patients showed a minor increase in rhinorrhea during the first postoperative week. Of the 481 patients, 469 (97.5%) were followed-up at 6 months with no severe MWA-related complications, such as septal perforation, synechiae formation, or orbit and brain complications. Conclusion MWA is a technically feasible alternative method for patients with arterial epistaxis.

Introduction: Most of traumatic tympanic membrane perforations have inverted or everted edges, however, the effects of inverted and everted edges on the spontaneous healing of the eardrum remain controversial. Objective: We investigated the influence of inverted or everted edges on the spontaneous healing of traumatic tympanic membrane perforations. Methods: The clinical records of patients with a traumatic tympanic membrane perforations who met the study criteria were retrieved and categorized into two groups, based on whether the eardrum was inverted or everted. The features along the edge of each inverted or everted eardrum were described using 30° and 70° endoscopes. Results: In total, 196 patients (196 ears) met the inclusion criteria; of these, 148 had inverted or everted eardrums while 48 did not. Of the 148 patients with inverted or everted eardrums, the perforation edges were everted in 77 patients, inverted in 44 patients, drooping in 17 patients, and both inverted and everted in 10 patients. The perforation shape was triangular in 18.9% of patients, sector-shaped in 11.5%, kidney-shaped in 14.2%, ovoid in 20.3%, and irregularly shaped in 35.1% of patients. The difference was not significant between the with and without inverted/everted eardrum edges groups in terms of the closure rate or closure time. Similarly, the difference was not significant between the with and without edge approximation groups in terms of the closure rate or closure time at the end of the 12-month follow-up period. Conclusion: This study suggests that endoscopic inspection can clearly identify inverted/everted eardrum edges using 30° and 70° endoscopes. The edge is glossy in inverted/everted eardrums, whereas the edge is rough and irregular in non-inverted/everted cases. The inverted/everted eardrums gradually became necrotic, but this did not affect the healing process. Additionally, edge approximation did not improve the healing outcome of traumatic tympanic membrane perforations. Resumo: Introdução: A maioria das perfurações de membrana timpânica traumáticas apresenta bordas invertidas ou evertidas; no entanto, os efeitos dessas configurações sobre a cicatrização espontânea do tímpano continuam a ser uma questão controversa. Objetivo: Investigar a influência de bordas invertidas ou evertidas sobre a cicatrização espontânea de perfurações traumáticas de membrana timpânica. Método: Os prontuários clínicos de pacientes com perfuração traumática de membrana timpânica que preencheram os critérios do estudo foram recuperados e categorizados em dois grupos, baseados na configuração invertida ou evertida das bordas da membrana timpânica. As características de configuração da borda de cada membrana foram descritas com o uso de endoscópios de 30° e 70°. Resultados: No total, 196 pacientes (196 orelhas) preencheram os critérios de inclusão; desses, 148 apresentavam bordas de membranas timpânicas invertidas ou evertidas, enquanto 48 não. Dos 148 pacientes, as bordas da perfuração estavam evertidas em 77 pacientes, invertidas em 44 pacientes, caídas em 17 pacientes e ambas invertidas e evertidas em 10 pacientes. O formato da perfuração era triangular em 18,9% dos pacientes, em forma de fatia de pizza em 11,5%, em forma de rim em 14,2%, ovoide em 20,3% e de forma irregular em 35,1% dos pacientes. A diferença não foi significante entre os grupos com e sem membrana timpânica invertida/evertida em termos de taxa ou tempo de fechamento. Da mesma forma, a diferença não foi significativa entre os grupos com e sem aproximação das bordas em termos de taxa de fechamento ou tempo de fechamento no fim do período de seguimento de 12 meses. Conclusões: Este estudo sugere que a avaliação com endoscópios de 30° e 70° pode identificar claramente as bordas invertidas/evertidas das perfurações de membranas timpânicas. A borda da perfuração timpânica em casos invertidos/evertidos é brilhante, enquanto a borda é áspera e irregular em casos não invertidos/evertidos. O rebordo timpânico invertido/evertido gradualmente torna-se necrótico, mas isso não afetou o processo de cicatrização. Além disso, a aproximação das bordas não melhorou o resultado da cicatrização. Keywords: Traumatic, Tympanic membrane perforation, Edge approximation, Spontaneous healing, Palavras-chave: Traumática, Perfuração da membrana timpânica, Aproximação da borda, Cicatrização espontânea

OBJECTIVE The use of epidermal growth factor (EGF) to achieve closure of human traumatic tympanic membrane perforations (TMPs) was recently reported. However, pretreatment factors affecting healing outcomes have seldom been discussed. This study was performed to evaluate pretreatment factors contributing to the success or failure of TMP healing using EGF. DESIGN AND PARTICIPANTS This was a retrospective cohort study of 95 TMPs who were observed for at least 6 months after EGF treatment. Eleven factors considered likely to affect healing outcome were evaluated by univariate and multivariate logistic regression analyses. INTERVENTIONS Each traumatic TMP was treated by daily topical application of EGF. The main outcome measures were complete closure versus failure to close and mean closure time. RESULTS A total of 95 patients were included in the analyses. The total closure rate was 92.6% at 6 months, and the mean closure time was 10.5 ± 4.8 days. The closure rate was not significantly different according to the duration of perforation ≤3 days and >3 days (P = 0.816). However, the mean closure time was significantly different according to the duration of perforation (P

We evaluated the graft and hearing outcomes of patients with chronic perforations treated via the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and external auditory canal (EAC) packing.Thirty-nine patients with chronic perforations and residual tympanic membranes around the perforation margins were treated using the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and EAC packing. Patients were followed-up for 6 months.For all 39 patients with unilateral perforations, the graft success rate was 100% (39/39) at 6 months after surgery. The mean air-bone gap significantly (P 0.05) improved from 13.41 ± 8.34 dB preoperatively to 7.45 ± 3.81 dB postoperatively in patients with small and medium perforations; the mean air-bone gap significantly improved from 20.57 ± 9.41 dB preoperatively to 9.84 ± 2.41 dB postoperatively in patients with large perforations. The lateral perichondrium gradually became necrotic and crust at postoperative 2-3 months and migrated into the EAC in all patients.The cartilage-perichondrium over-underlay myringoplasty without de-squamatization of the TM and EAC packing is feasible, affording a high graft success rate and good hearing improvement. The lateral perichondrium may gradually become necrotic and crusted, and migrate along the EAC over time.

Background/objective. Most researchers consider that basic fibroblast growth factor (bFGF) facilitates the repair of chronic tympanic membrane (TM) perforations in chronic otitis media (COM). However, the addition of biological materials affects bFGF levels. This study was performed to compare the effects of bFGF alone and myringoplasty for the repair of chronic perforations. Study design. A prospective cohort control study. Materials and methods. Patients with chronic central perforations who met the inclusion criteria were divided into two groups, i.e., bFGF alone group and underlay myringoplasty group. In the bFGF alone group, the epithelium was removed circumferentially around the perforation edge to create fresh edges. Approximately, 0.1–0.15 mL of bFGF solution was applied twice daily for 3 months to the TM, to keep the edges moist without a scaffold. In the myringoplasty group, the perichondrium graft was placed underneath the TM remnant by endoscopy. TM closure and hearing outcomes were evaluated at 12 weeks after surgery or at the end of bFGF treatment. Results. A total of 29 patients consisting 13 in the bFGF alone group and 16 in the myringoplasty group were finally included in the analysis. Of the 13 patients in the bFGF alone group, the perforations were small in 6 and medium in 7; the etiology was secondary to COM in 11 and to trauma in 2. One patient with an unhealed perforation continued bFGF treatment until 6 months, while the others stopped at 3 months. Of the seven medium-sized perforations, none of the five COM perforations closed, while the two traumatic perforations achieved complete closure within 2 and 4 weeks, respectively. The successful closure rate was 28.6% (2/7). Successful closure was achieved in 66.7% (4/6) of the six small perforations with COM, with a mean closure time of 4.75 weeks. Of the 16 patients in the myringoplasty group, all perforations were medium-sized and were secondary to COM in 15 cases and traumatic in 1 case; all achieved complete closure. Conclusions. bFGF alone facilitated the repair of chronic traumatic perforations and small perforations with COM, but not medium-sized perforations with COM. These observations indicated that the regenerative conditions of traumatic perforations are better than those of COM perforations when using bFGF alone, and that graft materials could play a critical role in the regeneration of larger-sized chronic perforations with COM.

We compare the long-term efficacy of the cartilage–perichondrium modified over-underlay technique and transtympanic underlay alone technique using endoscopic myringoplasty without tympanomeatal flap elevating for repairing large chronic perforations. Nine chronic large perforations with mucosal chronic otitis media were recruited and randomly allocated to endoscopic cartilage–perichondrium modified over-underlay myringoplasty (MOUM, n = 55) and endoscopic cartilage–perichondrium transtympanic underlay alone myringoplasty (TUAM, n = 54). The graft success rate, hearing gain, mean operation time and postoperative complications were compared between the groups at 6 and 24 months. In total, 99 patients were finally analysed. The graft success rates 6 months after surgery between MOUM and TUAM groups were not significantly different (100.0% vs 96.0%, p = 0.484). However, the MOUM group had a significantly higher success rate 24 months after surgery than the TUAM group (93.9% vs 76.0%, p = 0.028). In addition, postoperative ABG

Objective To investigate the Effect of concurrent nasal surgery on the eustachian tube function (ETF) and myringoplasty outcomes for the chronic perforations with coexistent nasal pathology. Materials and methods We retrospectively reviewed the records of 93 patients with perforations who underwent same-day myringoplasty and nasal-septal surgery. Group A exhibited septal deviations (n = 34) and Group B inflammatory sinus disease (n = 59). Groups were compared with respect to pre- and postoperative air-bone gaps (ABGs), graft success rates and ETF (Eustachian tube score [ETS] and seven-item Eustachian Tube Dysfunction Questionnaire [ETDQ-7]) at 6 and 24 months. Results Graft success rates were 100.0% in Group A and 98.3% in Group B at 6 months postoperatively (P = 0.445). Graft success rates were 85.3% in Group A and 96.6% in Group B at 24 months postoperatively (P = 0.046), the re-perforation rate was significantly higher in Group A than in Group B (P = 0.015). Although the preoperative ETS was similar between two groups, the postoperative ETS in the Group B was significantly higher compared with Group A regardless of at postoperative 6th and 24th months. In addition, difference was significant for the patients with positive Valsalva maneuver among two groups at postoperative 24th months. Also, the improvement in the ETDQ-7 score in the B group was significantly higher than that in the A group at postoperative 6th and 24th months. Conclusions Concurrent nasal surgery and myringoplasty is feasible. In addition, ESS improves ETF and thus long-term outcomes of myringoplasty for the chronic perforations with inflammatory sinus disease.

NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes. Moreover, AAV9-GDF11 markedly alleviated heart function in MI mice. Meanwhile, GDF11 overexpression also decreased the pyroptosis of hypoxic cardiomyocytes. PROMO and JASPAR prediction software found that transcription factor HOXA3 was predicted as an important regulator of NLRP3, and was confirmed by ChIP assay. Further analysis identifying GDF11 promoted the Smad2/3 pathway resulted in HOXA3 overexpression. Taken together, our study implies that GDF11 prevents cardiomyocytes pyroptosis via HOXA3/NLRP3 signaling pathway in MI mice.

Vibrio vulnificus (V. vulnificus) is an estuarine bacterium that is capable of causing rapidly fatal infection in humans. Proper polarization and bactericidal activity of macrophages play essential roles in defending against invading pathogens. How macrophages limit V. vulnificus infection remains not well understood. Here we report that tuberous sclerosis complex 1 (TSC1) is crucial for the regulation of V. vulnificus-induced macrophage polarization, bacterial clearance, and cell death. Mice with myeloid-specific deletion of TSC1 exhibit a significant reduction of survival time after V. vulnificus infection. V. vulnificus infection induces both M1 and M2 polarization. However, TSC1 deficient macrophages show enhanced M1 response to V. vulnificus infection. Interestedly, the absence of TSC1 in myeloid cells results in impaired bacterial clearance both in vivo and in vitro after V. vulnificus infection. Inhibition of the mammalian target of rapamycin (mTOR) activity significantly reverses V. vulnificus-induced hypersensitive M1 response and resistant bactericidal activity both in wild-type and TSC1-deficient macrophages. Moreover, V. vulnificus infection causes cell death of macrophages, possibly contributes to defective of bacterial clearance, which also exhibits in a mTORC1-dependent manner. These findings highlight an essential role for the TSC1-mTOR signaling in the regulation of innate immunity against V. vulnificus infection.

In this paper, we have explored non-gravitational interaction dark energy model between dark energy and cold dark matter (CDM). The main purpose of this work is to explore the deviations from &Lambda, C D M and to distinguish the evolution trajectory of the interaction dark energy model with different parameters. Six forms of interaction were focused on. We have analyzed the deceleration parameters of the coupled model and explored the theoretical models through s t a t e f i n d e r h i e r a r c h y and the O m diagnostic. We have considered that the Equation of State (EoS) parameter w and parameter &xi, take different values on the interaction dark energy model respectively and keep another parameter unchanged. It was found that q ( z ) is the worst of the four diagnoses. O m , S 3 ( 1 ) and S 4 ( 1 ) are good tools to distinguish the interaction dark energy model from &Lambda, C D M . S 3 ( 1 ) is a better diagnostic tool when the state parameter w changes and the coupling parameter &xi, is fixed, while S 4 ( 1 ) works better when the coupling parameter &xi, changes and the state parameter w is fixed.

The brown planthopper (BPH), Nilaparvata lugens, is a serious migratory rice pest, which is distributed in the broad area of the tropical and temperate Asian-Pacific region. However, we know little about key aspects regarding its evolution such as how they diverged and dispersed worldwide. By resequencing and analyzing 358 BPH genomes from 92 populations across the world, we uncover the genetic relationships among their worldwide populations and the history of their global dispersal. We recovered five genetic groups representing the major population structures. Of these, Australian BPHs were shown large genetic divergence with Asian BPHs; two distinct groups have formed in South and Southeast/East Asia that show strong genetic admixture in the southwest border regions of China and west Thailand with Myanmar; two local populations in Bangladesh and Fujian province of China, respectively, unexpectedly separated with surrounding populations. We also find the genetic similarity and closely phylogenetic relationships between majority of East Asian BPHs and Indo-china peninsula BPHs, indicating that Southeast Asia mainland is the major insect sources and overwintering sites for East Asia. Our study provides important molecular evidence to address BPH evolution and other key aspects of its biology such as insecticides resistance and rice varieties virulence.

ObjectiveA systematic review was conducted to investigate the effectiveness of fibroblast growth factor-2 on the regeneration of tympanic membrane perforation.MethodsThe PubMed database was searched for relevant studies. Experimental studies, human randomised controlled trials, prospective single-arm studies and retrospective studies reporting acute and chronic tympanic membrane perforations in relation to two healing outcomes (success rate and closure time), were selected.ResultsAll 11 clinical studies investigating the effect of fibroblast growth factor-2 on traumatic tympanic membrane perforations in humans reported a success rate of 89.3–100 per cent, with a closure time of around 2 weeks. Three studies of fibroblast growth factor-2 combined with Gelfoam showed that the success rate of chronic tympanic membrane perforation was 83–98.1 per cent in the fibroblast growth factor-2 group, but 10 per cent in the gelatine sponge groups.ConclusionFibroblast growth factor-2 with or without biological material patching promotes regeneration in cases of acute and chronic tympanic membrane perforation, and is safe and efficient. However, the best dosage, application time and administration pathway of fibroblast growth factor-2 are still to be elucidated.

In insect eggs, the chorion has the essential function of protecting the embryo from external agents during development while allowing gas exchange for respiration. In this study, we found a novel gene, Nilaparvata lugens chorion protein (NlChP), that is involved in chorion formation in the brown planthopper, Nilaparvata lugens. NlChP was highly expressed in the follicular cells of female adult brown planthoppers. Knockdown of NlChP resulted in oocyte malformation and the inability to perform oviposition, and electron microscopy showed that the malformed oocytes had thin and rough endochorion layers compared to the control group. Liquid chromatography with tandem mass spectrometry analysis of the eggshell components revealed four unique peptides that were matched to NlChP. Our results demonstrate that NlChP is a novel chorion protein essential for egg maturation in N. lugens, a hemipteran insect with telotrophic meroistic ovaries. NlChP may be a potential target in RNA interference-based insect pest management.

Objective We evaluated microwave ablation (MWA) for treatment of isolated pharyngeal benign lesions, in terms of technical feasibility, efficacy, and safety. Methods The patients with pharyngeal benign lesions were treated with endoscopic MWA with a 2450-MHz single cooled-shaft microwave antenna and sent for histological examination. Postoperative pain intensity was measured via visual analogue scale (VAS) on the 12th hour and the third postoperative days. Results Of the 137 patients with pharyngeal benign lesions who met the inclusion criteria. The most commonly involved site was the uvula (n = 66, 48.2%), followed by the lateral pharyngeal wall (n = 37, 27.0%), the nasopharyngeal posterior wall (n = 23, 16.8%) and the soft palate (n = 11, 8.0%). All of the procedures were completed using local anesthesia and were well-tolerated by the patients. The ablation time was 5–10 min, with an average duration of 6.3 ± 1.8 min. The most common pathology was papilloma (n = 96, 70.1%), followed by nasopharyngeal cysts (n = 21, 15.3%), polyp (n = 10, 7.3%), epidermoid cysts (n = 8, 5.8%) and Thornwaldt cysts (n = 2, 1.5%). The mean VAS pain score was 2.36 ± 1.08 on postoperative 12th hour and 1.21 ± 0.54 on postoperative third day. At the 6-month follow-up examination, there were no severe complications, such as recurrence, bleeding, or synechiae of the nasal cavity, eustachian tube injury, in any of the patients. Conclusions The MWA for the treatment of isolated pharyngeal benign lesion is feasible and alternative to conventional surgical methods, it allows excision of the lesion while providing hemostasis, involves only a short ablation time and has a very low risk of complications. Most of our patients well-tolerate the procedure, which may be performed under local anesthesia in the outpatient setting.

This study investigated the influence of the degree of bleeding from the remnant eardrum on the spontaneous healing of human traumatic tympanic membrane perforations (TMPs).A case series with chart review.A tertiary university hospital.The clinical records of traumatic TMP patients who met the case selection criteria were retrieved and categorized into two groups based on the documented degree of bleeding from the remnant eardrum: with and without bleeding. The demographic data and spontaneous healing outcomes (i.e., healing rate and duration) of these two TMP types were analyzed using the chi-squared test or t-test.One-hundred and eighty-eight cases met the inclusion criteria and were analyzed. Of these, 58.5% had perforations without bleeding and the remaining 41.5% had perforations with bleeding. The overall closure rate at the end of the 3-month follow-up period was 90.9% for perforations without bleeding and 96.2% for perforations with bleeding; the difference was not statistically significant (P0.05). However, the average closure time differed significantly between the two groups (P0.05): 29.4±3.7days for perforations without bleeding and 20.6±9.2days for perforations with bleeding. The closure rate was significantly different between the groups (62 vs. 15.6%, P0.01) within 2weeks for medium-sized perforations. In total, 11 (39.3%) large-sized perforations achieved complete closure in the group with bleeding, while none of the large-sized perforations closed in the group without bleeding within 2weeks. The closure rate of medium-sized perforations was not significantly different (79.2 vs. 92%, P0.05) between the groups without and with bleeding within 4weeks, while the closure rate of large-sized perforations was significantly different between the groups without and with bleeding (27.2 vs. 75%, P=0.0).This study shows that traumatic TMPs with bleeding significantly shortened the closure time compared to TMPs without bleeding. This finding indicates a significant correlation between the prognosis of traumatic TMPs and the degree of eardrum bleeding: severe bleeding from and a hematoma in the remnant eardrum appear to be good signs.

Vitellogenin (Vg) is precursor of vitellin. Here, we identified a Vg (NlVg) and two Vg-likes (NlVg-like1 and NlVg-like2) in the brown planthopper, Nilaparvata lugens. Phylogenetic analyses showed that NlVg-like1 and NlVg-like2 are not clustered with the conventional insect Vgs associated with vitellogenesis. Temporo-spatial expression analyses showed that the NlVg and NlVg-like2 transcript levels increased significantly 24 h after emergence and were primarily expressed in female adults. However, NlVg-like1 was expressed during all stages, and in both genders. Tissue-specific analyses showed that all three genes were most highly expressed in the fat body. The injection of double-stranded RNA targeting NlVg showed that NlVg is essential not only for oocyte development but also for nymph development. The knockdown of NlVg-like1 in female adults resulted in failure to hatch or death before eggshell emergence in 18% of offspring embryos, suggesting that NlVg-like1 plays an important role during late embryogenesis. Approximately 65% of eggs laid by females that were treated with double-stranded RNA targeting NlVg-like2 failed to hatch, indicating that NlVg-like2 plays a role in nutrition absorption during oocyte, or embryonic development. Our results illustrate the structural and functional differences among the Vg and Vg-like genes and provide potential targets for RNA-interference-based insect pest management strategies.