A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers.

Objective: The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR, rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods: A total of 1,727 patients with cancer (gastric/liver/colorectal: 460/480/787) and 800 healthy controls were recruited. Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and confirmed using Sanger sequencing. Twenty-four eligible studies were included in the meta-analysis. Results: After Bonferroni correction, the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population. The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS, gastric, and liver cancer in the Chinese population. Conclusion: The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers (especially liver and gastric cancer) in the Chinese population.

An underlying mechanism behind interventional pulmonology techniques for refractory asthma treatment: Neuro-immunity crosstalk.

Asthma is a common disease that seriously threatens public health. With significant developments in bronchoscopy, different interventional pulmonology techniques for refractory asthma treatment have been developed. These technologies achieve therapeutic purposes by targeting diverse aspects of asthma pathophysiology. However, even though these newer techniques have shown appreciable clinical effects, their differences in mechanisms and mutual commonalities still deserve to be carefully explored. Therefore, in this review, we summarized the potential mechanisms of bronchial thermoplasty, targeted lung denervation, and cryoablation, and analyzed the relationship between these different methods. Based on available evidence, we speculated that the main pathway of chronic airway inflammation and other pathophysiologic processes in asthma is sensory nerve-related neurotransmitter release that forms a "neuro-immunity crosstalk" and amplifies airway neurogenic inflammation. The mechanism of completely blocking neuro-immunity crosstalk through dual-ablation of both efferent and afferent fibers may have a leading role in the clinical efficacy of interventional pulmonology in the treatment of asthma and deserves further investigation.

Case report: Circulating tumor DNA technology displays temporal and spatial heterogeneity in Waldenström macroglobulinemia during treatment with BTK inhibitors.

Background: Waldenström macroglobulinemia (WM) is a rare subtype of B-cell lymphoma. Rituximab-based combination therapy and Bruton's tyrosine kinase (BTK) inhibitors have greatly improved the prognosis of WM. Despite the high response rate and good tolerance of BTK inhibitors in treatment of WM, a proportion of patients still experience disease progression. Case presentation: We report a 55-year-old man with relapsed WM. The patient achieved partial remission after six courses of CHOP chemotherapy and multiple plasma exchanges in initial treatment. He was admitted to the hospital with abdominal distension, and was diagnosed with relapsed WM and subsequently started on zanubrutinib. Disease progression and histological transformation occurred during treatment. We performed liquid biopsies on transformed plasma, tumor tissue and ascites at the same time and found high consistency between ascites and tissues. Moreover, we detected resistance mutations of BTK inhibitors (BTK, PLCG2) in ascites that were not detected in plasma or tissue. Eventually, the patient died during the 15-month follow-up after relapse. Conclusion: We describe a rare case of WM transformation to DLCBCL treated with chemoimmunotherapy and BTK inhibition. We analyzed tumor DNA obtained at different anatomic sites and circulating tumor DNA (ctDNA) derived from plasma and ascites specimens, with apparent significant temporal and spatial heterogeneity. The case specifically highlights the clinical value of ctDNA of ascites supernatant from WM patients, which is a more convenient and relatively noninvasive method compared with traditional invasive tissue biopsy.

Development and Validation of a Prognostic Model to Predict Hearing Recovery for Patients With Chronic Otitis Media.

OBJECTIVE: To explore the factors affecting postoperative hearing recovery in chronic otitis media (COM) patients, establish a clinical prediction model for hearing recovery, and verify the accuracy of the model. METHODS: Data of patients with COM who were admitted to our hospital between January 1, 2012 and September 30, 2020 were retrospectively analyzed. We collected data on relevant clinicopathological characteristics of patients. The patients were randomly divided into the development cohort and validation cohorts. A postoperative air-bone gap (ABG) ≤20 dB was defined as successful hearing recovery. Univariate and multivariable logistic regression analyses were used to investigate the association of several prognostic factors with hearing recovery. These factors were then used to establish a nomogram. The model was subjected to bootstrap internal validation and performance evaluation in terms of discrimination, calibration, and clinical validity. RESULTS: This study included 2146 patients with COM: the development cohort comprised 1610 patients (mean [standard deviation; SD] age, 44.1 [14.7] years; 733 men [45.5%]) and the validation cohort included 536 patients (mean [SD] age, 42.9 [14.4] years; 234 men [43.7%]). Multivariable logistic regression analysis showed that age, duration of onset, styles of surgery (tympanoplasty, canal wall up-CWU, or canal wall down-CWD), ossicular prosthesis, granulation or calcified blocks around the ossicular chain, ossicular chain integrity, duration of drilling, eustachian tube dysfunction, mixed hearing loss, semicircular canal fistula, and second surgery were associated with hearing recovery. A nomogram based on these variables was constructed. The area under the curve was 0.797 (95% confidence interval [CI], 0.778-0.812) in the development cohort and 0.798 (95% CI, 0.7605-0.8355) in the validation cohort. CONCLUSIONS: This study demonstrated the various clinical factors correlated with hearing recovery in patients with COM. The nomogram developed with these data could provide personalized risk estimates of hearing recovery to enhance preoperative counseling and help to set realistic expectations in patients.

Benzotrithiophene-based MOFs: interchromophoric interactions affected Ln(III) crystallization selectivity and optoelectronic properties.

Metal-organic frameworks (MOFs) provide an ideal platform for the assembly of chromophores and thus show wide potential applications in optoelectronic devices. The spatial arrangement and interaction of the incorporated chromophores play a key role in the generation of coherent optical and electronic properties. In this work, two series of benzo-(1,2;3,4;5,6)-tristhiophene (BTT) based Ln-MOFs (Ln-1s and Ln-2s) were synthesized. These two series of MOFs present different assembly states of BTT chromophores, that is, BTT-containing ligands exist as separated monomers in Ln-1s but gather as dimers in Ln-2s. From the comparison between these two series of MOFs and theoretical calculations, we show for the first time that this chromophore assembly state difference could affect the crystallization selectivity of MOFs towards different Ln3+ ions. In addition, the interaction between BTT chromophores in the dimer also leads to the red-shifted photoluminescence and enhanced photocurrent of Ln-2s relative to those of Ln-1s. The results of this work demonstrate the multiple functions of interchromophoric interactions in the structures and optoelectronic properties of MOFs.

Bilateral Posterior Auricular Masses: A Case of Kimura's Disease.

Kimura's disease (KD) is currently considered a rare chronic inflammatory disease of unknown etiology. It is more common in the Asian population, especially in young and middle-aged men, and can involve the lymph nodes, salivary glands, and subcutaneous tissues. It has been reported in adults and children, and is often accompanied by elevated peripheral blood eosinophils and elevated serum immunoglobulin E (IgE). Herein, we report a case of KD in a 46-year-old man with bilateral masses behind the ears since childhood that had gradually enlarged over 40 years. The patient's peripheral blood eosinophils were elevated, and interestingly, homocysteine levels were also elevated. After surgical resection of the bilateral posterior auricular masses, follow-up over 5 years indicated good recovery and no signs of recurrence.

Corrigendum: Correlation of Bromodomain Protein BRD4 Expression With Epithelial-Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps.

[This corrects the article DOI: 10.3389/fmed.2020.00413.].

Correlation of Bromodomain Protein BRD4 Expression With Epithelial-Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps.

Objectives: This study aimed to explore the relationship between bromodomain-containing protein 4 (BRD4), epithelial-mesenchymal transition (EMT), and disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We performed immunofluorescent (IF) staining to evaluate the expression of BRD4 in the polyp tissues of CRSwNP and inferior turbinate mucosa of healthy controls. The relationship between BRD4 and EMT was evaluated by the BRD inhibitor JQ1 and BRD4 siRNA in primary human nasal polyp-derived epithelial cells. Disease severity was scored by using the Lund-Mackay scores of paranasal sinus computed tomography (CT) scans. Results: The expression of BRD4 in patients with CRSwNP was significantly higher than that in healthy controls. The loss of BRD4 function by the BRD inhibitor JQ1 and BRD4 siRNA resulted in the reduction of E-cadherin, increasing vimentin, and Snai1 mRNA expression. Moreover, the expression of BRD4 was related to the total CT scan scores (r = 0.4682, P = 0.0210). Conclusions: BRD4 had higher expression in CRSwNP than in healthy controls and might be associated with EMT in CRSwNP. BRD4 mRNA expression was associated with disease severity in CRSwNP.

Efficacy and safety of terbinafine hydrochloride spray and 3% boric acid alcohol ear drops in otomycosis.

Background: Although otomycosis is a disease spread throughout the world, there are only a few of studies about it.Objective: We aimed to evaluate the clinical efficacy of terbinafine hydrochloride spray (THS) in combination with 3% boric acid alcohol (3% BAA) ear drops compared to 3% BAA ear drops in otomycosis.Methods: This was a randomised, parallel-group, double-blind study involving 320 patients of both sexes aged 18 years or older.Results: The clinical cure rate was higher (p = .01) with THS in combination with 3% BAA ear drops than with 3% BAA ear drops alone. The change of mean total symptom score was significant with THS in combination with 3% BAA ear drops (p = .035). No differences were found in the percentage of patients reporting resolution of otalgia between patients receiving THS in combination with 3% BAA ear drops and those receiving only 3% BAA ear drops. Resolution rates of pruritus, otorrhea, aural fullness, tinnitus and hypoacusis (p = .005, p = .004, p = .002, p = .001, p = .004, respectively) was higher with THS in combination with 3% BAA ear drops, as was eradication (p = .001). There were seven mild adverse events, three with the THS in combination with 3% BAA ear drops (not related to the treatment) and four when 3% BAA was administered alone (not related to the treatment).Conclusions: THS in combination with 3% BAA ear drops is a more effective treatment for otomycosis than 3% BAA ear drops alone. The THS in combination with 3% BAA ear drops also has an excellent safety profile.Significance: To provides a safe and effective method for treating otomycosis.

Inhibition of NF-κB activation improves insulin resistance of L6 cells.

To explore the role of NF-κB activation in the development of insulin resistance and investigate whether or not that the inhibition of NF-κB activation by PDTC will improve the insulin resistance of L6 cells exposed to H2O2. L6 cells were treated with H2O2, PDTC or both H2O2 and PDTC for 4 hours. The uptake of glucose with stimulation of insulin, the expression of P38-MAPK, p- P38-MAPK, NF-κBp65, p- NF-κBp65, IRS-1, IRS-2, p-IRS-2, PI3K, IκBα, p- IκBα, caspase-8 and GLUT4, the production of ROS, TNF-α, IL-6 and IL-1ß as well as the apoptosis rate of L6 cells were determined and compared in L6 treated with H2O2 alone or both H2O2 and PDTC. Compared with the L6 cells treated with H2O2 alone, the L6 cells treated with both H2O2 and PDTC showed (1) significantly lower production of ROS, TNF-α, IL-6 and IL-1ß; (2) significantly decreased expression of P38-MAPK, p- P38-MAPK and NF-κBp65, p- NF-κBp65, p- IκBα and caspase-8; (3) significantly lower rate of apoptosis; (4) significantly higher expression of IRS-2, p-IRS-2 (Tyr 612), PI3K and GLUT4; (5) significantly higher uptake of glucose with stimulation of insulin; (6) significantly increased expression of Bcl2 and decreased ratio of Bax to Bcl2. Based on the findings of the present study, inhibition of NF-κB activation by PDTC would improve the insulin resistance of L6 cells exposed to H2O2.

Comparative Study of Endolymphatic Sac Decompression and Vestibular Neurectomy in Intractable Meniere's Disease.

To comparative study the clinical effect of endolymphatic sac decompression (ELSD) and vestibular neurectomy (VN) in intractable Meniere's disease (MD). The study included 30 MD intractable patients, 21 of which underwent ELSD and nine of which were treated by VN via retrosigmoid approach. Follow-up period ranged from 3 to 6 years. In 21 patients by ELSD, excellent vertigo control and good control were noted in 11 patients (52.4 %) and 4 patients (19.0 %), partial control in 4 and no control in 2 patients. All the 9 patients by VN, vertigo was excellent control. ELSD can improve hearing and tinnitus, but VN not. VN can achieve much better effect in improving vertigo in intractable MD patients. But relative to ELSD, it has much more disadvantages.

Surgical management of facial paralysis resulting from temporal bone fractures.

CONCLUSION: To achieve good facial reanimation in cases with facial paralysis resulting from temporal bone fractures, the ideal timing for surgical intervention is at least within 1 month of injury and an appropriate surgical approach should be selected depending on the site of facial nerve injury. OBJECTIVE: This paper aimed to address the ideal time for surgical intervention and the appropriate surgical approach for patients with facial paralysis resulting from temporal bone fractures. METHODS: We retrospectively investigated 60 patients with facial paralysis due to temporal bone fractures who underwent facial nerve decompression via different operative approaches within 1 month after trauma, of which 48 were surgically treated by the middle cranial fossa approach (80%), 8 by a pure transmastoid approach (13.3%), and four by a combined transmastoid and middle cranial fossa approach (6.7%). The House-Brackmann (H-B) grading system was used to evaluate the recovery of facial nerve function. RESULTS: The follow-up period for all the patients was 1 year. Among 60 patients who were surgically treated, 39 achieved grade I of facial nerve function, 18 achieved grade II, two achieved grade III, and one achieved grade IV according to the H-B grading system.