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Meng-Yu Fu,1 Jie Hao,2 Lun-Hui Ye,3 Wei Jiang,2 Ying-Wen Lv,1 Jie-Liang Shen,2 Tao Fu1 1Department of Orthopaedics, The Thirteenth People’s Hospital of Chongqing (The Geriatric Hospital of Chongqing), Chongqing, 400053, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Anesthesiology, The Thirteenth People’s Hospital of Chongqing (The Geriatric Hospital of Chongqing), Chongqing, 400053, People’s Republic of ChinaCorrespondence: Jie-Liang Shen; Tao Fu, Email 18996078008@qq.com; cqsdssrmyyft@163.comBackground: Since the application of ultrasound-guided erector spinae plane block (ESPB) in 2016, the approach has been gradually applied to perioperative analgesia in various surgeries. In recent years, more and more studies have focused on the effect of ESPB in perioperative analgesia of lumbar spinal surgery, but its clinical effect remains controversial.Objective: This systematic review and meta-analysis was designed to explore the efficacy and safety of ESPB used for perioperative pain management in lumbar spinal surgery.Methods: The Pubmed, Web of Science, Cochrane Library, and EMBASE databases were comprehensively searched for relevant articles from inception to March 2022. Randomized controlled trials (RCTs) comparing ESPB with placebo or without ESPB in lumbar spinal surgery were included. The Review Manager 5.3 software was employed for this meta-analysis.Results: Nineteen RCTs with 1381 participants were included for final analysis. ESPB group exhibited lower intraoperative consumption of sufentanil and remifentanil, lower total opioid consumption within 24 h and 48 h after surgery, lower incidence of rescue analgesia, longer time to first rescue analgesic and lower number of PCA button presses compared to the control group (P< 0.05). Moreover, the ESPB group had significantly lower pain scores at rest and on movement within 48 h after surgery compared with the control group (P< 0.05). In terms of opioid-related adverse reactions, ESPB reduced the incidence of postoperative nausea, vomitting, somnolence and itching in comparison to the control group (P< 0.05). ESPB-related serious complications were not reported in included studies.Conclusion: This meta-analysis demonstrated that ESPB used in lumbar spinal surgery was effective in relieving postoperative pain, decreasing the perioperative consumption of opioids, as well as decreasing the incidence of postoperative opioid-related adverse reactions.Keywords: erector spinae plane block, lumbar spinal surgery, perioperative analgesia, randomized controlled trial, meta-analysis

Meng-Zhu Yao,1 Ming-Yi Huang-Fu,1 Hui-Na Liu,1 Xia-Rong Wang,1 Xiaoxia Sheng,2 Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 2Hangzhou SoliPharma Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China Abstract: Nano-hydroxyapatite/polyamide 66 (nHA/PA66) porous scaffolds were fabricated by a phase inversion method. Carbon nanotubes (CNTs) and silk fibroin (SF) were used to modify the surface of the nHA/PA66 scaffolds by freeze-drying and cross-linking. Dexamethasone was absorbed to the CNTs to promote the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). The cell viability of BMSCs was investigated by changing the concentration of the CNT dispersion, and the most biocompatible scaffold was selected. In addition, the morphology and mechanical property of the scaffolds were investigated. The results showed that the nHA/PA66 scaffolds modified with CNTs and SF met the requirements of bone tissue engineering scaffolds. The dexamethasone-loaded CNT/SF-nHA/PA66 composite scaffold promoted the osteogenic differentiation of BMSCs, and the drug-loaded scaffolds are expected to function as effective bone tissue engineering scaffolds. Keywords: BMSCs, tissue engineering, porous scaffold, carbon nanotubes, silk fibroin, surface modification, dexamethasone

The Topological Hall effect (THE) is a fascinating physical phenomenon related to topological spin textures, serving as a powerful electrical probe for detecting and understanding these unconventional magnetic orders and skyrmions. Recently, the THE has been observed in strontium ruthenate (SrRuO 3 , SRO) thin films and its heterostructures, which originates from the disruption of interfacial inversion symmetry and Dzyaloshinskii-Moriya interaction (DMI). Here, we demonstrate a practically pure proton doping effect for controlling the DMI and THE in the SRO epitaxial films using the Pt electrode-assisted hydrogenation method. The hydrogenation process can realize approximately 0.8 protons per unit cell incorporating into the SRO films (thickness >10 nm) without causing significant lattice expansion and oxygen vacancies. Consistent with first-principles calculations, atomic-scale observations confirm that the proton doping induces a vertical displacement of Ru and O atoms in hydrogenated SRO (H-SRO), which remarkably enhances the DMI and leads to the emergence of the THE. More importantly, the proton doping drives two distinct topological signals in the ferromagnetic H-SRO, exhibiting greater THE values but no occurrence of structural transition. Our study has demonstrated that catalysis-assisted hydrogenation is an efficient strategy for manipulating the emerging THE and magnetic textures in correlated oxide thin films.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare form of B-cell lymphoma which can potentially affect the stomach, spleen, salivary glands, skin, lungs, orbit, and, rarely, the thymus. Patients with Sjögren's syndrome (SjS) are at a 15-20 times increased risk of developing lymphoma compared to the general population.Here, we present a case of primary thymic MALT lymphoma and associated diffuse cystic lung disease, incidentally identified on routine chest imaging. Thymic MALT lymphoma has to date been reported primarily in women of Chinese origin, mainly without cystic lung disease. Diffuse cystic lung disease is well documented in women with SjS and the differential diagnoses also include lymphangioleiomyomatosis, which occurs almost exclusively in women.In the case presented, CT and positron emission tomography-CT showed a large hypermetabolic anterior mediastinal mass, as well as multiple thin-walled bilateral pulmonary cysts of widely varying sizes, without abnormal uptake. The patient was largely asymptomatic. Lung function testing, however, revealed restriction rather than obstruction, which is unusual in diffuse cystic lung disease. Biopsy of the mediastinal mass confirmed thymic MALT lymphoma which was treated medically with resultant improved lung function. This case highlights the association between SjS and MALT lymphoma, illustrates features which enable distinction between different causes of cystic lung disease in SjS, and comments on the multiplicity of SjS-related lung manifestations., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To propose and validate a CT radiomics model utilizing radiomic features from lymph nodes (LNs) with maximum short axis diameter (MSAD) < 1 cm for predicting small metastatic LN (sMLN) in patients with resectable esophageal squamous cell carcinoma (ESCC)., Methods: A total of 196 resectable patients with ESCC undergoing surgery were retrospectively enrolled, among whom 25% had sMLN. 146 out of 196 patients (from hospital 1) were randomly divided into the training (n = 116) and testing cohorts (n = 30) at an 8:2 ratio, while the remaining 50 patients from hospital 2 constituted the external validation cohort. Least absolute shrinkage and selection operator binary logistic regression was employed for radiomics feature dimensionality reduction and selection, and multivariable logistic regression analysis was used to construct the radiomics prediction model. The clinical features were statistically selected to develop the clinical model. And both the selected radiomics and clinical features were used to develop the combined model. The predictive value of models was assessed using the area under the receiver operating characteristic curves (AUC)., Results: The LN radiomics model was constructed with 9 radiomics features, the clinical model was developed with 3 clinical features, and the combined model was developed using both the LN radiomics and clinical features. However, no statistical radiomics features from ESCC were extracted in dimensionality reduction. Compared to the clinical model, the combined model exhibited superior predictive ability (AUC: 0.893 vs. 0.766, P = 0.003), and the LN radiomics model showed slightly better predictive ability (AUC: 0.860 vs. 0.766, P = 0.153). It was validated in the test and external validation cohorts., Conclusion: The combined model could assist in preoperatively identifying sMLN in resectable ESCC. It is beneficial for more accurate N staging and clinical comprehensive staging of ESCC, thereby facilitating the clinical physician to make more personalized and standardized treatment strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The incidence and mortality rates of early pulmonary embolism (PE) after thoracic surgery are high. Thrombolytic therapy is the basic treatment of PE. The aim of this study is to explore the safety and efficacy of thrombolytic therapy for patients with early postoperative PE., Methods: Data of forty patients excluding three patients with sudden death were analyzed. The included patients were divided into: thrombolysis + anticoagulation (group A, 21 cases) and anticoagulation (group B, 16 cases). Twenty patients had esophageal cancer and 17 had lung tumors. Bleeding, drainage volume, pulmonary infection, and perioperative mortality were compared between the groups. Factors related to perioperative mortality were analyzed by multivariate logistic regression., Results: The mortality rates of group A (19.0%) and B (81.3%) differed significantly. No massive hemorrhage or significant drainage volume differences were observed. Group A's D-dimer (D-D) level decreased, group B's D-D level increased, and was significantly different between after surgery and on the fourth day of treatment. Group B's partial oxygen pressure was significantly different between the third and fourth day of treatment, it gradually increased in group A, and remained unaltered in group B. Multivariate logistic regression supported a significant survival rate improvement., Conclusions: Thrombolytic therapy is safe and effective for PE early after thoracic surgery in the absence of absolute contraindications for anticoagulation and thrombolysis, and it can reduce mortality in patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-782/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objective: The present study was designed to investigate whether acellular dermal matrix (ADM) grafts could prevent Frey's syndrome (FS) and improve esthetic scores following parotidectomy., Methods: From January 2015 to December 2019, 175 patients underwent parotidectomy. We divided the patients into two groups: the ADM group and the control group. We included in each group 30 patients according to a propensity score matched analysis., Results: FS was subjective in 1 patient (3%) from the ADM group and 9 patients (30%) from the control group ( P =0.015). Patients in the ADM group had a subjective esthetic score of 6.1 + 1.7 compared with 5.2 + 1.7 in the control group. The subjective esthetic score for patients in the ADM group was higher than that for patients in the control group ( P =0.040)., Conclusion: The present clinical study suggests that ADM grafts are effective in preventing FS and improving esthetic scores after parotidectomy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The proton-electron coupling effect induces rich spectrums of electronic states in correlated oxides, opening tempting opportunities for exploring novel devices with multifunctions. Here, via modest Pt-aided hydrogen spillover at room temperature, amounts of protons are introduced into SmNiO 3 -based devices. In situ structural characterizations together with first-principles calculation reveal that the local Mott transition is reversibly driven by migration and redistribution of the predoped protons. The accompanying giant resistance change results in excellent memristive behaviors under ultralow electric fields. Hierarchical tree-like memory states, an instinct displayed in bio-synapses, are further realized in the devices by spatially varying the proton concentration with electric pulses, showing great promise in artificial neural networks for solving intricate problems. Our research demonstrates the direct and effective control of proton evolution using extremely low electric field, offering an alternative pathway for modifying the functionalities of correlated oxides and constructing low-power consumption intelligent devices and neural network circuits.

Purpose: To develop CT radiomics models of resectable esophageal squamous cell carcinoma (ESCC) and lymph node (LN) to preoperatively identify LN+., Materials and Methods: 299 consecutive patients with ESCC were enrolled in the study, 140 of whom were LN+ and 159 were LN-. Of the 299 patients, 249 (from the same hospital) were randomly divided into a training cohort (n = 174) and a test cohort (n = 75). The remaining 50 patients, from a second hospital, were assigned to an external validation cohort. In the training cohort, preoperative contrast-enhanced CT radiomics features of ESCC and LN were extracted, then integrated with clinical features to develop three models: ESCC, LN and combined. The performance of these models was assessed using area under receiver operating characteristic curve (AUC), and F-1 score, which were validated in both the test cohort and external validation cohort., Results: An ESCC model was developed for the training cohort utilizing the 8 tumor radiomics features, and an LN model was constructed using 9 nodal radiomics features. A combined model was constructed using both ESCC and LN extracted features, in addition to cT stage and LN+ distribution. This combined model had the highest predictive ability among the three models in the training cohort (AUC = 0.948, F1-score = 0.878). The predictive ability was validated in both the test and external validation cohorts (AUC = 0.885 and 0.867, F1-score = 0.816 and 0.773, respectively)., Conclusion: To preoperatively determine LN+, the combined model is superior to models of ESCC and LN alone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Lung cancer is the second most common form of malignant tumor and has the highest mortality rate worldwide. Among its subtypes, lung adenocarcinoma is the most prevalent. Leptomeningeal metastasis (LM) is rare and is characterized by a dismal prognosis, with overall survival periods typically spanning 4 to 6 weeks without treatment. However, in specific cases, survival can be extended to 4 to 6 months with appropriate therapy. The recent approval of third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib, aumolertinib, and furmonertinib, has introduced promising treatment options for individuals with non-small cell lung cancer (NSCLC) who develop LM after developing resistance to first- and second-generation TKIs. These third-generation TKIs exhibit an enhanced ability to penetrate the blood-brain barrier (BBB), opening up new avenues for managing this challenging condition., Case Summary: We report the case of a 48-year-old Chinese man diagnosed with advanced NSCLC harboring an epidermal growth factor receptor ( EGFR ) mutation. Following a pulmonary lobectomy and postoperative adjuvant therapy with gefitinib, the patient was diagnosed with LM, which was confirmed by his neurologic symptoms, cerebrospinal fluid cytologic analysis, and cranial enhancement magnetic resonance imaging. Subsequently, he received oral treatment in the form of 160 mg of furmonertinib daily. After 5 days of furmonertinib therapy, the patient recovered from lethargy, with an obvious improvement in cognitive function. Follow-up visits revealed a 6-month survival period following the LM diagnosis. Patients with NSCLC and LM typically present with severe symptoms, and the efficacy of systemic treatment, intrathecal chemotherapy, and radiotherapy remains unsatisfactory. We hope that this specific case provide valuable insights into the management of patients with EGFR mutation-associated NSCLC with LM., Conclusion: Furmonertinib, a third-generation EGFR TKI with notable BBB penetration, shows promise in LM control and the rapid alleviation of intracranial symptoms. Further investigations into appropriate dosage and toxicity management are imperative., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Chen, Liu, Shu, Fu, Gou, Lei and Jia.)

Purpose: To develop a novel CT-based model to predict pathological complete response (pCR) of locally advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant PD-1 blockade in combination with chemotherapy., Methods: 117 consecutive patients with locally advanced ESCC were stratified into training cohort (n = 82) and validation cohort (n = 35). All patients underwent non-contrast and contrast-enhanced thoracic and upper abdominal CT before neoadjuvant PD-1 blockade in combination with chemotherapy (CT pre ), and after two cycles of the therapy before esophagectomy (CT post ), respectively. Univariate analyses and binary logistic regression analyses of ESCC quantitative and qualitative CT features were performed to determine independent predictors of pCR. Prediction performance of the model developed with independent predictors from training cohort was evaluated by receiver operating characteristic (ROC) analysis, and validated by Kappa test in validation cohort., Results: In training cohort, the difference in CT attenuation between tumor and background normal esophageal wall obtained from CT pre (ΔTN pre ), tumoral increased CT attenuation after contrast-enhanced scan from CT post images (ΔT post ) and gross tumor volume (GTV) from CT pre were independent predictors of pCR (odds ratio = 1.128 (95% confidence interval (CI): 0.997-1.277), 1.113 (95%CI: 0.965-1.239) and 1.133 (95%CI: 1.043-1.231), respectively, all P-values < 0.05). Logistic regression model equation (0.121 × ΔTN pre  + 0.107 × ΔT post  + 0.125 × GTV - 9.856) to predict pCR showed the best performance with an area under the ROC of 0.876, compared with each independent predictor. The good performance was confirmed by the Kappa test (K-value = 0.796) in validation cohort., Conclusions: This novel model can be reliable to predict pCR to neoadjuvant PD-1 blockade in combination with chemotherapy in locally advanced ESCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Endothelial-mesenchymal transition (EndMT) is one of the critical factors leading to vascular remodeling in pulmonary hypertension (PH). Recent studies found that the expression of Cerebellin-2 (CBLN2) is significantly increased in the lung tissue of patients with PH, suggesting that CBLN2 may be closely related to the development of PH. This study aims to investigate the role and potential mechanism of CBLN2 in the hypoxia-induced EndMT of PH rats., Material and Methods: Hypoxia-induced PH rat model or EndMT cell model was constructed to investigate the role of CBLN2 in the process of endothelial mesenchymal transition during PH. The effects of CBLN2 siRNA, KC7F2 (HIF-1α inhibitor), and PDTC (NF-κB inhibitor) on hypoxia-induced EndMT were observed to evaluate the potential mechanism of CBLN2 in promoting EndMT., Key Findings: The right ventricular systolic pressure and pulmonary vascular remodeling index in hypoxia-treated rats were significantly increased. The transformation of endothelial cells (marked by CD31) to mesenchymal cells (marked by α-SMA) can be observed in the pulmonary vessels of PH rats, and the expression of CBLN2 in the intima was also significantly up-regulated. In the hypoxia-induced HPAECs, endothelial cell markers such as VE-cadherin and CD31 expression were significantly down-regulated, while mesenchymal-like cell markers such as α-SMA and vimentin were increased considerably, along with the increased expressions of CBLN2, p-p65, HIF-1α, and Twist1; CBLN2 siRNA, PDTC, and KC7F2 could inhibit those phenomena., Significance: CBLN2 can promote EndMT by activating NF-κB/HIF-1α/Twist1 pathway. Therefore, CBLN2 may be a new therapeutic target for PH., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no financial or conflicts of interest to disclose.

Objective: To detect the body surface temperature of the relevant back- shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back- shu points under the condition of lung disease., Methods: Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography., Results: The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group ( P <0.01, P <0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups ( P <0.01, P <0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) ( P >0.05)., Conclusion: The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.

: This report describes the spontaneous extrusion from between the eyelids of a presumed conjunctivolith in a patient with resolving severe herpes zoster ophthalmicus. A 57-year-old man presented for ophthalmologic assessment and management due to severe left herpes zoster ophthalmicus. At one subsequent ophthalmologic assessment, a conjunctivolith spontaneously egressed the lateral commissure of the OS when the lateral fornix was inspected. The conjunctivolith was retrieved from the floor of the consulting room. Electron microscopic analysis and energy dispersive spectroscopy was undertaken to determine its composition. Scanning electron microscopy showed that the conjunctivolith was composed of carbon, calcium, and oxygen. Transmission electron microscopy diagnosed Herpes virus within the conjunctivolith. Conjunctivoliths, or possible lacrimal gland stones, are a very rare phenomenon, and their etiology is currently unclear. In this case, there was likely to have been an association between herpes zoster ophthalmicus and the conjunctivolith., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: To assess whether specific selective neck dissection (SND) with involved levels is a feasible treatment for isolated regional failure in nasopharyngeal carcinoma (NPC) after radiation., Material and Methods: Between January 2011 and December 2019, a total of 46 patients were assigned to undergo SND in the Department of Head and Neck Surgery at our center. The dissection extent of specific SND usually only involved levels of lymph node sites for isolated regional failure; in addition, lesions of level II or III involved removing both level II and III lymph nodes. The patients' clinical, MRI and pathological characteristics, overall survival (OS), disease-free survival (DFS) and regional-free survival (RFS) were evaluated and analyzed., Results: Level II was the most commonly involved cervical nodal region in 28 neck dissection specimens (54.9%), followed by level III with positive nodes in 11 specimens (21.6%). Eleven patients (34.8%) had post-SND locoregional recurrence without distant metastasis. Of the patients, 7 patients (30.4%) had regional recurrence, and only one patient (2.8%) had lymph node recurrence on the side of SND. In addition, 8 patients (17.4%) had post-SND distant metastasis. The OS, DFS, and RFS of the patients were 76.1%, 58.7%, and 69.6%, respectively, at 3 years. The OS, DFS, and RFS values of patients who underwent SND were similar to those of patients who underwent comprehensive neck dissection (CND) and/or SND in published articles., Conclusion: Specific SND was shown to be an effective and feasible treatment for isolated regional failure in NPC., Competing Interests: Declaration of Conflict of InterestsThe author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A refractory cervical anastomotic fistula with sinus formation will seriously impede a patient's return to normal life. It is necessary to find ways to shorten the recovery time for such patients. We used a multilayered, pursestring inverted suture-embedding method for 7 patients, 6 of whom recovered; 1 patient with severe anastomotic stricture and failed. A multilayered, pursestring inverted suture-embedding method can be used to treat persistent neck anastomotic fistula with sinus formation, but it is not suitable for patients who still have a fistula to the mediastinum, thoracic cavity, or severely narrowed anastomoses., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O 2 ) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O 2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Photoelectrocatalysis (PEC) has shown great advantages in sustainable organic synthesis and wastewater treatment because the PEC process can minimize electron-hole recombination, thereby improving the photocatalytic performance. Here, we report a convenient procedure for preparing immobilized BiOX-TiO 2 photoelectrocatalytic electrodes from a titanium-oxo compound (TOC)-modified carbon fiber cloth (CFC). Crystalline TOCs composed of Ti 12 cations and bismuth halide anions, [Ti 12 O 14 (O i Pr) 18 ][Bi 3 Br 11 (THF) 2 ] ( 1 ) and [Ti 12 O 14 (O i Pr) 18 ][Bi 4 I 14 (THF) 2 ] ( 2 ), were grown on CFC. Taking advantage of the easy hydrolysis of the titanium-oxo cation and bismuth halide anion, we could easily transform these CFC-immobilized crystals into BiOX-TiO 2 /CFC (X = Br or I) photocatalysts, which facilitates recycling of the catalysts. The photocatalytic dye degradation test showed that the efficiency did not decrease obviously after 10 photocatalytic cycles. Using BiOX-TiO 2 -modified CFC as electrodes, electrocatalysis (EC), photocatalysis (PC), and PEC were examined. PEC showed an attractive synergistic effect of EC and PC. These TOC-modified CFCs would be potential candidates for catalytic electrodes for sustainable wastewater purification.

Competing Interests: The authors have no financial or conflicts of interest to disclose.

Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite the numerous titanium-oxo clusters (TOCs) which have been reported, the nature of small clusters (nuclearity < 10) as model compounds showed large deviation from that of nanoscale TiO materials. Therefore, theoretical and experimental studies for large TOCs merit more attention. We recently prepared and crystallographically characterized a series of large TOCs: Ti 11 O 15 (O i Pr) 16 (Cophen) ( 1 ), Ti 11 O 15 (O i Pr) 16 (Mnphen) ( 2 ), Ti 10 O 14 (OEt) 16 (Mnphen) 2 ( 3 ), and Ti 10 O 14 (OEt) 16 (Mnphphen) 2 ( 4 ) (phen = 1,10-phenanthroline, phphen = 4,7-biphenyl-phen). These compounds are derivatives of a Ti 12 parent cluster by replacing one or two of the five-coordinated titanium atoms of the Ti 12 cluster with a transition metal M, Co(II) and Mn(II), that is chelated by a phen group. The effects of mono- and bis-substituted Mphen on the charge and structure of the clusters are discussed. Theoretical evaluation of the frontier orbitals of the clusters is carried out on the basis of the precisely defined crystal structures. Different from the dye molecule to TiO core charge transfer for the dye-modified TOCs, charge transfer in these clusters is from TiO/TiOM to phen/Mphen. The effects of different metal ions and the number of substituted Mphen moieties on the photocurrent properties are evaluated. The results will be of interest to research on cluster chemistry, especially on the TOC chemistry.

Titanium oxides and bismuth halides or oxyhalides have been known to be excellent semiconductors with both excellent photocatalytic and photoelectric properties. The design of supersalts assembled by titanium-oxo clusters (TOCs) and bismuth iodide clusters is a hopeful strategy for exploring the chemistry and application of new titanium-oxo clusters. We report herein a series of unusual ionic TOCs with Ti 12 oxo cluster cations and bismuth iodide anions, [Ti 12 O 15 (O i Pr) 17 ] 3 [Bi 3 I 12 ] (Bi 3 ), [Ti 12 O 14 (O i Pr) 18 ][Bi 4 I 14 (THF) 2 ] (Bi 4 ), and [Ti 12 O 14 (O i Pr) 18 ][Ti 11 BiO 14 (O i Pr) 17 ][Bi 6 I 22 ] (Bi 6 ). Single-crystal X-ray analysis revealed that the type and charge of the Ti 12 clusters varied with the charges of different bismuth iodide clusters. Taking advantage of the easy hydrolysis of the TOCs and BiI clusters in water, we used these supersalt crystals as single-source precursors to prepare a p-n-type BiOI-TiO photocatalyst. The heterojunction materials were carefully characterized by powder X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, etc. The synergistic effect of the two components of BiOI and TiO on the photocatalytic degradation of RhB in water is demonstrated. This is a very convenient method for obtaining a p-n-type BiOI-TiO heterojuction photocatalyst by just placing the ground TOC crystals into water.

The Bokashi leachate (BL) is a by-product from the anaerobic digestion of food waste, following the Bokashi composting method. Bokashi leachate is acidic and it contains effective microorganisms hence it has potential to be a functional feed additive to the plant proteins based diets for fish farming. This study evaluated the growth performance and feed utilization of the red tilapia (Oreochromis sp.) fingerlings fed with the BL supplemented soybean meal (SBM) based diets. After an 8-week feeding trial, fish fed with the 5% BL supplemented SBM diet attained the highest weight gain. This result was significantly higher (p < 0.05) than those fed with the 0% BL supplemented SBM diet, and comparable (p > 0.05) to those fed with the control full fish meal (FM) diet. Generally, dietary inclusion of BL enhanced the fish feed intake on the SBM diet but it did not show clear sign of improvement in their feed utilization. In addition, no significant difference was found across the hepatosomatic index and viscerosomatic index from all dietary treatments. These outcomes concluded that dietary inclusion of BL can enhance the feed intake and growth performance of the red tilapia fingerlings fed with the SBM based diet without compromising their health, and the optimum BL inclusion level was 5%. Nevertheless, further study on the properties and substances content of the BL produced from different types and ratios of food waste is strongly recommended. In this study, BL was also discovered to be capable of reducing the crude fiber content in the SBM diets. Such observation deserves a further exploitation on the application of BL to manipulate the crude fiber content in the plant proteins based diets in fish farming., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aimed to review our experience with the clinical characteristics and management of deep neck infections (DNIs) and determine the changing trends of their characteristics over time in southern China. Patients diagnosed with a DNI between January 2009 and December 2018 were screened retrospectively for their demographic characteristics, etiology of infection, site of infection, microbiology, treatment, and complications. In total, 127 patients were included: 41 (32.3%) were treated between 2009 and 2013 (group A), and 86 (67.7%) were treated between 2014 and 2018 (group B). The most common site of infection in group A was the parapharyngeal space (15 patients, 36.6%), while that in group B involved multiple spaces (36 patients, 41.9%). The leucocyte count (×10 9  cells/L) was 13.23 ± 4.19 in group A and 16.04 ± 4.33 in group B ( p  < 0.001). Streptococcus viridans was the most common bacteria in both groups. The mean hospital stay was 21.46 ± 33.09 days in group A and 10.44 ± 6.19 days in group B. The rate of diabetes mellitus (DM) in group A was lower than that in group B (8/41 and 33/86, respectively; p  = 0.034). Airway obstruction was the most common complication in both groups. DNIs are more likely to show multi-space involvement, affect more DM patients, and be associated with higher leucocyte counts over time. We infer that the duration from morbidity to admission and that from admission to operation play roles in the successful management of DNIs, possibly causing fewer complications, lower mortality rates, and shorter hospital stays. DM patients require increased attention.

Objective: To investigate the effect of norcantharidin (NCTD) to proliferation of leukemia cells through disrupting key regulators of sonic Hedgehog (SHH) pathway and its downstream transcription factor SOX2., Methods: CCK8 was used to detected the HL60 and NB4 cells after inhibited by NCTD, SMO and GLI1 inhibitor for 24 hours. Expression level of SMO, GLI1 and SOX2 in HL60 cells with NCTD treatment was detected by immunoblot. HL60 cells were transfected with pcDNA3.1 plasmid expressing GLI1 or SOX2. Empty vector and pcDNA3. 1-EGFP were divided into negative and positive control group, respectively. The expression of exogenous GLI1 or SOX2 in HL60 cells was confirmed by immunoblot, and growth curve of HL60 cell was checked by CCK8. Proliferation of genetic modified HL60 cells treated by various dose of NCTD was detected., Results: NCTD, SMO/GLI1 inhibitors could inhibit the proliferation of NB4 and HL60 cells in a dose-dependent manner. Compared with solvent (DMSO)-treated control group, NCTD remarkably decreased protein level of SMO, GLI1 and SOX2. GLI1 and SOX2 were overexpressed in HL60 cells as compared with pcDNA3.1 empty vector-transfected group. Growth curve demonstrated significant proliferative advantage of GLI1/SOX2-transfected cells. CCK8 assay indicated that GLI1/SOX2-overexpressed HL60 cells were more resistant to NCTD treatment., Conclusion: NCTD attenuates HL60 proliferation via targeting the Hedgehog/SOX2 axis.

Black-TiO 2 has become increasingly interesting as a promising photoactive material. Most of the preparations for black-TiO 2 involve either high temperature calcination, plasma, lengthy chemical reactions or dealing with dangerous or toxic chemicals. We found, by accident, that Mo-Ti oxo-clusters are efficient catalysts for the hydrogenation of a TiO 2 electrode to black-TiO 2 at room temperature. A series of Mo-Ti oxo-clusters, [Ti 4 Mo 4 O 10 (OR) 14 (X-BA) 2 ] (BA = benzoate, X = H (1), F (2), Cl (3), and Br (4)), were prepared and were characterized by crystallography. They have a Mo 4 Ti 4 structure with Mo(v)-Mo(v) metal-metal interactions. The activated hydrogen (H*) generated by electrochemically catalytic water splitting turns the TiO 2 electrode to black-TiO 2 at room temperature, due to the reduction of Ti(iv) to H + Ti(iii). The potentials applied for water reduction must generally be higher than the overpotential at the TiO 2 electrode (-1.0 V vs. RHE). In this work, the onset potential of hydrogen evolution significantly decreased to -0.1 V vs. RHE. Using this blackened 1-TiO 2 electrode, the effective electrochemical catalytic degradation of a dye was examined in comparison with the degradation using the white TiO 2 electrode. This work provides a method for the facile preparation of a black-TiO 2 film, and is a step forward in black-TiO 2 research.

Incorporation of Eu complexes into various organic or inorganic matrixes is one of the acceptable strategies to obtain displaying materials having practical applications. In this work, we report a convenient approach to preparing high luminescent organic-inorganic hybrid materials and films from the europium-titanium oxo-clusters (EuTOCs) having photoactive antenna ligands. Three Eu 2 Ti 4 oxo-clusters were synthesized and crystallographically characterized. They are the first reported lanthanide-TOCs coordinated with 1,10-phenanthroline (phen) and 2,2'-bipyridine (bpy) as photoactive ligands, Eu 2 Ti 4 O 6 (phen) 2 (pa) 10 ( 1 ) (pa = propionate), Eu 2 Ti 4 O 6 (bpy) 2 (pa) 10 ( 2 ), and Eu 2 Ti 4 O 6 (phen) 2 (MA) 10 ( 3 ) (MA = methacrylate). Benefitting from the photoactive antenna ligands and the rigid cluster structures, these clusters showed bright red luminescence with quantum yield in the range of 60-80% and long lifetime up to 3.0 ms. Unlike those physically mixed polymeric materials, the MA coordinated compound 3 can be self-polymerized to form a brilliant luminescent film. The film coated slide was used to develop a fluorescence sensor for biomolecule ascorbic acid (AA). The low detection limit and reusable properties suggest great potential for such EuTOC films in real applications.

Background: The present study was designed to investigate the presence or absence of calcification and whether calcification size affect the diagnostic accuracy of ultrasonography (US) and computed tomography (CT) in predicting the benign or malignant nature of thyroid nodules., Material and Methods: From May 2014 to April 2019, 445 patients underwent thyroid US and neck CT before thyroid surgery. In each case, US and CT were retrospectively examined by radiologists. We divided the patients into 3 groups according to the type of calcification: no calcification, microcalcification, and macrocalcification. And macrocalcification group divided into rim calcifications and non-rim calcifications groups. We evaluated the diagnostic accuracy of US and CT for differentiating malignant from benign thyroid nodules using histopathological results as a reference standard., Results: In the overall population, adding CT to US resulted in greater sensitivity, lower specificity, and lower accuracy in the prediction of the benign or malignant nature of nodules. In the group with no calcification, US had a significantly greater accuracy than CT and combined US/CT. In the group with macrocalcification, especially in rim calcifications, adding CT to US resulted in greater sensitivity than US, and CT exhibited greater sensitivity and accuracy than US., Conclusion: US is superior to CT for the prediction of the benign or malignant nature of nodules in thyroid lesions according to calcification and CT is also currently not recommended as a routine imaging tool for thyroid nodules. However, the superior sensitivity and accuracy of CT in lesions with macrocalcification especially in rim calcifications may enable CT to play a complementary role in identifying benign and malignant nodules.

Objective: The aim of this study is to analyze the clinical features of the pseudoaneurysm of the cervical vascular in patients with nasopharyngeal carcinoma after radiotherapy, and to summarize the clinical signs of patients with cervical vascular aneurysm, and to provide a basis for improving the success rate of treatment. Method: Patients with hemorrhage disease were treated by digital subtraction angiography （DSA） after radiotherapy for nasopharyngeal carcinoma are included. According to the presence or absence of pseudoaneurysm （PSA）, patients are divided to pseudoaneurysm group （PSA group） and non-pseudoaneurysm group（non-PSA group）, analysis of gender, age, presence or absence of tumor recurrence, presence or absence of recurrent radiotherapy, history of nasopharyngeal surgery after radiotherapy, needed to open the airway before the interval therapy, time to the end of radiotherapy. Result: The rate of tumor recurrence was 80% （12/15） in patients with pseudoaneurysm and 60%（9/15） in recurrent radiotherapy, which was significantly higher than that in patients with non-pseudular aneurysms. The average time to the end of radiotherapy is 36.5 months in patients with pseudoaneurysm, significantly shorter than non-pseudoaneurysm patients（106.7 months）. Conclusion: The high-risk clinical features of patients with cervical vascular pseudoaneurysm include: ①recurrence of nasopharyngeal carcinoma; ②history of recurrent radiotherapy; ③interval time is shorter between the hemorrhage and the end of radiotherapy, usually taking place within a few months to two years after recurrent radiotherapy. Patients with the above characteristics need to be screened early, and the DSA should be used as early as possible to confirm the cervical vascular condition and effectively control the hemorrhage., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

The tumor microenvironment is the cellular environment that is also described as the "soil" for supporting tumor growth, proliferation, invasion and metastasis, as well as protecting tumor cells from immunological recognition. Notably, tumor cells can grow much faster than other normal organs and invade surrounding tissues more easily, which results in abnormal expression of enzymes in the tumor microenvironment, including matrix metalloproteinases, cathepsins, phospholipases, oxidoreductases, etc. In opposite, due to the high selectivity and catalytic activity, these enzymes can promote nanoparticles to recognize tumor tissues more accurately, and the more accumulation of drugs at primal tumor sites will enhance therapeutic efficacy with lower systemic toxicity. Therefore, one promising antitumor strategy is to design stimulus-responsive nanoscale delivery systems triggered by the enzymes with the support of various nanocarriers, such as liposomes, micelles and inorganic nanoparticles, etc. In this review, numerous facts were cited to summarize and discuss the typical types of enzyme-stimulus responsive nanoscale delivery systems. More importantly, we also focused on their recent advancements in antitumor therapy, and offered the direction for further studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Neoadjuvant chemotherapy (NAC) significantly extends survival in advanced esophageal squamous cell carcinoma (ESCC), but the short-term outcomes for cT4 ESCC remain controversial. Many NAC regimens have been previously reported, although no study has reported a regimen of irinotecan and nedaplatin for cT4 potential resectable ESCC. We evaluated the short-term outcomes of NAC with irinotecan and nedaplatin in a single cycle followed by esophagectomy on cT4 resectable ESCC. A total of 51 patients with cT4 potentially resectable ESCC were eligible for this study. Twenty of these patients underwent NAC, and the other 31 patients underwent surgery alone. The toxicities and response of NAC were evaluated. The clinicopathologic characteristics, responses, toxicities, surgical outcomes, postoperative complications, and survival time between the two groups were analyzed. No significant differences were found in clinicopathologic characteristics between the groups (P > 0.05). The response rate of NAC was 75% (15/20). The differences in the long-axis diameter of the tumor and cT stage between pre- and post-NAC were significant (P < 0.05). Twenty-four toxic events occurred in 11 patients of the NAC group, and 20/24 of these were mild. The R0 resection rates in the NAC group and the surgery alone group were 85% and 64.5%, with no statistically significant difference (P > 0.05). Differences in the pathological T stage and pathological tumor-node-metastasis (TNM) stage were significant (P < 0.05). The overall survival (OS) time and mortality in the NAC group versus the surgery alone group were 31.57 ± 3.06 months versus 15.24 ± 1.46 months and 25% versus 61.3%, respectively. The differences in OS and mortality were significant (P < 0.05). The NAC group and R0 resection were significant and independent predictors of positive prognosis. NAC with irinotecan and nedaplatin in a single cycle followed by esophagectomy on cT4 resectable ESCC as a new NAC is safe and effective., (© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Objective: To observe the early therapeutic effect of low-dose clarithromycin for chronic nasosinusitis with nasal polyps. Method: Clarithromycin was 250mg a day and budesonide nasal apray was once a day.Follow-up time was 12 weeks. The number of postoperative clarithromycin+budesonide nasal apray treatment group and simple budesonide nasal apray treatment group were forty. The early therapeutic effect of patients was assessed by SNOT-20 and EAS score before treatment,2 weeks,4 weeks,8 weeks,and 12 weeks. Result: Before treatment,at 2 weeks and 12 weeks,there was no significant difference between the two groups in the results of the SNOT-20 score. But there were significant differences at 4 weeks and 8 weeks.Before treatment and at 12 weeks, there was no statistically significant difference between the two groups in the results of the EAS score.But there were significant differences at 2 weeks,4 weeks,and 8 weeks. Conclusion: The early use of low-dose clarithromycin has a definite curative effect on patients of chronic rhinosinusitis with nasal polyps.The larger randomized controlled trials were still needed to verify the specific mechanism and optimal dosage., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD)., Methods: In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P<0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P<0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P<0.01). 18% patients (18/100) stated that the disease had affected their work., Conclusion: In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.

Breast cancer is the leading cause of cancer-related death for women, and multidrug resistance (MDR) is the major obstacle faced by chemotherapy for breast cancer. We have previously synthesized a doxorubicin (DOX) derivative by conjugating DOX with triphenylphosphonium (TPP) to achieve mitochondrial delivery, which induced higher cytotoxicity in drug-resistant breast cancer cells than DOX itself. Due to its amphiphilicity, TPP-DOX is difficult to physically entrap in nanocarriers. Thus, we linked it to hyaluronic acid (HA) by a novel ionic bond utilizing the specific bromide ion of TPP to form supra-molecular self-assembled structures (HA-ionic-TPP-DOX). The product was analyzed uisng 1 H-NMR, 13 C-NMR and mass spectrometry. The HA nanocarriers (HA-ionic-TPP-DOX) were shown to self-assemble into spherical nanoparticles, and sensitive to acidic pH in terms of morphology and drug release. Compared with free DOX, HA-ionic-TPP-DOX produced much greater intracellular DOX accumulation and mitochondrial localization, leading to increased ROS production, slightly decreased mitochondrial membrane potential, increased cytotoxicity in MCF-7/ADR cells and enhanced tumor targeting in vivo. In xenotransplant zebrafish model with the MCF-7/ADR cell line, both TPP-DOX and HA-ionic-TPP-DOX inhibited tumor cell proliferation without inducing significant side effects compared with free DOX. In addition, we observed a better anti-tumor effect of HA-ionic-TPP-DOX on MCF-7/ADR cells in zebrafish than that of TPP-DOX treatment. Furthermore, HA-ionic-DOX-TPP exhibited favorable biocompatibility and anti-tumor effects in MCF-7/ADR tumor-bearing nude mice in comparison with the effects of TPP-DOX and DOX, suggesting the potential of HA-ionic-TPP-DOX for the targeted delivery and controlled release of TPP-DOX, which can lead to the sensitization of resistant breast tumors.

Most polyps were originated from the contact areas of uncinate process, the middle turbinate or the ethmoid infundibulum. Polyp originated from nasal septum is extremely rare. We report a rare case of a 44-year old woman with unilateral polyp of nasal septum., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

To compare the differences in dietary status and knowledge of esophageal cancer (EC) between residents of high- and low-incidence areas. We investigated dietary conditions and EC knowledge among residents in high- and low-EC incidence areas (Yanting and Qingzhen counties). Residents in Yanting consumed more pickled vegetables, salted meat and barbecued food (P < 0.05). Analysis of the past ten-year trend in Yanting consumed fresh vegetables/fruits, beans, sauerkraut, hot food, and barbecued food had gradually increased, and the trend was less than that in Qingzhen County. However, the gradual increasing trend in consumption of pickled vegetables, pickled meat, and spicy food over the past 10 years was greater (P < 0.05). Drinking water in Yanting County was healthier than that in Qingzhen County (P < 0.05). In terms of EC knowledge, the proportions of residents in Yanting who had a clear understanding, knowledge or had heard of EC or knew the common causes, primary symptoms, therapeutic measures, preventive measures, and government interventions for EC were all higher than in Qingzhen (P < 0.05). Residents in Yanting had greater EC knowledge but more harmful dietary habits than those in Qingzhen.

Multidrug resistance (MDR) is the major obstacle for chemotherapy. In a previous study, we have successfully synthesized a novel doxorubicin (DOX) derivative modified by triphenylphosphonium (TPP) to realize mitochondrial delivery of DOX and showed the potential of this compound to overcome DOX resistance in MDA-MB-435/DOX cells. (1) To introduce specificity for DOX-TPP to cancer cells, here we report on the conjugation of DOX-TPP to hyaluronic acid (HA) by hydrazone bond with adipic acid dihydrazide (ADH) as the acid-responsive linker, producing HA- hydra-DOX-TPP nanoparticles. Hyaluronic acid (HA) is a natural water-soluble linear glycosaminoglycan, which was hypothesized to increase the accumulation of nanoparticles containing DOX-TPP in the mitochondria of tumor cells upon systemic administration, overcoming DOX resistance, in vivo. Our results showed HA- hydra-DOX-TPP to self-assemble to core/shell nanoparticles of good dispersibility and effective release of DOX-TPP from the HA- hydra-DOX-TPP conjugate in cancer cells, which was followed by enhanced DOX mitochondria accumulation. The HA- hydra-DOX-TPP nanoparticles also showed improved anticancer effects, better tumor cell apoptosis, and better safety profile compared to free DOX in MCF-7/ADR bearing mice.

Background: The functional characterization of non-coding microRNAs (miRNAs) has been shown to be associated with the pathophysiology of the disease, but it is still a challenging task to elucidate the pathogenesis of microRNAs and disease. In addition, the understanding of the role of miRNAs in the development of LSCC still needs further exploration., Materials and Methods: In this study, to identify miRNAs that play a key role in LSCC, we analyzed miRNA and mRNA sequence data from 162 LSCC samples from the TCGA database, and screened specific miRNAs and mRNAs by differential gene expression analysis. And then, construct a differentially expressed miRNAs and mRNAs interaction network., Results: In our investigation, 23 miRNAs (P < 0.01, log2FoldChange > 2) and 331 mRNAs (P < 0.01, log2FoldChange > 4) were identified differentially expressed in LSCC and reduced the number of loosely linked miRNAs and mRNAs according to appropriate thresholds. Finally, 13 miRNAs and 35 mRNAs were enriched in a network., Conclusions: Our study provides the most comprehensive information on the expression of miRNAs in LSCC and identifies the known oncogenic miRNAs (such as miR-163a), as well as aberrant expression of novel miRNAs involved in cell regulation and metabolic defects that occur during development of LSCC.

Currently, the limited penetration of nanoparticles remains a major challenge for antitumor nanomedicine to penetrate into the tumor tissues. Herein, we propose a size-shrinkable drug delivery system based on a polysaccharide-modified dendrimer with tumor microenvironment responsiveness for the first time to our knowledge, which was formed by conjugating the terminal glucose of hyaluronic acid (HA) to the superficial amidogen of poly(amidoamine) (PAMAM), using a matrix metalloproteinase-2 (MMP-2)-cleavable peptide (PLGLAG) via click reaction. These nanoparticles had an initial size of ∼200 nm, but once deposited in the presence of MMP-2, they experienced a dramatic and fast size change and dissociated into their dendrimer building blocks (∼10 nm in diameter) because of cleavage of PLGLAG. This rapid size-shrinking characteristic not only promoted nanoparticle extravasation and accumulation in tumors benefited from the enhanced permeability and retention effect but also achieved faster nanoparticle diffusion and penetration. We have further conducted comparative studies of MMP-2-sensitive macromolecules (HA-pep-PAMAM) and MMP-2-insensitive macromolecules (HA-PAMAM) synthesized with a similar particle size, surface charge, and chemical composition and evaluated in both monolayer cells and multicellular spheroids. The results confirmed that the enzyme-responsive size shrink is an implementable strategy to enhance drug penetration and to improve therapeutic efficacy. Meanwhile, macromolecule-based nanoparticles with size-variable characteristics not only promote drug penetration, but they can also be used as gene delivery systems, suggesting great potential as nano-delivery systems.

Transoral robotic surgery (TORS) is a relatively new technique in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome, which has been shown to be safe and feasible. TORS provides a minimally invasive, visualization method, which brings an unprecedented breakthrough in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome. In this paper, the application and development prospect of TORS in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome will be reviewed., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: Progressive cardiac conduction disease (PCCD) is a common pediatric heart conduction disorder. It is an autosomal inheritance of rare mutations, which leads to familial cases of PCCD. In these cases, the His-Purkinje system's conductive capacity is progressively deranged, involving either right or left bundle branch block. Also, QRS complexes display widening is an important characteristic that culminates in complete AV block, syncope, and sudden death. Mutations in TRPM4 gene that encodes for transient receptor potential melastatin 4 have recently been reported to cause familial cases of PCCD and heart block. TRPM4 conducts a Ca2+-activated non-selective monovalent cationic current leading to a negative plasma membrane potential. TRPM4 channels let Na+ ion influx, causing membrane depolarization, whereas, at positive membrane potentials, TRPM4 channels repolarize the membrane by facilitating K+ ion efflux from the cell. TRPM4 protein contains many regulatory motifs that confer voltage dependence, ATP/ADP sensitivity, and Ca2+ responsiveness. Mutational studies revealed the significance of the two-calmodulin binding sites at the N-terminus of for Ca2+ dependent activation of this channel. Mutations that reduce deSUMOylation increase the steady-state levels of active TRPM4 channels on the membrane without alteration of its sensitivity to Ca2+ or ATP or its voltage dependence of activation. Increased TRPM4 function interferes with cardiac conduction and eventually contributes to heart block. Both gain and loss of function mutations of TRPM4 are implicated in the cardiac block. Currently, the major therapeutic management of cardiac block due to TRPM4 mutations is implantation of a pacemaker to reinstate normal current propagation through AV node.

Objective: To analyze the links between NFATC1 gene polymorphism and congenital heart disease in children., Patients and Methods: In the present study, we selected 85 children patients with congenital heart disease who were hospitalized from February 2013 to February 2015 as research subjects (observation group), and 92 healthy subjects as control group. Restriction fragment length polymorphism (RFLP) was used for analysis of NFATC1 gene in samples from each group., Results: The distribution of NFATC1 genotype and allele between the observation group (children with congenital heart disease) and the control group showed no significant difference (p >0.05), but AA, GG genotypes, and allele frequency between pathological samples of children with congenital heart disease and the control group displayed significant difference (p <0.05) (X2 = 16.04, p <0.05; X2 = 16.29, p <0.05). Further analyses showed that AA, GG, AG genotype and allele frequency among children with congenital heart disease in observation group also showed a difference, i.e., homozygote (AA, GG) ratio in children with severe congenital heart disease is relatively high., Conclusions: There is a correlation between NFATC1 genes and the incidence of congenital heart disease in children, and a correlation between different genotypes and allele frequency and the incidence of the disease.