Inhibitory Effect of Evodiamine on Psoriasis Lesions and Itching in Mice.

Purpose: This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus. Methods: Imiquimod-induced psoriasiform dermatitis in mice was used as a model, and evodiamine was topically applied for seven days. The mice were observed daily for skin damage on the back, clinical score and their scratching behavior was recorded. Blood samples were collected on the final day of the experiment, and the serum levels of pruritus-associated inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) -23, and IL-17A were measured using enzyme-linked immunosorbent assay. Histopathological changes were observed in Hematoxylin and Eosin-stained skin specimens. The expression levels of transient receptor potential vanilloid (TRPV) 1, TRPV3, TRPV4, and the pruritus-related mediators Substance P (SP), nerve growth factor (NGF), and calcitonin gene-related peptide (CGRP) in the skin lesions were analyzed using Western blot and qRT-PCR. The effect of evodiamine on the exploratory behavior, motor, and coordination abilities of mice was assessed using open field, suspension, and Rota-Rod experiments. Molecular docking was utilized to verify the binding of evodiamine to the residues of TRPV1, TRPV3, and TRPV4. Results: Evodiamine reduced pruritus and inhibited inflammation by decreasing the levels of inflammatory mediators TNF-α, IL-23, and IL-17A in the serum of Imiquimod-induced mice and attenuated the mRNA and protein expression levels of SP, NGF, CGRP, TRPV1, TRPV3, and TRPV4 in the skin. Conclusion: Evodiamine is an effective treatment for psoriasis and pruritus, due to its ability to inhibit immune inflammation and pruritic mediators.

Transcriptome and Metabolome Analysis of Rice Cultivar CBB23 after Inoculation by Xanthomonas oryzae pv. oryzae Strains AH28 and PXO99A.

Bacterial leaf blight (BLB), among the most serious diseases in rice production, is caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23, the broadest resistance gene against BLB in rice, is widely used in rice breeding. In this study, the rice variety CBB23 carrying the Xa23 resistance gene was inoculated with AH28 and PXO99A to identify differentially expressed genes (DEGs) associated with the resistance. Transcriptome sequencing of the infected leaves showed 7997 DEGs between the two strains at different time points, most of which were up-regulated, including cloned rice anti-blight, peroxidase, pathology-related, protein kinase, glucosidase, and other coding genes, as well as genes related to lignin synthesis, salicylic acid, jasmonic acid, and secondary metabolites. Additionally, the DEGs included 40 cloned, five NBS-LRR, nine SWEET family, and seven phenylalanine aminolyase genes, and 431 transcription factors were differentially expressed, the majority of which belonged to the WRKY, NAC, AP2/ERF, bHLH, and MYB families. Metabolomics analysis showed that a large amount of alkaloid and terpenoid metabolite content decreased significantly after inoculation with AH28 compared with inoculation with PXO99A, while the content of amino acids and their derivatives significantly increased. This study is helpful in further discovering the pathogenic mechanism of AH28 and PXO99A in CBB23 rice and provides a theoretical basis for cloning and molecular mechanism research related to BLB resistance in rice.

Intelligent method to predict intensive care unit admission after drainage operation in patients with deep neck space abscess: A multicenter retrospective study.

BACKGROUNDS: A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA. METHODS: We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models. RESULTS: We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935. CONCLUSION: We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation.

Cold-induced inhibition of photosynthesis-related genes integrated by a TOP6 complex in rice mesophyll cells.

Photosynthesis is the most temperature-sensitive process in the plant kingdom, but how the photosynthetic pathway responds during low-temperature exposure remains unclear. Herein, cold stress (4°C) induced widespread damage in the form DNA double-stranded breaks (DSBs) in the mesophyll cells of rice (Oryza sativa), subsequently causing a global inhibition of photosynthetic carbon metabolism (PCM) gene expression. Topoisomerase genes TOP6A3 and TOP6B were induced at 4°C and their encoded proteins formed a complex in the nucleus. TOP6A3 directly interacted with KU70 to inhibit its binding to cold-induced DSBs, which was facilitated by TOP6B, finally blocking the loading of LIG4, a component of the classic non-homologous end joining (c-NHEJ) pathway. The repression of c-NHEJ repair imposed by cold extended DSB damage signaling, thus prolonging the inhibition of photosynthesis in leaves. Furthermore, the TOP6 complex negatively regulated 13 crucial PCM genes by directly binding to their proximal promoter regions. Phenotypically, TOP6A3 overexpression exacerbated the γ-irradiation-triggered suppression of PCM genes and led to the hypersensitivity of photosynthesis parameters to cold stress, dependent on the DSB signal transducer ATM. Globally, the TOP6 complex acts as a signal integrator to control PCM gene expression and synchronize cold-induced photosynthesis inhibition, which modulates carbon assimilation rates immediately in response to changes in ambient temperature.

Retraction Notice to: lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-ß-Induced Epithelial-Mesenchymal Transition.

[This retracts the article DOI: 10.1016/j.omtn.2020.08.003.].

Discovery of potent ebola entry inhibitors with (3S,4aS,8aS)-2-(3-amino-2-hydroxypropyl) decahydroisoquinoline-3-carboxamide scaffold.

Ebola virus (EBOV), one member of the family Filoviridae, can causes hemorrhagic fever and other severe diseases in humans with a high mortality rate (25-90%). Until recently, there were no approved drugs and very limited treatment method for Ebola virus disease. In this study, we discovered a series of potent Ebola entry inhibitors with the (3S,4aS,8aS)-2-(3-amino-2-hydroxypropyl)decahydroisoquinoline-3-carboxamide scaffold from high-throughput screening in reported pseudotyped virus system. Further optimization resulted a most potent compound 28 (IC50= 0.05 µM, SI = 98), which displayed 3-fold potency compared to the known inhibitor Toremifene (IC50= 0.17 µM, SI = 55). Moreover, compound 28 exhibited the remarkable selectivity between EBOV-GP and VSV-G (Spec. Index = 58), thus could exclude nonspecific effects. Structure-activity relationship and molecular docking analysis of the new chemical scaffold provided more information on the binding modes and the spare volume at the binding cavity, thus can guide the design of the further potent compounds.

Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression.

Mitochondrial dynamics can regulate Major Histocompatibility Complex (MHC)-I antigen expression by cancer cells and their immunogenicity in mice and in patients with malignancies. A crucial role in the mitochondrial fragmentation connection with immunogenicity is played by the IRE1α-XBP-1s axis. XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Mitochondrial fission inhibition with Mdivi-1 upregulates MHC-I expression on cancer cells and enhances the efficacy of adoptive T cell therapy in patient-derived tumor models. Therefore mitochondrial fission inhibition might provide an approach to enhance the efficacy of T cell-based immunotherapy.

Bacteriological analysis based on disease severity and clinical characteristics in patients with deep neck space abscess.

BACKGROUND: Deep neck space abscess (DNSA) is a serious infection in the head and neck. Antibiotic therapy is an important treatment in patients with DNSA. However, the results of bacterial culture need at least 48 h, and the positive rate is only 30-50%, indicating that the use of empiric antibiotic treatment for most patients with DNSA should at least 48 h or even throughout the whole course of treatment. Thus, how to use empiric antibiotics has always been a problem for clinicians. This study analyzed the distribution of bacteria based on disease severity and clinical characteristics of DNSA patients, and provides bacteriological guidance for the empiric use of antibiotics. METHODS: We analyzed 433 patients with DNSA who were diagnosed and treated at nine medical centers in Guangdong Province between January 1, 2015, and December 31, 2020. A nomogram for disease severity (mild/severe) was constructed using least absolute shrinkage and selection operator-logistic regression analysis. Clinical characteristics for the Gram reaction of the strain were identified using multivariate analyses. RESULTS: 92 (21.2%) patients developed life-threatening complications. The nomogram for disease severity comprised of seven predictors. The area under the receiver operating characteristic curves of the nomogram in the training and validation cohorts were 0.951 and 0.931, respectively. In the mild cases, 43.2% (101/234) had positive culture results (49% for Gram-positive and 51% for Gram-negative strains). The positive rate of cultures in the patients with severe disease was 63% (58/92, 37.9% for Gram-positive, and 62.1% for Gram-negative strains). Diabetes mellitus was an independent predictor of Gram-negative strains in the mild disease group, whereas gas formation and trismus were independent predictors of Gram-positive strains in the severe disease group. The positivity rate of multidrug-resistant strains was higher in the severe disease group (12.1%) than in the mild disease group (1.0%) (P < 0.001). Metagenomic sequencing was helpful for the bacteriological diagnosis of DNSA by identifying anaerobic strains (83.3%). CONCLUSION: We established a DNSA clinical severity prediction model and found some predictors for the type of Gram-staining strains in different disease severity cases. These results can help clinicians in effectively choosing an empiric antibiotic treatment.

Discovery of highly potent SARS-CoV-2 Mpro inhibitors based on benzoisothiazolone scaffold.

The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (Mpro) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 Mpro inhibition with an IC50 value of 116 nM and selectivity against SARS-CoV-2 Mpro when compared to PLpro and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.

A novel risk score for the prediction of airway management in patients with deep neck space abscess: a multicenter retrospective cohort study.

BACKGROUND: Airway management, including noninvasive endotracheal intubation or invasive tracheostomy, is an essential treatment strategy for patients with deep neck space abscess (DNSA) to reverse acute hypoxia, which aids in avoiding acute cerebral hypoxia and cardiac arrest. This study aimed to develop and validate a novel risk score to predict the need for airway management in patients with DNSA. METHODS: Patients with DNSA admitted to 9 hospitals in Guangdong Province between January 1, 2015, and December 31, 2020, were included. The cohort was divided into the training and validation cohorts. The risk score was developed using the least absolute shrinkage and selection operator (LASSO) and logistic regression models in the training cohort. The external validity and diagnostic ability were assessed in the validation cohort. RESULTS: A total of 440 DNSA patients were included, of which 363 (60 required airway management) entered into the training cohort and 77 (13 required airway management) entered into the validation cohort. The risk score included 7 independent predictors (p < 0.05): multispace involvement (odd ratio [OR] 6.42, 95% confidence interval [CI] 1.79-23.07, p < 0.001), gas formation (OR 4.95, 95% CI 2.04-12.00, p < 0.001), dyspnea (OR 10.35, 95% CI 3.47-30.89, p < 0.001), primary region of infection, neutrophil percentage (OR 1.10, 95% CI 1.02-1.18, p = 0.015), platelet count to lymphocyte count ratio (OR 1.01, 95% CI 1.00-1.01, p = 0.010), and albumin level (OR 0.86, 95% CI 0.80-0.92, p < 0.001). Internal validation showed good discrimination, with an area under the curve (AUC) of 0.951 (95% CI 0.924-0.971), and good calibration (Hosmer-Lemeshow [HL] test, p = 0.821). Application of the clinical risk score in the validation cohort also revealed good discrimination (AUC 0.947, 95% CI 0.871-0.985) and calibration (HL test, p = 0.618). Decision curve analyses in both cohorts demonstrated that patients could benefit from this risk score. The score has been transformed into an online calculator that is freely available to the public. CONCLUSIONS: The risk score may help predict a patient's risk of requiring airway management, thus advancing patient safety and supporting appropriate treatment.

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-Specific CAR T Cells in Solid Tumors.

PURPOSE: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types. EXPERIMENTAL DESIGN: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with in vitro and ex vivo experiments. RESULTS: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines in vitro. A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers in vitro and ex vivo, including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions. CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.

LncRNA LTSCCAT promotes tongue squamous cell carcinoma metastasis via targeting the miR-103a-2-5p/SMYD3/TWIST1 axis.

Abnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g) for 6 days and then performed LncRNA sequencing on P.g-LPS-treated CAL27 cells and untreated CAL27 cells. LTSCCAT was upregulated in P.g-LPS-treated CAL27 cells compared with untreated CAL27 cells. LTSCCAT induced epithelial-mesenchymal transition and promoted the invasion and metastasis of TSCC in vitro and in vivo. LncRNA LTSCCAT was upregulated in TSCC patients with periodontitis and was correlated with metastasis and poor prognosis. We predicted through an online database and confirmed by dual-luciferase reporter assays that LTSCCAT is a competitive endogenous RNA for the regulation of miR-103a-2-5p. Another dual-luciferase reporter assay confirmed that miR-103a-2-5p has a binding site at the 3'-UTR of the histone methylation transferase SMYD3 and inhibits its translation. Chromatin immunoprecipitation experiments demonstrated that SMYD3 binds directly to the promoter region of TWIST1 and promotes its transcription, which is related to H3K4 trimethylation. The effect of pcDNA/LTSCCAT on expression was attenuated by miR-103a-2-5p mimics. The RF and SVM classifier predicts that LTSCCAT can bind to SMYD3, whereas the RNA immunoprecipitation (RIP) assay confirms that it cannot. In addition, we predicted the combination of LTSCCAT and SMYD3 through software, but the RIP assay confirmed that LTSCCAT could not be combined with SMYD3. For the first time, we showed that periodontitis promotes the invasion and metastasis of TSCC and clarified the molecular mechanism of LTSCCAT to promote invasion and metastasis of TSCC, providing a potential therapeutic target for clinical treatment of TSCC.

Application of Coblation Tonsillectomy with Inferior Pole Capsule Preservation in Pediatric Patients.

OBJECTIVES/HYPOTHESIS: To evaluate the application and advantages of coblation tonsillectomy with inferior pole capsule preservation in pediatric patients with tonsillar hypertrophy and recurrent tonsillitis. STUDY DESIGN: Retrospective chart review. METHODS: A total of 726 children who were diagnosed with either tonsillar hypertrophy or recurrent tonsillitis were included. Children were divided into two groups according to the surgical technique: conventional coblation tonsillectomy and coblation tonsillectomy with inferior pole capsule preservation. The duration of surgery, intraoperative hemorrhage volume, and postoperative pain, as well as postoperative hemorrhage data in the format of time, location, and degree were compared between the two groups. RESULTS: Of the 726 children included, conventional coblation tonsillectomy was performed in 320 children, coblation tonsillectomy with inferior pole capsule preservation was performed in 406 children. There were no significant differences in duration of surgery or intraoperative hemorrhage volume between the two groups. Children who underwent coblation tonsillectomy with inferior pole capsule preservation showed a remarkable improvement in postoperative pain on days 3 and 5 postoperatively. Additionally, the coblation tonsillectomy with inferior pole capsule preservation group exhibited a significantly lower total postoperative hemorrhage rate, secondary hemorrhage rate, and hemorrhage rate in the inferior pole compared with that in the conventional coblation tonsillectomy group. During the 1-year follow-up period, no cases of tonsillar re-hypertrophy or recurrent tonsillitis were observed in either group. CONCLUSION: For pediatric tonsillar hypertrophy and recurrent tonsillitis, coblation tonsillectomy with inferior pole capsule preservation is a safe and effective technique, capable of reducing postoperative pain and hemorrhage, especially secondary hemorrhage at the inferior pole. LEVEL OF EVIDENCE: 3b Laryngoscope, 131:1157-1162, 2021.

The effect of silencing the endoplasmic reticulum stress-related protein calnexin on the proliferation, invasion, and migration of tongue squamous cell carcinoma cells / 口腔疾病防治

Objective@#To investigate the effect of silencing the endoplasmic reticulum stress-related protein calnexin on the proliferation, invasion, and migration of tongue squamous cell carcinoma cells. @* Methods @#Calnexin siRNA was transfected into SCC-9 and SCC-25 tongue squamous cell carcinoma cells, and the expression of calnexin was detected by qRT-PCR. The silencing effect of calnexin siRNA was further verified by Western blotting. CCK-8 assay was applied to detect the effect of silencing calnexin on the proliferation of tongue squamous cell carcinoma cells; Transwell assay was used to detect the effect of silencing calnexin on the invasion and migration of tongue squamous cell carcinoma cells.@* Results @#qRT-PCR showed that calnexin siRNA could effectively downregulate the expression of calnexin. Western blot analysis further confirmed the silencing effect of calnexin siRNA on calnexin. The CCK-8 assay showed that silencing calnexin expression on the 4th and 5th days could inhibit the proliferation of tongue squamous cell carcinoma cells, and the difference was statistically significant (P < 0.01). The Transwell assay showed that knockdown of calnexin could inhibit the invasion and migration of tongue squamous cell carcinoma cells (P < 0.001).@*Conclusion@#Knockdown of calnexin can inhibit the proliferation, invasion, and migration of tongue squamous cell carcinoma cells.

The microRNA miR-29c-5p inhibits cell proliferation and migration by targeting TMEM98 in head and neck carcinoma.

Head and neck squamous cell carcinoma (HNSCC), which occurs frequently worldwide, is characterized by high risk of metastasis. MicroRNAs (miRNAs) play crucial roles in tumorigenesis and cancer development. In this study, miR-29c-5p was identified using three high throughput microarrays. We measure miR-29c-5p expression in HNSCC tissues and cell lines. To determine the function of miR-29c-5p in HNSCC, we evaluated its effects in vitro on cell proliferation, the cell cycle, apoptosis, and cell migration. We employed a mouse tumor xenograft model to determine the effects of miR-29c-5p on tumors generated by HNSCC cell lines. The miR-29c-5p expression was lower in HNSCC tissues than in normal tissues. Upregulated miR-29c-5p expression in HNSCC cells inhibited migration and arrested cells in the G2/M phase of the cell cycle. Further, upregulated miR-29c-5p expression inhibited the proliferation of HNSCC cells in vivo and in vitro. In addition, transmembrane protein 98 (TMEM98) was identified as a direct target of miR-29c-5p by using a luciferase reporter assay. These findings provide new insights that link the regulation of miR-29c-5p expression to the malignant phenotype of HNSCC and suggest that employing miR-29c-5p may serve as a therapeutic strategy for managing patients with HNSCC.

lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-ß-Induced Epithelial-Mesenchymal Transition.

The transforming growth factor-ß (TGF-ß)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-ß/Smads signal. The present study was conducted to test the hypothesis that lnc-TSI inhibits metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the TGF-ß/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-ß/Smads signal. Depleting lnc-TSI enhanced tumor cell invasion and metastasis in vitro and ccRCC lung metastasis in vivo, whereas overexpressing lnc-TSI inhibited ccRCC cell invasion and tumor metastasis. Mechanistic studies indicated that lnc-TSI specifically inhibited the phosphorylation of Smad3 and subsequent EMT by binding with the MH2 domain of Smad3 to block the interaction between Smad3 and TGF-ß receptor I in ccRCC cells. In a cohort of 150 patients with ccRCC, expression of lnc-TSI in tumors was negatively correlated with phosphorylated (p)Smad3 and activated EMT markers. Patients with expression of tumor lnc-TSI greater than or equal to the median at radical nephrectomy had a higher survival rate compared to those with lnc-TSI below the median during follow-up. These findings reveal a new regulatory mechanism of ccRCC metastasis and suggest a potential molecular target for the development of anti-cancer drugs.

UBR5 regulates proliferation and radiosensitivity in human laryngeal carcinoma via the p38/MAPK signaling pathway.

Laryngeal carcinoma (LCC) is a common malignant tumor with low radiosensitivity and generally poor response rates. The ubiquitin protein ligase E3 component n­recognin 5 (UBR5) has prognostic implications in several neoplasms; however, its role in LCC and radiotherapy sensitivity remains unknown. Immunohistochemistry and bioinformatics analyses were performed to measure UBR5 protein and mRNA expression in LCC and adjacent non­tumor tissues. The gene and protein expression of UBR5 in LCC and HuLa­PC cell lines were measured using quantitative PCR and western blot analyses. Following transfection with small interfering RNA or UBR5 overexpression plasmid in LCC cells, the proliferation, cell cycle distribution, invasion, migration and radiosensitivity of LCC cells were analyzed. UBR5­related lncRNA, targeted miRNA and protein­protein interaction networks were analyzed using bioinformatics. Finally, the expression of the p38/mitogen­activated protein kinase (MAPK) pathway was evaluated following UBR5 silencing in M2E cells treated with radiation. Increased UBR5 expression was observed in LCC tissues compared with adjacent non­tumor tissues, and it was correlated with poor overall survival of LCC patients. After overexpression or silencing of UBR5 in M2E and M4E LCC cells, cell proliferation and radiosensitivity were significantly increased or decreased, respectively, compared with the control groups. The percentage of S phase cells decreased in the UBR5 si­RNA group compared with that in the control group, while overexpression of UBR5 exerted no effect on the cell cycle. In addition, the expression of Bcl­2 and p38 was decreased in the si­UBR5 combined with radiation groups. The level of phosphorylated p38 expression was increased after combination of si­UBR5 with radiation. The small molecule inhibitor of p38/MAPK signaling, SB203580, decreased the viability of UBR5­overexpressing cells and the survival fraction when cells were exposed to radiation. These findings demonstrated that UBR5 may be involved in regulating cell proliferation and sensitivity to radiotherapy in LCC via the p38/MAPK pathway, thereby highlighting its possible value for the development of new therapeutic strategies and targets for the treatment of this disease.

[Application of combined intracapsular and extracapsular hypothermic plasma tonsillectomy in reducing intraoperative and postoperative hemorrhage in children with OSA].

Objective:The aim of this study is to explore the application and advantages of combined intrathecal and extrathecal hypothermic plasma tonsillectomy in reducing intraoperative and postoperative hemorrhage in OSA children. Method:We retrospectively reviewed 726 cases who were diagnosed as OSA. All patients were divided into two groups according to the surgical method: 320 cases by total tonsillectomy and 406 cases by combined extracapsular and intracapsular tonsillectomy. The intro operative bleeding volume, post operative haemorrhage data as time, location and degree in the two groups were compared. Result:There was no statistical difference in the intro operative bleeding volume in the two groups [（9.3±4.6） mL]vs [（7.6±3.5） mL], t=12.687, P=0.235. Two patients who underwent combined extracapsular and intracapsular tonsillectomy presented with post operative haemorrhage, the total post operative haemorrhage rate was significantly decreased that in the total tonsillectomy group（14 cases）（χ²=10.779, P=0.001）. The 2 patients in combined extracapsular and intracapsular tonsillectomy group were secondary haemorrhage, with location in the upper pole and medium, grade A haemorrhage; while in the 14 cases in in the total tonsillectomy group, there were 2 cases presented with primary haemorrhage and 12 cases with secondary haemorrhage; with regard to location of haemorrhage, 1 in the upper pole, 2 in the medium, 11 in the lower pole; 5 cases presented with grade A haemorrhage, 8 with grade B haemorrhage and 1 with grade C haemorrhage. The haemorrhage rate at 7 days after surgery （χ²=5.697, P=0.017）, at the lower pole（χ²=11.961, P=0.001） and grade B（χ²=8.097, P=0.004） were all significantly decreases in the combined extracapsular and intracapsular tonsillectomy group. Conclusion:Plasma tonsillectomy combined with intrathecal and extrathecal hypothermic tonsillectomy is a safe and effective method, which has obvious advantages in reducing the postoperative hemorrhage, especially the secondary hemorrhage of Subtonsillar Pole.

[Application of fibreoptic endoscope evaluating of oropharyngeal swallowing in post-irradiated patients with nasopharyngeal carcinoma].

Objective:The aim of this study is to investigate the effect of fibreoptic endoscopic of sallowing （FEES） in the assessment of pharyngeal dysphagia in post-irradiated patients with nasopharyngeal carcinoma. Method:Fifty-three NPC patients with post-irradiated underwent FEES and video fluoroscopy（VF）.The results were analyzed using the Bolus Residue Scale and Rosenbek's penetration aspiration scale. Result:The agreement in the detection of penetration and aspiration between FEES and VF of liquid（κ=0.56, 95%CI 0.38-0.73） and porridge（κ=0.64, 95%CI 0.43-0.81） was "fair". The detection rates of penetration on FEES with liquid and porridge were 60% and 51%, the detection rates of aspiration on VF with liquid and porridge were 70% and 53%. There were no statistical differences. The agreement in the detection of pharyngeal residue between FEES and VF of liquid （κ=0.38, 95%CI0.12-0.62） and porridge （κ=0.66, 95%CI 0.44-0.86） was "fair". The detection rates of pharyngeal residue on FEES and VF with porridge were 43% and 45%, the difference was not statistically significant. The detection rates of pharyngeal residue on FEES and VF with liquid were 44% and 24%, and the difference was statistically significant. Conclusion:FEES is an effective and valuable tool for evaluating pharyngeal dysphagia in post-irradiated patients with nasopharyngeal carcinoma.

lncRNA CISAL Inhibits BRCA1 Transcription by Forming a Tertiary Structure at Its Promoter.

Cisplatin-based neoadjuvant chemotherapy has been shown to improve survival in patients with squamous cell carcinoma (SCC), but clinical biomarkers to predict chemosensitivity remain elusive. Here, we show the long noncoding RNA (lncRNA) LINC01011, which we termed cisplatin-sensitivity-associated lncRNA (CISAL), controls mitochondrial fission and cisplatin sensitivity by inhibiting BRCA1 transcription in tongue SCC (TSCC) models. Mechanistically, we found CISAL directly binds the BRCA1 promoter and forms an RNA-DNA triplex structure, sequestering BRCA1 transcription factor-GABPA away from the downstream regulatory binding region. Importantly, the clinical relevance of these findings is suggested by the significant association of CISAL and BRCA1 expression levels in TSCC tumors with neoadjuvant chemosensitivity and overall survival. We propose a new model where lncRNAs are tethered at gene promoter by RNA-DNA triplex formation, spatially sequestering transcription factors away from DNA-binding sites. Our study uncovers the potential of CISAL-BRCA1 signaling as a potential target to predict or improve chemosensitivity.