[Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen].

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p.

The article "LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p, by M.-M. Wu, W.-D. Shen, C.-W. Zou, H.-J. Chen, H.-M. Guo, published in Eur Rev Med Pharmacol Sci 2020; 24 (11): 6031-6038-DOI: 10.26355/eurrev_202006_21497-PMID: 32572917" has been withdrawn from the authors due to some technical issues in the data retrieval. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21497.

[Reconstruction of complex tissue defects in temporal region: report of 3 cases].

Objective: To discuss the techniques and repairing methods of various degree of compound tissue defects in the auriculotemporal region. Methods: Retrospective analysis was conducted on three cases of different repairing methods for huge compound tissue defects in different degrees in the auriculotemporal region after the resection of the malignant tumor or sinus tract due to repeated infection in our hospital. Results: Following total removal of the tumors or sinus tract in all patients, we applied retroauricular lingual flap transfer repairing, latissimus dorsi flap free transfer repairing and vascular anastomosis, scalp tissue expansion in stage Ⅰ, then repairing the lesion with expanded scalp and filling the huge mastoid cavity with abdominal fat in stage Ⅱ, respectively, according to the characteristics of compound tissue defects in the auriculotemporal region. All free flaps survived well. Conclusions: The anatomy of the auricular-temporal area is complex and involves important vascular and neural structures of head and neck and lateral skull base. The huge composite tissue defect following auriculotemporal region surgery, which is composed of skin, muscle and bone tissue, needs to be repaired in one stage. Therefore, flexible repairing methods should be chosen based on different situations, for attaining the goal of completely removing tumor and lesions, and then, covering the operation cavity.

Accurate diagnosis of colorectal cancer based on histopathology images using artificial intelligence.

BACKGROUND: Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. METHODS: Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. RESULTS: Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. CONCLUSIONS: This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p.

OBJECTIVE: The aim of this study was to explore the functional changes of long non-coding ribonucleic acid (lncRNA)-HEIH on hepatocellular carcinoma (HCC) Huh7 and Hep3B cells. PATIENTS AND METHODS: The expression changes of HEIH in 18 pairs of HCC tissues and adjacent normal tissues were detected by quantitative real time-polymerase chain reaction (qRT-PCR). According to its expression changes in HCC cells silenced by short hairpin ribonucleic acid (shRNA) transfection in vitro, these cells were divided into sh-HEIH group and sh-NC group. The effects of lowly expressed HEIH on the proliferation, migration and apoptosis of HCC cells were examined through functional assays. Western blotting was adopted to determine the expression changes of epithelial-mesenchymal transition (EMT) proteins, vimentin, matrix metalloproteinase (MMP)-2 and MMP-3. In addition, the role of HEIH downstream effector micro RNA (miR)-199a-3p in HCC was explored. RESULTS: Compared with adjacent normal tissues, HEIH was highly expressed in HCC tissues (p<0.01). HEIH silencing significantly inhibited the proliferation and migration, but induced the apoptosis of Huh7 cells (p<0.05). The expressions of vimentin and MMP-2 in sh-HEIH group were remarkably lower than those in sh-NC group (p<0.05). Furthermore, miR-199a-3p was identified as the downstream effector of HEIH. The expression of miR-199a-3p increased markedly in Huh7 and Hep3B cells with silenced HEIH expression (p<0.01). Moreover, when miR-199a-3p expression was inhibited, the effects of HEIH on Huh7 and Hep3B cells were weakened, manifested as notably enhanced cell proliferation and migration capabilities (p<0.05). CONCLUSIONS: LncRNA-HEIH suppresses HCC cell growth and metastasis by up-regulating miR-199a-3p. Our findings suggest that HEIH may be a promising target for HCC treatment.

[Clinical diagnosis and surgical management of 110 cases of facial nerve schwannomas].

Objective: To elucidate the clinical behavior, causes of misdiagnosis, surgical management, and outcomes of facial nerve schwannomas (FNS). Methods: A retrospective review in Chinese People's Liberation Army General Hospital from January 1, 2002 to December 31, 2015 was carried out and evaluated 110 patients with FNS, including 50 males and 60 females, aged 16-67 years old. The appropriate surgical strategy was selected based on each patient's clinical manifestations, facial nerve function, and imaging characteristics. After surgery, patients received follow-up visits to assess their facial nerve functions, with the effect of treatment compared to the reality before surgery. The Kruskal-Wallis H test was used to distinguish between the pre- and post-operation facial nerve functions in patients who had different facial nerve functions before the operations. Results: 110 cases of FNS mainly presented with facial paralysis, hearing loss, tinnitus, otalgia, dizziness, and facial spasm. 20 of the cases were misdiagnosed as Bell's Palsy, 6 were mistaken for chronic otitis media/cholesteatoma with radical mastoidectomy, 3 were mistaken for Meniere's disease, 1 was misdiagnosed as petrous bone cholesteatoma, and 4 were mistaken for acoustic neuroma. 81.8 % (90/110) of the patients had multiple segments of the facial nerve, including the vertical segment of the facial nerve, accounting for 65.5% (72/110), followed by the labyrinthine/geniculate segment, for 61.8% (68/110), and the horizontal segment, for 55.5% (61/110). The appropriate surgical approaches were chosed based on the sizes and scopes of the tumors evaluated by imaging: transmastoid approach in 73 cases, translabyrinthe approach in 14 cases, middle cranial fossa approach in 13 cases, retrosigmoid approach in 3 cases, transmastoid-middle cranial fossa approach in 3 cases, and transmastoid-neck approach in 4 cases, with all the patients undergoing a total/subtotal resection of the tumor. Eighty-seven patients had their facial nerves reconstructed. Among them, 6 received facial nerve end-to-end anastomosis, 55 received great auricular nerve graft, and 26 were subjected to facial nerve-hypoglossal nerve anastomosis. Because of long histories, facial muscle atrophies, or other reasons, the remaining patients were not received facial nerve reconstruction. The House-Brackmann(H-B) grading scale was used to evaluate the facial nerve function pre- and post-operation. Patients with better facial nerve functions and shorter history of facial paralysis before operation would get relatively better facial nerve function. The before and after operation comparisons revealed that the recovery of the facial nerve functions in patients with H-B Ⅰ-Ⅲ was better than the improvement in patients with H-B Ⅳ-Ⅴ. The difference was statistically significant (Kruskal-Wallis H test, H=8.508, P<0.05). Conclusions: The diagnosis of patients with unknown facial paralysis, hearing loss, and tinnitus should take into account the possibility of FNS. CT and other imaging examinations of the temporal bone can avoid misdiagnosis and determine the tumor size and extent of lesions, as well as provide the basis for the choice of the surgical approach. After tumors have been completely resected, facial nerve reconstruction can be performed simultaneously, according to the defect of the nerve.

[Neurofeedback therapy in the treatment of tinnitus].

Neurofeedback therapy is a fast-growing field of tinnitus treatment, which is a new type of biofeedback therapy. In the past, the "muscle tone" and "blood flow" were used as feedback signals in biofeedback therapy to treat tinnitus, however there was no long-term follow-up report. Instead, neurofeedback therapy utilizes EEG (electroencephalogram) as the feedback signal, which is also called EEG biofeedback therapy. At present, most treatments of tinnitus only record subjective measures of patients as evaluation indicators, whereas neurofeedback therapy is more convincing for using comprehensive evaluation including changes of brain wave as objective indicators and subjective measures of patients. A significant number of tinnitus patients have varying degree of hearing loss. As neurofeedback therapy takes advantage of EEG as feedback signal that is delivered to the patients through visual information, it has unique advantages of being not affected by the degree of hearing loss compared to the sound masking or other sound treatment. Long-term follow-up results showed that the efficacy of neurofeedback therapy was stable after half a year of short-term treatment. This paper summarizes the progress of the various types of biofeedback therapy in the treatment of tinnitus, and focuses on the neurofeedback therapy for the mechanism, indication, process, efficacy evaluation, defect and prospect of neurofeedback therapy in tinnitus treatment in order to help promote the development of domestic clinical neurofeedback therapy in tinnitus.

[Petrous bone cholesteatoma: surgery approach and outcomes].

Objective: To investigate the choice of surgical approach of petrous bone cholesteatoma (PBC)and surgical outcomes. Methods: A retrospective study was performed on 90 patients diagnosed and treated for PBC from January 2000 to December 2014 by the Chinese People's Liberation Army General Hospital otolaryngologists. According to Sanna's classification, 40 out of the 90 cases were supralabyrinthine, five infralabyrinthine, four infralabyrinthine-apical, 25 massive and 16 apical. Five cases underwent transmastoid and retrolabyrinthine approach, translabyrinthine approach was performed on six patients, 19 cases underwent subtotal petrosectomy, seven cases underwent transotic approach, 41 cases underwent middle fossa approach, combined transmastoid/middle fossa approach was performed on 11 cases, translabyrinthine and sphenoid sinus approach were performed on one case. Supralabyrinthine cases mainly applied middle fossa approach (77.5%, 31/40) and combined transmastoid and middle-fossa approach(20.0%, 8/40). Combined transmastoid-retrolabyrinthine approach were applied for all the infralabyrinthine cases (100.0%, 5/5). Infralabyrinthine-apical cases mainly applied subtotal petrosectomy (75.0%, 3/4). Massive cases mainly applied subtotal petrosectomy (60.0%, 15/25), transcochlear approach (20.0%, 5/25), and translabyrinthine approach (16.0%, 4/25). Apical cases mainly applied middle fossa approach (62.5%, 10/16). Results: Ninty percent (18/20) of the patients who had preoperative grade Ⅰ facial nerve function maintained in the postoperative period. Out of 90 cases, only 11 cases received open cavity, and the rest cases received cavityobliteration. There were three cases of recurrence, four cases of cavity infection, three cases of cerebrospinal fluid leakage, and one case of epidural hematoma, who all received surgeries. Conclusions: Sanna's classification should be used to classify different kinds of PBC cases, choose the best surgical approach for different cases, and preserve or repair facial function during removal of PBC, and thus reduce recurrence and complications.

[The surgical treatment of middle ear cholesteatoma complicated with peripheral facial paralysis (with 22 cases)].

Objective:To summarize the clinical characteristics, the surgical methods and the recovery of facial nerve function outcomes in patients with the middle ear cholesteatoma complicated with peripheral facial paralysis.Method:Retrospective analysis method was used on patients treated for middle ear cholesteatoma associated with peripheral facial paralysis. Facial nerve decompression and great auricular nerve grafting were performed for restoration of facial nerve. Facial nerve function was assessed with the House-Brackmann (H-B) grade scale. Spearman test was employed for statistic analysis.Result:Surgical exploration revealed that the cholesteatoma was mainly located in epitympanic cavity, mastoid and sinus tympani, which mainly damaged the tympanic segment of facial nerve. Nineteen cases with facial nerve edema, including complete sheath (n=15) and sheath defect (n=4), were performed decompression. Among which 15 recovered to H-B Ⅰ, 3 recovered to H-B Ⅱ, 1 recovered to H-B Ⅳ. Three cases with facial nerve disrupt underwent great auricular nerve grafting, 1 recovered to H-B Ⅳ, 2 recovered to H-BⅤ. The rate of recovery to H-B Ⅰ or Ⅱ in patients underwent surgery within 2 weeks was 92.3%(12/13).Conclusion:When the middle ear cholesteatoma complicated with peripheral facial paralysis, surgery should be carried out as soon as possible. After removed the cholesteatoma completely, facial nerve decompression could acquire a better facial nerve function recovery compared to great auricular grafting.

[Effect of targeted inhibition of hypoxia-inducible factor-1α by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole on the progression of non-alcoholic fatty liver disease in rats].

Objective: To investigate the effect of targeted inhibition of hypoxia-inducible factor-1α (HIF-1α) by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on the progression of non-alcoholic fat liver diseases (NAFLD) in rats. Methods: A total of 72 male Sprague-Dawley rats were randomly divided into normal group, model group, and intervention group, and the rats were given high-fat feed to establish the rat model of fatty liver disease. After the establishment of the model, the rats in the intervention group were given intraperitoneally injected YC-1 (at a dose of 2 mg/kg) every two weeks and were observed at 4, 8, 12, and 16 weeks. Blood samples and liver tissues were collected after the end of intervention, and blood lipid, biochemical markers for liver function, fasting blood glucose, and insulin were measured. Histopathological examinations were performed, and insulin resistance index was calculated. Real-time PCR was used to measure the mRNA transcriptional levels of HIF-1α, peroxisome proliferator-activated receptor α, and nuclear factor-kappa B (NF-κB), and Western blot was used to measure their protein expression levels. An analysis of variance with group design and the Kruskal-Wallis H test were used for comparison of continuous data between multiple groups, and the least significant difference method was used for comparison between any two groups. P <0.05 was considered statistically significant. Results: Compared with the model group, the intervention group had significant reductions in the serum levels of alanine aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol after 12 weeks of continuous administration (P < 0.05); after 8 weeks of continuous injection of YC-1, the intervention group had significant alleviation in hepatic steatosis and significant improvement in inflammation degree (P < 0.05), and after 12 weeks of continuous injection of YC-1, the intervention group had a significant reduction in liver fibrosis degree (P < 0.05); after 12 and 16 weeks of continuous administration, the intervention group had a significant increase in the mRNA expression of peroxisome proliferator-activated receptor α and a significant reduction in the mRNA expression of NF-κB. The protein expression of HIF-1α, peroxisome proliferator-activated receptor α, and NF-κB in fatty liver tissues at different time points showed similar results as the mRNA expression. There were no significant differences in insulin resistance index at each time point between the model group and the intervention group. Conclusion: Targeted inhibition of YC-1 can effectively delay the progression of experimental fatty liver disease and improve lipid metabolism, but it has no significant effect on insulin resistance.

A novel HLA-B*40 allele, B*40:01:40, identified in a Chinese individual.

A new allele, officially named B*40:01:40, was detected in a Chinese individual by sequence-based typing (SBT). The new allele differs from B*40:01:01 by a single nucleotide exchange at position 99 in codon 9, which results in synonymous substitution and seems not to compromise the HLA complex and T-cell receptor interaction.

Effects of TiO2 nanoparticles on nutrition metabolism in silkworm fat body.

Silkworm (Bombyx mori) is an important economic insect with a fat body that plays a crucial role in the storage and transfer of nutrients. It is also known that TiO2 nanoparticles (NPs) can improve feed efficiency and promote silk protein synthesis in the silkworm. In this study, we profiled gene expression in the silkworm fat body after TiO2 NP treatment, validated the major RNA-seq findings, and determined the contents of trehalose and triglyceride, the activity of lipase, and the amount of total proteins. RNA-seq analysis revealed that TiO2 NP treatment caused significant expression changes in 341 genes (P≤0.01), 138 of which were upregulated while the other 203 were downregulated. The expression levels of two target genes in the insulin signaling pathway and two protein metabolism-related target genes, three lipid metabolism-associated target genes, two carbohydrate metabolism related target genes and expression levels of seven heat shock protein genes were increased, and that of threonine dehydratase gene and fatty acid transport protein gene were decreased. The RNA-seq results of 16 genes were validated by quantitative real-time PCR. The lipase activity, content of trehalose, and amount of total proteins were elevated by 3.86-fold, 1.34-fold, and 1.21-fold, respectively, and the content of triglyceride was decreased by 0.94-fold after TiO2 NP treatment. These results indicated that TiO2 NPs activated the insulin signaling pathway, promoted the metabolism of protein, fat, and carbohydrate, and improved nutrition metabolism. Our study provides new support for the understanding of the beneficial effect of TiO2 NPs on silkworm nutrient metabolism.

Effects of mutations on the structure and function of silkworm type 1 acetylcholinesterase.

AChE is the target of organophosphate (OP) and carbamate (CB) pesticides, and mutations in the gene can significantly reduce insects' sensitivity to these pesticides. Bombyx mori is highly sensitive to pesticides. To investigate the effects of mutations on AChE1 structure and function, we used a prokaryotic system to express B.mori wild type AChE1 (wAChE1) and mutant AChE1 (mAChE1) in this study. Active AChE1 proteins were obtained after refolding and purification, and wAChE1 and mAChE1 had similar activities. After incubation with 10(-6)M physostigmine and 10(-3)mg/mL phoxim, the remaining enzyme activity of mAChE1 was 4.42% and 8.86% higher than that of wAChE1's, respectively. Three-dimensional analysis of mutation AChE1 (mAChE1) revealed that the Ser and Ala side chains extended toward the central part of S285 with distances of just 2.80Å and 3.68Å, respectively, which changed the spatial structure of the active center and reduced its sensitivity to pesticides. These results indicated that the mutations altered the 3D structure of AChE1, which may affect the binding of physostigmine and phoxim to the serine residue at the active center, leading to reduced sensitivity. Our study helps understand the relationship between AChE1 mutations and pesticide resistance and provides a new direction for the cultivation of new pesticide-resistant varieties of B.mori.

Mechanisms of TiO2 NPs-induced phoxim metabolism in silkworm (Bombyx mori) fat body.

Silkworm is an important economic insect. Abuse of organophosphorus pesticides in recent years often leads to poisoning of silkworms, which significantly affects sericulture development by reducing silk production. Previous studies have shown that TiO2 NPs can effectively mitigate the damages caused by organophosphorus pesticides in silk glands and nerve tissues. The fat body is an important metabolic detoxification organ of silkworms, but it is unknown whether TiO2 NPs affect pesticide metabolism in fat body. In this study, we characterized the transcription of antioxidant genes and enzyme activity in fat body after TiO2 NPs and phoxim treatments using transcriptome sequencing, real-time PCR, and enzyme activity assay. Transcriptome sequencing detected 10 720, 10 641, 10 403, and 10 489 genes for control group, TiO2 NPs group, phoxim group, and TiO2 NPs+phoxim group, respectively. The TiO2 NPs+phoxim group had 705 genes with significantly differential expression (FDR<0.001), among which the antioxidant genes thioredoxin reductase 1 and glutathione S-transferase omega 3 were significantly upregulated. In phoxim group, the expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase delta (GSTd), and thioredoxin peroxidase (TPx) were increased by 1.365 -fold, 1.335 -fold, 1.642 -fold, and 1.765 -fold, respectively. The level changes of SOD, CAT, GSTd, and TPx were validated by real time PCR. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H2O2) were increased by 1.598 -fold, 1.946 -fold, and 1.506 -fold, respectively, indicating that TiO2 NPs treatment can relieve phoxim-induced oxidative stress. To clarify the mechanism of TiO2 NPs's effect, the transcription levels of P450 gene family were measured for the TiO2 NPs+phoxim group; the expression levels of CYP4M5, CYP6AB4, CYP6A8, and CYP9G3 were elevated by 2.784 -fold, 3.047 -fold, 2.254 -fold, and 4.253 -fold, respectively, suggesting that high expression of P450 family genes can enhance the metabolism of phoxim in the fat body. The results of this study indicated that TiO2 NPs treatment promoted the transcriptional expression of the P450 family genes to improve the fat body's ability to metabolize phoxim and reduce phoxim-induced oxidative stress. This may be the main mechanism of TiO2 NPs' mitigation of phoxim-induced damages in the fat body.

Identification of a novel HLA-DRB1*14 allele, HLA-DRB1*14:150, in a Chinese individual.

HLA-DRB1*14:150 shows one nucleotide difference when compared with DRB1*14:54:01 at codon 49 (A > P).

HLA-A*02:513, a novel HLA-A*02 allele.

HLA-A*02:513 shows one nucleotide difference with A*02:07:01 (125G > A).