[Surgical issues and managements in cochlear reimplantation in 32 children].

Objective:To summarize the clinical characteristics of children undergoing surgery of cochlear reimplantation, focus on various problems and management in cochlear reimplantation, in order to avoid related problems in surgery of cochlear reimplantation and the initial implantation. Methods:A total of 32 children who underwent cochlear reimplantation in Peking University Third Hospital from July 2018 to July 2022 were retrospectively analyzed, and the duration from the initial implantation was from 1 year to 8 years. The cochlear implant mapping was performed 4 weeks after the operation, and the auditory performance was evaluated. Results:Special intraoperative issues included 32 cases with bone and soft tissue hyperplasia at various sites（2 cases with obvious bone hyperplasia in cochlear window, 1 case with obvious bone hyperplasia in subperiosteal tunnel of wire）, 5 cases with bone defects in important structures（including the posterior wall of the external auditory canal, the facial nerve canal, and the subperiosteal pocker of the receiver-stimulator）, 1 case with cholesteatoma, 4 cases with other lesions or foreign bodies, 4 cases with abnormal position of the electrodes（migration or reversal）. All operations were successfully completed without complications. Postoperative recoveries were smooth. Conclusion:In the initial cochlear implantation, attention should be paid to retain residual hearing as much as possible, fully consider the possibility of postoperative bone hyperplasia, avoid large amounts of non-absorbable adhesive materials, avoid bone defects in important structures（such as facial nerve canal or posterior wall of the external auditory canal）, pay attention to the depth and orientation of electrode implantation. The possibility of "hidden injury" mentioned above should be fully considered in surgery of cochlear reimplantation to avoid new injury or complication.

Response to comment on "Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma".

This article is a response to "comment on 'Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma'" by Gopal Sharma. With this comment, author highlighted the strengths and limitations of the study. With this response, we respond to this and make a comparison of the results and conclusions.

Efficacy and Safety of Chinese Patent Medicine for the Prevention and Treatment of Radiotherapy and Chemotherapy-Induced Oral Mucositis: A Systematic Review and Meta-Analysis.

Background: Radiotherapy and chemotherapy-induced oral mucositis can affect cancer patients' quality of life, even necessitate cancer therapy and influence prognosis. Chinese patent medicines (CPMs) have been widely used as complementary alternative medicines for the prevention and treatment of oral mucositis, and their efficacy and safety require further evaluation. Therefore, this study was conducted to provide references for clinical practice. Methods: Ten databases were searched electronically and manually to identify randomized controlled trials (RCTs) from their inception to August 2021, concerning the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis with CPMs. The prevalence, pain level, and the severity of radiotherapy and chemotherapy-induced oral mucositis, as well as the effectiveness rate and adverse effects of CPMs, were set as the outcome criteria. The assessment criteria of the Cochrane Handbook were used to determine study quality and bias, and meta-analysis was conducted using Review Manager 5.4.1 software. Results: A total of 2,312 cases from 27 RCTs were included. Most studies were considered to have a low or unclear risk of bias. More research is available on the use of CPMs in the prevention of radiotherapy and chemotherapy-induced oral mucositis than in its treatment. As for the prevention, it was proved that CPMs could significantly reduce the prevalence of radiotherapy and chemotherapy-induced oral mucositis, especially for the severe types, and decrease pain levels (p < 0.05). For treatment, CPMs could alleviate the symptoms, promote the healing of ulceration in radiotherapy and chemotherapy-induced oral mucositis, and thus improve the efficiency of clinical treatment (p < 0.05). The results of subgroup analyses were mainly consistent with the above results. The adverse effects of CPMs mainly included gastrointestinal reactions and bitter taste, and no serious adverse events were reported. Conclusions: This systematic review and meta-analysis indicated CPMs might be effective for the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis through reducing the prevalence, decreasing the occurrence of severe types, alleviating the symptoms, and promoting the healing of ulceration. However, due to the limited number of eligible studies and the publication bias, more high-quality, double-blinded, placebo-controlled RCTs are still needed in future research. Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY2021100100].

Genome-wide association study of serum tumor markers in Southern Chinese Han population.

BACKGROUND: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers. METHODS: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci. RESULTS: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037. CONCLUSION: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.

LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. METHODS: Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. RESULTS: LINC01414 rs699467 (OR = 0.73, 95% CI 0.56-0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31-0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31-6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). CONCLUSION: Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

Glucocorticoid-Induced Exacerbation of Mycobacterial Infection Is Associated With a Reduced Phagocytic Capacity of Macrophages.

Glucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this study, we have used a larval zebrafish model for tuberculosis, based on Mycobacterium marinum (Mm) infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemic Mm infection. The exacerbated Mm infection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific for Mm, since it was also observed upon infection with Salmonella Typhimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.

Disruption of Cxcr3 chemotactic signaling alters lysosomal function and renders macrophages more microbicidal.

Chemotaxis and lysosomal function are closely intertwined processes essential for the inflammatory response and clearance of intracellular bacteria. We used the zebrafish model to examine the link between chemotactic signaling and lysosome physiology in macrophages during mycobacterial infection and wound-induced inflammation in vivo. Macrophages from zebrafish larvae carrying a mutation in a chemokine receptor of the Cxcr3 family display upregulated expression of vesicle trafficking and lysosomal genes and possess enlarged lysosomes that enhance intracellular bacterial clearance. This increased microbicidal capacity is phenocopied by inhibiting the lysosomal transcription factor EC, while its overexpression counteracts the protective effect of chemokine receptor mutation. Tracking macrophage migration in zebrafish revealed that lysosomes of chemokine receptor mutants accumulate in the front half of cells, preventing macrophage polarization during chemotaxis and reaching sites of inflammation. Our work shows that chemotactic signaling affects the bactericidal properties and localization during chemotaxis, key aspects of the inflammatory response.

Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration.

Glucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited upon glucocorticoid treatment, whereas migration of macrophages is glucocorticoid resistant. We show that wounding-induced increases in the expression of genes that encode neutrophil-specific chemoattractants (Il8 and Cxcl18b) are attenuated by the synthetic glucocorticoid beclomethasone, but that beclomethasone does not attenuate the induction of the genes encoding Ccl2 and Cxcl11aa, which are required for macrophage recruitment. RNA sequencing on FACS-sorted macrophages shows that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas only a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using a tnfa:eGFP-F reporter line and analysis of macrophage morphology. We conclude that differentiation and migration of macrophages are regulated independently, and that glucocorticoids leave the chemotactic migration of macrophages unaffected, but exert their anti-inflammatory effect on these cells by inhibiting their differentiation to an M1 phenotype. The resistance of macrophage-dominated diseases to glucocorticoid therapy can therefore not be attributed to an intrinsic insensitivity of macrophages to glucocorticoids.

Association of neck dissection with survival for early stage N0 tongue cancer: A SEER population-based study.

The management of the node negative neck in patients with tongue cancer remains a complex and controversial issue, especially in those with early stage tumors. Patients with negative cervical lymph nodes generally have a good prognosis. However, in patients without neck dissection, neck recurrences may occur after excision of the primary tumor due to occult cervical metastases. It often results in poor salvage therapy options and short survival. We used Surveillance, Epidemiology, and End Results data from 2004 to 2013 to investigate the association of neck dissection with survival among early stage tongue cancer patients with negative lymph node metastasis. A total of 4274 eligible patients were subdivided into 2 groups according to their neck management strategies: neck dissection and observation. Univariate and multivariate Cox proportional hazards regression models were used to determine the independent factors of survival. The Kaplan-Meier method was employed for survival analysis. In the overall cohort, patients who underwent neck dissection had better survival than those who were managed with observation in both tongue cancer specific survival and overall survival. After adjusting for confounding variables, neck dissection strategy remains an independent prognostic factor for better survival. When stratifying the patients according to age, gender, race, marital status, histologic grade, stage and radiotherapy, patients in the neck dissection group had significantly better survival than those in the observation group. Neck dissection may improve survival for early stage tongue cancer patients with negative lymph node metastasis. These results may assist clinicians in selecting the most appropriate neck management strategy for individual patients.

Deep learning enables automated scoring of liver fibrosis stages.

Current liver fibrosis scoring by computer-assisted image analytics is not fully automated as it requires manual preprocessing (segmentation and feature extraction) typically based on domain knowledge in liver pathology. Deep learning-based algorithms can potentially classify these images without the need for preprocessing through learning from a large dataset of images. We investigated the performance of classification models built using a deep learning-based algorithm pre-trained using multiple sources of images to score liver fibrosis and compared them against conventional non-deep learning-based algorithms - artificial neural networks (ANN), multinomial logistic regression (MLR), support vector machines (SVM) and random forests (RF). Automated feature classification and fibrosis scoring were achieved by using a transfer learning-based deep learning network, AlexNet-Convolutional Neural Networks (CNN), with balanced area under receiver operating characteristic (AUROC) values of up to 0.85-0.95 versus ANN (AUROC of up to 0.87-1.00), MLR (AUROC of up to 0.73-1.00), SVM (AUROC of up to 0.69-0.99) and RF (AUROC of up to 0.94-0.99). Results indicate that a deep learning-based algorithm with transfer learning enables the construction of a fully automated and accurate prediction model for scoring liver fibrosis stages that is comparable to other conventional non-deep learning-based algorithms that are not fully automated.

Amelioration of Experimental Autoimmune Encephalomyelitis by Isogarcinol Extracted from Garcinia mangostana L. Mangosteen.

Isogarcinol is a new natural immunosuppressant that was extracted from Garcinia mangostana L. in our laboratory. Knowledge of its effects on treatable diseases and its mechanism of action is still very limited. In this study, we explored the therapeutic effect of isogarcinol in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Treatment with oral 100 mg/kg isogarcinol markedly ameliorated clinical scores, alleviated inflammation and demyelination of the spinal cord, and reduced intracranial lesions in EAE mice. The percentages of Th cells and macrophages were also strongly reduced. Isogarcinol appeared to act by inhibiting T helper (Th) 1 and Th17 cell differentiation via the janus kinase/signal transducers and activators of transcription pathway and by impairing macrophage function. Our data suggest that isogarcinol has the potential to be an effective therapeutic agent of low toxicity for treating MS and other autoimmune diseases.