Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor.

Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it's acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT1A receptor antagonist WAY100635. We determined that CBD increases 5-HT1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.

[Quality evaluation of salt-fired Eucommiae Cortex based on HPLC fingerprint, multi-component content determination, and chemometrics].

This study established an HPLC fingerprint and multi-component content determination method for salt-fired Eucommiae Cortex, and evaluated the quality of salt-fired Eucommiae Cortex from different sources using fingerprint similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least square discriminate analysis(OPLS-DA). HPLC was launched on a Cosmosil 5C_(18)-MS-Ⅱ column(4.6 mm×250 mm, 5 µm) by gradient elution with a mobile phase of methanol-0.2% phosphoric acid aqueous solution at a flow rate of 1.0 mL·min~(-1), detection wavelength of 238 nm, column temperature of 30 ℃, and an injection volume of 10 µL. The results of fingerprint similarity evaluation for 20 batches of salt-fired Eucommiae Cortex indicated that, except for batch S3 with a similarity of 0.893, the similarity of the other 19 batches was of ≥ 0.919, suggesting good similarity. Fourteen common peaks were calibrated and seven common peaks were identified including geniposidic acid. The mass fractions of geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, liriodendrin, and pinoresinol-4-O-ß-D-glucopyranoside were 0.062 0%-0.426 9%, 0.024 9%-0.116 5%, 0.009 5%-0.052 9%, 0.005 5%-0.034 8%, 0.115 9%-0.317 8%, 0.016 4%-0.108 8%, and 0.026 4%-0.039 8%, respectively. Using CA, PCA, and OPLS-DA, the 20 batches of salt-fired Eucommiae Cortex were classified into three categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, two differential quality markers, geniposidic acid and chlorogenic acid, were identified. The established HPLC fingerprint and multi-component content determination method is stable and reliable, providing a reference for quality control of salt-fired Eucommiae Cortex.

Histopathologic features and molecular genetic landscape of HER2-amplified endometrial carcinomas.

HER2 is an established therapeutic biomarker in advanced or recurrent endometrial serous carcinoma. Current clinical guidelines recommend HER2 testing exclusively in this endometrial carcinoma (EC) subtype; however, the full spectrum of ECs harboring HER2 amplification remains ill-defined. The present study characterizes the clinicopathologic and molecular features of HER2-amplified ECs across all histologic subtypes. Retrospective analysis of our institutional cohort of 2,042 ECs subjected to targeted clinical massively parallel sequencing identified 77 (3.8%) cases with HER2 amplification, a group comprised of serous (n = 29), endometrioid (low-grade, n = 2, high-grade, n = 1) and clear cell (n = 4) carcinomas, carcinosarcomas (n = 18) and high-grade ECs with ambiguous features (HGEC, n = 23). A co-existing TP53 mutation was identified in 94% (72/77) of HER2-amplified ECs. Other recurrent genetic alterations included amplification of CCNE1 (22%) and ERBB3 (10%), FBXW7 mutations or deletions (13%), and mutations in PIK3CA (40%) and PPP2R1A (13%). The HER2 immunohistochemistry score was 2+ or 3+ for all evaluable cases (n = 61). Apart from carcinosarcomas, which often showed lower HER2 expression, particularly in the sarcomatous component, HER2 immunohistochemical staining pattern and intensity were similar across EC subtypes. Intratumor heterogeneity in HER2 expression was common and correlated with genetic heterogeneity as detected by fluorescence in-situ hybridization. These results demonstrate the frequent co-occurrence of HER2 amplification with TP53 mutation and high-grade histology, rather than being specific to serous carcinoma, per se. Overall, these findings suggest that HER2 targeted therapy may be more broadly applicable to all high-grade EC histotypes and consideration should be given to expanding therapeutic eligibility.

Congenital sensorineural hearing loss as the initial presentation of PTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: clinical features and underlying mechanisms.

BACKGROUND: Germline variants in PTPN11 are the primary cause of Noonan syndrome with multiple lentigines (NSML) and Noonan syndrome (NS), which share common skin and facial symptoms, cardiac anomalies and retardation of growth. Hearing loss is considered an infrequent feature in patients with NSML/NS. However, in our cohort, we identified a group of patients with PTPN11 pathogenic variants that were primarily manifested in congenital sensorineural hearing loss (SNHL). This study evaluated the incidence of PTPN11-related NSML or NS in patients with congenital SNHL and explored the expression of PTPN11 and the underlying mechanisms in the auditory system. METHODS: A total of 1502 patients with congenital SNHL were enrolled. Detailed phenotype-genotype correlations were analysed in patients with PTPN11 variants. Immunolabelling of Ptpn11 was performed in P35 mice. Zebrafish with Ptpn11 knockdown/mutant overexpression were constructed to further explore mechanism underlying the phenotypes. RESULTS: Ten NSML/NS probands were diagnosed via the identification of pathogenic variants of PTPN11, which accounted for ~0.67% of the congenital SNHL cases. In mice cochlea, Shp2, which is encoded by Ptpn11, is distributed in the spiral ganglion neurons, hair cells and supporting cells of the inner ear. In zebrafish, knockdown of ptpn11a and overexpression of mutant PTPN11 were associated with a significant decrease in hair cells and supporting cells. We concluded that congenital SNHL could be a major symptom in PTPN11-associated NSML or NS. Other features may be mild, especially in children. CONCLUSION: Screening for PTPN11 in patients with congenital hearing loss and variant-based diagnoses are recommended.

[Psychological and behavioral problems in children and adolescents during the coronavirus disease 2019 epidemic: a Scoping review]. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæµè¡ŒæœŸé—´å„¿ç«¥å’Œé’å°‘å¹´çš„å¿ƒç†è¡Œä¸ºé—®é¢˜ï¼šScoping综述.

OBJECTIVES: To investigate the psychological and behavioral problems and related influencing factors in children and adolescents during the coronavirus disease 2019 (COVID-19) epidemic. METHODS: China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science were searched using the method of subject search for articles published up to March 31, 2022, and related data were extracted for Scoping review. RESULTS: A total of 3 951 articles were retrieved, and 35 articles from 12 countries were finally included. Most of the articles were from the journals related to pediatrics, psychiatry, psychology, and epidemiology, and cross-sectional survey was the most commonly used research method. Psychological and behavioral problems in children and adolescents mainly included depression/anxiety/stress, sleep disorder, internet behavior problems, traumatic stress disorder, and self-injury/suicide. Influencing factors were analyzed from the three aspects of socio-demographic characteristics, changes in living habits, and ways of coping with COVID-19. CONCLUSIONS: During the COVID-19 epidemic, the psychological and behavioral problems of children and adolescents in China and overseas are severe. In the future, further investigation and research can be carried out based on relevant influencing factors to improve the psychological and behavioral problems.

AI detection of mild COVID-19 pneumonia from chest CT scans.

OBJECTIVES: An artificial intelligence model was adopted to identify mild COVID-19 pneumonia from computed tomography (CT) volumes, and its diagnostic performance was then evaluated. METHODS: In this retrospective multicenter study, an atrous convolution-based deep learning model was established for the computer-assisted diagnosis of mild COVID-19 pneumonia. The dataset included 2087 chest CT exams collected from four hospitals between 1 January 2019 and 31 May 2020. The true positive rate, true negative rate, receiver operating characteristic curve, area under the curve (AUC) and convolutional feature map were used to evaluate the model. RESULTS: The proposed deep learning model was trained on 1538 patients and tested on an independent testing cohort of 549 patients. The overall sensitivity was 91.5% (195/213; p < 0.001, 95% CI: 89.2-93.9%), the overall specificity was 90.5% (304/336; p < 0.001, 95% CI: 88.0-92.9%) and the general AUC value was 0.955 (p < 0.001). CONCLUSIONS: A deep learning model can accurately detect COVID-19 and serve as an important supplement to the COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test. KEY POINTS: • The implementation of a deep learning model to identify mild COVID-19 pneumonia was confirmed to be effective and feasible. • The strategy of using a binary code instead of the region of interest label to identify mild COVID-19 pneumonia was verified. • This AI model can assist in the early screening of COVID-19 without interfering with normal clinical examinations.

The significance of enhancer of zeste homolog 2 (EZH2) expression in spindle cell lesions of the breast.

Spindle cell lesions of the breast are rare entities and pose a diagnostic challenge for pathologists due to overlapping morphologic and immunohistochemical features. We evaluated EZH2 expression in various benign (fibromatosis (n = 8), myofibroblastoma (n = 7), neurofibroma (n = 1), nodular fasciitis (n = 5), benign phyllodes tumor (n = 18)) and malignant (malignant phyllodes tumor (n = 8), metaplastic breast carcinoma (n = 16) and angiosarcoma (n = 8)) spindle cell lesions as a potential diagnostic and therapeutic marker. The EZH2 expression was evaluated semi-quantitatively to categorize the cases as 'low' and 'high' expression. All benign lesions showed low EZH2 expression, whereas high EZH2 expression was observed in the majority (28/32; 88%) of malignant lesions. The study results suggest that EZH2 may be used both as an additional diagnostic tool to reach an accurate diagnosis of the spindle cell lesions of the breast and as a therapeutic target for the malignant lesions.

Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss.

Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) - a protein that functions in the Jak/ STAT pathway- are associated with ADNSHL Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. ConclusionIFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.

Tumor budding in colorectal carcinoma: An institutional interobserver reliability and prognostic study of colorectal adenocarcinoma cases.

BACKGROUND: Colorectal carcinomas are one of the most commonly diagnosed malignancies. There are many prognostic factors relating to clinical course and disease progression, including tumor stage, metastasis, and tumor budding. In 2016, the International Tumor Budding Consensus Conference (ITBCC) created a system to uniformly assess tumor budding. This system includes a 3-tier system for the grading of tumor budding. In the past, there lacked uniform consensus, however the general grading practice was based on a 2-tiered system. Given that tumor budding is considered to have prognostic value, the accuracy and reproducibility of its assessment is vital. Our study aims to look at interobserver agreement in the scoring of tumor budding. DESIGN: A total of 233 cases of colorectal carcinoma diagnosed in our health system were retrospectively analyzed and routine H&E stained slides of these cases were collected. A representative slide for tumor budding was selected per case. Four investigators with different levels of experience and expertise evaluated the selected slide of each case for tumor budding. Scoring was based on the ITBCC protocol. Clinico-pathological data was collected for each case and analyzed with tumor budding scores. Tumor budding scores per individual investigator and consensus tumor budding score were compared to patient and tumor characteristics including patient survival, tumor grade, tumor stage, and lymph node status. RESULTS: Inter-observer agreement was calculated using Gwet's Agreement Coefficient (AC1) and associated 95% confidence intervals was used to compare the ratings made by 4 pathologists. Overall, there was variation among pathologists in tumor budding score (Gwet's agreement coefficient = 0.25 and 0.326 for 3-tier and 2-tier grading system, respectively). Results show higher reliability with the 2-tier system compared to the 3-tier system. Tumor stage was significantly associated with budding score for all individual investigators and the consensus value (p value < 0.001). CONCLUSION: There is low inter-observer agreement in the assessment of tumor budding in colorectal carcinoma. This suggests that it is difficult to uniformly grade tumor budding and that our classification system needs improvement. We found that the older 2-tier system (Hase et al.) results in slightly higher inter-observer agreement than the recently proposed 3-tier grading system (ITBCC, 2016), though both systems lead to suboptimal agreement. Worth noting is that observers with subspecialty GI training and more work experience had higher inter-observer agreement. Our results showed that subspecialty training tends to increase agreement more than overall work experience. In addition, our exploratory results showed that there is an association of tumor budding score to tumor stage. While increasing refinement in classification, the 3-tiered system resulted in decreased agreement in tumor budding assessment. Clearly, there is more work to be done in the identification and quantification of tumor buds.

Identification of TMPRSS3 as a Significant Contributor to Autosomal Recessive Hearing Loss in the Chinese Population.

Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Mutations in the TMPRSS3 (transmembrane protease, serine 3) gene cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study, three pathogenic mutations in TMPRSS3 were identified in one Chinese family. To evaluate the importance of TMPRSS3 mutations in recessive deafness among the Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL) families and identified 6 that carried seven causative TMPRSS3 mutations, including five novel mutations (c.809T>A, c.1151T>G, c.1204G>A, c.1244T>C, and c.1250G>A) and two previously reported mutations (c.323-6G>A and c.916G>A). Each of the five novel mutations was classified as severe, by both age of onset and severity of hearing loss. Together with our previous study, six families were found to share one pathogenic mutation (c.916G>A, p.Ala306Thr). To determine whether this mutation arose from a common ancestor, we analyzed six short tandem repeat (STR) markers spanning the TMPRSS3 gene. In four families, we observed linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate that mutations in TMPRSS3 account for about 4.6% (7/151) of Chinese ARNSHL cases lacking mutations in SLC26A4 or GJB2 and that the recurrent TMPRSS3 mutation p.Ala306Thr is likely to be a founder mutation.

A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated heritability (0.7); however, only a small number of associated genetic loci have been reported to date. In contrast, over 100 loci have now been reproducibly associated with either blood lipid profile and/or coronary artery disease (CAD) (both risk factors for AAA) in large-scale meta-analyses. This study employed a staged design to investigate whether the loci for these two phenotypes are also associated with AAA. Validated CAD and dyslipidaemia loci underwent screening using the Otago AAA genome-wide association data set. Putative associations underwent staged secondary validation in 10 additional cohorts. A novel association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839 G allele, which has been previously associated with both dyslipidaemia and CAD, reached genome-wide significance in 11 combined independent cohorts (meta-analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76-0.85, P = 7.2 × 10(-14)). Modelling for confounding interactions of concurrent dyslipidaemia, heart disease and other risk factors suggested that this marker is an independent predictor of AAA susceptibility. In conclusion, a genetic marker associated with cardiovascular risk factors, and in particular concurrent vascular disease, appeared to independently contribute to susceptibility for AAA. Given the potential genetic overlap between risk factor and disease phenotypes, the use of well-characterized case-control cohorts allowing for modelling of cardiovascular disease risk confounders will be an important component in the future discovery of genetic markers for conditions such as AAA.

Targeted gene capture and massively parallel sequencing identify TMC1 as the causative gene in a six-generation Chinese family with autosomal dominant hearing loss.

Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the transmembrane channel-like gene1 (TMC1) are known to cause autosomal dominant and recessive forms of nonsyndromic hearing loss linked to the loci of DFNA36 and DFNB7/11, respectively. We characterized a six-generation Chinese family (5315) with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 82 known deafness genes, next-generation sequencing and bioinformatic analysis, we identified TMC1 c.1714G>A (p. D572N) as the disease-causing mutation. This mutation co-segregated with hearing loss in other family members and was not detected in 308 normal controls. In order to determine the prevalence of TMC1 c.1714G>A in Chinese ADNSHL families, we used DNA samples from 67 ADNSHL families with sloping audiogram and identified two families carry this mutation. To determine whether it arose from a common ancestor, we analyzed nine STR markers. Our results indicated that TMC1 c.1714G>A (p.D572N) account for about 4.4% (3/68) of ADNSHL in the Chinese population.

Treatment strategies for huge central neurocytomas.

Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.

[Analysis of infection status and pathogenic features of human metapneumovirus among children in Hangzhou between year 2009 and 2011].

OBJECTIVE: To study the infection status and pathogenic features of human metapneumovirus (hMPV) among children with acute respiratory tract infection in Hangzhou. METHODS: A total of 372 children less than 14 years old with acute respiratory tract infections were recruited as subjects from the pediatric clinic or intensive care unit (ICU) of 3 hospitals in Hangzhou during November 2009 to January 2010, and November 2010 to January 2011. A total of 372 specimens were collected, including 351 respiratory swab, 9 nasopharyngeal aspirate material, 8 endotracheal aspirate material and 4 sputum. The total nucleic acid was then extracted from the specimens, and the nucleoprotein (N) gene of hMPV was amplified by RT-PCR, whose positive products were sequenced and analyzed. Africa green monkey kidney cells (Vero-E6) were applied to culture hMPV among the positive samples; meanwhile fluorescence quantitative RT-PCR was adopted to test other respiratory virus infection. RESULTS: Out of 372 patients, 42 (11.2%) were positive for N gene of hMPV. The positive rate of hMPV among boys was 11.5% (26/226), and correspondingly 10.9% (16/146) among girls. The difference showed no statistical significance (χ(2) = 0.026, P > 0.05). The youngest patient was only 2 month-old and the eldest patient was 14 years old. The median of the patients' age was 24 months. Fifteen positive samples amplified by RT-PCR were sequenced, and all turned out to be subtype B1; whose similarity to GD165 found in Guangdong was 98.1% - 99.5% and similarity to BJ1897 in Beijing was 87.8% - 89.2%. The co-infection rate between hMPV and other respiratory virus was 45.2% (19/42); most of which was between hMPV and respiratory syncytial virus, whose rate at 26.1% (11/42). CONCLUSION: hMPV was the single genotype relevant with the acute respiratory tract infection disease among children in Hangzhou district; however, the co-infection with other respiratory virus did exist.

Endovascular embolization for basal ganglia and thalamic arteriovenous malformations.

Background: Basal ganglia and thalamic arteriovenous malformations (AVMs) represent a special subset of malformations. Due to the involvement of vital brain structures and the specifically fine and delicate angioarchitecture of these lesions, it presents unique therapeutic challenges and technical difficulties that require thorough treatment planning, individualized treatment strategies, and advanced techniques for good clinical outcome. Method: In this study, we presented a series of ruptured basal ganglia and thalamic AVMs embolized via a transarterial, transvenous or combined approach. Herein, we summarized our treatment experience and clinical outcomes to further evaluate the effectiveness and safety of endovascular embolization for these AVMs as well as the indications, therapy strategies, and techniques of embolization procedures. Results: Twelve patients with basal ganglia and thalamus AVMs were included in the study. Their average age was 23.83 ± 16.51 years (range, 4-57 years) with a female predominance of 67% at presentation. The AVMs were located in the thalamus in 3 (25%) patients, in the basal ganglia in 3 (25%) patients, and in both sites of the brain in 6 (50%) patients. There were 5 AVMs located on the left side and 7 on the right. The mean nidus diameter was 3.32 ± 1.43 cm (range 1.3-6.1 cm). According to the Spetzler-Martin grading classification, 4 (33.3%) brain AVMs were Grade III, 7 (58.3%) were Grade IV, and 1 (8.3%) was Grade V. All of them presented with bleeding at admission: four of these patients presented with an intracerebral hemorrhage (ICH), 8 ICH in combination with intraventricular hemorrhage (IVH), and no patient with subarachnoid hemorrhage (SAH). Among these patients treated with endovascular embolization, 7 patients were treated by the transarterial approach, 4 patients transvenous approach, and 1 patient underwent the combined approach. A single embolization procedure was performed in 6 patients (50%) and the other 6 cases (50%) were treated in a staged manner with up to three procedures. Procedure-related complications occurred only in two patient (16.7%). Complete AVM obliteration was obtained in 7 patients (58.3%), and partial obliteration was in 4 patients (33.3%). Overall, good or excellent outcomes were obtained in 7 patients (58.3%), and poor functional outcome was observed in 5 patients (41.7%) at the last follow-up. All survived patients achieved anatomic stabilization and there was no postoperative bleeding or recurrence in the follow-up. Conclusion: The management of the basal ganglia and thalamic AVMs is a great challenge, which needs multimodal individualized treatment to improve the chances of radiographic cure and good outcomes. Endovascular therapy is safe and effective in the treatment of cerebral AVMs particularly for deep-seated AVMs such as the basal ganglia and thalamus. Our results demonstrate a high rate of anatomic obliteration with an acceptable rate of complications in the endovascular treatment of these vasculopathies via a transarterial approach or a transvenous approach.

Development and Validation of a Deep Learning Predictive Model Combining Clinical and Radiomic Features for Short-Term Postoperative Facial Nerve Function in Acoustic Neuroma Patients.

OBJECTIVE: This study aims to construct and validate a predictable deep learning model associated with clinical data and multi-sequence magnetic resonance imaging (MRI) for short-term postoperative facial nerve function in patients with acoustic neuroma. METHODS: A total of 110 patients with acoustic neuroma who underwent surgery through the retrosigmoid sinus approach were included. Clinical data and raw features from four MRI sequences (T1-weighted, T2-weighted, T1-weighted contrast enhancement, and T2-weighted-Flair images) were analyzed. Spearman correlation analysis along with least absolute shrinkage and selection operator regression were used to screen combined clinical and radiomic features. Nomogram, machine learning, and convolutional neural network (CNN) models were constructed to predict the prognosis of facial nerve function on the seventh day after surgery. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate model performance. A total of 1050 radiomic parameters were extracted, from which 13 radiomic and 3 clinical features were selected. RESULTS: The CNN model performed best among all prediction models in the test set with an area under the curve (AUC) of 0.89 (95% CI, 0.84-0.91). CONCLUSION: CNN modeling that combines clinical and multi-sequence MRI radiomic features provides excellent performance for predicting short-term facial nerve function after surgery in patients with acoustic neuroma. As such, CNN modeling may serve as a potential decision-making tool for neurosurgery.

A newborn male with Myhre syndrome, hearing loss, and complete syndactyly of fingers 3-4.

BACKGROUND: Myhre syndrome is a rare multisystem genetic disorder that is caused by de novo heterozygous gain-of-function variants in SMAD4. Patients with Myhre syndrome exhibit several phenotypes at different ages such as small size, autism, developmental delay, left-sided heart defects, and hearing loss and often have a characteristic facial appearance. The early clinical diagnosis of Myhre syndrome remains a major challenge, particularly in the first year of life. METHODS: A Chinese male infant with syndactyly of fingers, hypertelorism, short palpebral fissures, and short philtrum was enrolled into the ENT department of the Chinese PLA General Hospital. Whole exome sequencing analysis was used to detect the disease-causing variant. A literature review of Myhre syndrome was also performed. RESULTS: A recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4 was detected confirming the clinical diagnosis of Myhre syndrome at the age of 38 days. The infant appears to be the youngest reported case of Myhre syndrome. At 23-month follow-up, the affected infant has dysmorphic facial features, growth retardation, and previously undescribed complete syndactyly. Review the literatures noted several common features in Myhre syndrome patients including hearing loss (72.7%), characteristic facial features (26.0%-54.5%), finger and toe abnormalities (3.9%-48.1%), short stature (45.5%), and respiratory (30.0%) and cardiovascular problems (65.0%). CONCLUSIONS: Clinicians should have a low threshold to perform genetic testing on patients with features suggesting Myhre syndrome even in the first year of life. Although some individuals with Myhre syndrome have normal hearing, early onset or progressive hearing loss usually occur in one or both ears in most patients, with remarkable phenotypic heterogeneity. Syndactyly may be minor such as typical 2-3 toe involvement, or more complicated as was observed in our patient.

Cochlear implantation in a patient with congenital microtia, cochlear hypoplasia, venous anomalies of the temporal bone and laryngomalacia: Challenges and surgical considerations.

RATIONALE AND PATIENT CONCERNS: Congenital hearing loss is often caused by an inner ear malformation, in such cases, the presence of other anomalies, such as microtia, and venous anomalies of the temporal bone and laryngomalacia makes it challenging to perform cochlear implantation surgery. DIAGNOSES: This study reports the case of a 28-month-old girl with congenital profound hearing loss, laryngomalacia, and malformed inner ear, who received cochlear implantation surgery. The bony structure, vessels and nerves were first assessed through magnetic resonance imaging and computed tomography before exploring the genetic basis of the condition using trio-based whole exome sequencing. Perioperative evaluation and management of the airway was then performed by experienced anesthesiologist, with the surgical challenges as well as problems encountered fully evaluated. INTERVENTIONS: Cochlear implantation was eventually performed using a trans-mastoid approach under uneventful general anesthesia. OUTCOMES: Due to the small size of the cochlea, a short electrode FLEX24 was inserted through the cochleostomy. LESSONS: Considering the high risk of facial nerve injury and limited access to the cochlea when patients present significant bony and venous anomalies, cochlear implantation in such patients require careful preoperative evaluation and thoughtful planning. In these cases, airway assessment, magnetic resonance venography, magnetic resonance arteriography, and magnetic resonance imaging and computed tomography can be useful to minimize the risks. Intraoperative facial nerve monitoring is also recommended to assist in the safe location of facial nerve.

[Systematic review and Meta-analysis on the auriculotherapy in treatment of insomnia].

OBJECTIVE: To review the effectiveness and safety of auriculotherapy in treatment of insomnia. METHODS: The articles were collated by computer retrieval from 8 databases from the initiation to April 30, 2021, i.e. PubMed, EMbase, the Cochrane Library, the Web of Science, CNKI, Wanfang database, VIP and Chinese biomedical literature database (SinoMed). Meta-analysis was conducted with RevMan5.3 software. RESULTS: A total of 38 articles were included, with 3 707 cases involved. The results showed: ①The effective rate of auriculotherapy was better than that of single application of western medication with sleeping pills (RR=1.26, 95%CI:1.15 to 1.39, Z=4.77, P<0.000 01), conventional acupuncture (RR=1.10, 95%CI: 1.05 to 1.16, Z=3.83, P=0.000 1) and Chinese herbal medicine (RR=1.41, 95%CI: 1.23 to 1.63, Z=4.80, P<0.000 01), respectively. ② The total score of PSQI was reduced remarkably under the auriculotherapy when compared with the single application of western medication (MD=-1.61, 95%CI: -2.61 to -0.60, Z=3.14, P=0.002) and Chinese herbal medicine (MD=-3.76, 95%CI: -4.84 to -2.68, Z=6.84, P<0.000 01). But the difference was not significant when compared with conventional acupuncture (MD=-1.02, 95%CI: -2.11 to 0.08, Z=1.82, P=0.07). ③Auricular point selection: the auricular points distributed in the areas of vagus nerve were more advantageous in reducing PSQI score (MD=-3.21, 95%CI: -4.45 to -1.96, Z=5.03, P<0.000 01) compared with the points in other areas. ④Stimulant selection: the difference in the effective rate was not significant among different stimulants (magnetic beads, the seeds of Vaccaria segetalis, micro-needles) (MD=1.62, 95%CI: 0.71 to 3.73, Z=1.14, P=0.25). ⑤Stimulation frequency: there was no significant difference between high-frequency stimulation and low-frequency stimulation of auricular point sticking in improving the effective rate and reducing PSQI score (P>0.05). But the result should be considered cautiously in terms of the sensitivity analysis. ⑥Adverse reactions: the case numbers of adverse reactions of auriculotherapy (auricular point sticking) were less than those of western medication (MD=0.15, 95%CI: 0.06 to 0.35, Z=4.38, P<0.000 1). CONCLUSION: Auriculotherapy has certain curative advantages in treatment of insomnia compared with western and Chinese medications as well as conventional acupuncture. This therapy may relieve the symptoms of insomnia and has less adverse effects. But those outcomes need to be further verified with more high-quality randomized controlled trials.

Genetic Analysis of the LOXHD1 Gene in Chinese Patients With Non-Syndromic Hearing Loss.

Non-syndromic hearing loss (NSHL) is a common neurosensory disease with an extreme genetic heterogeneity which has been linked to variants in over 120 genes. The LOXHD1 gene (DFNB77), encoding lipoxygenase homology domain 1, is a rare hearing loss gene found in several populations. To evaluate the importance of LOXHD1 variants in Chinese patients with NSHL, we performed genetic analysis on LOXHD1 in 2,901 sporadic Chinese patients to identify the aspect and frequency of LOXHD1 causative variants. Next-generation sequencing using a custom gene panel of HL was conducted on 2,641 unrelated patients and whole-exome sequencing on the remaining 260 patients. A total of 33 likely causative variants were identified in 21 patients, including 20 novel variants and 13 previously reported pathogenic variants. Each of the 20 novel variants was evaluated according to ACMG criteria. These findings showed that causative variants in LOXHD1 were found in about 0.72% (21/2,901) of Chinese NSHL patients. This study is by far the largest number of novel variants identified in this gene expanding the range of pathogenic variants in LOXHD1, and suggests that variants in this gene occur relatively commonly in Chinese NSHL patients. This extensive investigation of LOXHD1 in Chinese NSHL patients proposed six recurrent LOXHD1 variants. These findings may assist in both molecular diagnosis and genetic counseling.