[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.

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.

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.

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.

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.

Addition of an affected family member to a previously ascertained autosomal recessive nonsyndromic hearing loss pedigree and systematic phenotype-genotype analysis of splice-site variants in MYO15A.

Pathogenic variants in MYO15A are known to cause autosomal recessive nonsyndromic hearing loss (ARNSHL), DFNB3. We have previously reported on one ARNSHL family including two affected siblings and identified MYO15A c.5964+3G > A and c.8375 T > C (p.Val2792Ala) as the possible deafness-causing variants. Eight year follow up identified one new affected individual in this family, who also showed congenital, severe to profound sensorineural hearing loss. By whole exome sequencing, we identified a new splice-site variant c.5531+1G > C (maternal allele), in a compound heterozygote with previously identified missense variant c.8375 T > C (p.Val2792Ala) (paternal allele) in MYO15A as the disease-causing variants. The new affected individual underwent unilateral cochlear implantation at the age of 1 year, and 5 year follow-up showed satisfactory speech and language outcomes. Our results further indicate that MYO15A-associated hearing loss is good candidates for cochlear implantation, which is in accordance with previous report. In light of our findings and review of the literatures, 58 splice-site variants in MYO15A are correlated with a severe deafness phenotype, composed of 46 canonical splice-site variants and 12 non-canonical splice-site variants.

Differentiating non-lactating mastitis and malignant breast tumors by deep-learning based AI automatic classification system: A preliminary study.

Objective: To explore the application values of deep-learning based artificial intelligence (AI) automatic classification system, on the differential diagnosis of non-lactating mastitis (NLM) and malignant breast tumors, via its comparation with traditional ultrasound interpretations and the following interpretation conclusions made by the sonographers with various seniorities. Methods: A total of 707 patients suffering from breast lesions (475 malignant breast tumors and 232 NLM), were selected from the following three medical centers, including Zhejiang Cancer Hospital, Hebei Province Hospital of Traditional Chinese Medicine, and Yantai Affiliated Hospital of Binzhou Medical University, and the time period was set from April 2020 to September 2021. All selected cases firstly accepted the routine breast ultrasound diagnosis, followed by the interpretations from a senior sonographer with more than 15 years of work experience, and an intermediate-aged sonographer with more than 5 years of work experience, independently. Meanwhile, a third physician also interpreted the same ultrasound images by deep learning-based AI automatic classification system, independent of the interpretation results from the previous two physicians. The kappa test was performed to evaluate the consistency between the conventional ultrasound interpretation results and pathological results interpreted from physicians with different working experiences. Results: In total, 475 cases of malignant breast tumors (512 nodules) and 232 cases of NLM (255 nodules) were pathologically diagnosed. The accuracy, sensitivity, and specificity of conventional ultrasound interpretations vary from different sonographers with different working experiences. The accuracy, sensitivity, and specificity for intermediate-aged sonographers and senior sonographers were 76.92% (590/767), 84.71% (216/255), and 73.95% (374/512) and 87.35% (670/767), 86.27% (220/255), and 87.89% (450/512), respectively (P<0.001). In contrast, if the threshold was set as 0.5, the accuracy, sensitivity, and specificity from deep learning-based AI automatic classification system were 83.00%, 87.20%, and 85.33%, separately, and the area under the curve was 92.6. The results of the kappa consistency test indicated that the diagnosis results from the image interpretations by senior physicians and deep-learning based AI automatic classification system showed high consistency with postoperative pathological diagnosis results, and the kappa values are 0.72 and 0.71, respectively, with the P-value of less than 0.001. In contrast, the consistency between the image interpretation results from intermediate-aged physicians with less working experience, and postoperative pathological diagnosis results, seemed to be relatively lower, with a kappa value of only 0.53 and P-value of less than 0.001. Conclusions: The deep learning-based AI automatic classification system is expected to become a reliable auxiliary way to distinguish NLM and malignant breast tumors due to its high sensitivity, accuracy, and specificity.

[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.

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.

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.

[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.

A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome.

Mutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, clinical diagnosis presents a huge challenge. In this study, we described a pathogenic in-frame variant in FOXC1 in one 5-year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3 bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Furthermore, Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linke to the FOXC1 variant and is coincidental. Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.

Combined Endovascular and Surgical Treatment for Brain Arteriovenous Malformations in Biplanar Hybrid Operating Room.

OBJECTIVE: Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years. However, reports on one-session hybrid surgery for arteriovenous malformations (AVMs) are relatively rare. The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room (OR) at one stage. METHODS: We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018. The data for resection rate, microcatheter adhesion, surgical position and postoperative outcomes were analyzed. Total resection or near-total resection was achieved in all cases. RESULTS: A total of 13 patients were under combined endovascular and surgical procedures, and 7 experienced surgery with intraoperative digital subtraction angiography. Sitting position was applied in 3 of them; 2 niduses in cerebellum, and 1 in parietal lobe. Compared with admission modified Rankin Scale (mRS) in all patients, postoperative 12-month mRS showed a significant decline. Besides, 3 patients experienced microcatheter adhesion after endovascular embolization, thereafter underwent surgical adhesion removal while nidus resection was done. CONCLUSION: Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs. The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position. It also reduces the risk of microcatheter adhesion, which enables interventional radiologists to perform aggressively.

Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma.

Long non-coding RNA (lncRNA) are a class of non-coding RNAs demonstrated to play pivotal roles in regulating tumor progression. Therefore, deciphering the regulatory role of lncRNA in the development of glioma may offer a promising therapeutic target for treatment of glioma. We performed RT-qPCR analysis on the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-365 in glioma tissues and cell lines. Cell proliferation and viability was assessed with CCK8 assay. Cell migration was assessed by wound healing assay. Transwell assay was used to assess cell invasion capacity. Expression of CD133+ cells was detected by flow cytometry. Western blot assay was used to detection the expression of ELF4 and stemness-related protein SOX2, Oct4 and Nanog. Bioinformatics and dual-luciferase assay were used to predict and validate the interaction between PVT1 and miR-365. Elevated PVT1 expression was observed in glioma tissues and cells. Knockdown of PVT1 and overexpression of miR-365 inhibited proliferation, migration, invasion and promoted stemness and Temozolomide (TMZ) resistance of glioma cells. PVT1 regulated ELF4 expression by competitively binds to miR-365. PVT1 regulated the stemness and sensitivity of TMZ of glioma cells through miR-365/ELF4/ SOX2 axis. This study identified that PVT1 promoted glioma stemness through miR-365/ELF4/SOX2 axis.

[Effect of acupuncture on the cognitive function of migraine patients with depression/anxiety disorder].

OBJECTIVE: To observe the effect of five-element acupuncture on the cognitive function repair of migraine patients with depression/anxiety disorder. METHODS: The migraine patients with depression/anxiety disorder (19 cases, 5 cases dropped off) were taken as the observation group, and received five-element acupuncture twice a week for 8 weeks. Healthy subjects (19 cases) were selected by demographic data matching as the control group. The cognitive function was evaluated with the event related potential (ERP) technique, and the latency and amplitude of visual evoked potential P300 were adopted as the observation indexes. The headache days (every 4 weeks), headache intensity [visual analogue scale(VAS) score], and headache impact test-6 (HIT-6) score, Hamilton depression scale (HAMD) score and Hamilton anxiety scale (HAMA) score were used as the observation indexes for curative effect. RESULTS: Before the treatment, latency of target stimulus at Fz [ (417.5±34.3) ms] in the observation group was extended compared with the healthy subjects of the control group [(388.6±42.1) ms, P<0.05]. In the observation group, the latency of each point target stimulus [Fz: (376.1±36.2) ms, F3: (374.8±37.6) ms, F4: (372.0±37.6) ms] after treatment were shorter than those [Fz: (417.5±34.3) ms, F3: (417.4±33.8) ms, F4: (416.0±36.6) ms] before treatment (P<0.05). Before and after treatment, there was no significant difference in the amplitude of each point between the observation group and the control group (P>0.05). In the observation group, the headache days was shorter than that before treatment (P<0.01), and the VAS score, HIT-6 score, HAMD score and HAMA score were all lower than before treatment (P<0.01). CONCLUSION: There are some cognitive impairments in migraine patients with depression/anxiety disorder. Five-element acupuncture not only relieves headache, anxiety and depression effectively, but also improves the activation level of the frontal lobe. It significantly repairs the impaired cognitive function.

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.

GATA binding protein 3 (GATA3) as a marker for metaplastic spindle cell carcinoma of the breast.

Spindle cell lesions of the breast comprise a diverse set of tumors; harboring significant histological and immunohistochemical (IHC) overlap. Accurate diagnosis and classification of spindle cell lesions in the breast remains challenging, especially in core biopsies. In the current study, we evaluated a spectrum of spindle cell lesion of the breast with a panel of IHC antibodies in an effort to differentiate metaplastic spindle cell carcinoma from its benign and malignant mimickers. Our study included 92 patients who underwent breast core biopsies or breast resections at Northwell Health who were diagnosed with benign and malignant tumor/tumor-like spindle cell lesions. Tumors subtypes in this the study included: angiosarcoma, nodular fasciitis, fibromatosis, myofibroblastoma, phyllodes tumors (benign, borderline and malignant), primary sarcomas and metaplastic spindle cell carcinoma. Our biomarker panel included high molecular weight keratin (HMWK), CAM5.2, AE1/AE3, p63, CD34 and GATA3. GATA3 expression was significantly higher in metaplastic carcinomas (88.9 % vs 4.1 %, p < 0.001), when compared to other spindle cell lesions. The sensitivity and specificity for detecting metaplastic carcinomas reached 84.2 % and 97.3 %, respectively. Regarding cytokeratin panels, none of the three individual markers were as sensitive or specific for metaplastic breast carcinoma. GATA3 is the most specific and sensitive marker forfor the identification of metaplastic spindle cell carcinoma of the breast.

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.

Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal Carcinoma.

Colorectal cancer is a heterogenous disease with striking biological diversity. Colorectal carcinoma (CRC) is one of the most common malignancies, accounting for over 9% of all cancers worldwide. To put it in perspective, 5% of people will develop CRC in their lifetime. Biomarkers specific to a particular cancer type can assist in the evaluation of survival probability and help clinicians assess treatment modalities, an example being programmed death ligand-1 (PD-L1). With regards to PD-L1, this is the first study to evaluate the SP-142 antibody clone in CRC. The Ventana PD-L1 (SP-142) assay for PD-L1 expression identifies patients who may benefit from treatment with atezolizumab. SP-142 was chosen as large stage 3 clinical trials are being undertaken with atezolizumab in CRC. Indoleamine 2,3-dioxygenase (IDO-1) was also chosen as there are several ongoing trials for Epacadostat, the best-in-class oral IDO-1 enzyme inhibitor, in many solid tumors. For solid tumors, IDO-1-based immune escape has the potential to inhibit monotherapeutic efficacy of PD-L1-based therapeutics. In this study, a total of 223 cases of CRC were retrospectively reviewed and clinicopathologic data were analyzed in relation to PD-L1 and IDO-1 protein expression. Moreover, tumor-infiltrating lymphocytes, mismatch repair deficiency, high mitotic index, and worse survival outcomes were found in cohorts with significant PD-L1 and IDO-1 expression. Both PD-L1 and IDO-1 are actionable biomarkers, with potential therapeutic implications in CRC. Our findings support the theoretical foundation for targeting PD-L1 and IDO-1 in CRC, which now needs verification in well-designed robust clinical trials.