Objective To improve the efficiency and accuracy of videonystagmography calibration test results while enabling effective recognition of saccadic undershoot waveform by developing a dual-stream architecture-based deep learning model. Methods A vestibular function calibration test recognition model with cross-modal feature fusion was constructed by integrating vision transformer (ViT) and a modified ConvNeXt convolutional network. The model utilized trajectory pictures and spatial distribution maps as inputs, employed a multi-task learning framework to classify calibration data, and to directly evaluate undershoot waveform. Results The model showed outstanding performance in assessing calibration compliance. The accuracy, sensitivity, specificity of the model in left side, middle, and right side were all greater than 90%, and AUC values were all greater than 0.99, with 97.66% of optimal accuracy (middle), 98.98% of optimal sensitivity (middle), 96.87% of optimal specificity (right side), and 0.997 of AUC (right side). The model also showed promising performance in undershoot waveform recognition with 87.50% of accuracy, 89.66% of sensitivity, 85.71% of specificity, 86.67% of F1 score, and 0.931 of AUC. Conclusions The proposed method not only significantly enhances the efficiency and accuracy of calibration test results, but also provides a novel solution for undershoot waveform recognition.

Objective:To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).Methods:A Chinese pedigree affected with VLCADD admitted at the First People′s Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed.Results:The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14: 1, C16: 1, C16: 2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c. 664G>A (p.G222R) and c. 1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14: 1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c. 1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120). Conclusion:The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c. 1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.

Objective:To analyze the genetic mutation characteristics of glucose-6-phosphate dehydrogenase (G6PD) deficiency among infants in Kunming.Methods:A total of 15 533 infants (7 994 males and 7 539 females) born in Kunming from January 1, 2018, to December 31, 2020, with an age range of 2 to 44 days, were selected. G6PD enzyme activity and gene mutation types were detected using fluorescence quantitative analysis, multicolor melting curve analysis (MMCA), and Sanger sequencing. Droplet digital PCR (ddPCR) was used for quantitative analysis of a newly identified variant family to determine the mutant allele proportion in family members. Meanwhile,the protein structure model and pathogenicity prediction of the novel variant were analyzed.Data analysis was conducted using SPSS 26.0. Specifically, chi-square tests were used for the detection rates of G6PD enzyme activity and gene mutations between different genders. One-way analysis of variance (ANOVA) was used for the comparison of enzyme activity among different mutation types.Results:Among 15 533 infants, 143 cases (129 males and 14 females) were tested positive for G6PD activity, with a detection rate of 0.92% (143/15 533). The difference in detection rates between males and females was statistically significant (χ 2=96.76, P<0.001). Out of 89 enzyme activity-positive cases (83 males and 6 females) underwent genetic testing, 77 (72 males and 5 females) were detected by MMCAand other 12 negative samples were underwent further Sanger sequencing, revealing mutations in 6 samples, all of which were males. Among the 83 individuals with gene mutations, 78 had heterozygous mutations, 1 had a homozygous mutation, and 4 had compound heterozygous mutations. A total of 12 mutation types were detected, with G6PD c.487G>A, c.1024C>T, c.1388G>A, and c.1376G>T being the most common, accounting for 74.70% (62/83) of all mutation types. The average G6PD enzyme activity of c.1376G>T was the lowest, and the differences were statistically significant compared to the average enzyme activity of the other three mutations ( P<0.05). One male infant with a newly identified G6PD c.242G>C mutation was detected, predicted to be pathogenic. ddPCR confirmed that the mother of the affected child was a c.242G>C mutant chimera, with a chimera proportion of 6.66%. Conclusions:In the Kunming region, the predominant G6PD deficiency gene mutation is c.487G>A, with the detection of a novel G6PD c.242G>C mutation. The application of ddPCR technology can assist in detecting the proportion of mutation chimeras.

In 2022,breast cancer ranks the first in incidence among all malignant tumors worldwide,and it's high recurrence and fatality rate has posed serious threat to human life and health.Triple negative breast cancer(TNBC)is known for its poor prognosis among all types of breast cancer,and is often associated with elevated expression of epidermal growth factor receptor(EGFR).EGFR is widely expressed on the surface of various cells.The signaling pathway mediated by EGFR is mainly involved in cell growth,proliferation and differentiation.EGFR overexpression is often closely related to tumor invasion,metastasis and prognosis.Therefore,elucidating the roles of EGFR in TNBC and developing prevention and treatment strategies correspondingly are helpful to prevent and control the occurrence of breast cancer,and improve patients'quality of life.This review summarizes the research progress in the roles of EGFR,the treatment strategies and drug resistance in TNBC,in order to provide more refence for treating and improving the prognosis of breast cancer.

Objective:To investigate the long-term follow-up results and the risk factors of bleeding among very elderly patients with non-valvular atrial fibrillation (NVAF).Methods:A total of 177 patients with NVAF admitted in Beijing Hospital from January 2016 to July 2016 were enrolled in the study, including 107 very elderly patients (aged≥80 years) and 70 elderly patients (aged 65-80 years). The demographic information, comorbid diseases, lifestyles, antithrombotic therapy, thromboembolism risks, bleeding risks, and medical history were documented. Patients were followed up for 5 years and the events of death, thromboembolism, bleeding and major bleeding were recorded.Results:There was no significant difference in the incidence of thromboembolic events between the two groups (15.9%(17/107) vs. 14.3%(10/70), P>0.05). The proportions of bleeding events and severe bleeding events in the very elderly group were higher than those in the elderly group (45.8%(49/107) vs.10.0%(7/70), 14.0%(15/107) vs. 1.4%(1/70), both P<0.05). According to the bleeding events during follow-up, very elderly patients were divided into bleeding group ( n=49) and non-bleeding group ( n=58). Compared with the non-bleeding group, patients in the bleeding group had an older age, a higher proportion of chronic cardiac insufficiency, chronic kidney disease, malignant tumor, bleeding history and higher bleeding risk score (HAS-BLED score) (all P<0.05). Multivariate logistic regression model analysis showed that age, HAS-BLED score, history of bleeding, and complicated malignant tumor were independent risk factors for bleeding events in very elderly patients with NVAF (all P<0.05). Conclusions:Very elderly patients with NVAF have a similar risk of thromboembolism compared with the younger elderly, but have significantly higher risk of the bleeding and major bleeding. Age, HAS-BLED score, bleeding history, and malignant tumor are independent risk factors for bleeding events in very elderly NVAF patients.

Dynasore is a small molecule that inhibits the GTPase activity of dynamin and mitochondria-related proteins both in vitro and in vivo,consequently preventing bacteria and viruses from entering cells via endocytic processes,impeding infection and spread of the pathogen.Dynasore is able to participate in cell survival,proliferation and apoptosis through a variety of dynamin protein-independent mechanisms such as reducing reactive oxygen species production,inhib-iting ferroptosis,lowering dynamin-related protein 1 activity to reduce mitophagy,and deeply engaging in vascular endo-thelial growth factor pathway.Here based on the molecular mechanisms and signaling pathways of dynasore involving in diseases,this review summarizes the role of dynasore in microbial infections,neurodegenerative diseases,and tumors.

Objective To observe and analyze functional areas of the cerebral cortex in C57BL/6 mice of various ages.Methods Improved alkaline phosphatase staining was used to reveal the microvascular morphology of the cerebral cortex in C57BL/6 mice,including the motor cortex(primary and secondary motor cortex),sensory cortex(primary and secondary somatosensory cortex),visual cortex(primary and secondary visual cortex),and auditory cortex(primary and secondary auditory cortex),olfactory cortex(extrarhinal and entorhinal cortex).Images were captured under an OLYMPUS BX51 microscope with Image-Pro Plus 5.1 software.The microvascular length density(Lv),microvascular surface area density(Sv),and microvascular volume density(Vv)were analyzed by Image-Pro Plus 5.1 software.Results Expression of alkaline phosphatase was abundant in cerebral cortical microvessels of adult and elderly mice,and slightly expressed in juvenile mice,but not in lactating mice.Pial blood vessels enter the cortex in T shape,Y shape,large arc,and small arc four manners.Lv,Sv and Vv in different parts of the same aged mice showed a decreasing trend in motor,sensory,visual,auditory and olfactory cortexes,and the microvascular density of Lv,Sv and Vv in motor and sensory cortexes was statistically significant compared with the olfactory cortex(P<0.05).The vascular density in all functional areas in elderly mice was lower than that in adult mice,but no statistical significance was found(P>0.05).Conclusions The expression of alkaline phosphatase in microvessels in functional areas of the cerebral cortex in C57BL/6 mice increases with age and reached its peak value in adulthood.The microvascular architecture in the brain provides morphological parameters to establish cerebrovascular disease models.

Objective:To investigate the relationship between cerebral small vessel disease and thyroid hormones in the elderly.Methods:A total of 314 subjects aged ≥60 years with records of head magnetic resonance image(MRI), serum thyroid function tests and physical examinations collected in the Department of Health Care Neurology of Beijing Hospital from May 2019 to November 2020 were consecutively included for this cross-sectional study.Participants were assigned into the cerebral small vessel disease group if their head MRI presentations met the following standards: the Fazekas score ≥3 points; the Fazekas score ≥2 points, with 1 cavity; new subcortical infarcts; or cerebral microhemorrhage.Differences in thyroid function were compared between the cerebrovascular disease group(n=129)and the group without cerebrovascular disease(control group, n=185).Results:A total of 314 subjects were enrolled, of whom 129 met the head MRI standards for cerebrovascular disease, and 185 who did not meet the standards entered the control group.Comparison of thyroid function found a statistically significant difference in FT3( t=3.270, P=0.001)between the two groups.As for the association of a specific type of cerebral small vessel disease with thyroid function, there was a statistically significant difference in the FT3 level between the lacunar infarction group and the non-lacunar infarction group( t=3.106, P=0.002)and between the cerebral microhemorrhage group and the non-cerebral microhemorrhage group( t=2.125, P=0.034). Groups with different Fazekas scores in white matter hyperintensity showed statistically significant differences in rT3( F=3.092, P=0.027), FT3( F=5.427, P=0.001)and FT4( F=2.646, P=0.049). After correction for hyperlipidemia, rT3 and FT4, it was found that age( OR=1.044, 95% CI: 1.022-1.067, P=0.000), hypertension( OR=0.533, 95% CI: 0.294-0.963, P=0.037)and FT3( OR=0.276, 95% CI: 0.159-0.478, P=0.000)were related to cerebral small vessel disease. Conclusions:FT3 levels at the lower end of the normal range are associated with cerebral small vessel disease in the elderly.

Objective:To investigate the incidence, neuroimaging features, and related factors for asymptomatic cerebral small vessel disease(CSVD)in the elderly population.Methods:A total of 201 elderly people with no neurological disease history who had undergone brain magnetic resonance imaging(MRI)examination from October 2019 to August 2020 were enrolled.We calculated the total CSVD score for each participant based on lacunar infarcts(LIs), white matter hyperintensities(WMH), enlarged perivascular spaces(EPVS), and cerebral microbleeds(CMBs)(0-4 points).CSVD neuroimaging features and the correlation between CSVD markers and clinical variables were analyzed.Results:In this study, 133 cases(66.2%)showed MRI features consistent with CSVD.Of whom, LIs were present in 44(21.9%), high-grade PVWMH in 88(43.8%), high-grade DWMH in 30(14.9%), basal ganglia EPVS in 61(30.3%), and CMBs in 92(45.8%).Total CSVD burden score( OR=1.876, 95% CI: 1.045-3.364, χ2=4.441, P=0.035), PVWMH( OR=2.821, 95% CI: 1.517-5.244, χ2=10.752, P=0.001), DWMH( OR=2.130, 95% CI: 1.108-4.092, χ2=5.145, P=0.023), and EPVS( OR=3.258, 95% CI: 1.675-6.334, χ2=12.129, P=0.000)were associated with hypertension.Total CSVD burden score, PVWMH, DWMH, EPVS, and CMB were correlated with increasing age( P<0.05).LIs was positively correlated with PVWMH( b=0.231, P=0.001), DWMH( b=0.247, P=0.000)and EPVS( b=0.215, P=0.001).There was a positive relationship between PVWMH and DWMH( b=0.546, P=0.000)as well as EPVS( b=0.388, P=0.000).DWMH was also positively correlated with EPVS( b=0.357, P=0.000)and CMB( b=0.177, P=0.009). Conclusions:The incidence of asymptomatic CSVD is high in the elderly population.The total CSVD score is a useful measure to evaluate asymptomatic cerebral small vessel disease in the elderly population.Neuroimaging features of asymptomatic CSVD are mainly correlated with age and hypertension.

Objective:To investigate the clinical features and associated chronic pain in corticobasal syndrome (CBS).Methods:Clinical data of 8 patients diagnosed as probable CBS or possible CBS admitted to Beijing Hospital during January 2010 to June 2020 were retrospectively analyzed. The clinical information included sex, age, course of disease, chief complaint, neurological examination, blood biochemistry, tumor marker, infection and other laboratory tests; the neuropsychological evaluation included Mini-Mental State Examination (MMSE) scale and Hamilton Depression Scale (HAMD); the imaging studies included cranial magnetic resonance imaging (MRI) and/or 18F-Fluorodeoxyglucose positron emission tomography ( 18F-FDG PET). Results:The main clinical manifestations were asymmetrical movement disorders, including rigidity, tremor, myoclonus and abnormalities in posture and gait. Patients showed poor response to levodopa treatment. Among 8 patients, 7 had apraxia, 5 patients had alien hand, and 5 patients had various degrees of cognitive dysfunction. The cranial MRI demonstrated mild cerebral atrophy which was slightly more severe in the contralateral side of the initially affected limb in 7 of the 8 patients. The 18F-FDG PET scan revealed asymmetric decreased metabolism in the frontal, parietal, temporal, and occipital lobe, as well as in basal ganglia, which was more severe in the contralateral side of the initially affected limb in 5 of the 8 patients. Six of the 8 patients were associated with pain, including dystonic pain in 3 patients, neuropathic pain in 1 patient, musculoskeletal pain in 1 patient, and unexplained pain in 1 patient. Pain was the onset symptom in 1 patient and pain was relieved by taking levodopa in another patient. Conclusions:CBS is characterized by asymmetric dyskinesia and cognitive impairment, and often associated with apraxia, cortical sensory deficits, and alien limb. The MRI and PET are helpful for CBS diagnosis. Pain may be one of the common non-motor symptoms in CBS.