Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

The overuse of medications for primary headache disorders is a worldwide phenomenon that plays an im-portant role in the chronicity of headache disorders.The high treatment cost and co-morbidity with various diseases pose a heavy burden on individuals and societies.In the third edition of the International Classification of Headache Disorders,medication overuse headache(MOH)is recognized as a separate secondary entity to most primary headache disorders.This article reviews the overview,epidemiology,pathophysiological mechanisms,diagnostic criteria,and treatments of MOH,discusses some unsolved questions,and summarizes the current debate on MOH.

Headache has high incidence and disability rates.The burden of headache in China has become an in-creasingly serious social problem.However,the diagnostic level of headache disorders varies among physicians due to the complexity of etiological classification.In order to help clinicians effectively improve the accuracy of clinical diagnosis,the Chinese People's Liberation Army(PLA)General Hospital led the development of the Clinical Decision Support Sys-tem(CDSS)for headache,and CDSS 2.0 has already been able to achieve a satisfactory diagnostic accuracy rate for head-ache.The Chinese PLA General Hospital has initiated the headache prevention and control base and system construction project in China.The application of CDSS to assist teaching in headache specialist training practice is an important means of headache specialist training.With the help of the CDSS system,neurologists are trained in headache specialty.Through the learning function of the CDSS,physicians can better understand the path of headache inquiry,improve the ability to identify secondary headache,be familiar with the ICHD-3 diagnostic criteria,learn standard headache cases,and improve the ability to employ standard treatment.In this paper,we will comprehensively discuss the role of the CDSS in the training of headache specialists and provide a summary and reflection,in order to provide a reference for the further development and improvement of headache specialist training in China.

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.

Objective:To investigate the clinical features of pregnant associated Takotsubo cardiomyopathy (PTCM).Methods:We reviewed reported PTCM cases published from January 2007 to June 2022 using the keywords "Tako-tsubo cardiomyopathy""Takotsubo cardiomyopathy" "stress cardiomyopathy" AND "parturition" "pregnancy" "cesarean delivery" "postpartum" "peripartum" "eclampsia" "abortion" in Pubmed and Web of Science databases and the corresponding Chinese words in Wanfang and Chinese Medical Journal Network. Age, obstetric history, mode of delivery, mode of anesthesia, etiological factors, clinical manifestations, treatment, and prognosis of PTCM were recorded. Descriptive statistical analysis was adopted.Results:A total of 55 articles were included, covering 60 patients with PTCM. (1) Age and time of onset: The age of onset was (32.4±6.0) years old. PTCM occurred most frequently during labor [42% (25/60)] and within one day postpartum [32% (19/60)] and during the gestational period [13%(8/60), 33.0 weeks (24.5-37.7 weeks)]. (2) Delivery-related factors: There were 38% (16/42) primiparas and 60% (25/42) multiparas. Among them, 67% (38/57) and 18% (10/57) were delivered by cesarean section and vaginal delivery, respectively. PCTM often lacks obvious triggers [40% (24/60)], with the most common inducing factor being pregnancy-related diseases [27% (16/60)]. (3) Clinical features: The initial symptoms of PTCM were dyspnea [44% (26/59)], followed by chest pain accompanied by dyspnea [17% (10/59)]. The most common subtype of PTCM was the apical type [45% (26/58)], followed by the basal type [24% (14/58)], while the biventricular type was the least common [3% (2/58)] in the PTCM classification. The left ventricular ejection fraction was (31.6±12.1) % at the onset of PTCM, which recovered to (58.2±7.6) % at discharge. PCTM was often complicated by pulmonary edema [67% (40/60)] and cardiogenic shock [55% (33/60)]. (4) Treatment and prognosis: Patients with PCTM usually require noninvasive or invasive ventilator-assisted ventilation [40% (23/58)]. One pregnant woman and five neonates died, while the remaining patients recovered well.Conclusions:PTCM should be considered in differential diagnosis of patients experiencing dyspnea and chest pain during labor and pregnancy. PTCM patients are younger and have more pulmonary edema and cardiogenic shock. Mechanical ventilation is often required, but the prognosis is favorable.

Objective:To explore the morbidity, clinical features and mortality of unilateral pulmonary edema (PE) in the intensive care unit (ICU).Methods:Clinical data of PE patients in ICU between January 2018 and January 2021 were retrospectively collected. All patients were divided into the bilateral PE and unilateral PE groups according to imaging manifestations. Etilogy, clinical performance, cardiac ultrasound parameters, complications, treatment and prognosis were compared between the two groups. Binary logistic regression analysis was used to screen out the risk factors of death.Results:Of the 314 PE patients, 14 (4.5%) were unilateral PE patients , and 11 (78.5%) were right-sided unilateral PE. There were no differences in age, gender, heart rate, respiratory rate and left ventricular eject fraction between the unilateral and bilateral PE groups. Compared with the bilateral PE group, systolic and diastolic blood pressure were significantly lower in the unilateral PE group [128 (102.7-138) mmHg vs. 135 (116-166) mmHg, 72 (54-88.2) mmHg vs. 82 (69-97.7)mmHg, respectively]. The incidence of cardiac arrest and hospital mortality were higher in the unilateral PE group [28.6% vs. 8.0%, 42.9% vs. 10%, all P<0.05]. Binary logistic regression analysis showed that age, unilateral PE, and use of vasoactive agent were associated with poor prognosis. Odds ratio of unilateral PE and use of vasoactive agent were 17.78 and 11.67, respectively. Conclusions:Unilateral PE is not rare, which is an independent risk factors for mortality and should be promptly recognized to avoid delays in treatment.

OBJECTIVE: To explore the feasibility of using the bidirectional local distance based medical similarity index (MSI) to evaluate automatic segmentation on medical images. METHODS: Taking the intermediate risk clinical target volume for nasopharyngeal carcinoma manually segmented by an experience radiation oncologist as region of interest, using Atlas-based and deep-learning-based methods to obtain automatic segmentation respectively, and calculated multiple MSI and Dice similarity coefficient (DSC) between manual segmentation and automatic segmentation. Then the difference between MSI and DSC was comparatively analyzed. RESULTS: DSC values for Atlas-based and deep-learning-based automatic segmentation were 0.73 and 0.84 respectively. MSI values for them varied between 0.29~0.78 and 0.44~0.91 under different inside-outside-level. CONCLUSIONS It is feasible to use MSI to evaluate the results of automatic segmentation. By setting the penalty coefficient, it can reflect phenomena such as under-delineation and over-delineation, and improve the sensitivity of medical image contour similarity evaluation.
Feasibility Studies ; Radiotherapy Planning, Computer-Assisted

Objective:To study the protective effect and effect of SphK1 overexpression on the injury of nerve cells induced by acrylamide.Methods:ACR with 99% purity was prepared into 1.25 mmol/L and 2.5 mmol/L solutions. SH-SY5Y cells were divided into control group (NC group) , experimental group and SphK1 activator group. The experimental group was given ACR solution with final concentration of 1.25 mmol/L and 2.5 mmol/L respectively for 24 h. In the SphK1 activator group, on the basis of the exposure concentration of the experimental group, the SphK1 specific activator (12-) phorbol tetradecanoate (-13-) acetate (PMA) solution[prepared by dimethyl sulfoxide (DMSO) , the final concentration was 100 nmol/l], and other treatments were the same as the experimental group. Control group (NC group) added PMA solution into normal cells. Western blot was used to detect the expression of SphK1 protein; CCK-8 was used to detect the proliferation of SH-SY5Y cells; hoechst33342 method was used to observe the morphological changes of nerve cells; flow cytometry was used to analyze the apoptosis of cells.Results:Compared with NC group, the expression of SphK1 protein in the experimental group and the SphK1 activator group was significantly lower ( P<0.05) . Compared with the experimental group, the expression of SphK1 protein in each concentration of SphK1 activator group was increased, and the difference was statistically significant ( P<0.05) . In addition to 1.25 mmol/L SphK1 activator group, compared with NC group, the relative growth survival rate of experimental group and 2.5 mmol/L SphK1 activator group were lower, the difference was statistically significant ( P<0.05) . Compared with the experimental group, the relative survival rate of cells in the SphK1 activator group was higher, and the difference was statistically significant ( P<0.05) . With the increase of exposure concentration, the cells in the experimental group showed the morphological characteristics of early apoptosis at ACR 1.25 mmol/L and late apoptosis at ACR 2.5 mmol/L. Compared with NC group, the apoptosis rate of experimental group and SphK1 activator group at ACR 2.5 mmol/L was significantly different ( P<0.05) ; compared with experimental group, the apoptosis rate of SphK1 activator group at ACR 2.5 mmol/L was lower, the difference was statistically significant ( P<0.05) . Conclusion:The SphK1 excessive expression plays the protective function to the nerve cell damage caused by acrylamide.

Objective:To study the protective effect and effect of SphK1 overexpression on the injury of nerve cells induced by acrylamide.Methods:ACR with 99% purity was prepared into 1.25 mmol/L and 2.5 mmol/L solutions. SH-SY5Y cells were divided into control group (NC group) , experimental group and SphK1 activator group. The experimental group was given ACR solution with final concentration of 1.25 mmol/L and 2.5 mmol/L respectively for 24 h. In the SphK1 activator group, on the basis of the exposure concentration of the experimental group, the SphK1 specific activator (12-) phorbol tetradecanoate (-13-) acetate (PMA) solution[prepared by dimethyl sulfoxide (DMSO) , the final concentration was 100 nmol/l], and other treatments were the same as the experimental group. Control group (NC group) added PMA solution into normal cells. Western blot was used to detect the expression of SphK1 protein; CCK-8 was used to detect the proliferation of SH-SY5Y cells; hoechst33342 method was used to observe the morphological changes of nerve cells; flow cytometry was used to analyze the apoptosis of cells.Results:Compared with NC group, the expression of SphK1 protein in the experimental group and the SphK1 activator group was significantly lower ( P<0.05) . Compared with the experimental group, the expression of SphK1 protein in each concentration of SphK1 activator group was increased, and the difference was statistically significant ( P<0.05) . In addition to 1.25 mmol/L SphK1 activator group, compared with NC group, the relative growth survival rate of experimental group and 2.5 mmol/L SphK1 activator group were lower, the difference was statistically significant ( P<0.05) . Compared with the experimental group, the relative survival rate of cells in the SphK1 activator group was higher, and the difference was statistically significant ( P<0.05) . With the increase of exposure concentration, the cells in the experimental group showed the morphological characteristics of early apoptosis at ACR 1.25 mmol/L and late apoptosis at ACR 2.5 mmol/L. Compared with NC group, the apoptosis rate of experimental group and SphK1 activator group at ACR 2.5 mmol/L was significantly different ( P<0.05) ; compared with experimental group, the apoptosis rate of SphK1 activator group at ACR 2.5 mmol/L was lower, the difference was statistically significant ( P<0.05) . Conclusion:The SphK1 excessive expression plays the protective function to the nerve cell damage caused by acrylamide.