Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

Objectives:To observe the incidence of residual shunt post patent foramen ovale(PFO)closure and the effect of PFO closure in these migraine patients at one year after PFO. Methods:This retrospective study included patients who underwent PFO closure for migraine in the Second Affiliated Hospital Zhejiang University School of Medicine from January 2019 to June 2022,patients were divided into the grade 0 shunt group(n=67),the grade Ⅰ shunt group(n=10),the grade Ⅱ shunt group(n=13)and the grade Ⅲ shunt group(n=16)according to the results of contrast transthoracic echocardiography(cTTE)at 1 year after PFO closure.The incidence of postoperative migraine attacks among different groups of patients were compared.The risk factors of residual shunt after PFO closure were explored. Results:The mean age of enrolled 106 patients with migraine was(35.80±11.70)years,of which 83 patients(78.30%)were female.One year after PFO closure,the migraine attack and rating scale were significantly decreased compared to baseline in the grade 0 shunt group,in the grade Ⅰ shunt group and in the grade Ⅱ shunt group(all P<0.05),but not in the grade Ⅲ shunt group(P>0.05).The rate of significant and complete migraine was significantly higher in the grade 0 shunt group(58.21%),in the gradeⅠ shunt group(60.00%),in the grade Ⅱ shunt group(69.23%)as compared to the grade Ⅲ shunt group(18.75%,P=0.02)at one year after PFO.The rate of grade 0 shunt after PFO closure in patients with the microvesicles appearing in≥6 cardiac cycles in resting state before operation was significantly lower than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles in resting state(24.00%vs.83.87%vs.70.00%,P=0.04).Logistic multivariate regression analysis showed that patients with microvesicles appearing beyond 6 cardiac cycles in resting state were more likely to have residual shunts in postoperative cTTE compared to the patients with negative cTTE and microvesicles appearing within 6 cardiac cycles in the cTTE in resting state before operation(OR=0.06,95%CI:0.02-0.23,P<0.01;OR=0.014,95%CI:0.05-0.41,P<0.01). Conclusions:Migraine patients who underwent PFO closure and with grade 0 to grade Ⅱ residual shunt at one year after PFO are most likely to have significant remission of migraine,while the incidence of migraine remission is low in patients with grade Ⅲresidual shunt.The incidence of residual shunt after PFO closure is higher in patients with the microvesicles appearing in 6 cardiac cycles in resting state in the cTTE before operation than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles.

BackgroundSleep disorder can adversely affect human physical and mental health， with important implications for socioeconomic development. And higher vocational college students are subject to various pressures and stimuli exerted by academic studies， job seeking and family socioeconomic status， which may contribute to the onset insomnia symptom or sleep disorder. ObjectiveTo discuss the sleep status and influencing factors among higher vocational college students， and to provide references for improving their sleep status. MethodsIn January and February， 2022， a stratified random sampling method was utilized to enroll 3 300 students from five higher vocational colleges in Wenjiang district of Chengdu city. All the participants were assessed using Insomnia Severity Index （ISI）， Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and Generalized Anxiety Disorder Scale-7 （GAD-7）. Pearson correlation analysis was conducted to test the correlation of ISI with PHQ-9 and GAD-7 scores， and the Logistic regression analysis was performed to identify the influencing factors of insomnia symptom in higher vocational college students. ResultInsomnia symptom was detected in 81.90% （2 497 / 3 300） of higher vocational college students. The detection rate of insomnia symptom among vocational college students yielded statistical difference in terms of gender， family socioeconomic status， being an only child or having siblings， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom （χ²=21.032， 22.172， 8.983， 75.939， 36.781， 32.350， 54.512， 86.561， P<0.01 or 0.05）. Among higher vocational college students， ISI score was positively correlated with GAD-7 and PHQ-9 scores （r=0.620， 0.714， P<0.01）， and GAD-7 score was positively correlated with PHQ-9 score （r=0.824， P<0.01）. Gender， family socioeconomic status， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom were effective factors in predicting the insomnia symptom in higher vocational college students （P<0.01 or 0.05）. ConclusionFemale gender， average and below average family socioeconomic status， moderate-to-severe degree of psychological pressure exerted by academic studies or job seeking， spending 2~5 h， 5~7 h or >7 h on Internet per day， inadequate physical exercise and presence of depressive symptom are the risk factors for insomnia symptom in higher vocational college students.［Funded by Sichuan Provincial Primary Health Development Research Center in 2022， North Sichuan Medical College （number， SWFZ22-C-89）］

Objective:To summarize the clinical, pathological and muscle magnetic resonance imaging (MRI) features of human immunodeficiency virus (HIV)-associated nemaline myopathy (NM; HIV-NM).Methods:The present patient was a 23-year-old man with HIV infection who developed progressive proximal weakness and atrophy for more than 10 months. He was admitted to the Department of Neurology of Beijing Ditan Hospital in early June 2021. Electromyography showed myogenic findings. The serum creatine kinase was 202.4 U/L. CD 4+ count was 585×10 6/L. Serum monoclonal immunoglobulin (M protein) was negative. The patient underwent MRI examination of bilateral thigh muscles, biopsy of left biceps brachii and gene detection. The clinical, pathological and muscle MRI changes of HIV-NM were summarized based on the literature review. Results:MRI examination of bilateral thigh muscles showed edema changes. Muscle biopsy showed nemaline structures in some muscle fibers, accompanied by fiber atrophy and regeneration. No gene mutation related to clinical phenotype was found by second-generation sequencing. After intravenous immunoglobulin combined with prednisone, the patient′s weakness symptoms were significantly improved. A total of 17 cases of HIV-NM (including the present case) were identified in the literature, who were aged (33.7±9.1) years. Fifteen were males and two were females. All patients developed proximal limb weakness. Creatine kinase was normal or slightly elevated. Serum monoclonal protein was positive in 3 cases (3/7). Immunosuppressive therapy was effective.Conclusions:The main clinical characteristics of HIV-NM are progressive proximal limb weakness and muscle atrophy. The muscle pathology shows a large number of nemaline structures in atrophic muscle fibers. Muscle edema can be seen on muscle MRI. This is the first report of HIV-NM in China, which may be a special subtype of immune myopathy.

Objective:To compare the left ventricular (LV) reverse remodeling after transcatheter aortic valve replacement (TAVR) between patients with bicuspid aortic valve (BAV) stenosis and tricuspid aortic valve (TAV) stenosis.Methods:The data of patients who underwent TAVR procedure from March 2013 to December 2018 in the Second Affiliated Hospital of Zhejiang University were retrospectively reviewed. The patients were divided into BAV group and TAV group according to cardiac computed tomography. Echocardiographic parameters, including aortic valve peak velocity (Vmax), mean gradient (PGmean), effective orifice area(EOA), interventricular septum diastolic thickness (IVSd), left ventricular posterior wall diastolic thickness (LVPWd), left ventricular end diastolic diameter( LVEDd), LV mass index (LVMI), ΔLVMI%, left ventricular ejection fraction( LVEF) of the two groups at baseline, 1 week, 1 month and 1 year post TAVR procedure were obtained and compared.Results:①Compared with preoperative measurements, both groups showed decreases in Vmax, PGmean and increase in EOA at 1 week, 1 month, 1 year follow-ups(all P<0.05). No significant differences were found in Vmax, PGmean, EOA, moderate/sever perivalvular leakage(PVL), moderate/sever prosthetic-patient mismatch(PPM) between BAV group and TAV group at 1 year. ②Both groups showed decreases in IVSd, LVPWd, LVEDd at 1 month, 1 year post TAVR compared with those before the procedure (all P<0.05), as well as increases in LVEF at 1 week, 1 month, 1 year (all P<0.05). Downward trends of LVMI were detected in both groups within 1 year follow-up( P<0.05). ③Compared to TAV group, BAV group showed smaller baseline LVMI( P<0.05), while there were no significant differences in ΔLVMI% post TAVR for all follow-up times of the two groups(all P>0.05). Repeated measures analysis of variance also showed no significant differences in downward trend of LVMI between the two groups after TAVR within 1 year( P>0.05). Conclusions:Left ventricular reverse remodeling can be detected in both BAV and TAV patients after TAVR, which starts from 1 week and can be lasted for 1 year post procedure. Patients with bicuspid morphology might experience similar reverse LV remodeling post TAVR versus patients with tricuspid morphology.

Objective:To explore the value of transesophageal echocardiography(TEE) guidance for transcatheter DragonFly? system edge-to-edge tricuspid regurgitation (TR) repair.Methods:Five cases who were chosen in the Second Affiliated Hospital, Zhejiang University School of Medicine from December 2020 to January 2021 with surgical high-risk and severe functional TR underwent transcatheter DragonFly edge-to-edge repair with the guidance of TEE. Preoperative TEE was used to evaluate the tricuspid valve anatomy and the origin and etiology of regurgitation in detail; intra-procedure guidance of TEE was performed during the DragonFly system for tricuspid valve edge-to-edge repair intervention and after release of the DragonFly clip, the effect of surgery was assessed immediately and compared with pre-procedure TEE.Results:A total of 10 DragonFly clips were implanted in 5 patients (3 in each of patients, 2 in 1 patient, and 1 in each of patients). One of the 3 clips in 1 patient fell off unilaterally from the septal valve after release, and the other 9 clips were well positioned and fixed. Immediately post-operation assessment by TEE depicted the TR in 3 patients declined to mild and 2 to moderate. The vena contracta area by using three-dimensional color blood flow quantitative assessment was reduced[(0.93±0.26)cm 2 vs (0.20±0.11)cm 2]. No complications such as serious tricuspid valve injury, pericardial tamponade, thromboembolism occurred in the 5 patients. Conclusions:TEE plays an important role in guiding and monitoring transcatheter DragonFly system edge-to-edge TR repair during the entire procedure.

Objective:To summarize the clinical features and pathological changes of peripheral tissues from patients with neuronal intranuclear inclusion disease (NIID) diagnosed by genetic tests.Methods:Repeat-primed polymerase chain reaction was used to confirm the GGC repeated expansion in the 5′ untranslated region of the NOTCH2NLC gene in patients with suspected NIID who had visited the Department of Neurology of Peking University First Hospital from January 2018 to February 2020. The clinical data and pathological changes of peripheral tissues from patients with genetically diagnosed NIID were collected retrospectively and analysed. Immunostaining with anti-p62 and anti-ubiquitin antibody was performed on peripheral biopsy specimens.Results:Totally nine patients with NIID who had GGC repeated expansion in the NOTCH2NLC gene were found. Five patients were familial (from three faimilies), and four patients were sporadic. The age of onset was 36-61(51.33±7.12) years. The most common symptoms in this NIID group were episodic emotion and personality change (8/9), paroxysmal disturbance of consciousness (6/9) and intermitant head discomfort (6/9). Other symptoms included cognitive dysfunction, limb weakness, limb sensory disturbance, bladder dysfunction, ataxia, seizures and psychiatric symptoms. Brain magnetic resonance imaging showed high signals along the corticomedullary junction on diffusion-weighted image in eight out of nine patients. Skin biopsied samples from nine patients demonstrated the presence of eosinophilic intranuclear inclusions (IIs), appearing in the nucleus of fibroblasts, fat cells and ductal epithelial cells of sweat glands on hematoxylin-eosin staining. IIs were positive on anti-p62 and anti-ubiquitin immunostaining. Electron microscopy indicated the IIs were composed of a pile of filament materials without membrane. Muscle biopsies from two patients showed no obvious neurogenic or myogenic pathologic changes, except in one patient several rimmed vacuoles fibers were found. In one patient sural nerve biopsy showed severe demyelinating pathological changes. No IIs were found in the muscles and peripheral nerve tissue either by histological examination or by immunohistochemical staining with anti-p62 or anti-ubiquitin, while IIs were found by immunofluorescence staining with both anti-p62 and anti-ubiquitin in three patient′s tissue. Conclusions:The phenotype of this NIID patient group is adult-onset NIID, with episodic encephalopathy as the main clinical manifestation. Skin biopsy has high pathological diagnostic value for NIID. The immunofluorescence staining with anti-p62 and anti-ubiquitin is easier to detect the presence of IIs than histological staining and immumohistochemical staining.

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

Objective ToevaluatetheimagedifferencesofCTinsubtypepapillaryrenalcellcarcinoma(PRCC).Methods Aretrospective analysisof30multiphaseCTenhancedimagesofPRCCconfirmedbyoperationandpathologyinourhospitalwasperformed,followed byacomparativestudyofCT multistageenhancedperformanceandpathology.Results typeⅠ16cases,typeⅡ14cases,ofwhich 11casesofⅡtypePRCC wereirregularorlobulated,and4casesoftypeⅠshowedlobulated,therewarestatisticallysignificant differencesbetweenthetwogroups(P＝0.003).Venoustumorthrombusin5casesoftypeⅡPRCC,4casesoftypeⅡPRCClymph nodemetastasis,perirenalinvasionin6casesofⅡtypePRCC,but1caseofⅠPRCChadvenousthrombus,perirenalinvasionin2 cases,nocaseoflymphnodemetastasis,therewereobviousdifferencesbetweenthetwogroups(P＝0.044,P＝0.022,P＝0.025). PRCCplainscanCTvalue,CTvalueofexcretoryperiod,CTvalueaddedinthesubstantiveperiod,CTincrementduringexcretionperiod, therewarenosignificantstatisticalsignificancebetweentypetwogroups(P＝0.893,P＝0.169,P＝0.559,P＝0.155).CTvalueof corticalphase,CTvalueinperenchymalphase,CTvalueincrementincarticalphasehadsignificantlydifferencesbetweentwogroups (P＝0.013,P＝0.046,P＝0.008).Conclusion Therearecertaindifferenceintumormorphology,outsideinvasionsignsandenhancement degreebetweentypeⅠandtypeⅡPRCCandⅡtypePRCCispronetoappearperirenalinvasion,tumorthrombusandlymphnode metastasis.CTscanningishelpfulindifferentialdiagnosisofsubtypesofPRCC.

Objective: To explore the relationship between the cognitive impairment and cerebral lesions using 7.0 Tesla magnetic resonance imaging (MRI) in CADASIL patients. Methods: Thirty five CADASIL patients confirmed by serum NOTCH3 gene detection in Peking University First Hospital from June 2015 to November 2018 were enrolled, including 19 males and 16 females, of which the age of onset was (39.28±8.31) years, the age of admission was (44.61±8.42) years, and the course of disease was (5.29±3.65) years. 7.0 Tesla MRI was performed in all the patients. The numbers of lacunar infarcts and microbleeds were counted and the white matter changes were evaluated with age-related white matter rating scale (ARWMrs). Neuropsychological tests were used to evaluate the global cognition, memory, attention, executive function, visuo-spatial function and language function separately. The z score was calculated to evaluate the impairment extent in different scales. The correlation analysis was performed between image changes and neuropsychological tests. Thirty nine normal controls including 20 males and 19 females with age of (42.54±8.92) years were also enrolled, and the same neuropsychological tests were performed in these subjects. Results: The numbers of microbleeds and lacunar infarcts were 13.71±10.29 and 5.89 (8.74). The ARWMrs score was 11.26±5.31. There were 21 patients (60%) presented with cognitive impairment. In comparison with the controls, the patients presented with global cognitive impairment (MMSE score 26.87±3.95 vs 29.08±0.95), including executive (finishing time of Stroops-c: 80.00 (103.75) s vs 67.79 (16.00) s, correct number of Stroops-c: 48.00 (44.26) vs 50.00 (2.00), time of trail making A test: 55.5 (81.5) s vs 39.0 (5.0) s, time of trail making B test: 171.0 (159.5) s vs 103.0 (54.0) s, false number of trail making B test: 0(2) vs 0(0)), memory (number of register memory: 16.13±5.41 vs 21.1±15.21, number of long term recall: 4.78±2.83 vs 7.41±2.24, number of cue recall memory: 4(6) vs 8(4), number of recognition memory: 10.00 (2.25) vs 11.00 (2.00)), attention (number of digital span: 4.42±1.46 vs 7.89±1.65, correct number of symbol digitalis modality test: 38.47±17.29 vs 51.41±13.00), visuo-spatial (Rey-osterrich: 34 (5) vs 36 (2)) and language function (number of semantic fluency: 14.70±5.54 vs 17.46±5.63) (P<0.05). The z score demonstrated impaired executive function, followed by visuo-spatial dysfunction. The number of lacunar infarcts and microbleeds significantly correlated with short term recall memory (r=-0.404, -0.393), long term recall memory (r=-0.375, -0.395), cue memory (r=-0.395, -0.437), Stroops-c time (r=0.412, 0.503), trails making A test time (r=0.400, 0.434)(P<0.05). The number of lacunar infarcts significantly correlated with symbol digitalis modality test (r=-0.475) (P<0.05). The number of microbleeds significantly correlated with digital span test (r=-0.390), Boston naming test (r=-0.382) and semantic fluency (r=-0.449) (P<0.05). ARWMrs score significantly correlated with MMSE score (r=-0.357), rigister memory (r=-0.342), trails making A finishing time (r=0.425), trails making B finishing time (r=0.463) and correct numbers of trails making B (r=0.392) (P<0.05). Conclusions CADASIL presented with global cognitive impairment, especially executive function and visuo-spatial function. The white matter changes, lacunar infarcts and microbleeds affected different cognitive function.