Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.

Adipose progenitor cells(APCs) represent a prominent stromal cellular component of adipose tissue and are now identified as highly heterogenous populations. However, the role of APCs in regulating systemic metabolism remains unknown. Using single cell RNA-sequencing, we investigated the role of the APC subpopulations in regulating development of type 2 diabetes. CD9 + CD55 low APCs are the novel subset identified in this study, which is significantly increased in type 2 diabetic patients. Transplantation of these cells from type 2 diabetic patients into adipose tissue caused glycemic disturbance in mice. Depletion of pathogenic APCs improved obesity-related glycemic disturbance. Collectively, our data provide deeper insights into human APC functionality and highlights APCs as a potential therapeutic target to combat type 2 diabetes. This study has been published in Nature Communications, 2024, 15(1): 4827.

Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

Objective: To investigate the mechanism of moxibustion in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), by observing the effects of moxibustion at Tianshu (ST25) and Shangjuxu (ST37) on microRNA-133b (miRNA-133b), pituitary homeobox family factor 3 (Pitx3)/tyrosine hydroxylase (TH), and neurotransmitters in the brain tissue of IBS-D rats. Methods: Healthy Sprague-Dawley rats were randomly divided into a normal group, a model group, a moxibustion group, and a Western medicine group, with 12 rats in each group. Except for the normal group, the IBS-D rat model was established by mother-offspring separation and acetic acid enema combined with restraint stress stimulation in all the other groups. No intervention was performed in the normal and model groups. Mild moxibustion was applied to both Tianshu (ST25) and Shangjuxu (ST37) in the moxibustion group. Rifaximin was given by gavage in the Western medicine group. The physical status of rats in each group was observed at different periods. After the intervention, hematoxylin- eosin staining was performed to observe the histopathological morphology of rat colon; enzyme-linked immunosorbent assay was used to measure the levels of dopamine (DA), noradrenaline (NE), and 5-hydroxytryptamine (5-HT) in plasma, colon, and midbrain tissue of rats; the relative expression levels of miRNA-133b, Pitx3 mRNA, and TH mRNA in the midbrain tissue were measured by real-time fluorescence quantitative polymerase chain reaction, and the relative expression levels of Pitx3 and TH proteins in the midbrain tissue were measured by Western blotting and immunofluorescence. Results: The body weights of rats among groups and at different time points were statistically different (P<0.01). The body weight of the normal group was higher than that of the other groups over time (P<0.01). After modeling, the minimum volume threshold of abdominal withdrawal reflex (AWR) was significantly lower (P<0.01) and the loose stool rate was significantly higher (P<0.01) in the model, moxibustion, and Western medicine groups compared with the normal group; the miRNA-133b expression in the midbrain tissue was significantly lower (P<0.01), the expression levels of Pitx3 and TH in the midbrain tissue were significantly higher (P<0.01), and the levels of DA, NE, and 5-HT in plasma, colon and midbrain tissue were significantly higher (P<0.01). After the intervention, the minimum volume threshold of AWR was significantly higher (P<0.01), the loose stool rate was significantly lower (P<0.01), the miRNA-133b expression was significantly increased (P<0.01 or P<0.05) and the expression levels of Pitx3 and TH were significantly decreased (P<0.01) in the midbrain tissue, the levels of DA, NE, and 5-HT in plasma, colon, and midbrain tissue were significantly reduced (P<0.01) in the moxibustion and Western medicine groups compared with the model group; the levels of 5-HT in the colon and midbrain tissue of the moxibustion group were significantly lower than those in the Western medicine group (P<0.05), and there was no statistical difference compared with the remaining groups (P>0.05). Linear correlation analysis showed that miRNA-133b was negatively correlated with Pitx3 (r<0, P<0.01); Pitx3 with TH, TH with DA, and NE with 5-HT were positively correlated (r>0, P<0.01).Conclusion: Moxibustion at Tianshu (ST25) and Shangjuxu (ST37) improves diarrhea symptoms and visceral hypersensitivity in IBS-D rats. The mechanism may be related to up-regulating miRNA-133b, inhibiting Pitx3/TH, and reducing neurotransmitter expression levels in the midbrain tissue.

The clinical manifestations and examination results of a case of Creutzfeldt-Jakob disease (CJD) admitted to the Department of Neurology of Peking Union Medical College Hospital,Chinese Academy of Medical Sciences in August 2020 were analyzed, and a comprehensive neuropsychological assessment and assessment of apraxia were conducted. The neuropsychological characteristics of apraxia in CJD patient and the progress in the research and evaluation of apraxia were reviewed. The patient was a 65-year-old male with insidious onset and progressive symptoms, whose clinical manifestations were apraxia, rapidly progressing dementia, and extrapyramidal symptoms. The magnetic resonance imaging showed hyper-intense signal in diffusion weighted imaging in bilateral cerebral hemispheres, and 14-3-3 protein in cerebrospinal fluid was positive, which were consistent with the probable CJD diagnostic criteria. The patient exhibited prominent signs and symptoms of ideomotor apraxia. It has been reported in the literature that apraxia can also be the main neuropsychological manifestation of CJD. It is necessary to pay attention to the standard evaluation and timely identification of apraxia in clinical diagnosis.

The clinical data of a case of Weave syndrome admitted in the Department of Endocrinology, Children′s Hospital of Nanjing Medical University in October 2018 were retrospectively analyzed.The patient was a 9 years and 2 months old girl, who was hospitalized because of " growing too fast for 9 years" . After birth, the child is found to grow fast and have mental retardation, slurred speech, a blurred vision, a long face, a protruding forehead, ocular hypertelorism, epicanthus, nasal bridge pit, finger pads on both hands and feet, uncoordinated gaits, and intoeingpigeon toes.A novel heterozygous c. 1720A>G (p.K574E) mutation was detected in the exon 15 of the EZH2 gene of the patient.This mutation has not been reported at home and overseas.Sanger sequencing revealed that the patient′s parents did not carry the mutation.The disease is an autosomal dominant genetic disorder, and the parents and sibling of the patient have no corresponding symptoms, so it is inferred that the mutation is spontaneous.Based on the peculiarity of the face, clinical manifestations and the results of molecular genetics, the child was diagnosed as Weaver syndrome.

Objective: To evaluate the value of cerebrospinal fluid markers expecially total-tau protein (T-tau), phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: sCJD (according to 2009 Brain criteria, 2018 Neurology amended criteria), Alzheimer's disease (AD; the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment, matched for sex and age, in the Department of Neurology, Peking Union Medical College Hospital from 2018 to 2019 were enrolled. Twelve sCJD patients, 49 AD patients and 14 normal controls were enrolled. Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly, and further stored in -80 ℃ and disposed according to widely used standards. The levels of T-tau and P-tau were measured by ELISA. The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded. Moreover, specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype. Results: Using Mann-Whitney U test, T-tau concentrations were found higher in patients with sCJD (1 211(448, 2 227) pg/ml) than in AD patients (549(314, 1 078) pg/ml; U=178, P=0.034 9), and both groups had higher T-tau than the control group (127(79, 192) pg/ml; U=20, 73, P<0.01). The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15, 42) pg/ml; U=82, P<0.01), but not in sCJD patients (32(24, 47) pg/ml). The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01, 54.53)) than in AD patients (7.45(4.79, 10.43); U=87, P<0.01). Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram. Nine sCJD patients, whose CSF samples were tested in the Chinese Center for Disease Control and Prevention, carried an M/M genotype at codon 129 and E/E at codon 219. Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD, which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

Objective To investigate the detection rate of motoric cognitive risk syndrome (MCR)and explore the possible risk factors.Methods A total of 429 elderly patients from geriatric department of Zhejiang Hospital from October 2014 to September 2018 were recruited in the crosssectional study.General information and functional assessment including fall history,self-reported visual impairment and hearing impairment,depressive symptom,cognitive function and gait speed were collected.Patients with MCR were screened out according to the MCR diagnostic criteria.Multiple logistic regression analysis was used to analyze the associated risk factors.Results Seventeen patients(4.0％)met the MCR diagnostic criteria.The proportions of obesity,polypharmacy,cerebral vascular diseases,self-reported hearing impairment,depressive symptoms and slow gait were higher in MCR patients than in non-MCR patients(P＜0.05).Compared with non-MCR patients,MCR patients had lower mini mental state examination (MMSE) scores (P ＜ 0.01).After adjusting for associated confounding factors,multiple logistic regression analysis showed obesity (OR =3.74,95 ％ CI:1.14-12.23,P ＜ 0.05) and depressive symptoms (OR =5.79,95％ CI:1.76-19.06,P ＜ 0.01) were risk factors for MCR.Conclusions MCR is not uncommon in elderly patients.Obesity and depressive symptoms are closely associated with an increased risk of MCR.

Objective: To explore the best indication for veneers and to improve the repair success rate by investigating the effects of different types of dentin exposure on the shear bond strength of cast porcelain veneers with two new veneer bonding systems. Methods: Bonding interfaces with 0%, 25%, 50%, 75% and 100% dentin exposure were designed and fabricated. The bonding interfaces were divided into groups A, B, C, D and E. Sixty 4-mm x 4-mm x 2-mm (length x width x thickness) ceramic specimens were bonded by using two bonding systems, The VN-A, VN-B, VN-C, VN-D and VN-E groups were bonded with Variolink bonding system, and the PF-A, PF-B, PF-C, PF-D and PF-E were bonded with Panavia F bonding system (six specimens per group). The bonded specimens were stored in a distilled water bath at (37 + 1)℃ for 24 hours. The fracture load was tested by a universal testing machine, and the fracture type was observed by scanning electron microscopy. Results : The VN-A (25.14 ± 3.40 MPa), VN-B (22.54 ± 4.48 MPa), VN-C (19.59 ± 2.21 MPa), PF-A (20.61 ± 2.42 MPa), PF-B (18.08 ± 4.11 MPa), PF-C (17.06 ± 2.29 MPa) groups’ shear bond strengths were above 17 MPa. The VN-A group had the highest shear bond strength value. There was no statistically significant difference in bond strength between the VN-A group and the VN-B and VN-C groups (P > 0.05) or the PF-A and PF-B groups (P > 0.05); however, the differences between VN-A and the VN-D and VN-E groups (P < 0.05) and between PF-A and the PF-C and PF-D and PF-E groups (P < 0.05) were statistically significant. The differences between the VN-A group and PF-A group (P < 0.05) were statistically significant. The fracture modes of the VN-A, PF-A, VN-B, PF-B, and VN-C groups mainly included resin cement cohesive failure and mixed failure; the VN-D, VN-E, PF-C, PF-D and PF-E groups were dominated by interface failure and mixed failure. Conclusion When the dentin exposure is greater than 50%, the shear bond strength value of the veneer was significantly affected. To obtain a better clinical effect, the dentin exposure rate should be less than 25%.