This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*

To develop a milestone-based evaluation system for the core "knowledge and skills" competency of neurology residents that is tailored to China's medical context, so as to provide precise guidance for their training and assessment.

To explore the effectiveness of "near peer learning" (NPL) in the electromyography(EMG)teaching module for neurology residents.

Resident training is a necessary path to cultivate excellent clinical doctors. Based on the Consensus on Core Competency Framework for Residency Education Among China Consortium of Elite Teaching Hospitals for Residency Education, Department of Neurology from Peking Union Medical College Hospital has established a training program for neurology residents with a graded evaluation system and a progressive clinical responsibility concept guided by core competency. Overcoming the teaching difficulties of neurology and considering the clinical characteristics of neurology, we have established a series of replicable and promotable neurology residency training curriculum through inheritance and innovation, which provides reference for the continuous improvement of China's neurology residency training program.

  Objective  This study aimed at describing the frequency of rare variants of monogenic cerebral small vessel diseases (CSVD) in a cohort of patients with CSVD, and to explore its clinical relevance.  Methods  This study included CSVD patients visiting the Neurology Department of Peking Union Medical College Hospital(PUMCH) from March 2017 to January 2022, collecting their demographic and clinical information and DNA samples for whole-exome sequencing. Descriptive analysis and statistical analysis were conducted exploring the differences between monogenic CSVD-related gene mutation carriers and noncarriers.  Results  A total of 292 patients were included, 51.03% of whom carried one or more rare variants of monogenic CSVD-related genes. The most common rare low-frequency variants were located in the NOTCH3 gene (70 patients, 23.97%), followed by HTRA1 and COL4A1/COL4A2 (22 patients, 7.53%) respectively. Among the subgroup of patients without a family history of stroke (n=176), the frequency of rare variants was as high as 47.16%. Compared with non-carriers, the carriers were diagnosed at a younger age (58.76±13.71 vs. 63.46±13.21, P=0.003). No difference was found in phenotypes among single-SNP carriers, multiple-SNPs carriers, and noncarriers.  Conclusions  The frequency of rare mutation of monogenic CSVD-related genes were relatively high in Chinese CSVD cohort. The most common rare variant was within the NOTCH3, followed by HTRA1 and COL4A1/COL4A2 genes. For CSVD patients of unknown causes, genetic screening should not be neglected even if there is not a family history of the disease.

Objective:To explore whether there were changes in midbrain morphology related to motor function in patients with cerebral small vessel disease (CSVD).Methods:The study was conducted on a subset of patients with CSVD registered at the Department of Neurology of Peking Union Medical College Hospital from 2010 to 2018. All magnetic resonance imaging images were taken with a 3.0 T nuclear magnetic resonance imager. The measurement of anteroposterior diameter of the mesencephalon and the tegmentum of mesencephalon was performed on a personal computer with the image processing software RadiAnt DICOM Viewer. Several clinical manifestations of dyspraxia, dysphagia, dysarthria and dysuria were evaluated by interviewing the patient and family members living with the patient. Kinect depth camera combined with self-developed software platform was used to conduct quantitative evaluation of patients′ motor function. Three parameters, namely walking speed, walking time of three meters and time of standing up and sitting down, were selected from the obtained parameters. SPSS 17.0 software was used for statistical analysis.Results:A total of 176 patients were included, aged 30-88 (64.16±11.57) years. One hundred and fifteen patients were males, accounting for 65.34%. In patients with CSVD, anteroposterior diameter of the mesencephalon and the tegmentum of mesencephalon were negatively correlated with age ( B=-0.032, P<0.001; B=-0.020, P=0.006). The anteroposterior diameter of the mesencephalon was negatively correlated with symptoms of dyskinesia ( OR=0.006, 95% CI 0-0.135, P=0.001), even when the age and gender were adjusted ( OR=0.014,95% CI 0-0.416, P=0.013). The anteroposterior diameter of the mesencephalon was negatively correlated with symptoms of dysuria ( OR=0.046,95% CI 0.002-0.936, P=0.045), but no longer correlated when the age and gender were adjusted. The anteroposterior diameter of tegmentum of mesencephalo was also negatively correlated with symptoms of dyskinesia ( OR=0.035,95% CI 0.002-0.684, P=0.027), but no longer correlated after adjusting for age and gender. Video recording and evaluation of motor function were performed on 87 patients. Spearman correlation analysis showed that none of the three motor function scores was correlated with age or gender. The anteroposteric diameter of the midbrain was positively correlated with walking speed ( r=0.231 ,P=0.040) and negatively correlated with walking time of three meters ( r=-0.304, P=0.005), but not with standing up and sitting down time, while the anteroposteric diameter of tegmentum of mesencephalo was not correlated with all of them. Conclusion:There are changes in mesencephalon morphology in patients with CSVD, structural parameters of mesencephalon are related to motor function and urination function, and mesencephalon atrophy may be an independent related factor for symptoms of dyskinesia in patients with CSVD.

AIM: To investigate the application of two-stage estimation (TSE) on adjustment for treatment switch in oncology trials. METHODS: The theory and implementation of TSE method was described, and was applied to adjust the data from a two-arm randomized controlled trial of anti-tumor drugs. The changes of survival curves and hazard ratio of two groups after adjustment for cross-over were evaluated. In addition, the results of two-stage estimation and rank preserving structural failure time model (RPSFT) were compared. RESULTS: After adjustment for cross-over using TSE methods, the results showed that the median survival time of control group was shorter than the original one, and the hazard ratio was lower than the observed value. Moreover, TSE method showed similar results to rank preserving structural failure time model. CONCLUSION: The TSE method is relatively simple to use, reliable and has a good practice property in cross-over analysis of oncology trials. At the same time, it is necessary to pay attention to its application scopes.

Objective To analyze the incidence and risk factors of de novo malignant tumors in renal transplant recipients. Methods Clinical data of 1 549 renal transplant recipients were retrospectively analyzed, including the basic status, pathological type and incidence rate of patients with de novo malignant tumors after renal transplantation. The survival situation of these patiensts was assessed. And the risk factors of de novo malignant tumors after renal transplantation were identified. Results The incidence rate of de novo malignant tumors in renal transplant recipients was 3.03%(47/1 549). The 47 recipients were (48±12) years old when undergoing renal transplantation, and they were (55±12) years old when diagnosed malignant tumors. The time interval between transplantation and diagnosis was 66 (36, 100) months. Among the de novo malignant tumors, colorectal cancer was the most common, with a cumulative incidence rate (CIR) of 0.58%. The survival time of 47 recipients with de novo malignant tumors after renal transplantation was 59 (2, 135) months, and the 5-year survival rate was 50%. The recipients with the age > 45 years old when undergoing renal transplantation was a risk factor for de novo malignant tumors after renal transplantation (P < 0.05). Conclusions The incidence rate of de novo malignant tumors is relatively high in renal transplant recipients. The recipients with the age > 45 years old when undergoing renal transplantation is a risk factor for de novo malignant tumors.

Objective     To establish a model of transplanting neonatal cardiomycytes into the wall of rat inferior vena cava. Methods     Neonatal cardiomyocytes (n=6, 5×106cells each, A group) or medium (n=6, B group) only were transplanted into the wall of inferior vena cava in female Fisher rats. At 21 days after transplantation, the contraction of transplanted cardiomyocytes was assessed and the inferior vena cava was processed for histology. Results     Distinct rhythmic beating of the vena cava at the site of cell transplantation before and after the aorties were clamped (at a rate 141± 47 rpm and 88± 44 rpm which was dramaticly lower than aortic beating, with a statistical difference at P value of 0.03). Cardiomyocyte was seen in 6 rats who had neonatal cardiomyocyte transplantation, but not in 6 rats receiving media. Hematoxylin and eosin staining showed viable cardiomyocytes in the wall of the vena cava in 6 rats treated with neonatal cardiomyocytes, but not in 6 rats receiving media. Conclusion     This study shows that neonatal cardiomyocytes can survive, mature and spontaneously and rhythmically contract after they are transplanted in the wall of inferior vena cava.

Objective To investigate the effect of FAM83A on the stem cell-like phenotype, chemosensitivity and radiosensitivity of PANC-1 cells, aiming to provide new ideas for clinical combination therapy of pancreatic cancer. Methods The PANC-1 cells with stable silencing FAM83A were constructed by using lentivirus and validated by qPCR and Western blot. Flow cytometry was used to detect the number of CD133 positive cells and cellular apoptosis; the sphere formation assay was used to test the ability of sphere formation of PANC-1 cells;the effect of gecitabine on the cell viability was detected by MTT assay;the effect of radiation on the proliferation of PANC-1 cells was detected by colony formation assay; the effect of FAM83A on Wnt/β-catenin pathway was examined by Western blot. Results The expressions of FAM83A protein ( 0.83 ± 0.08 ) and mRNA ( 0.29 ± 0.03 ) in PANC-1 cells with stable silencing FAM83A were significantly lower than those in the scrambled control group, respectively (1.95 ± 0.19, 0.98 ± 0.09;t=9.410, 12.600, P<0.05). After silencing FAM83A, the expression of stem cell marker CD133 (8.97 ± 0.62) and the sphere formation ability (8 ± 1) also decreased significantly compared with the scrambled group, respectively (21.60 ± 2.60, 25 ± 3; t=8.184, 9.311, P<0.05), and the stem cell-like phenotype of PANC-1 cells was also significantly inhibited. When PANC-1 cells were silenced by FAM83A and further treated with 50 μmol/L gecitabine at 72 h, the activity of FAM83A-silenced PANC-1 cells (32.33 ± 3.05)％ was significantly lower than that of the gecitabine alone treated group (63.06 ± 5.98)％ (t=6.378, P<0.05), and the apoptosis rate of FAM83A-silenced PANC-1 cells (76.52 ± 8.34) ％ was significantly higher than that of gemcitabine alone group (40.88 ± 4.91)％(t=7.929, P<0.05). After silencing FAM83A combined with IR irradiation, the activity of PANC-1 cells (43.25 ±4.21)％ was significantly lower than that of IR alone (78.13 ± 7.98)％ (t=6.694, P<0.05), and the apoptosis rate (44.56 ± 5.32)％ was significantly increased compared with IR alone (15.15 ±1.95)％ (t = 8.990, P < 0.05). After silencing FAM83A, the expression of Active-β-catenin was significantly decreased while the expression of p-β-catenin was significantly increased, the expression of β-catenin in the nucleus was significantly reduced, although total β-catenin had no significant change, and the activity of Wnt/β-catenin signaling pathway was significantly inhibited. Conclusions Silencing FAM83A could significantly reduce the stem cell-like traits and enhance the chemosensitivity and radiosensitivity of pancreatic cancer cells to gemcitabine and radiation via Wnt/β-catenin signaling pathway, which may provide a new target for targeted and combination therapy of pancreatic cancer.