The incidence of knee osteoarthritis(KOA)is in-creasing year by year,seriously affecting patients'health.Mes-enchymal stem cells are multipotent cells with multiple differen-tiation functions.The extracellular vesicles released by these cells can carry various"cargo"to corresponding cells and tis-sues,exerting biological functions.They have shown great clini-cal potential in the treatment of KOA.This study reviews the therapeutic effects and mechanisms of extracellular vesicles se-creted by mesenchymal stem cells from different tissues such as bone marrow,adipose tissue,and synovium in KOA.It is found that miRNA is an important biological component in exerting therapeutic effects.The study also discusses the research pro-gress of engineered extracellular vesicles in KOA,pointing out the current challenges in clinical application,such as standard-ized acquisition of extracellular vesicles and difficulties in targe-ted action,aiming to provide a certain reference for the basic re-search and clinical application of extracellular vesicle therapy for KOA.

Aim To explore the ameliorative effects of berberine(BBR)on diabetic nephropathy(DN)in mice and investigate its potential mechanisms through transcriptomic analysis.Methods 8-week-old db/db mice were randomly assigned into four groups:model group(DN group),BBR 50 mg·kg-1 group(BBR-L group),BBR 100 mg·kg-1 group(BBR-H group),and empagliflozin 10 mg·kg-1 group(EMPA group).Age-matched db/m mice were used as the control group(NC group),with eight mice in each group.Each group received intragastric administration once daily for eight weeks.After the treatment,serum,u-rine,and kidney samples were collected to evaluate re-nal function indicators and observe renal pathological changes.Differentially expressed genes(DEGs)in kidney tissue were identified through transcriptomic a-nalysis,followed by KEGG and GO enrichment analy-sis.Potential targets were further validated using mo-lecular docking,molecular dynamics simulations,West-ern blot,and immunohistochemistry.Results Both BBR and EMPA significantly reduced fasting blood glu-cose levels in DN mice,improved renal function,and alleviated renal injury and fibrosis.Compared to the NC group,855 DEGs were identified in the DN group,while 194 DEGs were identified in the BBR-H group compared to the DN group.KEGG enrichment analysis indicated that the mechanisms underlying BBR's effects on DN were primarily related to type 1 diabetes and bile secretion pathways.Molecular docking results demonstrated a strong binding affinity between BBR and FXR and a moderate binding affinity with SHP.Molecular dynamics simulations corroborated the doc-king results.FXR and SHP protein expression signifi-cantly decreased in the DN group compared to the NC group.At the same time,BBR treatment significantly increased the expression of these proteins compared to the DN group.Conclusion BBR may mitigate DN-in-duced renal injury by modulating bile acid and lipid homeostasis through the FXR-SHP pathway.

Objective:Empirical analysis of the multiple driving paths of service capabilities of home-and community-based integrated health and social care in China,for providing useful reference for promoting the system improvement.Methods:Based on the World Health Organization's Integrated Care for Older People(ICOPE)implementation framework,an analysis framework for service capabilities of home-and community-based integrated health and social care was constructed.39 districts(counties)in Wuxi,Jiaozuo,Changsha,Chengdu,and Chongqing were included.The fuzzy-set qualitative comparative analysis(fsQCA)method was used to analyze the configuration paths of high or non-high-level service capabilities of home-and community-based integrated health and social care.Results:The service capabilities of home-and community-based integrated health and social care is improved by the configuration of various factors.Four path configurations might contribute to the development of service capabilities of home-and community-based integrated health and social care,and three path configurations might hinder the development.Institutional support,financing mechanism and the demand level of regional aging population are the key factors.Conclusions:Service capabilities of home-and community-based integrated health and social care are affected by the interaction and interrelation between multiple factors.Strategies should be jointly implemented from different aspects to improve service capabilities.

Objective:To investigate the clinical and gene variant characteristics of PCDH19 gene related epilepsy, and improve the ability of clinicians in early disease identification. Methods:The clinical data of 3 PCDH19 gene related epilepsy patients admitted to Children′s Hospital Affiliated to Zhengzhou University from October 2018 to August 2023 diagnosed by gene detection were reviewed and analyzed. Results:All the patients are female, and the onset age of seizure ranged in their infancy. Seizures in clusters and fever sensitivity were observed in all patients, and were very hard to control by single-drug treatment. Proband 1 was seizure-free after 2 kinds of anti-epileptic drug treatment, but with mild degree of intellectual disability. Proband 2 had refractory epilepsy with severe degree of intellectual disability. Proband 3 was seizure-free after 2 kinds of anti-epileptic drug treatment and without intellectual disability. In the first family, the proband carried heterozygous c.369C>G variant in the PCDH19 gene which was identified as de novo after parental validation. In the second family, the proband carried c.1652T>A variant inherited from her mother. In the third family, the proband carried c.278G>A variant inherited from her father. The 3 mutations had not been reported in the Human Gene Mutation Database. Conclusions:PCDH19 gene related epilepsy is one special kind of X-linked inherited epilepsy syndrome characterized by seizures in clusters and sensitivity to fever. And gene detection can help with early diagnosis and make rational clinical strategies in time. The variants c.369C>G, c.1652T>A and c.278G>A have enriched the gene variant spectrum of PCDH19.

Objective To develop an automatic urine volume detection and collection device to solve the problems of routine urine test.Methods An automatic urine volume detection and collection device was developed with the components of a main control system,a detection system,a prompting system and a grasping and moving system.The main control system consisted of two STM32 microcontrollers and a reset switch;the detection system was made up of a weighing module,an infrared module and indicator lights,which had its urine volume automatic detection algorithm developed based on the Keil5 platform;the prompting system realized voice broadcasting through the voice module fixed on the back panel of the box;the grasping and moving system was composed of a rail drive motor(86CM stepper motor),a photoelectric switch and a motorized gripper.Results The device developed tested urine samples with an accuracy of 99.44％,and could collect qualified samples automatically and quickly.Conclusion The device developed detects urine volume and collects samples automatically,and enhances the accuracy and efficiency of urine examination.[Chinese Medical Equipment Journal,2024,45(4):66-69]

Objective To investigate the epidemiological characteristics and spatial distribution characteristics of Clonorchis sinensis human infections in Guangdong Province from 2016 to 2022, so as to provide insights into formulation of the clonorchiasis control measures in the province. Methods Xinhui District of Jiangmen City, Longmen County of Huizhou City and Wengyuan County of Shaoguan City in Guangdong Province were selected as fixed surveillance sites for human clonorchiasis from 2016 to 2022, and additional 10% to 15% counties (districts) endemic for clonorchiasis were sampled from Guangdong Province as mobile surveillance sites each year from 2016 to 2022. A village (community) was randomly selected from each surveillance site according to the geographical orientations of east, west, south, north and middle, and subjects were randomly sampled from each village (community). C. sinensis eggs were detected in subjects’ stool samples using the Kato-Katz technique, and the prevalence and intensity of C. sinensis infections were calculated. In addition, subjects’ gender, age, ethnicity, educational level and occupation were collected. The Guangdong Provincial 1:1 million electronic map in vector format was downloaded from the National Geomatics Center of China, and kernel density analysis and spatial autocorrelation analysis of C. sinensis human infections in Guangdong Province from 2016 to 2022 were performed using the software ArcGIS 10.7. Results A total of 153 188 residents were tested for C. sinensis infections in Guangdong Province from 2016 to 2022, including 75 596 men (49.35%) and 77 592 women (50.65%), and there were 5 369 residents infected with C. sinensis, with 3.50% overall prevalence of infections. The prevalence rates of severe, moderate and mild C. sinensis infections were 0.76%, 7.26% and 91.97% among C. sinensis-infected residents in Guangdong Province from 2016 to 2022, and there were age-, gender-, ethnicity-, occupation- and educational level-specific prevalence of C. sinensis human infections (χ² = 2 578.31, 637.33, 52.22, 2 893.28 and 1 139.33, all P values < 0.05). Global spatial autocorrelation analysis showed a cluster in the prevalence of C. sinensis human infections in Guangdong Province (Moran’s I = 0.63, Z = 27.31, P < 0.05). Kernel density analysis showed that the prevalence of C. sinensis human infections with a high kernel density in Guangdong Province was mainly distributed along the Zhujiang River basin in Pearl River Delta areas, followed by in eastern and northern Guangdong Province. In addition, local spatial autocorrelation analysis identified 73 high-high clusters of the prevalence of C. sinensis human infections in Guangdong Province. Conclusions The prevalence of C. sinensis human infections was high in Guangdong Province from 2016 to 2022, and mild infection was predominant among all clonorchiasis cases, with spatial clusters identified in the prevalence of C. sinensis human infections. Targeted clonorchiasis control measures are required among high-risk populations and areas.

AIM: To evaluate macular light sensitivity and fixation stability in anisometropic amblyopia by microperimetry.METHODS: In this cross-sectional study, 39 children(39 eyes with amblyopia and 39 fellow eyes)who were initially diagnosed with monocular anisometropic amblyopia between July 2020 and January 2022 and 42 patients with normal best corrected visual acuity(BCVA)but suffered from improper refraction were selected, and the right eyes were selected as control group. Microperimetry(MP-3)was used to measure the average threshold(AT)of macular light sensitivity at 10°and fixation stability [including the percentage of fixation points within 2° and 4°(P1, P2), bivariate contour ellipse area(BCEA)for 68.2%, 95.4% and 99.6% of points] in amblyopic eyes, fellow eyes and normal control group. The AT and fixation stability of amblyopic eyes, fellow eyes and normal control group were compared.RESULTS: Children with amblyopia had significantly lower AT than fellow eyes and right eyes of normal control group(all P<0.017), and there were no differences in the macular light sensitivity of both fellow eyes and normal control group(P=0.555). The P1 was significantly lower in amblyopic eyes than in fellow eyes and normal control eyes(all P<0.017), and there were no differences in P1 between fellow eyes and normal control group(P=0.887).There were no differences in P2, 68.2%BCEA, 95.4%BCEA and 99.6%BCEA in patients among the three groups(all P>0.05). Moreover, there was no correlation between BCVA and AT, P1, P2, 68.2%BCEA, 95.4%BCEA and 99.6%BCEA in amblyopic eyes, fellow eyes and normal control eyes(all P>0.05).CONCLUSION: The macular light sensitivity and fixation stability within 2° may be decreased in eyes with anisometropic amblyopia.

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.
Male ; Female ; Humans ; Child ; Infant ; Epilepsy/genetics* ; Retrospective Studies ; Drug Resistant Epilepsy ; Uridine ; Evoked Potentials, Visual ; Anemia ; Electroencephalography/adverse effects* ; Neurodegenerative Diseases

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.