1.Establishment and evaluation of a streptozotocin-induced diabetic encephalopathy rat model
Simin CHEN ; Yingjun HU ; Wenrui YAN ; Le JI ; Mengli SHAO ; Ze SUN ; Hongxing ZHENG ; Shanshan QI
Chinese Journal of Tissue Engineering Research 2024;28(2):237-241
BACKGROUND:Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model,high-sugar and high-fat diet-induced model and spontaneous animal model.Establishing a simple,easy,short-cycle,safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs. OBJECTIVE:To further explore and evaluate the method of building diabetic encephalopathy rat models. METHODS:Twenty Sprague-Dawley rats were randomly divided into control(n=10)and model(n=10)groups.Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity,and those in the control group were given the same amount of citrate buffer.During the experiment,the body mass,feed intake,water intake and blood glucose were measured.After 8 weeks,the glucose tolerance and oxidative stress levels were measured,and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups. RESULTS AND CONCLUSION:Compared with the control group,the food intake,water intake,encephalization quotient,blood glucose and area under the blood glucose curve were significantly increased in the model group,while the body mass decreased significantly(P<0.01).Histopathological examination of the brain showed that compared with the control group,the number of surviving nerve cells was significantly reduced in the model group(P<0.01),with more significant pathological damage of nerve cells.Compared with the control group,the activities of serum superoxide dismutase,catalase and glutathione in the model group were significantly decreased(P<0.01),and the content of oxidative malondialdehyde was significantly increased(P<0.05).The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group,while the expression of Bcl-2 decreased(P<0.01).In conclusion,an 8-week injection of 45 mg/kg streptozotocin can cause obvious pathological damage to the brain tissue of diabetic rats,to successfully establish the rat model of diabetic encephalopathy.
2.Advantages and challenges of brain organoid modeling for genetic diseases of the nervous system
Siqi HUANG ; Yinghong YANG ; Xiaofang SUN ; Yingjun XIE
Chinese Journal of Neurology 2024;57(9):1030-1036
Brain organoids are self-organized 3D aggregates generated by human embryonic stem cells or human induced pluripotent stem cells. Their cell type and structure are similar to embryonic human brain, which are good in vitro models for the study of neurogenetic diseases and have been widely used in the study of neurogenetic diseases. This paper will discuss the advantages and challenges of brain organoids in the modeling of genetic diseases of the nervous system.
3.A phase Ⅱ clinical study of the efficacy and safety of antaitasvir phosphate combined with yiqibuvir for the treatment of chronic hepatitis C in adults
Lai WEI ; Hongxin PIAO ; Jinglan JIN ; Shufen YUAN ; Xuan AN ; Jia SHANG ; Wenhua ZHANG ; Jiabao CHANG ; Tong SUN ; Yujuan GUAN ; Bo NING ; Jing ZHU ; Wentao GUO ; Qingwei HE ; Lin LUO ; Yulei ZHUANG ; Hongming XIE ; Yingjun ZHANG
Chinese Journal of Hepatology 2024;32(7):637-642
Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA
4.Expert consensus on the rational use of psychotropic drugs related to intensive care medicine
Shenglin SHE ; Zhen SONG ; Tongwen SUN ; Jingguo ZHAI ; Yan YU ; Ningbo YANG ; Maosheng FANG ; Wenbin GUO ; Man WANG ; Guanglei XUN ; Lulu ZHANG ; Xijia XU ; Xiaoli WU ; Qinling WEI ; Fang LIU ; Huiping LI ; Xingrong SONG ; Youping WANG ; Yingjun ZHENG ; Xueqin SONG
Chinese Journal of Nervous and Mental Diseases 2024;50(9):513-524
Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.
5.Clinical significance of monitoring NUP98::NSD1 fusion genes before and after allogeneic hematopoietic stem cell transplantation
Yake SHANG ; Xinan PAN ; Yingjun CHANG ; Yaqin QIN ; Yu WANG ; Chenhua YAN ; Yuqian SUN ; Xiaojun HUANG ; Xiaosu ZHAO
Chinese Journal of Hematology 2023;44(12):1010-1015
Objective:This study aimed to observe the dynamic changes of NUP98::NSD1 expression before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Moreover, the clinical value of measurable residual disease (MRD) was analyzed.Methods:Sixteen AML patients who were diagnosed with the NUP98::NSD1 fusion gene and received allo-HSCT at Peking University People’s Hospital were included. The NUP98::NSD1 fusion gene and leukemia-associated immunophenotype (LAIP) were monitored before and after transplantation to evaluate their MRD status.Results:The median follow-up time for all patients was 526 days (139-1136 days) , with four patients (25.0%) experiencing hematological recurrence at a median of 474 days (283-607 days) after transplantation. Three patients (18.8%) died, two of whom (12.5%) died of leukemia recurrence. The median expression level of NUP98::NSD1 in newly diagnosed patients with complete data was 78.5% (18.9%-184.4%) at the time of initial diagnosis. The recurrence rate was higher in NUP98::NSD1-positive patients after transplantation, with 44.4% of patients experiencing recurrence, whereas no recurrence occurred in NUP98::NSD1-negative patients after transplantation. The area under the receiver operating characteristic curve predicted by the NUP98::NSD1 level after transplantation was 1.000 (95% confidence interval: 1.000-1.000, P=0.003) . Among the four patients with recurrence, NUP98::NSD1 was more sensitive than flow cytometry residual (FCM) and Wilms’ tumor gene 1 (WT1) . Conclusions:The NUP98::NSD1 fusion gene can be used to evaluate the MRD status of allo-HSCT. NUP98::NSD1-positive patients after transplantation have a high relapse rate and poor prognosis. NUP98::NSD1 was more sensitive than FCM and WT1 in predicting posttransplant relapse.
6.Effect of phacoemulsification with different corneal micro-incision sizes on postoperative corneal healing
Ning REN ; Lixia SUN ; Hong CUI ; Zhengri LI ; Chenglin LI ; Haiyan JIN ; Yingjun LI
Chinese Journal of Experimental Ophthalmology 2021;39(4):319-326
Objective:To investigate the effect of phacoemulsification using different corneal micro-incision sizes on the postoperative corneal healing.Methods:A non-random controlled study was performed.Seventy-six patients (76 eyes) with age-related cataract who underwent phacoemulsification and cataract extraction combined with intraocular lens (IOL) implantation in Yanbian University Hospital from May 2016 to May 2017 were enrolled.The subjects were divided into 2.2 mm incision group (37 eyes) and 1.8 mm incision group (39 eyes) according to corneal incision size.The intraoperative cumulative dissipated energy (CDE) and ultrasound time of the two groups were measured and compared.The corneal incision structure and corneal thickness of operative eyes were measured by anterior segment optical coherence tomography before surgery and at postoperative 1 day, 1 week and 1 month.The corneal endothelial cells count, the central corneal thickness (CCT), and the corneal volume in the central corneal diameters of 3.0 mm (CV3) and 10.0 mm (CV10) were measured by Pentacam.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Yanbian University Hospital (No.2015153), and written informed consent was obtained from all subjects before surgery.Results:There were statistically significant differences in the corneal endothelial cells count, CCT, CV3, CV10, and corneal thickness at epithelial side of the incision between pre-operation and post-operation in each group ( Ftime=17.717, 67.356, 17.577, 13.559, 80.076; all at P<0.01).But there was no statistically significant difference in the indexes between the two groups ( Fgroup=0.788, 0.706, 3.692, 4.341, 4.182; all at P>0.05).The number of corneal endothelial cells in the two groups was gradually decreased after surgery, and was significantly reduced at one month after surgery in comparison with the pre-operation, and the differences were statistically significant (both at P<0.05).At 1 day after surgery, the CCT, CV3, CV10, and corneal thickness at epithelial side of the incision in the two groups were increased significantly in comparison with the pre-operation and the differences were statistically significant (all at P<0.05), and the differences were not statistically significant between preoperative and postoperative 1 week or 1 month (all at P>0.05).With time going by, the indexes were back to normal gradually.The incidence of endothelial gaping and dislocation at the corneal incision in the 1.8 mm incision group was 12.8% (5/39) and 5.1% (2/39), which were significantly higher than 0.0% (0/37) and 2.7% (1/37) in the 2.2 mm incision group, and the differences were statistically significant ( χ2=5.078, P=0.024; χ2=0.295, P=0.590).At 1 day after surgery, corneal thickness at the endothelial side in the 1.8 mm incision group was significantly thicker than that in the 2.2 mm incision group, and the difference was statistically significant ( P=0.042), and the corneal thickness at endothelial side of the incision was positively correlated with CDE in the two groups ( r=0.231, P=0.025; r=0.347, P=0.003). Conclusions:Compared with 2.2 mm incision, 1.8 mm corneal incision results in higher incidence of endothelial gaping and dislocation at the corneal incision, greater corneal thickness at endothelial side of the incision and slower recovery.
7.Feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia
Yingjun YANG ; Xing WEI ; Gang ZOU ; Fenhe ZHOU ; Luming SUN
Chinese Journal of Obstetrics and Gynecology 2021;56(4):244-250
Objective:To investigate the feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia.Methods:This was a retrospective analysis of all fetuses requiring intrauterine transfusion (IUT) in the Shanghai First Maternity and Infant Hospital between January 2010 and December 2019. According to the different ways of IUT, they were divided into intrahepatic venous transfusion group and umbilical venous transfusion group, fetal outcomes and the incidence of procedure-related complications between the two groups were compared.Results:A total of 97 IUTs were performed on 48 fetuses. Among them, 16 cases were performed in the intrahepatic vein (31 transfusions), 32 cases were performed in the cord of the umbilical vein (66 transfusions).There were no significant differences between the two groups in age, labor history and the proportion of fetal hydrops before the first transfusion. In the intrahepatic venous transfusion group, the posterior placenta was 14/16, which was significantly higher than 78% (25/32) in the umbilical venous transfusion group ( P<0.01). The live-birth rates of the two groups were 13/16 and 75% (24/32). There was no significant difference between the two groups ( P>0.05). Before intrahepatic venous transfusion, the proportion of fetal hydrops was significantly higher than that of umbilical venous transfusion [55% (17/31) vs 24% (16/66), P<0.05]. Puncture success rate of intrahepatic venous transfusion and umbilical venous transfusion were both 100%. In the umbilical venous transfasion group, the incidence of needle slippage (5%, 3/66) and the abnormality of fetal heart rate (11%, 7/66) were higher than those in the intrahepatic venous transfasion group [0 and 3% (1/31)], but there were no significant differences between the two groups (all P>0.05). There were no cases of fetal loss within 24 hours, premature rupture of membranes, infection within 7 days and emergency cesarean section after IUT in both groups. Conclusions:Fetal intravascular transfusion via the intrahepatic vein is safe and feasible in the treatment of fetal anemia. But the requirements of puncture technique are relatively high, so it is recommended to be carried out in experienced fetal treatment center.
8.The prevalence of sarcopenia and its related factors among China's elderly population aged 60 and over
Chao SUN ; Liming HOU ; Weiming JIAN ; Yingjun GONG ; Xiaoming WANG
Chinese Journal of Geriatrics 2021;40(8):981-986
Objective:To investigate the prevalence of sarcopenia among community-dwelling Chinese elderly and to explore the related factors.Methods:Data were obtained from the China Health and Retirement Longitudinal Survey(CHARLS)in 2015, an open national database.According to the criteria of the Asian Working Group(AWGS)on Sarcopenia in 2014, a cross-sectional survey was conducted on 7 584 Chinese residents aged 60 years and over who had undergone the standard sarcopenia test.General socio-demographic characteristics and living habits were compared between different gender groups.The prevalence of sarcopenia was analyzed with stratification.Multivariate Logistic regression analysis was used to analyze risk factors for sarcopenia.Results:The overall prevalence of sarcopenia was 6.4%(95% CI: 5.9-7.0)among the Chinese population aged 60 years or older.In the stratified analysis, the prevalence of sarcopenia was higher in males(9.9%, 95% CI: 9.0-10.9)than in females(3.0%, 95% CI: 2.4-3.5), in rural areas(7.2%, 95% CI: 6.5-7.9)than in urban areas(4.3%, 95% CI: 3.4-5.2), and in smokers(8.8%, 95% CI: 7.6-10.0)than in non-smokers(4.2%, 95% CI: 3.6-4.8). Multivariate Logistic regression showed that male gender( OR=5.368, 95% CI: 4.126-6.985)and old age( OR=1.191, 95% CI: 1.172-1.210)were risk factors for sarcopenia.In addition, the occurrence of sarcopenia was significantly associated with physical pain( OR=2.181, 95% CI: 1.695-2.673), alcohol consumption( OR=1.426, 95% CI: 1.057-1.923), low education level( OR=2.875, 95% CI: 1.577-5.241), increased waist circumference( OR=0.982, 95% CI: 0.973-0.990), decreased peak expiratory flow( OR=0.995, 95% CI: 0.994-0.997)and increased cystatin C levels( OR=2.088, 95% CI: 1.247-3.495)( P<0.05). Conclusions:The prevalence of sarcopenia is high among community-dwelling elderly in China, and the occurrence of sarcopenia is closely related to age, gender, education level, Waist circumference and alcohol consumption.
9.Negative effects of donor specific anti-HLA antibody on poor hematopoietic recovery in patients with hematological diseases receiving haploidentical stem cell transplantation and rituximab for desensitization
Zhidong WANG ; Yuqian SUN ; Chenhua YAN ; Fengrong WANG ; Xiaodong MO ; Meng LYU ; Xiaosu ZHAO ; Wei HAN ; Huan CHEN ; Yuhong CHEN ; Yu WANG ; Lanping XU ; Xiaohui ZHANG ; Kaiyan LIU ; Xiaojun HUANG ; Yingjun CHANG
Chinese Journal of Internal Medicine 2021;60(7):644-649
Objective:To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization.Methods:Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m 2) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results:There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n=46) experienced lower PHR (4.4% vs. 27.5%, P=0.003), and higher 3-year EFS (79.5% vs. 59.8%, P=0.020) compared to those with DSA MFI≥5 000 (group B, n=37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR ( HR=6.101, P=0.021). PHR was associated with higher NRM ( HR=4.110, P=0.026), lower DFS ( HR=3.656, P=0.019) and OS ( HR=3.656, P=0.019). Conclusion:Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.
10.Positive MRD suggests a poor prognosis for ALL patients with or above CR2 before allogeneic transplantation
Zhidong WANG ; Siqi LI ; Yuqian SUN ; Chenhua YAN ; Fengrong WANG ; Xiaodong MO ; Meng LYU ; Xiaosu ZHAO ; Wei HAN ; Huan CHEN ; Yuhong CHEN ; Yazhe WANG ; Yanrong LIU ; Yu WANG ; Lanping XU ; Xiaohui ZHANG ; Kaiyan LIU ; Xiaojun HUANG ; Yingjun CHANG
Chinese Journal of Laboratory Medicine 2021;44(12):1145-1152
Objective:To investigate the value of minimal residual disease (MRD) in prediction of prognosis in acute lymphoblastic leukemia (ALL) patients with or above complete remission 2 (CR2) underwent.Methods:A retrospective analysis was performed on 201 ALL patients who received allogeneic stem cell transplantation (allo-SCT) and pretransplant disease status ≥CR2 in Peking University People′s Hospital from January 2009 to December 2018. MRD was measured by multi-parameter flow cytometry at 1 month before transplantation and 1 month, 2 months, 3 months, 4 months, 6 months, 9 months or 12 months after transplantation. To investigate the influence of dynamic changes of MRD before and after transplantation on prognosis.Results:201 ALL patients, including 126 males and 75 females, with a median age of 18 years. The 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), leukemia-free survival (LFS) and overall survival (OS) of all cases were 34%, 16%, 50%, and 56%, respectively. Positive pre-SCT MRD patients with higher 3-year CIR (47% vs 26%, P=0.003), lower 3-year LFS (40% vs 55%, P=0.047) and OS (42% vs 60%, P=0.065) than those with negative one. Subjects with positive post-MRD had higher 3-year CIR (73% vs 22%, P<0.001) and lower 3-year LFS (28% vs 56%, P=0.005) and OS (32% vs 60%, P=0.040) compared with those with negative one. Multivariate analysis showed that both pre-MRD and post-MRD were associated with higher CIR ( HR=1.823, P=0.018; HR=3.474, P<0.001), lower LFS ( HR=1.779, P=0.007; HR=2.185, P=0.001) and OS ( HR=1.609, P=0.034; HR=1.970, P=0.001). Negative pre-and post-SCT MRD group had lower 3-year CIR (17%, 42%, 82%; P<0.001) and higher 3-year LFS (61%, 44%, 18%; P<0.001) and OS (63%, 47%, 27%; P<0.001) compared with those unrisen post-SCT MRD group, and increased post-SCT MRD group. Multivariate analysis showed that pre-and post-SCT MRD dynamics were associated with CIR, LFS and OS ( P<0.01 for all) independently. The pre-and post-SCT MRD dynamics could better distinguish CIR (C=0.669) from that of pre-SCT MRD (C=0.587) and post-SCT MRD (C=0.629). Conclusion:Our data suggest that pre-SCT MRD, post-SCT MRD and the dynamic peri-SCT MRD could be used to predict transplant outcome of ALLpatients with or above CR2 who underwent allo-SCT.

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