OBJECTIVE To investigate the effect of berberine on differentiation of rat bone marrow mesenchymal stem cells (MSCs) to adipocytes and its mechanism. METHODS Rat MSCs were isolated and cultured, adipocytic differentiation was induced with adipogenesis-inducing medium (AIM). Cells were assigned into 6 groups:normal control, AIM group, AIM+berberine 0.1, 0.3, 1 and 3 μmol·L-1 groups, respectively. Morphology characteristics of mesenchymal stem cells were observed under an inverted microscope and adipocyte levels were analyzed by oil O staining. Alkaline phosphatase (ALP) activity was detected using p-nitrophenyl phosphate as a substrate. The cell survival was determined by MTT assay. Expressions of peroxisome proliferator activated receptor γ (PPARγ), fatty acid binding protein (aP2) and CCAAT enhancer-binding protein α (C/EBPα) mRNA were detected by semiquantitative RT-PCR. RESULTS Compared with normal control group, MSCs adipogenic differentiation, PPARγ, aP2 and C/EBPα mRNA expression significantly increased in AIM group (P<0.01), ALP activity in AIM group significantly decreased (P<0.01). Compared with AIM group, berberine inhibited MSCs adipogenic differentiation (P<0.01) and berberine 0.1, 0.3, 1 and 3 μmol·L-1 increased ALP activity by 26%, 54%, 81% and 122%, respectively. Berberine 3 μmol·L-1 significantly downregulated PPARγ expression (0.91±0.10 vs 1.34±0.06) (P<0.01), aP2 (1.05±0.10 vs 1.53±0.09) (P<0.01) and C/EBPα mRNA (1.24±0.06 vs 1.54±0.09) (P<0.01). Berberine had no effect on proliferation of MSCs. CONCLUSION Berberine inhibits differentiation of MSCs into adipocytes, which might be closely related to the downregulation of PPARγ, aP2 and C/EBPα mRNA.

Objective To investigate the effect of hypertonic saline on the expressions of aquaporin 4 (AQP4) and caspase-3 in the brain edema area after traumatic brain injury (TBI) in rats Methods Seventy-two male SD rats weighing 220-250 g were selected and randomly divided into three groups (24 rats per group):sham operation group (Group A),traumatic brain injury + normal saline group (Group B) and traumatic brain injury + hypertonic saline group (Group C).Moderate TBI model was induced by Feeney's free falling method.Normal saline and hypertonic saline were delivered respectively.The neurological score was measured at 6,24,and 48 hours after operation.The brain water content was measured,and the blood brain barrier stability was detected by Evans blue staining.AQP4 positive cells was detected by immunohistochemistry.The expressions of AQP4 and caspase-3 protein in brain tissue were detected by Western blot,and the apoptosis of neurons in brain tissue by TUNEL method.Results Compared with Group A,the neurological score of Group B were obviously decreased,while the water content in the brain tissue,Evans blue staining,AQP4 positive cells,AQP4 (6 hours:1.73 ±0.31 vs.0.33 ±0.13;24 hours:2.47 ±0.27 vs.0.33 ±0.14;48 hours:2.18 ± 0.19 vs.0.33 ±0.12),caspase-3 protein expression(6 hours:0.53 ±0.18 vs.0.34 ±0.07;24 hours:0.58 ±0.16 vs.0.33 ± 0.08;48 hours:0.59 ± 0.11 vs.0.33 ± 0.07) and apoptosis index in brain tissue in Group B were significantly increased (all P ＜ 0.05).Compared with Group B,the neurological score of Group C were obviously increased,while the water content in the brain tissue,Evans blue staining,AQP4 positive cells,AQP4 (6 hours:1.51 ±0.27 vs.1.73 ±0.31;24 hours:2.13 ±0.13 vs.2.47±0.27;48 hours:1.84 ±0.22 vs.2.18 ±0.19) and Caspase-3 protein expression (6 hours:0.44±0.09vs.0.53±0.18;24 hours:0.46±0.10vs.0.58±0.16;48 hours:0.48±0.12 vs.0.59 ± 0.11) and apoptosis index in brain tissue of Group C were significantly decreased (all P ＜ 0.05).Conclusion Hypertonic saline can attenuate TBI-induced brain edema and have a significant neuroprotective effect,possibly by down-regulating the expressions of AQP4 and caspase-3.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the central nervous system. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (eculizumab, inebilizumab, and satralizumab). Neurol Neuroimmunol Neuroinflamm published international Delphi consensus on the management of AQP4-IgG+ NMOSD in May 31, 2023. Twenty-five statements reached consensus after two voting rounds by 24 Delphi panel experts. Inebilizumab and satralizumab have been listed in China, and off-label immunosuppressants and biologics are also used in clinical practice. However, there are no standard treatment recommendations in use of these biologics and maintenance therapy of NMOSD. Therefore, the interpretation of this consensus, focusing on the initial use of monoclonal drugs, the conversion between monoclonal drugs and immunosuppressants, as well as the application and safety of special populations, is conducive to improving the normative and effective use of of monoclonal drugs in NMOSD y ophthalmologists and neurologists

Objective:To compare the chemical composition of decoction and granules of Sangju Decoction; To provide a method for quality evaluation of Sangju Decoction.Methods:HPLC was used to establish fingerprints, and a comprehensive comparative study was conducted on the traditional decoction and formula granules of Sangju Decoction from four aspects: chemical composition type, fingerprint similarity, chemical pattern recognition analysis, and representative index component content.Results:The fingerprint similarity of the 10 batches of traditional decoction was >0.988. 35 peaks were identified and 12 peaks were identified as common peaks (neochlorogenic acid for peak 7, chlorogenic acid for peak 10, cryptochlorogenic acid for peak 11, 1,3-dicaffeoylquinic acid for peak 13, rutin for peak 17, lenoside A for peak 19, lignan for peak 20, isochlorogenic acid B for peak 24, ammonium glycyrrhizate for peak 25). The fingerprint similarity of the formulation pellets was >0.983, and 29 characteristic peaks were identified. Compared with the traditional decoction, some batches of the granules lacked peaks 14, 26, 27, 30, 32 and 34, and clustering analysis (CA), principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) could distinguish between the two. The contents of the 10 index components neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 1,3-dicaffeoylquinic acid, forsythia ester glycoside A, grass glycosides, isochlorogenic acid B, 3,5-O-dicaffeoylquinic acid, forsythia glycosides, monkshood glycosides in the traditional soup were higher than that in the granules, and the contents of rutin and ammonium glycyrrhizate in the granules were higher than that in traditional decoction.Conclusions:The content and composition of traditional decoction and formula granules of Sangju Decoction are significantly different. The combination of fingerprinting and chemical pattern identification effectively can effectively evaluate the difference between traditional decoction and formula granules of Sangju Decoction, which can lay a foundation for the quality control and rational clinical application of formula granules of Sangju Decoction.

Objective To investigate the effect of comprehensive geriatric assessment on health management outcomes and quality of life in elderly patients with coronary heart disease.Methods A total of 100 elderly patients with coronary heart disease admitted into our hospital from April 2017 to April 2018 were enrolled in this study and randomly divided into a control group(n=50)receiving routine nursing intervention and an observation group (n =50)undergoing individualized health management after comprehensive geriatric assessment.Length of hospital stay,incidence of adverse events and quality of life were compared between the groups.Results The length of hospital stay was shorter in the observation group than in the control group[(10.6 ± 1.4) d vs.(15.5 ± 1.5) d,t =16.7,P＜0.05].Patients in the observation group had higher satisfaction than those in the control group[(55.6±1.4)vs.(45.5±1.5),t =34.2,P＜0.05],The incidence of cardiac adverse events was lower in the observation group than in the control group(20.0％ vs.52.0％％,x2 =5.0,P＜0.05).The scores for quality of life were higher in the observation group than in the control group(P＜0.05).Conclusions Comprehensive geriatric assessment can effectively shorten the length of hospital stay,reducethe incidence of cardiac adverse events,and improve the satisfaction and quality of life in elderly coronary heart disease patients,and should be recommended in clinical practice.

Objective:To investigate the clinical features, diagnosis, treatment and prognosis of Scimitar syndrome.Methods:A retrospective analysis of clinical data of 13 children with scimitar syndrome from January 2013 to November 2020, including clinical symptoms, chest X-ray, echocardiography, cardiac CT and cardiac catheterization prognosis and follow-up.Results:13 children with scimitar syndrome were diagnosed, including 7 girls and 6 boys with a average age of 17 months(21 days to 10 years).3 cases <5 kg in weight. Ten patients presented with the infantile form and 3 with the adult form of scimitar syndrome. 13 infantile form had lower respiratory tract infections, heart failure, and growth retardation, of which 8 cases were with severe pulmonary arterial hypertension. 3 adult form were diagnosed because of heart murmur. 12 cases had coexisting cardiac lesions, including 12 atrial septal defect, 2 patent ductus arteriosus, 1 right ventricular double outlet/ventricular septal defect, 4 right lung and right pulmonary artery dysplasia, 2 right lung dysplasia, 6 additional systemic arterial supply to the right lung. Ten patients had pulmonary venous drainage correction surgery, one patient only underwent right ventricular double-outlet correction, three patients died of severe pulmonary hypertension; one patient lost the opportunity of surgery due to obstructive pulmonary hypertension, and one patient was complicated by nervous system The disease gave up treatment. One corrected case was stenosed during discharge and 2 corrected children became stenotic during follow-ups.Conclusion:Found with the median or dextrocardial heart, recurrent respiratory infections, or unexplained pulmonary hypertension, the possibility of scimitar syndrome should be considered. The combination of echocardiography and cardiac CTA can confirm the diagnosis as soon as possible. The risk factors for mortality included infantile form and severe preoperative pulmonary hypertension. Long-term follow-up is still required after operation, and surgical intervention is required again if necessary.

Objective:To summarize and analyze the efficacy, experience and follow-up results of 300 cases of transposition of the great arteries (TGA) intervened by arterial switch operation.Methods:It was a retrospective, single-center study involving 300 TGA patients intervened by arterial switch operation between January 2010 and December 2017 in Guangdong Provincial People′s Hospital.Their clinical data were retrospectively analyzed.There were 236 male patients and 64 females.Among them, 128 cases (42.7%) were TGA with ventricular septal defect (TGA/VSD), and 172 cases (57.3%) were TGA with intact ventricular septal defect (TGA/IVS). The mean age and weight at operation were (23.8±39.2) cases days, and (3.5±0.8) kg, respectively.There were 193 cases (64.3%) with usual coronary artery patterns, and 107 cases (35.7%) with unusual coronary artery patterns.Among the 107 cases with unusual coronary artery patterns, 21 cases (7.0%) were involved with the intramural coronary artery, and 17 (5.7%) presented the single-ostium coronary pattern.Non normal distribution data were used the Mann- Whitney U test.Categorical measures were compared by Chi- square test or Fisher′ s exact test.Survival probability and freedom from events were calculated by the Kaplan-Meier method, and difference in survival probability by the Log Rank test. Results:All patients were successfully intervened by arterial switch operation, 73.3% of patients with TGA/IVS underwent the surgery within 3 weeks after birth, and 85.9% of patients with TGA/VSD underwent surgery within 3 months.The mean cardiopulmonary bypass time and aortic occlusion time were (193±68) min, and (122±39) min, respectively.Twenty-five patients (8.3%) died in hospital.Thirty cases had low cardiac output syndrome, 1 implanted with a permanent pacemaker due to complete atrioventricular block.A total of 254 patients were followed up for 1 month to 10 years.Three patients with single-ostium coronary pattern died at the follow-up period.The 5-year and 10-year survival rates were both 90.7%.During the follow-up, 49 cases (49/254 cases, 19.3%) had pulmonary artery stenosis, 66 cases (66/254 cases, 26.0%) had aortic valve regurgitation, 47 cases (47/254 cases, 18.5%) had pulmonary valve regurgitation, and 4 (4/254 cases, 1.6%) had aortic anastomotic stenosis.Among the 21 patients (21/254 cases, 8.3%) requiring reintervention, 17 patients (17/254 cases, 6.7%) underwent a total of 18 reinterventions, including 12 interventions of pulmonary artery plasty, 4 of percutaneous balloon pulmonary valvuloplasty, 1 of aortic reconstruction at anastomosis and 1 of pacemaker exchange due to battery exhaustion.Conclusions:Arterial switch operation is the optimal treatment for TGA.The long-term follow-up results of arterial switch operation are satisfactory in TGA children, with a low risk of long-term reoperation.

Objective To investigate the neuroprotective effect of Benztropine on retinal ganglion cells (RGCs) death and optic nerve injury in rats model of non-arteritis anterior ischemic optic neuropathy (rNAION).Methods A total of 25 Sprague-Dawley rats were randomly divided into Benztropine treatment group (n=13)and PBS control group (n=12).The right eye was set as the experimental eye.rNAION model was established by using rose Bengal combined with laser photodynamic method.The rats in the Benztropine treatment group were received intraperitoneal injection with Benztropine 10 mg/kg (0.2 ml) daily for 3 weeks,while the rats in the PBS control group were received intraperitoneal injection with an equal volume of PBS.At 1,3 and 7 days after modeling,the retinal and optic disc conditions of the rats were observed by direct ophthalmoscopy.Retrograde labeling,fluorescence microscopy and transmission electron microscopy were used to observe the survival of RGCs and the damage of the optic nerve myelin and axon at 4 weeks after modeling.The RGCs density and survival rate of the two groups were compared by One-Way Anova.Results At 1 and 3 days after modeling,the optic disc edema was observed in the rats of rNAION model group.At 7 days after modeling,the optic disc edema decreased and the boundary was blurred compared with 3 days after modeling.After 4 weeks,the RGCs density in the PBS group was 308± 194/mm2 and the survival rate was 13.7％.The density of RGCs in the Benztropine group was 1173+868/mm2 and the survival rate was 47.6％.The differences of RGCs density and survival rate were significant between the two groups (F=7.552,8.184;P=0.015,0.012).Myelin disintegration,axon degeneration,onion-like body and gliosis were observed in the optic nerve sections of rNIAON in the PBS group,while the damage ofaxon and myelin structure in the Benztropine group was significantly less than that in the PBS group.Conclusions Benztropine group showed higher RGC survival rate,less damage ofaxon and myelin structure on rNAION model.This study explored the potential neuroprotective effect of Benztropine.

【Objective】 To construct an in-vitro model of erythrocyte antibody-mediated complement activation, and establish quantitative detection methods based on flow cytometry and spectrophotometry, so as to explore the correlation of anti-body titers and complement activation speed, and provide a methodological basis for studying the adverse transfusion reactions of anti-body mediated complement hemolysis. 【Methods】 Mouse monoclonal antibody that recognized human C3b and fluorescent secondary antibody were used to label C3b fragments on erythrocytes, and the deposition of C3b fragments after complement activation was detected by flow cytometry. The absorbance at 540 nm of the supernatant in the complement activation reaction system was measured by spectrophotometry as the amount of hemoglobin released was related to the absorbance. 【Results】 The complement activation system was constructed according to the ratio of 3% red blood cell suspension (mixed for 6 people) 1∶anti-Tj^a 1∶complement 2. The repeatability was good (P value>0.05) as different red blood cell mixtures had been used to repeat the detection reaction system. When using 32×, 64× and 128× dilutions of anti-Tj^a mediated complement activation, the deposition of C3b fragments has been detected by flow cytometry at 30 s, 1 min and 2 min, respectively, and MFI peaked at 5 min, 10 min and 30 min, respectively. No obvious hemolysis has been observed within 1.5 h. 【Conclusion】 In vitro model of anti-Tj^a-mediated complement activation demonstrates the speed of complement activation is related to the concentration of antibody. At a certain antibody concentration, the speed of complement activation has been slowed down, and no obvious hemolysis observed.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic functional bowel disorder characterized by abdominal pain and diarrhea， with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders， especially IBS-D. 5-Hydroxytryptamine （5-HT）， as an important brain-gut peptide regulating gastrointestinal function， affects brain activity， gastrointestinal motility， pain perception， mucosal inflammation， and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years， traditional Chinese medicine （TCM） has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM， this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway， aiming to provide a scientific basis for TCM treatment of this disease.