Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

Objective:To analyze the effect of inhibiting excessive mitochondrial fission mediated by dynamic related protein 1 (Drp1) on the function of injured cells and mitochondria in the septic myocardium, and to explore the protective effect of maintaining mitochondrial dynamic balance in the pathogenesis of sepsis induced cardiomyopathy(SIC).Methods:Rat H9C2 cardiomyocytes were cultured and stimulated with lipopolysaccharide (LPS) to establish a model of SIC. Mitochondrial division inhibitor 1 (Mdivi-1) was given 30 min before LPS stimulation. They were divided into the control group, LPS stimulated group (LPS), Mdivi-1 control group (Mdivi-1), and LPS+Mdivi-1 intervention group (LPS+Mdivi-1). CCK-8 was used to detect the cell viability, and lactate dehydrogenase (LDH) was used to detect cellular damage. A MitoTracker probe was used to observe mitochondrial morphology by laser scanning confocal microscopy, JC-1 staining was used to detect mitochondrial membrane potential level, a DCFH-DA probe was used to detect total ROS level, and an AnnexinV-FITC/PI probe was used to detect the cell apoptosis ratio. The expression levels of mitochondrial fission protein Drp1 and fusion proteins Optic Atrophy 1(Opa1) and Mitofusin2 (Mfn2) were detected by real-time PCR and Western blot. One-way ANOVA was used to compare the differences between groups, and the LSD- t test was used for pairwise comparisons between groups. Results:Compared with the control group, cell viability, the average length of mitochondria and the mitochondrial membrane potential were decreased, and ROS production, the cell apoptosis rate and LDH were increased in the LPS group (all P<0.05). After Mdivi-1 intervention, compared with the LPS-stimulated group, the cell viability was increased, myocardial cell damage was reduced, the average length of mitochondria was prolonged, mitochondrial dysfunction was alleviated, and the cell apoptosis rate was inhibited in the LPS+Mdivi-1 group (all P<0.05). Conclusions:Mdivi-1 might inhibit mitochondrial fission mediated by Drp1, maintain mitochondrial dynamic balance, alleviate mitochondrial dysfunction and protect myocardial cells from LPS-induced injury.

【Objective】 To investigate the effect of autologous blood transfusion(ABT) drainage system and simple drainage(using drainage bags) on the prognosis of patients after lumbar surgery. 【Methods】 The patients admitted to the Department of Orthopedics of our hospital from August 2018 to September 2020 who underwent posterior open lumbar internal fixation and fusion were divided into two groups according to different drainage methods adopted after surgery: 50 patients were randomly selected from the patients who received postoperative ABT system for drainage as ABT group, and 50 patients were randomly selected from the patients who received postoperative drainage by drainage bag as simple drainage bgroup(the control group). The postoperative drainage volume, actual postoperative drainage, total dominant blood loss, total autologous blood transfusion volume, as well as the postoperative anemia indexes, infection indexes and albumin levels in d1, d3 and d7 of the 2 groups were retrospectively analyzed. 【Results】 The gender, age, operation duration and operation segment of the 2 groups were comparable (P>0.05), and preoperative Hb, Hct, ALB, WBC, NE%, intraoperative blood loss, intraoperative autologous blood transfusion volume and actual postoperative drainage volume were similar (P>0.05). There were no significant differences in Hb, Hct, ALB, WBC, NE% and CRP in postoperative d1, d3 and d7, as well as in preoperative and postoperative Hb, Hct and ALB, and in postoperative and preoperative WBC, NE% and CRP (P>0.05). The postoperative drainage volume (mL) and total dominant blood loss (mL) in ABT group and the control group were 554.40±176.82 vs 337.80±102.43, and 1 048.40±282.87 vs 791.80±277.02, respectively (P<0.05). 【Conclusion】 The use of ABT drainage system after lumbar surgery increased the drainage volume compared with simple drainage, but the improvement of anemia, albumin and infection was not obvious. ABT system should not be used routinely for drainage after lumbar surgery.

At present,there are still many problems in critical care medicine education and teaching,such as imperfect theoretical system,inconsistent teaching materials,uneven teaching staff,lack of practice opportunities and places.The development of intensive care medical teaching should be combined with "organ-system-centered" teaching reform,strengthen the construction of the theoretical system,drive the development of teaching staff,build high-quality practice bases,promote the curriculum to be more specialized,optimized and standardized,so as to promote the development of the subject.

Objective To explore the viscoelasticity of relaxed myocardium in vivo through indentation method with an intervention ultrasound indentation system (IUIS). Methods Old myocardial infarction (OMI) models of canine were established by ligating left anterior descending branch of coronary artery for 3 months. The indentation creep tests were used respectively in OMI group and shame group (n=8, each) by IUIS in middle and advanced diastole stage in vivo. Test data were processed with three-parameter solid viscoelasticity model, and the viscoelastic parameters, such as instantaneous elastic modulus (E1), relaxation modulus (E∞), creep elastic modulus (E2) and viscous damping coefficient (η) in normal and infarcted myocardium were obtained and compared. Results All the parameters of E1, E∞, E2 and η increased obviously in OMI group than in sham group shown as follows: 27.81±6.74kPa vs. 6.78±2.43kPa; 17.87±3.59kPa vs. 4.52±1.56kPa; 49.54±14.35kPa vs. 16.82±12.37kPa and 1.97±0.78Pa.s vs. 0.66±0.40Pa.s. The differences were statistically significant (P<0.05). Conclusions IUIS is a feasible method to assess the viscoelasticity of relaxed myocardium in vivo. Three-parameter viscoelasticity model can be used to describe creep properties of relaxed myocardium. Both elastic modulus and viscosity resistance have increased in infarcted myocardium.

Objective To summarize clinical phenotypes and pathological characteristics in myopathies with tubular aggregates (TAs).Methods We reviewed 5 697 patients who performed muscle biopsies in our department between January 2001 and July 2015.We collected the cases with TAs and made classification based on their clinical diagnoses and pathological changes.Results Fifty-seven patients (1.00％) showed TAs in muscle specimens,including 50 (87.72％) males and 7 (12.28％) females.According to clinical,neurophysiological,pathological and genetic analysis,the diagnoses included 23 (40.35％) cases of periodic paralysis,7 (12.28％) cases of chronic alcohol intoxication,6 (10.53％) cases of congenital myasthenic syndrome,5 (8.77％) cases of exercise-induced cramps,3 (5.26％) cases of necrotizing myopathy,1 (1.75％) case of stromal interaction molecule 1-associated myopathy,limbgirdle muscular dystrophy 2E,myotonic dystrophy,myotonia congenita,paramyotonia congenitia,hypothyroid myopathy respectively.Other cases of unknown cause included unclassified distal myopathy,external ophthalmoplegia,white matter lesions,mental retardation,stroke,early onset weakness,pulmonary arterial hypertension.Besides TAs,pathological changes also included necrosis of muscle fibers (3 cases,5.26％),neurogenic changes (3 cases,5.26％) and muscular dystrophic changes (1 case,1.75％).Conclusions Our results indicated that TAs are usually found in males and could present in many types of hereditary or acquired neuromuscular disease as independent or accompanying changes.Periodic paralysis,chronic alcohol intoxication and congenital myasthenic syndrome are 3 major diseases causing myopathies with TAs.

Objective To investigate the effect of α-galactosidase A (GLA) gene mutation on cell autophagy and to elucidate its mechanism preliminarily.Methods Two families were diagnosed by ultrastructural pathological examination,GLA gene activity test and GLA gene mutation screening.Mutant type recombinant expression plasmid of two pedigrees (pcDNA3.1-GFP-ex1 (EX1 group),pcDNA3.1-GFP-ex3 (EX3 group)) and wild type recombinant expression plasmid of GLA (pcDNA3.1-GFP-GLA,GLA group) were constructed.Hela cell line (control group) was transiently transfected with recombinant expression plasmid according to lipofectin transfection.The relative gene expression of Beclin-1 was measured with real-time PCR,and protein expression level of LC3-Ⅱ/LC3-Ⅰ,Beclin-1 and P62/SQSTM1 was examined by Western blotting.Results The LC3 protein values of groups EX1,EX3,GLA and control were 1.495 ± 0.064,1.490 ± 0.020,1.285 ± 0.021,1.260 ± 0.042,respectively;P62/ SQSTM1 values were 0.555 ± 0.086,0.480 ± 0.084,0.785 ± 0.439,0.980 ± 0.278,respectively;Beclin-1 mRNA 2-△Ct values were 0.011 ±0.003,0.008 ±0.002,0.005 ±0.001,0.003 ±0.001,respectively;Beclin-1 protein values were 1.178 ±0.098,1.209 ±0.092,0.931 ±0.100,0.796 ±0.184,respectively.Compared with the wide type group,the level of LC3-Ⅱ/LC3-Ⅰ protein was significantly higher in the mutant type groups(t =5.118,4.984;P =0.007,0.008),though no statistically significant difference was found in the expression levels of P62/SQSTM1 (t =1.052,1.400;P =0.323,0.199).Besides,the expression levels of Beclin-1 mRNA (t =3.800,2.445;P =0.005,0.040) and protein (t =2.424,2.729;P =0.042,0.026) were significantly higher in the mutant type groups.Conclusions GLA gene mutation can induce cell autophagic dysfunction,and signaling pathway of autophagic activation may be Beclin-1 dependent.

Objective To analyze membrane attack complex (MAC) expression in different types of idiopathic inflammtory myopathy (IIM).Methods We enrolled 57 cases of dermatomyositis (DM) , 37 cases of polymyositis (PM) ,9 cases of sporadic inclusion body myositis (sIBM) and 15 cases of autoimmune necrotizing myopathy with anti-signal recognition particle antibodies (SRP-ANM) in Department of Neurology at Peking University First Hospital from 2011 to 2014, and used x2 test or Fisher exact test to analyze MAC expression in muscle fibers and endomysial capillaries respectively.Results The total MAC expression in DM, PM, sIBM and SRP-ANM was 75.4％ (43/57), 86.5％ (32/37), 4/9 and 13/15 respectively.The MAC expression in muscle fibers was 50.9％ (29/57), 81.1％ (30/37) , 3/9 and 13/15 respectively.The MAC expression in endomysial capillaries was 49.1％ (28/57) , 24.3％ (9/37) , 1/9 and 6/15 respectively.The MAC expression in muscle fibers and endomysial capillaries of sIBM was less than other types of IIM.The MAC expression in muscle fibers of PM and SRP-ANM was higher than DM and sIBM, but there was no statistically significant difference between PM and SRP-ANM.The MAC expression in endomysial capillaries of DM and SRP-ANM was higher than PM and sIBM, while there was no statistically significant difference between DM and SRP-ANM (x2 =0.397, P =0.574).The MAC expression in four types of IIM had regional distribution, of which 11.6％ (5/43) of DM showed bundle distribution.Conclusion There are differences in the damage of MAC in various types of IIM, the damage of MAC in SRP-ANM indicated the pattern of both DM and PM.

Objective To explore the application value of real-time three-dimensional echocardiography (RT-3DE) in diagnosis of structural heart disease through a comparison with two dimensional echocardiography (2DE).Methods Ninety-two patients with heart disease were enrolled from October 2009 to February 2014 , all of whom were examined by RT-3DE.By cutting and spiraling structural 3D images of lesions in regions of interest , we made a diagnosis of lesions .In addition, the size of atrial(ASD) and ventricular septal defects (VSD),based on surgical results,was measured and analyzed.By comparing the coherence and difference of diagnosis on structural heart disease examined by 2DE and RT-3DE, the accuracy and superiority of RT-3DE were evaluated.Results (1)The 3D images of 92 patients with heart disease were successfully obtained by RT-3DE.The structure of lesions was displayed directly from various angles .In addition, the position, scope and degree of lesions and the spatial relationship of adjacent structures were accurately confirmed.RT-3DE provided more direct, accurate and abundant information than 2DE.(2)In the diagnosis of congenital heart disease, the diagnostic accordance rate of RT-3DE was the same as that of 2DE, but was slightly higher in the diagnosis of valvular disease and other lesions .( 3 ) Compared with 2DE, the ASD maximum diameters obtained from RT-3DE were more correlaed with surgical findings (r=0.94,0.86),so were the VSD maximum diameters (r=0.93, 0.84).Conclusion RT-3DE is easy to operate and quick to produce image ,which can provide more spatial information than 2DE in structural heart disease diagnosis , increase the accuracy rate of diagnosis , and serve as a supplement to 2DE.

BACKGROUND:There was no effective method to thoroughly treat tibial bone defect and soft tissue defect. The application of Ilizarov technique solved shortening deformity, soft tissue injury and joint contracture to some degrees.
OBJECTIVE:To discuss the effects of Ilizarov external fixation on treatment of tibial bone defect and the parameter selection of Ilizarov steel ring.
METHODS:We retrospectively analyzed the clinical data of 67 patients with tibial bone defects, who were treated and fol owed up from March 2007 to January 2012. Al patients had fracture of tibia and received one-stage operation. After treatment, postoperative limb suffered from tibia osteomyelitis and soft tissue injury. Ilizarov external fixation was placed in the limb. The length of defected tibia and area of defected soft tissues were compared at 1, 3 and 6 months after external fixation and final fol ow-up. The ankle joint Kofoed score and knee joint ROM score were observed before and after external fixation. In final fol ow-up, functional recovery was evaluated in accordance with diagnosis and treatment criteria of Johner-Wruhs fracture of shaft of tibia.
RESULTS AND CONCLUSION:A total of 67 patients were fol owed up for 6 to 35 months. Bone defects in 67 cases were rebuilt and the fracture was healed, but five cases had poor healing. Among 44 cases of soft tissue injury, wound had healed in 40 cases, and wound had not healed in 4 cases. The length of tibia defect and the area of soft tissue defects were improved at 1, 3, and 6 months after the operation (P<0.05). After operation, the ankle joint Kofoed score and knee joint ROM were significantly better than those before operation (P<0.05). During final fol ow-up, the excellent and good rate of each therapeutic plan was 85%. For the tibial osteomyelitis bone defect with the merged skin defect, the trauma was smal using Ilizarov technique, which can avoid several complicated operations, shorten the time and reduce the expenses of treatment, but there were some weaknesses and limitations. The size and material of Ilizarov external fixation affect the efficiency of the fixation and postfixation adjustment.