A single-center, retrospective analysis of relapse and progression patterns of primary central nervous system lymphoma: can whole brain radiotherapy be replaced? / 南方医科大学学报

OBJECTIVE@#To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment.@*METHODS@#This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions.@*RESULTS@#MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area.@*CONCLUSIONS@#Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.

Tibial bone transport over an intramedullary nail in combination with antibiotic-loaded calcium sulphate for treatment of segmental bone defect / 国际外科学杂志

Objective:To analyze the clinical outcomes of tibial bone transport over an intramedullary nail in combination with antibiotic-loaded calcium sulphate for treatment of segmental bone defect.Methods:A retrospective analysis was conducted by enrolling 11 surgically treated patients with tibial segmental bone defect after the debridement for tibial infection or osteomyelitis who were admitted in Lower Limb Surgery Ward of Traumatic Orthopedic Department, Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from Jan. 2018 to Jan. 2020. The collected clinical materials and data included gender, age, injury mechanism, smoke or alcohol, comorbidities, intraoperative bleeding loss, bone defect length, resorption time of calcium sulphate, bone transport time, external fixation time, external fixation index, complications and Paley bone and functional criteria. SPSS 24.0 software was used to analyze the data.Results:Eleven patients were followed up for 8 to 31 months (average 23.2 months). All patients achieved bone healing and the infection was eradicated with no sign of recurrence. The mean length of defect was (8.1±1.6) cm, mean resorption time of calcium sulphate was (6.6±2.6) months, bone transport time was (11.4±2.8) weeks, external fixation time was (4.7±1.2) months, external fixation index was (0.58±0.07) month/cm and full weight bearing time was (6.1±1.4) months. The complication rate was 36.4% including deep vein thrombosis, delayed union of the docking site, pin tract infection and sterile draining of the wound. Paley bone evaluation results were excellent and good in 10 patients (90.9%) and functional results were excellent and good in 11 patients (100%).Conclusion:Tibial bone transport over an intramedullary nail in combination with antibiotic-loaded calcium sulphate is a safe, reliable and successful method for segmental bone defect and eradication of infection which reduces external fixation time and complication rate, allows patients perform weight bearing and return to daily life earlier.

Vitamin E reduces radiation injury of hippocampal neurons in mice by inhibiting ferroptosis / 南方医科大学学报

OBJECTIVE@#To explore the protective effect of vitamin E (VE) against radiation injury of hippocampal neurons in mice and explore the possible mechanism.@*METHODS@#Cultured HT-22 and U251 cells with or without exposure to 8 Gy irradiation were treated with VE (200 μmol/L for 24 h), ferroptosis inhibitor (ferrostatin-1, 5 μmol/L for 24 h), apoptosis inhibitor (ZVAD-FMK, 2 μmol/L), or necroptosis inhibitor (100 μmol/L). MTT assay was used to evaluate the cell viability after the treatments, and reduced glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (lipid ROS), and intracellular iron ion levels were detected for assessment of ferroptosis. The mice exposed to 16 Gy irradiation with or without vitamin E (500 U/kg) treatment for 6 weeks were assessed for behavioral changes and cognitive functions using Morris water maze test.@*RESULTS@#Treatment with VE significantly promoted the cell survival following irradiation in HT-22 cells ( < 0.05) but not in U251 cells ( > 0.05). Ferrostatin-1, but not ZVAD or the necroptosis inhibitor, promoted the survival of HT-22 cells following the irradiation. Exposure to irradiation significantly increased ferroptosis-related oxidative stress level in HT-22 cells, manifested by decreased GSH level and increased MDA, lipid ROS and intracellular iron ion levels ( < 0.05); treatment with VE and ferrostatin-1 both obviously reversed radiation-induced ferroptosis-related oxidative stress in the cells ( < 0.05). In Morris water maze test, the mice with radiation exposure showed obviously increased exploration time and distance ( < 0.05), which were significantly decreased after treatment with VE ( < 0.05).@*CONCLUSIONS@#Vitamin E reduces radiation injury by inhibiting ferroptosis in the hippocampal neurons in mice.

Protective effect of tanshinoneⅡA on radiation injury of cochlea / 实用医学杂志

Objective To explore the protective effects on radiation injury of guinea pigs 'cochlea by sul-fotanshinoneⅡA sodium injection. Methods 20 guinea pigs(40 ears)were randomly divided into control group , radiotherapy(RT)group,radiotherapy and drug(RT+D)group and drug(D)group. The guinea pigs in the RT+D group and the D group were injected intraperitoneally with tanshinone on 2 days before the irradiation and last-ed for 7 days,while the guinea pigs in the control group and the RT group were injected intrapertoneally with equal amount of physiological saline at the same time. All the guinea pigs underwent audiologic test with DPOAE and ABR at different time points before and after the irradiation,which were d0,d7 and d8w. All pigs were sacrificed after the completion of the audiologic experimental and for histologic observation. Results After the irradiation, the DPOAE amplitudes of the guinea pigs in both RT group(F=1134.064,P<0.001)and RT+D group(F=664.185,P < 0.001)decreased significantly,but the range in the RT + D group was lower than in the RT group (P<0.001). The ABR threshold of the guinea pigs raised significantly in the RT group(F=12.228,P=0.002 <0.05),but not in the RT+D group(F=2.867,P=0.102>0.05). Histological examination showed that the dam-age degree of hair cells,stria vascularis and the spiral ganglion cells in the organ of Corti of the guinea pigs were lower than in the RT + D group,but higher in the RT group. Conclusion Sulfotanshinone ⅡA sodium injection can provide protection against radiation injury of guinea cochlea.

Effects of Shexiang Wulong Pills on the expression levels of miR-146a, miR-130 and miR-223 of peripheral blood in patients with RA / 中成药

AIM To explore the effects of Shexiang Wulong Pills (Moschus Artifactus,Aconiti Radix Cocta,Pheretima,etc.) drug serum on the expression levels of miR-146a,miR-130 and miR-223 in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA).METHODS PBMCs were extracted from blood of 30 cases of RA patients,cells were divided into three groups,blank control group,serum-free groupand Shexiang Wulong Pills drug serum group.After 48 hours,total RNA was extracted,then the expression levels of three miRs were detected by RT-PCR.RESULTS Compared with the serum-free group,the expression levels of miR-146a,miR-130 and miR-223 in the Shexiang Wulong Pills drug serum group were significantly decreased (P ＜ 0.01).CONCLUSION Shexiang Wulong Pills can inhibit inflammation in RA patients by down-regulating the expression levels of miR-223,miR-130 and miR-146a in PBMCs.

Protective effect of tanshinoneⅡA on radiation injury of cochlea / 实用医学杂志

Objective To explore the protective effects on radiation injury of guinea pigs 'cochlea by sul-fotanshinoneⅡA sodium injection. Methods 20 guinea pigs(40 ears)were randomly divided into control group , radiotherapy(RT)group,radiotherapy and drug(RT+D)group and drug(D)group. The guinea pigs in the RT+D group and the D group were injected intraperitoneally with tanshinone on 2 days before the irradiation and last-ed for 7 days,while the guinea pigs in the control group and the RT group were injected intrapertoneally with equal amount of physiological saline at the same time. All the guinea pigs underwent audiologic test with DPOAE and ABR at different time points before and after the irradiation,which were d0,d7 and d8w. All pigs were sacrificed after the completion of the audiologic experimental and for histologic observation. Results After the irradiation, the DPOAE amplitudes of the guinea pigs in both RT group(F=1134.064,P<0.001)and RT+D group(F=664.185,P < 0.001)decreased significantly,but the range in the RT + D group was lower than in the RT group (P<0.001). The ABR threshold of the guinea pigs raised significantly in the RT group(F=12.228,P=0.002 <0.05),but not in the RT+D group(F=2.867,P=0.102>0.05). Histological examination showed that the dam-age degree of hair cells,stria vascularis and the spiral ganglion cells in the organ of Corti of the guinea pigs were lower than in the RT + D group,but higher in the RT group. Conclusion Sulfotanshinone ⅡA sodium injection can provide protection against radiation injury of guinea cochlea.

Research advances in diagnosis and therapy of Niemann-Pick disease type C / 中国当代儿科杂志

Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal lipid storage disease associated with impaired intracellular cholesterol trafficking. A wide spectrum of clinical phenotype has been described, with a possible onset at all ages of life from the neonatal period to adulthood, more often in childhood. Typically, hepatosplenomegaly, dystaxia, dysphagia, dysarthria and dementia are presented in NPC patients. Neurologic symptoms vary according to the onset age, but prolonged neonatal cholestasis, splenomegaly, cataplexy and vertical supranuclear gaze palsy are more specific signs to the diagnosis of the disease. Impaired cholesterol trafficking and unesterified cholesterol accumulation in the late endosomes and lysosomals, as a results of mutations in NPC1 or NPC2 genes, are initial for the disease, and defective cellular autophagy, defective lysosomal calcium homeostasis and oxidative stress may all play roles in the physiological processes. The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies or of pathogenic mutation of NPC1/NPC2 genes. Miglustat, the only available treatment approved to date, can alleviate neurological symptoms and slow disease progression when administered earlier.

Hemodynamics-based numerical comparison between two options of modified B-T shunt / 医用生物力学

Objective To analyze and compare hemodynamic features of two different options for modified B-T shunt (MBTS) surgery, namely end-to-side(ETS) and side-to-side (STS), so as to provide references for clinical treatment of single ventricle heart defect syndrome. MethodsThe real geometric model was reconstructed by medical images obtained from a patient with hypoplastic left heart syndrome (HLHS); MBTS surgery was simulated through virtual operations; a lumped parameter model (LPM) was constructed based on physiological data of the patient; the post-operational boundary conditions of computational fluid dynamics (CFD) models (namely STS model and ETS model) were predicted based on the LPM; numerical simulation was conducted on two CFD models by using finite volume method. Results Flow details and wall shear stress distributions were all obtained for two models. The mean oscillatory shear index (OSI) of ETS model and STS model in part of pulmonary arteries was 3.058×10-3 and 13.624×10-3, respectively, while the energy loss was 116.5 and 94.8 mW, respectively, and blood flow rate ratios of left pulmonary artery to right pulmonary artery (RRPA/LPA) were 0.8 and 1.72, respectively. Conclusions There were nearly no differences between two CFD models in energy loss, which led to a relatively small impact on the surgery. The STS model had a more balanced pulmonary artery blood perfusion and a smaller mean OSI in part of pulmonary arteries, therefore, the STS model was superior to the ETS model. This study provides an important theoretical support and reference for treating patients with HLHS.

Hemodynamics-based numerical comparison between modified B-T shunt and central shunt / 医用生物力学

Objective Modified B-T shunt (MBTS) and central shunt (CS) are two common surgical procedures for the treatment of tetralogy of fallot (TOF). The purpose is to analyze and compare the hemodynamic features of MBTS and CS. Methods 3D anatomy was reconstructed by medical images obtained from a patient with TOF, and two computational models were generated through virtual operations. A lumped parameter model was constructed to predict the post-operational boundary conditions. Computational fluid dynamics (CFD) was performed for the two models. Results A persistent pulmonary blood perfusion was observed in each model both during the systolic phase and diastolic phase, but the maximum velocities in the shunt were different for the two models. The pressure drop of the shunt in CS model was higher than that in MBTS model. The wall shear stress of the shunt in the MBTS model ranged unevenly from 0.025 to 340 Pa, while the wall shear stress in CS model ranged relatively evenly from 32.2 to 72.6 Pa. Conclusions Pulmonary artery blood was increased effectively for both options. The blood perfusion of right upper extremity was decreased in the MBTS model. More blood was directed into the pulmonary artery in CS model. Attention should be paid to the fact that the pressure gradient was large at the proximal anastomosis in both models in clinic. This study provides important theoretical references for surgeons to make choice from the surgery options in the treatment with TOF.

Recent development and application of hemodynamics / 医用生物力学

The study of hemodynamics, which refers to dynamics inside the blood circulation, mainly includes the flow rate, flow resistance, pressure, shear stress, disturbed flow, as well as their associations in between. Therefore, with its important significance in the clinical treatments of vessel curvature, arterial stenosis or occlusion, pathological artery branches and aneurism, study about hemodynamics is essential to human health. Currently, extensive researches on hemodynamics have been conducted with respect to artery bypass, coronary arterial stenosis, abdominal aortic aneurysm, atherosclerosis, cerebral aneurysm and swirling flow. With the development of such research on hemodynamics, surgical planning and interventional therapy have improved rapidly. The influence mechanism of hemodynamic parameters, including pressure, flow resistance, flow rate, wall shear stress, blood viscosity, flow separation, turbulent flow, vortex on the post-operation complications could be deeply explored with the help of more and more clinical apparatus and have gained some achievements.

Numerical study on multiscale simulation for hemodynamics of systemic-pulmonary shunt procedure based on lattice Boltzmann method / 医用生物力学

Objective Based on time-coupled multiscale coupling algorithm, to simulate the hemodynamics after systemic-pulmonary shunt procedure on single ventricular patient so as to obtain the local three-dimensional (3D) fluid field and global hemodynamic information before and after surgery. MethodsFirstly, the 0D-3D coupled multiscale hemodynamic model of systemic-pulmonary shunt procedure was established based on the lumped parameter model (0D) before surgery and the shunt model (3D), then the 0D-3D interface coupling condition and the time coupling algorithm were discussed. Secondly, the multiscale simulation of 3D CFD (computational fluid dynamics) model coupled with 0D lumped parameter model was realized based on lattice Boltzmann method. Finally, the multiscale simulation results were compared with patient’s 0D simulation results to study the hemodynamic changes before and after surgery. Results The global hemodynamic change and local 3D flow pattern were obtained by this multiscale simulation. The pulmonary blood flow distribution ratio was increased from 32.21% to 57.8%. Conclusions The systemic-pulmonary shunt procedure can effectively increase the blood supply of pulmonary circulation by implanting the shunt between the systematic circulation and pulmonary circulation. The geometrical multiscale method can effectively simulate both the coarse global and detailed local cardiovascular hemodynamic changes, which is of great significance in pre-operation planning of cardiovascular surgery.

Hemodynamic comparison between elastic and rigid vessels for the central shunt / 医用生物力学

Objective To study the hemodynamics of central shunt (CS) by numerical simulation and investigate the effects of the elastic and rigid vessel wall on distributions of hemodynamic parameters in the vessel. Methods Two idealized CS models were constructed, one with a rigid wall (the rigid model) and the other with an elastic wall (the elastic model). Numerical calculation was conducted by the finite element method, and the elastic model adopted the fluid structure interaction. Results The distribution of flow velocity and pressure in both models were generally the same. About 68.9% of the aortic blood was directed into the pulmonary artery for the rigid model, as compared to 70% for the elastic model. The pressure drops within the shunt for the elastic model and rigid model were about 7.668 8 kPa and 7.222 3 kPa, respectively. The maximum variation in the average cross sections along the shunt was about 2.2% for the elastic model, appearing at the proximal end to side (ETS) anastomosis. The maximum difference of wall shear stress (WSS) between the two models at five key regions of each was about 16.1%. Conclusions Generally, the global flow structure in both the CS models remains unchanged; the elasticity of the vessel wall slightly influenced the flow distributions and pressure drop of the shunt; the effect from elasticity of the vessel wall on average cross sections along the shunt was higher at the proximal ETS anastomosis than that at the distal ETS anastomosis; the hypothesis that the vessel wall is rigid is acceptable in CS numerical simulations for the treatment of tetralogy of Fallot (TOF). However, the coupling of flow dynamics and wall mechanics may lead to a more reliable simulation result in the CS.

Numerical study on bilateral bidirectional Glenn shunt / 医用生物力学

Objective To predict the influence of connecting position between left superior vena cava (LSVC) and pulmonary artery on bilateral bidirectional Glenn (BBDG) shunt by numerical simulation. Methods Firstly, a 3D anatomical geometrical model was reconstructed by the medical images of a hypoplastic left heart syndrome (HLHS) patient with LSVC. Secondly, based on haptic deformations, several computational models were virtually generated, and computational fluid dynamics (CFD) numerical simulations were conducted using finite volume method. Finally, hemodynamic parameters were analyzed and evaluated. Results Flow recirculation was observed in the pulmonary artery between the LSVC and right superior vena cava (RSVC). The diameter of RSVC was defined as D. Varying the distance between LSVC and RSVC from 2D to 3.5D resulted in the least energy dissipation at 3D and the most at 2D. The blood flow rate ratios of left pulmonary artery to right pulmonary artery (LPA/RPA) ranged from 0.65-1.11. Conclusions Too close distance between LSVC and RSVC would bring out unfavorable hemodynamic distributions and consume more energy in the treatment of BBDG shunt. This study is of significance for surgeons to evaluate the optimal Fontan options in the treatment of HLHS accompanied by LSVC.

Radiation-induced G2 phase arrest may contribute to the radioresistance of breast cancer stem cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate radiation-induced cell cycle changes of human breast cancer stem cells enriched by suspension culture.</p><p><b>METHODS</b>The tumorigenicity of human breast cancer stem cell line MCF-7 cultured in serum-free media was confirmed in NOD/SCID mice, and the radiosensitivity of the cells was tested by clone formation assay following radiation exposure. Flow cytometry was performed to evaluate radiation-induced cell cycle changes, and the protein expression of pCDC25C (ser216) was measured by Western blotting.</p><p><b>RESULTS</b>After the exposure to 2 Gy radiation, the survived fraction of the cells in suspension culture and those in adherent culture was 0.856 ∓ 0.061 and 0.783 ∓ 0.097, respectively, and the cells in suspension culture showed an obviously greater capacity of tumorigenicity in NOD/SCID mice. The radiation exposure resulted in an obvious increase in the proportion of G2 phase cells from (22.03 ∓ 2.12)% to (45.83 ∓ 2.25)% and significantly increased the expression of pCDC25C (ser216).</p><p><b>CONCLUSION</b>Radiation- induced G2 phase arrest may contribute to the resistance of the breast cancer stem cells to radiotherapy.</p>

B-mode ultrasound for defining planning target volume in intensity-modulated radiotherapy for prostate cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To define the planning target volume (PTV) margins in intensity-modulated radiotherapy (IMRT) for prostate cancer without imaging guidance using B-mode acquisition and targeting (BAT) ultrasound-based prostate localization.</p><p><b>METHODS</b>Ten patients with prostate cancer underwent BAT ultrasound alignment before each IMRT session. The set-up deviations, each consisting of isocenter displacements in 3 directions (anterior-posterior, right-left lateral, and superior-inferior), were recorded for a total of 225 times and analyzed with Kolmogorov-Smimov (K-S) method.</p><p><b>RESULTS</b>The isocenter shift in each direction, which represented an average from all the patients, was 3.56∓2.71 mm, 4.08∓3.99 mm, and 3.20∓2.92 mm in the lateral (RL), anteroposterior (AP), and superior-inferior (SI) dimensions, respectively, and the deviations in each direction conformed to a normal distribution (P=0.806, P=0.061, and P=0.106, respectively). In the absence of imaging guidance for IMRT for prostate cancer, the PTV margin should expand by 8.97 mm in the right, 1.87 mm in the left, 12.05 mm in the anterior, 3.91 mm in the posterior, 9.06 mm in the superior and 2.66 mm in the inferior to allow 95% isodose curve to cover 90% of the clinical target volume.</p><p><b>CONCLUSION</b>The ultrasound imagining guided localization, with simple operation, nonirradiation and small systemic error, can be real-time corrected.</p>

Clinical,neuroimaging and myopathological features of MELAS:a retrospective analysis of 31 patients / 中华神经科杂志

Objective To investigate the clinical,neuroimaging and myopathological features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS).Methods The clinical manifestations,neuroimaging and myopathological features of 31 patients with MELAS diagnosed in our Neuromuscular Center in the recent 7 years were retrospectively analyzed.A3243G point mutations were analyzed by RFLP method in 10 patients.Results ①Clinical features:There were 18 male patients and 13 female patients.The age of onset ranged from 3 to 43 years,averaging 21.9 years.The averaged duration was 4.9 years.Thirteen patients in this group had family history of maternal inheritance pattern.The main clinical manifestations included short stature(26 patients),recurrent headache and vomiting(24 patients), muscle weakness(22 patients),epileptic seizure(21 patients),cognitive decline(19 patients),visual disturbance(17 patients),sensorineural deafness(16 patients),ataxia(6 patients),psychiatric symptom (8 patients),external ophathalmoplegia(2 patients)and diabetes mellitus(9 patients).The serum CK level was slightly elevated in 6 patients,and the fasting blood lactic acid was increased in 15 of the 18 detected patients.②Neuroimaging features:The stroke-like lesions were mostly confined to cerebral cortex, including temporal lobe(24 patients),occipital lobe(21 patients),parietal lobe(12 patients)and frontal lobe(4 patients).Three patients had deep white matter involvement.Migrating stroke-like lesions were confirmed in 4 patients by repeated cranial CT/MRI examination.In addition,cerebral atrophy(17 patients)and bilateral basilar ganglion calcification(11 patients)were found.③Myopathological features: Scattered ragged red fibers(RRF)in various number were found in all the patients by MGT staining.Other founding included strongly SDH-reactive blood vessel(27 patients),COX enzyme deficiency(19 patients), and mild to moderate lipid storage in RRF(20 patients).④MtDNA analysis showed 9 patients with A3243G point mutation in all the detected 13 patients.Conclusion The clinical and neuroimaging features may offer important clue to the diagnosis of MELAS,but a definite diagnosis of MELAS relies on the myopathology and mtDNA mutation analysis.