A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Gaming-based virtual reality therapy for the rehabilitation of upper extremity function after stroke / 中华物理医学与康复杂志

Objective To investigate the effects of playing virtual reality games on the recovery of hemiplegic upper extremities after stroke.Methods Thirty stroke patients with hemiplegic upper extremities were randomly assigned to a treatment group (n=15) or a control group (n=15).Both groups received routine medication and conventional physical therapy,while the treatment group was additionally given (Nintendo) gaming-based virtual reality therapy.Before and after 2 weeks of treatment,the patients in both groups were evaluated using the Fugl-Meyer Assessment for the Upper Extremities (FMA-UE),Brunnstrom staging and co-contraction ratios (CRs).Surface electromyogram signals from the biceps brachii and triceps brachii were also recorded during maximum isometric voluntary flexion and extension of the affected elbow.Results No significant differences in any of the measurements were observed between the 2 groups before or after the intervention.Both groups demonstrated significant increases in their average FMA-UE score,Brunnstrom staging and CRs.Conclusions Virtual reality gaming using a Wii controller is as effective as conventional therapy in enhancing upper extremity motor function and elbow flexion and extension after stroke.

Survey deep vein thrombosis and its risk factors in patients after stroke / 中华神经科杂志

Objective To study incidence of deep vein thrombosis (DVT) in the acute phase and follow-up period after stroke, and to investigate risk factors of DVT. Methods This was a prospective study at multi-centers. Ultrasonography was used for detecting DVT on both lower extremities in all patients at 10-14 days after the onset of stroke. All patients were followed up for 6 months after discharge. The incidence of DVT was examined in the acute phase and in the follow-up period of stroke. A variety of patient and treatment related factors were compared between stroke patients with DVT and without DVT to identify DVT risk factors. Results The incidence of DVT in the acute period of stroke was 4. 49%. Among DVT patients, 51.6% patients presented clinical DVT symptoms. By multiple factors logistic regression analysis,age ( ≥70 years, OR = 1.63, 95% CI 1.08-2. 84), bedridden( OR =4. 85, 95% CI 2.65-9. 68 ), wells score ≥ 2 ( OR = 3.96, 95% CI 1.86-7. 86 ), lower limbs NIHSS score ≥ 3 ( OR = 4. 56, 95% CI 2. 07-8. 85 ), high D-dimer ( OR = 3.45, 95% CI 2. 01-8. 52 ), low BI scores ( OR = 2. 98, 95% CI 1.52-6. 47 ), rehabilitation therapy ( OR = 1.82, 95% CI 1.22-3.43 ) and anticoagulant therapy ( OR =1.91,95% CI 1. 34-4. 92 ) were independent risk factors of DVT in the acute phase of stroke. Among them, the rehabilitation therapy and anticoagulant therapy were protective factors. The incidence of DVT in the follow-up periods was 1. 51%. Age ( ≥ 70 years, OR = 1.82, 95% CI 1.21-3.98 ), bedridden after discharge( OR = 5. 12, 95% CI 2. 82-11.32), lower limbs NIHSS score ≥3 ( OR = 4. 25, 95% CI 2. 11-7. 87), low BI score( OR = 2. 18, 95% CI 1.18-6.23 )at the time of discharge and DVT in acute period (OR =3.81,95%CI 1.87-7.48)were independent risk factors of DVT in the follow-up period of stroke.Conclusions Stroke patients, particularly old-aged stroke patients, are a high-risk group of developing DVT. 48.4% DVT patients had no clinical DVT symptoms but were diagnosed only by ultrasonography.There are multiple independent risk factors of DVT after stroke. It is necessary to monitor and prevent DVT in the stroke patients with the risk factors. The rehabilitation therapy and anticoagulant therapy may decrease incidence of DVT.

Combining somatosensory evoked potential with a modified cerebral hemorrhage scale for the prediction of extremity function / 中华物理医学与康复杂志

Objective To evaluate the extremity function of patients with intracerebral hemorrhage (ICH)using short-latency somatosensory evoked potentials (SEPs) and a modified intracerebral hemorrhage (MICH) scale.Methods On admission, SEP was applied in the examination of 61 patients with ICH. P40 latency and the amplitude of posterior tibial nerve potentials in both the healthy and affected extremities were measured. Abnormalities were classified based on the margin of lower extremity SEP latency and the main waveform changes. MICH was measured simultaneously to prepare a prognosis. The modified Rankin scale (MRS) score was assessed 3 months after the attack as well.Results Compared with the healthy side, there were significant differences in posterior tibial nerve P40 latency and amplitude on the affected side among patients with ICH. P40 latency and MRS scores on the affected side 3 months after the attack were positively correlated. On the unaffected side, P40 amplitude and the MRS score 3 months after the attack were negatively correlated. The MICH score on admission and the MRS score 3 months after the attack were positively correlated. Based on MRS scores (MRS≥4 indicating a poor prognosis), the predictive sensitivities for a poor prognosis of SEP and the MICH scale in patients with ICH were 80.77% and 84.61% respectively, while the specificities were 62.68% and 88.57% respectively, and the accordance rates were 70.5% and 86.9% respectively. Conclusions SEP and the MICH scale are closely correlated with the prognosis for extremity function in patients with ICH.The combination of SEP with the MICH scale might be helpful in predicting the prognosis of the patients with ICH.