Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective To investigate the expression of PI3K, AKT and PTEN in gliomas. Methods The pathological specimens of 66 glioma patients who underwent surgery in our hospital and Huashan Hospital from January to December 2017 were analyzed, and another 50 normal pathological specimens were selected as reference group. Immunohisto-chemistry was used to detect the expressions of phosphatidylinositol 3-kinase, protein kinase B and homologous phos-phatase-tensin. The expression of three indicators between glioma tissues and normal brain tissues was compared to analyze the correlation between the three positive expressions in glioma tissues. Results The positive expression rates of PI3K and AKT in normal brain tissue were significantly lower than those in low-grade gliomas and high-grade gliomas, and the difference was significant (P＜0. 05). And the positive expression rates of PI3K and AKT in the low-grade gliomas were significantly lower than those in high-grade gliomas, and the difference was statistically significant (P＜ 0. 05). The positive rate of PTEN protein in normal brain tissue was 100. 0％, which was significantly higher than that in low-grade glioma and high-grade glioma, with significant difference (P＜0. 05). And the positive rate of PTEN protein in the low malignant glioma was significantly higher than that in high grade glioma, and the difference was statistically significant (P＜0. 05). Conclusion PI3K and AKT are highly expressed and PTEN is low-expressed in gliomas, which is related to the degree of malignancy.

Objective To explore the effect of keratinocyte growth factor(KGF)on the lung tissue and expres-sion of transforming growth factor - β1(TGF - β1 )in newborn rats with hyperoxia. Methods The 108 newborn SD rats were randomly divided into air group,hyperoxia group and KGF intervention group,and each group had 36 rats. The rats in every group were randomly divided into the 3,7,14 days subgroups,and each group had 12 rats. The rats in the hy-peroxia group and KGF intervention group were continually exposed to more than 950 mL/ L of oxygen box until the end of the experiment. KGF intervention group simultaneously undertook oxygen inhalation,hypodermic injection of 1 mg/ d recombinant human KGF(rhKGF)on the back on the first 3 days and 0. 5 mg/ d 3 days later till the end of the experi-ment. Air group and hyperoxia group were offered equivalent 9 g/ L saline. The rats in the air group took air. The sub -groups of the 3,7 and 14 days were cut for lung tissue in the corresponding time,observing lung tissue by light micro-scope for pathological changes and TGF - β1 protein expressed in the lungs was determined by immunohistochemistry. Results Air group sprout pulmonary alveolus on the 7th day,and the alveolaration finished on the 14th day,while hy-peroxia group had alveolar growth retardation and pulmonary fibrosis,but pulmonary fibrosis was not obvious in KGF in-tervention group. There was a significant difference on 7th day and 14th day between hyperoxia group and air group in TGF - β1(9. 43 ± 0. 64 vs 8. 62 ± 0. 52,P ﹤ 0. 05;9. 97 ± 0. 49 vs 8. 66 ± 0. 48,P ﹤ 0. 01). There was no significant difference between KGF intervention group and air group in TGF - β1(8. 67 ± 0. 55 vs 8. 56 ± 0. 43,8. 77 ± 0. 52 vs 8. 62 ± 0. 52,8. 81 ± 0. 47 vs 8. 66 ± 0. 48,all P ﹥ 0. 05). There's a significant difference on 7th day and 14th day be-tween hyperoxia group and KGF intervention group in TGF - β1(all P ﹤ 0. 05). Conclusions KGF can inhibit the pro-tein expression of TGF - β1 ,and this may be one of the possible mechanism underlying the protective effect of KGF a-gainst lung injury.

Objective To investigate the role of Heme oxygenase-1 in the effect of hyperbaric oxygen preconditioning (HBOP) against the brain edema formation after experimental intracerebral hemorrhage in rats.Methods The study was carried out by animal experiment in two steps by using 54 Spradgue-Dawley rats weighting from 300-350 g.In the first step,rats were treated with HBOP (HBOP group,n =3) or with sham pre-conditioning (Sham pre-conditioning group,n =3).All the rats were sacrificed 24 h after the preconditioning,and basal ganglion of brain tissue was taken for detect HO-1 level by using western blot analysis.In the second step,rats were divided into 4 groups (n =12 in each group):HBOP +ZnPP group,in which rats had a micro-pump intra-peritoneally implanted containing a specific HO-1 inhibitor ZnPPⅨ (Zinc protoporphyrin IX,0.01 mg/kg),Sham pre-conditioning + Znpp group,HBOP + DMSO group,in which rats with a intra-peritoneal micro-pump containing 2 mL Dimethyl sulfoxide (DMSO,a solvent vehicle) and Sham pre-conditioning + DMSO group before HBOP.At 24 hours after the pre-conditioning,rats received an infusion of 100 μL autologous blood into the caudate nucleus to form a simulated intracerebrum hemorrhage (ICH),and were sacrificed 72 h later for brain water content measurements.All data were analyzed by using Stata 7.0 software and statistical analyses were carried out by two-tailed Student t test.Results Compared with the Sham pre-conditioning group,the HBOP group had significant higher level of HO-1.Compared with the Sham pre-conditioning + DMSO group,the HBOP + DMSO group had a significant lower level of water content in the ipsilateral basal ganglion [(81.4 ± 0.9) ％ vs.(82.6 ± 0.8) ％ (P ＜ 0.05)],however,peritoneal infusion of ZnPP Ⅸ before HBOP abolished HBOP-induced protection against brain edema formation after experimental ICH [(82.8 ± 0.9) ％ vs.(82.6 ± 0.7) ％ (P ＞ 0.05)].Conclusions Hyperbaric oxygen preconditioning attenuate brain edema formation after experimental ICH in rats,and this protection is attributed to the activation of HO-1.

Objective To investigate the clinical efficacy of pre-hospital mild hypothermia in patients with severe craniocerebral injury,and to explore the possible mechanism by the changes of serum Malondialdehyde (MDA).Methods 120 cases of severe craniocerebral injury were divided into pre-hospital mild hypothermia group (group A,65 cases) and control group(group B,55 cases) by random number table.Patients in group A were gave pre-hospital mild hypothermia treatment,and patients in group B were gave mild hypothermia therapy only after hospitalization.Comparison of the change of serum MDA at admission,the 7th and 14th day between two groups,and the functional outcomes were evaluated by GOS score in 6 months after treatment.Results The MDA levels of two group at seventh days and 14 days were higher than that at admission [(10.4 ± 1.5)nmol/L and (8.2 ± 1.2)nmol/L in group A,(12.6 ± 1.9)nmol/L and (10.0 ± 1.4)nmol/L in group B,P ＜0.05],and it was the highest at 7th day,and its in group A was significantly lower than that in group B at 7th,14th day [(6.9 ± 1.1) nmol/L in group A,(6.6 ±1.0) nmol/L in group B,P ＜ 0.05].The good prognosis rate was 47.7％ (31 cases) in group A,higher than the 38.2％ (21 cases) in group B;The mortality rate was 12.1％ (8 cases) in group A,lower than the 21.4％ (12 cases)the group B,and the difference was statistically significant (Z =-2.132,P ＜ 0.05).Conclusion Pre-hospital mild hypothermia treatment can improve the prognosis of patients with severe craniocerebral injury and alleviate the damage of brain tissues.

Objective To evaluate percutaneous endoscopic gastrostomy (PEC) in long-term coma patients at different phases who received trans-nasal feeding in Department of Neurosurgery. Methods A total of 51 patients who received trans-nasal feeding because of long-term coma were randomly divided into 2 groups to undergo PEG at 25-39 days after coma (n =24) or at 40-60 days (n = 27) , respectively. The rates of upper gastrointestinal bleeding, average episodes of bleeding, average hemostatic time, the rates of aspiration and aspiration pneumonia were compared between the 2 groups. Results The rates of upper gastrointestinal bleeding, aspiration and aspiration pneumonia in post-PEG patients were significantly lower than those in pre-PEG patients (P < 0.05). Before the procedure of PEG, the rates of upper gastrointestinal hemorrhage,average episodes of bleeding, rates of aspiration and aspiration pneumonia in 25-39-day group were significantly lower than those in 40-60-day group (P < 0.05). There was no significant difference between 2 groups, in regarding of either hemostatic time, or rates of upper gastrointestinal bleeding, aspiration and aspiration pneumonia after PEG (P > 0. 05). Conclusion PEG may decrease the rates of upper gastrointestinal bleeding, aspiration and aspiration pneumonia in neurosurgical patients receiving trans-nasal feeding because of long-term coma. PEG is preferably performed on 25-39 days of onset to 40-60 days. If there is no contraindication, 25-39 days after coma is likely to be the optimal time for PEG.

Objective To investigate the clinical effects of standard large trauma craniectomy in patients with acute posttraumatic brain swelling. Methods A cohort study was performed in 74 patients of acute posttraumatic brain swelling with midline shifting more than 5 mm, who were divided randomly into two groups: standard large trauma craniectomy group (n =37) and routine temporoparietal craniectomy group as control group (n =37). The vital sign, the intracranial pressure (ICP) and complications were observed during the treatment. The Glasgow outcome scale (GOS) and mortality rate as well as the complications were evaluated after treatment. Results The mean ICP in the large trauma craniectomy group at 24, 48, 72 and 96 hours was much lower than those of the control group ( P

Objective To observe the effects of mild hypothermia on the dynamic change of neuron specific enolase (NES) in serum, the damaged neuron number around the impact site and the content of brain tissue water following traumatic brain injury (TBI) in rats so as to provide a quantitative parameters to evaluate the protective effect of the mild hypothermia on the brain. Methods A total of 45 SD rats were subjected to a lateral moderate cortical impact injury caused by a free-falling object and divided randomly into three groups:⑴ sham operation group (Group A);⑵ normothermic group (Group B);⑶ hypothermia group (Group C). The Group C was treated with mild hypothermia and the Group B with normothermia immediately after injury. A series of samples were obtained directly 3, 6 and 24 respectively after trauma in three groups. Pathomorphological method was used to observe the number of the damaged cortical neurons around the impact site. The serum concentration of NSE and the water content of brain tissue water were measured by radio-immunoassay. Results Following TBI in rats, the serum level of NSE was significantly increased (P

Objective To study the clinicoradiologic significance of C sign.Methods 773 cases of standard ankle CR radiographs were presented for diagnosis of acute trauma and ankle pain. There were 565 males and 208 females, ages ranged from 10 to 81. There were 630 cases of acute trauma and 143 cases of painful ankle. C sign incidence, C sign figuration, distance of the medial facet of talocalcaneal joint, and the figuration of sustentaculum tali were studied. The relationship between C sign and talocalcaneal coalition was analysed.Results The incidence of C sign was 54.6%(422/773). The female incidence was 61.1%(127/208) ,which was more than that of male(52.2%,295/565)(P

Objective To study the incidence and radiologic findings of calcaneonavicular coalition.Methods CR films of foot andankle in 1361 cases were presented,which were evaluated for acute trauma or chronic pain.There were 588 cases of foot CR and 773 cases of ankle CR,age ranged from 10 years to 91 years(984 cases of 20~40 years).The prevalence of calcaneonavicular coalition was determined and the different significance of both male and female,acute trauma and chronic pain group were analysed.Results In 1361 cases,72 cases of calcaneonavicular coalition(5.3%) were demonstrated,8.7%(47/588)on foot CR films and 3.2%(25/773) on ankle CR films.Calcaneonavicular coalition was more dipicted on foot CR films than on ankle CR films(P0.05).Conclusion The foot CR films is more superexcellent than the ankle CR films on demonstrating calcaneonavicular coalition.