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

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians′ understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

Objective:To analyze epidemiological characteristics of leprosy in China from 2016 to 2020, and to provide a scientific basis for further elimination of leprosy.Methods:Data collation and statistical analysis were conducted on annual reports on leprosy epidemic surveillance in China (excluding Hong Kong, Macao, and Taiwan regions) from 2016 to 2020.Results:From 2016 to 2020, a total of 2 697 new cases of leprosy were reported in China, including 46 (1.71%) children, 894 (33.15%) females, 374 (13.87%) floating people, 2 443 (90.58%) multibacillary cases, and 546 (20.24%) cases of grade 2 disabilities. A total of 203 relapsed cases were reported in the meantime. By the end of 2020, there had been 1 893 registered leprosy cases in China, and the number of cases was 68.62% fewer than that in 2010 (6 032 cases) ; there were 36 (1.2%) counties or cities with a prevalence rate above 1 per 100 000, and 72 (17.73%) new cases suffered from grade 2 disabilities.Conclusion:From 2016 to 2020, the reported incidence and prevalence of leprosy in China steadily decreased year by year, and overall, leprosy was still lowly prevalent.

Objective:To explore the features and application value of MRI in the spectrum of fetal cloaca malformation.Methods:The clinical, MRI and ultrasound data of 6 fetuses with spectrum of cloaca malformation were retrospectively analyzed in Guangzhou Women and Children′s Medical Center Affiliated to Guangzhou Medical University from January 2017 to February 2021, and the MRI features of each subtype were analyzed.Results:Among the 6 fetuses of spectrum of the cloaca malformation, 5 were confirmed by postnatal imaging and surgery, and 1 was confirmed by induced labor autopsy, including 3 persistent cloaca, 1 posterior cloaca, 1 cloaca variant, and 1 urogenital sinus. The high signal on T 1WI of the rectal meconium disappeared or became weaker, and the signal on T 2WI of meconium of the dilated colon increased in the 3 cases of persistent cloaca and 1 case of posterior cloaca. All 6 cases showed colonic dilatation. All cases except 1 persistent cloaca showed vaginal and/or uterine effusion. Two cases of persistent cloaca, 1 case of posterior cloaca and 1 case of cloaca variant showed duplicated genital tract. Two cases of persistent cloaca showed only 1 perineal opening, which opened at the urethral orifice. One case of cloaca variant showed 2 openings, which opened at the urethral orifice and in front of the normal anus, respectively. Conclusion:Prenatal MRI can help to clarify the diagnosis of cloacal malformation spectrum and to determine its specific classification.

OBJECTIVE To study th e pharmacodynamics and pha rmacokinetics of Qinglian ningxin capsule in rats with ischemic arrhythmia. METHODS Totally 30 male SD rats were randomly divided into blank control group ，model control group ， Qinglian ningxin capsule group （4.00 g/kg），Artemisia annua group（1.43 g/kg），Coptis chinensis group（0.42 g/kg），with 6 rats in each group. Administration groups were given relevant medicine intragastrically ；model control group and blank control group were given normal saline intragastrically ，once a day ，for consecutive 7 days. After last medication ，except for blank control group，other groups were given Posterior pituitary injection via tail vein （1 u/kg） to induce ischemic arrhythmia model. electrocardiogram changes of rats in each group were recorded. Another 36 rats were randomly divided into Qinglian ningxin capsule model group and Qinglian ningxin capsule control group （4.00 g/kg），A. annua model group and A. annua control group （1.43 g/kg），C. chinensis model group and C. chinensis control group （0.42 g/kg）. After the rats in each model group were injected with Posterior pituitary injection （1 u/kg）via tail vein ，administration groups were given relevant drugs intragastrically ， and control groups were given constant volume of normal saline intragastrically. Blood was taken from the orbit at different time points（0，0.25，0.75，1，2，4，6，8，12 and 24 h）. The concentrations of berberine hydrochloride and artemisinin in plasma were determined by HPLC ，and the pharmacokinetic parameters were calculated by WinNonlin 7.0 software. RESULTS Compared with the model control groups ，Qinglian ningxin capsule could significantly improve the heart rate slowing of rats and redu ced the prolongation of PR interval and QT interval significantly ，and the effects were generally better than those of A. annua group and C. chinensis group（P＜0.05）. Compared with A. annua control group and C. chinensis control group ，cmax，AUC0－t and AUC 0－∞ of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule control group，while CL was decreased significantly ；t1/2z of artemisinin was prolonged significantly （P＜0.05）. Compared with Qinglian ningxin capsule control group ，cmax（except artemisinin ），AUC0－t，AUC0－∞，MRT0－t and MRT 0－∞（except artemisinin ）of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule model group ，while CL was decreased significantly（P＜0.05）. CONCLUSIONS Qinglian ningxin capsule could significantly improve ischemic arrhythmia better than A. annua and C. chinensis ，and can improve the absorption of berberine hydrochloride and artemisinin in model rats and slow down their elimination.

Objective:To compare the effect of intracorporeal anastamosis and extracorporeal anastamosis on abdominal infection associated with laparoscopic right hemicolectomy.Methods:The clinical data of 210 patients with colon cancer who underwent laparoscopic right hemicolectomy in Dalian Third Peoples′s Hospital, Liaoning Province from January 2015 to December 2019 were analyzed retrospectively.Among them, 79 patients underwent intracorporeal anastamosis (intracorporeal anastamosis group) and 131 patients underwent extracorporeal anastamosis (extracorporeal anastamosis group). The perioperative indexes and postoperative abdominal infection were compared between the two groups.Results:In intracorporeal anastamosis group, the intraoperative bleeding was (45.2±4.2) mL, the operative time was (161.3±22.4) min, the number of lymph node dissection was (30.8±9.6), the postoperative exhaust time was (3.3±1.2) d, and the postoperative hospital stay was (7.6±0.5) d. In extracorporeal anastamosis group was (42.1±5.0) mL, (167.3±26.7) min, (32.9±8.6), (3.4±1.0) d and (7.5±0.6) d, respectively, there were no significant difference between the two groups (t value were 0.417, 0.207, 0.829, 0.338 and 0.293, respectively; P value were 0.699, 0.845, 0.231, 0.734 and 0.802, respectively). In intracorporeal anastamosis group, the incidence of abdominal infection (with anastomotic fistula)was 13.9%(11/79), the incidence of abdominal infection (without anastomotic fistula)was 10.1%(8/79), and in extracorporeal anastamosis group was 1.5%(2/131)and 0.8%(1/131), the differences were statistically significant (χ 2=12.805, 10.238; P=0.003, 0.008). In intracorporeal anastamosis group, the incidence of respiratory system infection was 1.3%(1/79), the incidence of urinary system infection was 2.5%(2/79), the incidence of surgical incision infection was 1.3%(1/79). In extracorporeal anastamosis group was 3.1%(4/131), 0.8%(1/131) and 3.1%(4/131), respectively.There were no significant difference between the two groups (χ 2 value were 0.662, 0.420 and 0.662, respectively; P value were 0.364, 0.587 and 0.364, respectively). Conclusion:Laparoscopic right hemicolectomy with intracorporeal anastamosis and extracorporeal anastamosis have the same surgical effect, but intracorporeal anastamosis may increase the risk of postoperative abdominal infection.

Objective:To compare the effect of midcaudal combined approach and the cephalic middle approach in laparoscopic complete mesocolic excision (CME) in the treatment of right colon cancer complicated with incomplete intestinal obstruction.Methods:From January 2014 to January 2019, 90 patients with right colon cancer complicated with incomplete intestinal obstruction admitted to the Third People′s Hospital of Dalian were retrospectively analyzed.All patients underwent laparoscopic right hemicolectomy, CME plus D3 lymph node dissection.According to the choice of different surgical approaches, 44 patients were treated with the midcaudal combined approach (observation group) and the other 46 patients were treated with cephalic middle approach (control group). The intraoperative, postoperative and complications of the two groups were compared statistically.Results:Compared with the control group, the bleeding volume in the observation group was significantly reduced ((105.3±22.6) ml vs.(309.6±28.0) ml, t=13.698), the operation time was significantly shortened ((165.2±17.9) min vs.(219.5±21.5) min, t=8.327), and the differences were statistically significant (all P<0.05). There were no significant differences in the number of lymph nodes dissected ((21.4±7.8)vs.(20.4±6.6), t=0.534), the proportion of lymph nodes dissected≥12(86.4%(38/44)vs.84.8%(39/46), χ 2=0.208), the complications after operation(6.8%(3/44)vs.10.9%(5/46), χ 2=0.318), the length of hospital stay after operation ((11.8±1.6) d vs.(12.5±2.3) d, t=0.986), the difference was statistically significant (all P>0.05). Conclusion:It is safe and feasible to use the middle caudal approach in laparoscopic CME for right colon cancer complicated with incomplete ileus. Compared with the cephalic middle approach, it can reduce thebleeding volume and shorten the operation time.

BACKGROUND: Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease. METHODS: From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted. RESULTS: 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%). CONCLUSIONS Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.

Objective To kxplork thk valuk of dktkcting brain mktabolitks of prktkrm infants at full tkrm for prkdicting thk nkurodkvklopmkntal lkvkl,and to providk thk basis for karle clinical intkrvkntion. Methods Thirte casks of prktkrm infants wkrk collkctkd from thk Nkonatal Intknsivk Cark Rnit and Nkuro - Akhabilitation Dkpartmknt of Guangzhou Zomkn and Childrkn＇s Mkdical Ckntkr bktwkkn Mae 2015 and March 2016,thkn thke wkrk chkcckd be adopting brain magnktic rksonanck imaging and magnktic rksonanck spkctroscope at corrkctkd full tkrm,and assksskd be using Llbkrta Infant Motor Scalk(LIMS)and Gkskll dkvklopmkntal scalk kvaluation at corrkctkd agk of 6 months and corrkctkd of agk 1 ekar old. ResuIts In thk 30 casks of prktkrm infants,19 casks wkrk malk,11 casks wkrk fkmalk,and thk gkstational agk was 27+3 -31 wkkcs,and avkragk gkstational agk was(28. 8 ± 1. 0)wkkcs,and thk birth wkight was 800-1 400 g[(1 176. 3 ± 145. 1)g]. Thk stude found that meo-inositol( MI),MI╱crkatink( Cr)in basal ganglia wkrk nkgativkle corrklatkd with thk dkvklopmknt quotiknt at corrkctkd agk of 1 ekar old(r﹦ -0. 465,-0. 532;all P＜0. 05). Factic acid(Fac)╱Cr in hippocampus was nkgativkle corrklatkd with dkvklopmkntal quotiknt at corrkctkd agk of 6 months(r﹦ -0. 420,P＜0. 05);Fac,Fac╱Cr in pkrivkntricular wkrk nkgativkle corrklatkd with dkvklopmkntal quo-tiknt at corrkctkd agk of 1 ekar old(r ﹦ -0. 405,-0. 386;all P ＜0. 05). Fac╱Cr in pkrivkntricular was nkgativkle corrklatkd with LIMS scorks at corrkctkd agk 1 ekar old(r﹦ -0. 380,P＜0. 05);Fac,Fac╱Cr in ckrkbkllum wkrk nkga-tivkle corrklatkd with dkvklopmknt quotiknt at corrkctkd agk of 1 ekar old(r﹦ -0. 393,-0. 394;all P＜0. 05). Thkrk was no corrklation bktwkkn frontal lobk mktabolitks and nkurodkvklopmkntal lkvkl(P＞0. 05). ConcIusions Prktkrm infants brain mktabolitks at full tkrm contributk to prkdicting nkurodkvklopmkntal lkvkl. MI,Fac,MI╱Cr,Fac╱Cr ark of valuks for prkdicting nkurodkvklopmkntal lkvkl,and MI╱Cr is thk bkst prkdictor. Lmong frontal lobk,basal ganglia, hippocampus,pkrivkntricular and ckrkbkllum,thk pkrivkntricular is thk bkst arka for prkdicting nkurodkvklopmkntal lkvkl. Corrkctkd agk of 1 ekar old maebk thk bkst timk to prkdicting nkurodkvklopmkntal lkvkl.

BACKGROUND: Treatment of large bone defects is an important problem faced by orthopedic physicians. Allogeneic bone transplantation is a classic method, but it has many restrictions. The membrane guided bone regeneration technique has become an important method for the research nowadays.OBJECTIVE:To compare the effects of self-made high strength biodegradable nano-hydroxyapatite/multi(amino acid) copolymer (n-HA/MACP) guided bone regeneration membrane tube and allograft bone graft segment in the repair of large segmental bone defect in goats. METHODS: The model of 30 mm large segment bone defect in the middle section of the femur in 32 adult goats was established. Experimental group used self-made n-HA/MACP tube to bridge defects following bone plate fixation. The control group was treated with allograft bone graft bone segments combined with plate fixation. The animals were sacrificed at 4, 8, 12 and 16 weeks after operation, and the bone callus growth was observed in the specimens. The X-ray and histological observations were performed at the same time. Biomechanical measurement of plate fixation of allograft cortical bone segment was done at 12 and 16 weeks after operation. RESULTS AND CONCLUSION: (1) After 4 to 16 weeks, gross and pathological results showed fibrous callus growth inside and outside of the membrane tube, and the fibrous callus gradually hardened into a bony callus. Additionally, the callus was larger in the experimental group than in the control group. X-ray films showed significantly increased lateral callus density in the experimental group as compared with the control group. (2) Maximum bending strength was significantly higher in the experimental group than in the control group at 16 weeks (P < 0.05). Overall, the n-HA/MACP membrane tube used for bridging large segment bone defects in goats can obtain similar repair effects to the allograft cortical bone, and further achieve the better mechanical strength of the new bone segment than the allograft bone.