Objective To analyze the differences of the clinical and neuropathological features among the common Charcot-Marie-Tooth disease (CMT) subtypes.Methods There were 81 CMT patients confirmed by genetic testing from 2005 to 2015 in Department of Neurology,Peking University First Hospital,including 31 cases of CMT1A (38.3％),19 cases of CMTX1 (23.5％),16 cases of CMT2A2 (19.8％) and 15 cases of 9 rare types of CMT (1.2％-4.9％).We compared the onset age,duration,muscles weakness of legs,frequency of pes cavus,and main pathological changes of the sural nerve biopsy in 48 cases of the common CMT subtypes.Results The mean age of the onset was (12.00 ± 6.77) years in CMT1A patients,(11.81 ±4.65) years in CMTX1 patients and (5.00 ±2.68) years in CMT2A2 patients (Brown-Forsythe test,P =0.001).The duration was (12.00 ± 6.75) years in CMT1A patients,(8.50 ± 4.75) years in CMTX1 patients and (5.00 ± 2.73) years in CMT2A2 patients (Brown-Forsythe test,P =0.001).The muscle force of the dorsi flexors was Ⅳ (0,Ⅴ) in CMT1A patients,Ⅲ + (0,Ⅳ) in CMTX1 patients and 0 (0,Ⅳ) in CMT2A2 patients (H =11.359,P =0.020).The pes cavus appeared in 15/23 cases of CMT1A,10/16 cases of CMTX1 and 1/9 cases of CMT2A2 (Fisher test,P=0.017).The leukoencephalopathy appeared only in 3 cases of CMTX1 and the visual loss appeared only in 3 cases of CMT2A2.The onion-bulb formations of myelinated fibers appeared in 23/23 cases of CMT1 A,5/16 cases of CMTX1 and 2/9 cases of CMT2A2(Fisher test,P =0.000).The axonal regeneration appeared in 16/23 cases of CMT1A,16/16 cases of CMTX1 and 9/9 cases of CMT2A2 (x2 =7.666,P =0.016).There were significant differences among the three common CMT subtypes in the above parameters.Conclusions CMT1A,CMT2A2 and CMTX1 are the most common subtypes of CMT in the present study.For the clinical diagnosis,more attention should be paid to the onset of the disease,duration,muscles weakness,pes cavus,cerebral symptoms and visual loss.The present frequency of onion-bulb and the axonal regeneration of myelinated fibers help the different pathological diagnosis among them.

Objective To report the clinical and peripheral neuropathological findings in two patients with autosomal recessive Charcot-Marie-Tooth disease 2K(AR-CMT2K).Methods Case one was a nine year-old girl.She had distal weakness of lower limbs for six years, with calf atrophy and contracture of Achilles tendon for three years.Case two was an eight year-old boy.He had distal weakness of lower limbs with contracture of Achilles tendon and calf muscle atrophy for three years, and proximal weakness of low limbs for two years.The motor nerve conduction velocities in median nerves were 48.1 m/s in case one and 47.6 m/s in case two.The compound motor action potential amplitude of median nerves decreased by 46% in case one and 69% in case two.Sural nerve biopsies and gene targeted next-generation sequencing were performed in both patients.Results Density of myelinated fibers was 8 407/mm2 in case one and 7 714/mm2 in case two.The ratio of myelinated fibers with diameter over 8 μm was 2.6% in case one and 0 in case two.Both patients had small regenerating cluster of myelinated fibers.Thin myelinated fibers appeared in case one.In case two, atypical onion bulb formations with focal folded myelin appeared, and electromicroscopy revealed mitochondrial aggregate in axons.Compound heterozygous mutations of ganglioside-induced differentiation associated protein 1 gene were detected in both patients, including c.767A>G(p.H256R) and c.466G>A (p.A156T) in case one and c.767A>G and 845G>A(p.R282H) in case two.Conclusions Contracture of Achilles tendon may appear in early childhood of AR-CMT2K patients.The main pathological changes in sural nerve are loss of large myelinated fibers, mitochondrial aggregate in axons and myelin abnormalities.

Objective To summarize the clinical features of Chinese patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes ( MELAS).Methods A total of 190 patients with MELAS who presented to Peking University First Hospital between 1997 and 2015 were recruited.Among 190 patients, 175 were identified carrying mitochondrial DNA mutations, and the remaining 15 patients were diagnosed by muscle biopsy.The clinical features, including predisposing factors of stroke-like episodes, the onset symptoms and frequencies of various manifestations were analyzed and reported.Results In our cohort of MELAS patients, the male-to-female ratio was 1.44∶1.The median age of onset was 14 years ( from 7 months to 45 years).The peak onset ages were 8-12 years.The median onset age of the first stroke-like episode was 16 years ( from 1 to 53 years ).There were 66 ( 46.15%) patients who had predisposing factors before the onset, and fatigue and upper respiratory tract infection were the most common predisposing factors of stroke-like episodes in these patients ( 37.88%, 25/66 and 34.85%, 23/66, respectively).Other predisposing factors included emotional agitation, drinking alcohol, trauma, withdrawal of antiepileptic drugs, being frightened, satiation and hunger.Stroke-like episodes appeared in 70.53%(134/190) patients as an onset symptom and developed in all patients with disease progression.The neurological manifestations included seizure ( 89.42%, 169/189 ) , mental retardation or dementia (82.87%, 150/181), headache (74.30%, 133/179), hemianopia or cortical blindness (67.72%, 107/158), exercise intolerance (50.87%, 88/173), hemiplegia or hemianesthesia (47.44%, 74/156), sensorineural deafness (46.20%, 85/184), aphasia (39.47%, 60/152), behaviour disorder (17.71%, 31/175) and ophthalmoplegia ( 9.60%, 17/177 ).The manifestations of extra-nervous systems included hirsutism (67.57%, 100/148), vomiting (65.58%, 101/154), fever (62.07%, 90/145), short stature (45.32%, 63/139), diarrhea or constipation (43.48%, 70/161), low body mass index (26.62%, 37/139), diabetes mellitus (20.79%, 37/178) and kidney disease (3.16%, 6/190).Conclusions The majority of the patients in this study have the disease onset during childhood.There are more male MELAS patients than females.Most common clinical manifestations are seizure, mental retardation or dementia, headache, cortical blindness, hirsutism, vomiting and fever in this patient group.

Objective: To investigate the preventive effects of gelatin sponge debris pre-filling on bone cement leakage during percutaneous kyphoplasty (PKP) for vertebral osteoporotic fracture with cortical bone rupture. Methods: The data of 256 cases (294 segments) of osteoporotic vertebral compression fracture (OVCF) treated with PKP from January 2014 to July 2016 were retrospectively analyzed. There were 106 segments in 92 males and 188 segments in 164 females. In 119 cases, a total of 132 segments were pre-filled with gelatin sponge debris before bone cement injection. The average age was 74.4±7.7 years. In 137 cases, 162 segments were not pre-filled with gelatin sponge debris, with average age of 73.3±6.4 years. The incidences of cement leakage, visual analogue scale (VAS), Oswestry disability index (ODI), the change of anterior vertebral height and kyphosis angle before and after operation were compared between the two groups. Results: In gelatin sponge group, the incidence of cement leakage was 12.6% (15/119), including 3.4% (4/119), 0.8% (1/119), 1.7% (2/119), 5.0% (6/119) and 1.7% (2/119) of the endplate type, the lateral type, the anterior type, the posterior type and the mixed type. The incidence of cement leakage in non-gelatin sponge group was 23.4% (32/137), including 4.4% (6/137), 5.1% (7/137), 5.1% (7/137), 5.8% (8/137) and 2.9% (4/137) of the endplate type, the lateral type, the anterior type, the posterior type and the mixed type. The difference of total cement leakage rate between the two groups was significant (χ²=4.912, P=0.027). There was no significant difference in leakage rates among different types (P>0.05). Postoperative symptoms were improved in both groups. VAS score and ODI index were improved at 1, 3 and 6 months after operation (P<0.05). However, there was no significant difference in VAS score and ODI index at preoperative and post-operative follow-up between groups. There were no significant difference between the two groups in the height of the anterior edge of the injured vertebra before operation (17.3±3.2 mm, 17.5±5.4 mm), the kyphosis angle before operation (18.9°±2.0°, 18.7°±2.3°), the height of the anterior edge of the injured vertebra after operation (22.7±3.6 mm, 22.4±5.4 mm), and the kyphosis angle after operation (11.2°±1.4°, 11.9°±1.8°). Conclusion Gelatin sponge debris pre-filling can effectively reduce bone cement leakage after PKP in patients with vertebral cortical bone rupture. There was no significant effect on the improvement of symptoms after PKP.

Objective To compare the clinical efficacy of unilateral and bilateral short segment fixation in treating thoracolumbar fractures combined with unilateral pedicle fractures.Methods A retrospective case control study was conducted on the clinical data of 43 patients with thoracolumbar fractures with unilateral pedicle fractures admitted from January 2012 to December 2016.There were 24 males and 19 females,with a mean age of 48 years (range,19-68 years).Fractured segments included T10 in 1 patient,T11 in 6,T12 in 11,L1 in 19,and L2 in 6.According to the fixation method,the patients were divided into unilateral transpedicular fixation group (unilateral group,15 patients) and bilateral transpedicular fixation group (bilateral group,28 patients).All patients were treated with fixation via injured vertebrae combined with short segment fixation.The operation time,intraoperative blood loss,X-ray frequency,fracture healing time,intemal fixation removal time,preoperative and postoperative anterior vertebral height ratio,sagittal Cobb angle recovery,spinal canal invasion rate,visual analogue score (VAS),Oswestry dysfunction index (ODI),Frankel classification of spinal cord injury,incidence of screw deviation,and spinal lateral angulation were compared between the two groups.Results All patients were followed up for 12-26 months,with an average of 18.5 months.The operation time in unilateral group and bilateral group were (82.3 ± 14.7) minutes and (120.9 ± 12.8) minutes,respectively.The intraoperative blood loss was (186.1 ± 20.4)ml in unilateral group and (231.2 ± 39.6) ml in bilateral group.The number of fluoroscopy was (6.6 ± 1.2) times in unilateral group and (13.3 ± 2.0) times in bilateral group respectively.The incidence of screw deviation was 13％ (2/15) in unilateral group and 46％ (26/56) in bilateral group (P ＜ 0.05).There were no significant differences between the two groups in anterior vertebral height ratio,sagittal Cobb angle,spinal canal invasion rate,VAS,ODI,Frankel grade and spinal lateral angulation (P ＞ 0.05).Conclusions For thoracolumbar fractures combined with unilateral pedicle fractures,unilateral and bilateral transpedicular short segment fixation has similar reduction and fixation effects.Unilateral transpedicular short segment fixation has the advantages of shorter operation time,less bleeding,fewer fluoroscopy times,and lower screw deviation rate.

Objective:To compare effects of conservative treatment and percutaneous kyphoplasty on paravertebral muscle degeneration in patients with osteoporotic compression vertebral fractures.Methods:A retrospective case control analysis was conducted on 286 cases of osteoporotic compression vertebral fractures from January 2017 to December 2019. There were 54 males and 232 females, with a mean age of 67.7 (range, 52-90 years). According to the treatment, the patients were divided in to conservative treatment group (134 patients) and percutaneous kyphoplasty treatment group (152 patients). The pre-operation and post-operation of paravertebral muscle cross-sectional area (CSA) and fatty infiltration (FI% ) , bed rest time, visual analogue scale (VAS), Oswestry disability index (ODI), the sagittal view Cobb angle, and the anterior column height of fractured vertebra were compared between these two groups.Results:The two groups had no significant difference in CSA and FI% of paravertebral muscle in each plane of the intervertebral discs of the L 3-4、L 4-5 and L 5S 1. The CSA of multifidus in each plane of the intervertebral discs three months after operation were 6.56±1.26 cm 2, 6.87±1.31 cm 2, and 7.14±1.29 cm 2; the CSA of erector were 12.39±2.16 cm 2, 14.72±2.67 cm 2, and 16.45±3.09 cm 2; the CSA of psoas major were 7.05±1.52 cm 2, 8.12±1.75 cm 2, and 8.68±1.66 cm 2, which all were larger than those in conservative treatment group and showed significant difference between two groups ( P<0.05). However, the two groups had no significant difference in FI% of paravertebral muscle three months after operation. The CSA of multifidus in each plane of the intervertebral discs one year after operation were 6.43±1.23 cm 2, 6.62±1.42 cm 2, and 7.06±1.32 cm 2; the CSA of erector were 12.02±2.08 cm 2, 14.53±2.76 cm 2, and 16.39±2.84 cm 2; the CSA of psoas major were 6.98±1.47 cm 2, 8.01±1.59 cm 2, and 8.37±1.72 cm 2, which all were larger than those in conservative treatment group and showed significant difference between two groups ( P<0.05). The FI% of multifidus in each plane of the intervertebral discs one year after operation were 31.40%±5.84% , 32.54%±6.64% , and 33.26%±7.16% ; the FI% of erector were 22.64%±3.47% , 23.08%±3.72% , and 23.84%±3.99% ; the FI% of psoas major were 9.23%±2.20% , 9.72%±2.54% , and 10.98%±2.43% , which all were less than those in conservative treatment group and showed significant difference between two groups ( P<0.05). Two groups had significant difference in bed rest time as (9.21±2.52) d vs. (40.32±9.79) d ( t=37.79, P<0.001). The VAS, ODI score at the time of the first day after treatment and the last follow-up of the surgical treatment group were all significantly lower than those of conservative treatment group ( P<0.05). The operation could effectively improve the kyphosis deformity and reduce the loss the anterior column height of fractured vertebra compared with conservative treatment ( P<0.05). Conclusion:There exists paravertebral muscle degeneration of varying degrees during the course of the osteoporotic compression vertebral fractures. Compared to conservative treatment, percutaneous kyphoplasty treatment can not only significantly relieve pain in the short term, improve quality of patient's life, but also significantly delay the degeneration of paravertebral muscle.

Objective To explore the role of regulatory T-lymphocytes(Treg) in the immune pathogenesis of suba-cute thyroiditis (SAT). Methods The proportion of Treg in CD4+T cells in peripheral blood of 46 SAT patients and15 controls was detected using flow cytometry. And the concentration of interleukin-10(IL-10), transforming growth factor-beta1(TGF-β1) and prostaglandin E2(PGE2) in serum of 46 SAT patients and 15 controls was measured with ELISA. In addition, the Forkhead box protein 3 (Foxp3) positive cells in thyroid tissue of 29 SAT patients and20 controls was detected by immunohistochemistry. Results The proportion of Treg in peripheral blood of SAT pa-tients was significantly lower than that of controls (P＜0.05). And the concentration of TGF-β1 in serum of SAT patients was apparently higher than that of controls(P＜0.05). Additionally, the positive rate of Foxp3 in thyroid tissue of SAT patients was markedly higher than that of controls(P＜0.05).Conclusions The decrease of Treg may play an important role in the immune pathogenesis of SAT.

BACKGROUNDX-linked Charcot-Marie-Tooth type 1 (CMT1X) disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein (GJB1) gene (also known as connexin 32). This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations.

METHODSA total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJB1 mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing (NGS). Nucleotide alternations were confirmed with Sanger sequencing.

RESULTSThe CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years (ranging from 1 year to 42 years). The sudden onset of cerebral symptoms appeared in four patients (18.2%); two were initial symptoms. One case had constant central nervous system (CNS) signs. There were 19 different heterozygous mutations, including 15 known mutations and four novel mutations (c.115G>T, c.380T>A, c.263C>A, and c.818_819insGGGCT). Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 (TM1), 4.5% in TM2, 22.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 (EC1), 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-terminal domain. CMT1X with CNS impairment appeared in five (22.7%) of these patients.

CONCLUSIONSThis study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJB1 gene were hotspot in Chinese CMT1X patients.

Adolescent ; Adult ; Central Nervous System ; metabolism ; Charcot-Marie-Tooth Disease ; genetics ; pathology ; Child ; Child, Preschool ; Connexins ; genetics ; DNA Mutational Analysis ; Electrophysiology ; Female ; Genotype ; Humans ; Infant ; Male ; Mutation ; Phenotype ; Retrospective Studies ; Young Adult

Objective: Tracking the information on 1.69 million fetal cases across Guangxi Zhuang Autonomous Region (Guangxi) so as to study the occurrences of total and major birth defects in order to evaluate the ability on related prevention and control programs in Guangxi. Methods: Using the self-developed "Gui Women’s System" to establish a database of 1.69 million fetal cases in Guangxi and to analyze the distribution of time, space and population, as well as the outcomes of pregnancy, using the big data. Results: During the 29 months of observation, the overall live birth rate was 99.25%, with stillbirth rate during pregnancy as 0.44%, stillbirth rate during birth as 0.02%, and the 0-6 days mortality rate as 0.14%. The total detection rate on birth defects was 197.63/10 000; the incidence rate was 103.04/10 000, the birth rate was 102.55/10 000. The overall discovery rate of major birth defects was 48.33/10 000, with the incidence rate as 783 000, the birth rate as 0.58/10 000. The discovery rates of major birth defects in 14 cities were between 35 and 68/10 000, and the birth rate dropped significantly to less than 1.00 in 10 000. Nationalities showed that the number of pregnant women with birth defects more than 50 000 would include Hui (9.68/10 000), Yao (9.57/10 000), and Jing (9.37/10 000). With the increasing age of gestation, number of birth defects, incidence of major birth defects also increased. Ninety-five percent of the major birth defects were found within <28 weeks and with the top 5 kinds of major birth defects as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). The top 5 major birth defects appeared as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). Conclusion Programs leading to increase the rate on discovery of major birth defects were fundamental in effectively reducing the major birth defects.

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1⁺ SCs). Darbepoetin alpha (a long-acting EPO analog, EPO_anlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin^- Sca-1⁺ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPO_anlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin^- Sca-1⁺ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1⁺ SCs.
Animals ; Mice ; Ventricular Remodeling ; Erythropoietin ; Myocardial Infarction ; Heart ; Stem Cells