Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective:To explore the feasibility and clinical efficacy of oblique lateral interbody fusion (OLIF) in the treatment of adjacent segment disease (ASDis).Methods:Retrospective analysis was conducted on the data of 31 patients with ASDis treated by OLIF in four medical centers from June 2015 to December 2018. There were 17 males and 14 females. The average age was (65.7±3.4) years (range, 59 to 75 years). 19 cases received single-segment fixed fusion, 11 cases received double-segment fixed fusion and 1 case received three-segment fixed fusion. Original fixed fusion site: 1 case of L 1, 2, 3 cases of L 3, 4, 11 cases of L 4, 5, 4 cases of L 5S 1, 6 cases of L 3-L 5, 5 cases of L 4-S 1, and 1 case of L 3-S 1. The time from the initial fixation and fusion to this admission was 82.5±45.5 months (rang, 24 to 180 months). ASDis occurred at the proximal end of the fixed fusion segment in 28 cases and at the distal end in 3 cases. The types of ASDis: degenerative disc disease in 11 cases, lumbar spinal stenosis in 15 cases, degenerative spondylolisthesis in 2 cases, and degenerative scoliosis in 3 cases. The location of ASDis: 6 cases of L 2, 3, 12 cases of L 3, 4, 6 cases of L 4, 5, 3 cases of L 1-L 3, 1 case of L 2-L 4, and 3 cases of L 1-L 4. At admission, 3 cases of lumbar internal fixation had been removed and 28 cases of internal fixation remained. Stand-alone OLIF was performed in 19 cases, OLIF combined with pedicle screw fixation in 8 cases, and OLIF combined with cortical screw fixation in 4 cases. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the low back pain and lumbar function before operation and at the last follow-up, and the imaging results and complications were observed. Results:All patients were followed up. The follow-up time was 23.6±9.6 months (range, 12 to 60 months). The operation time was 73.8±25.3 mins (range, 40 to 180 min), and the intraoperative blood loss was 86.2±67.4 ml (range, 20 to 310 ml). The average blood loss in each segment was 24.8 ml. During the operation, there were 1 case of segmental vein injury, 7 cases of endplate injury, 2 cases of transient iliopsoas muscle weakness, 1 case of thigh pain and numbness, and 1 case of incomplete intestinal obstruction. There was no incision necrosis and infection. The VAS score of low back pain decreased from 5.9±1.9 before operation to 1.4±0.6 at the last follow-up, with a statistically significant difference ( t=8.47, P<0.001). The ODI index recovered from 45.2%±5.7% before operation to 13.8%±4.7% at the last follow-up, with a statistically significant difference ( t=7.92, P<0.001). The height of intervertebral space increased from 8.7±1.6 mm before operation to 11.4±1.9 mm after operation and 9.9±1.8 mm at the last follow-up. There was a statistically significant difference between postoperative and preoperative height of intervertebral space ( F=4.15, P=0.007). There was a statistically significant difference between the last follow-up and postoperative height of intervertebral space ( P=0.011). During the follow-up, there were 13 cases of fusion cage subsidence, 1 case of fusion cage displacement, and no case of internal fixation loosening or fracture. The intervertebral fusion rate was 94%(29/31) and the complication rate was 42%(13/31). Conclusion:ASDis is a common complication after lumbar fixation and fusion, and requires surgical treatment. OLIF is a reliable method to treat ASDis as it has advantages of small trauma, high fusion rate and low complication rate.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored.Methods:The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children′s Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively.Results:There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B 6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B 6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions:The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

Objective To investigate the feasibility and effectiveness of bilateral pedicle screw fixation combined with in-terbody fusion for the treatment of lumbar spondylolisthesis (degree Ⅱ or Ⅲ) through muscle-splitting approach. Methods There were 52 patients (16 males and 36 females) analyzed in our study from January 2012 to December 2015. The average age was 54.9 ± 7.21 years (from 35 to 70 years). The history of disease was from 10 months to 15 years, with an average of 66.6 ± 32.71 months. Diagnosis included:degenerative spondylolisthesis in 2 cases, and isthmic spondylolysis in 50 cases. The sites included L4,5 in 18 cases and L5S1 in 34 cases. The degree was Ⅱ in 35 cases and Ⅲ in 17 cases. 27 cases were treated by bilateral pedicle screw fixation combined with interbody fusion through median incision approach (open group) and 25 cases through muscle-split-ting approach (minimally invasive group). The clinical and imaging results were observed and compared between the two groups, including operation time, intraoperative blood loss, postoperative incision drainage, VAS score of lumbar incision pain at 72h post-operative, intraoperative and postoperative complications, interbody fusion rate, multifidus muscle areas and grades at 1 year post-operative, and the improvement of ODI index. Results All the cases were operated successfully. The operation time of open group was shorter than minimally invasive group. However, the intraoperative blood loss and postoperative incision drainage of minimally invasive group was statistically less than open group. The VAS scores of postoperative 72 h were 3.25 (2 to 6) in open group and 1.62 (1 to 3) in minimally invasive group. And the difference was statistically significant. The misplacement rate of pedi-cle screws of minimally invasive group was lower than open group. The average follow-up time was 25.5 months (ranged from 12 to 36 months). The multifidus muscle areas and grades of minimally invasive group were superior to open group at 1 year postopera-tively. Compared to preoperative, the slipping angle, slipping rate, sacral inclination angle and vertebral space height were signifi-cant improved after operation in two groups. The ODI index was improved postoperatively in both two groups, and the difference was statistically significant at the final follow-up. The interbody fusion rate was 92.6％in open group and 96％in minimally inva-sive group, and there was no significant difference between the two groups. No cerebrospinal fluid leak, never injury, pedicle frac-ture or wound infection was found after the operation in two groups. There was no pedicle screw loosening, cage shifting, or degen-eration of the adjacent segment observed during follow-up. Conclusion Bilateral pedicle screw fixation combined with inter-body fusion through muscle-splitting approach has advantages of small incision, less trauma, less bleeding, quick recovery and well clinical results, which can be a better choice in treating lumbar spondylolisthesis (degree Ⅱ or Ⅲ).

Objective To evaluate the effectiveness and radiographic outcomes of percutaneous kyphoplasty (PKP)/percutaneous vertebroplasty (PKP) in the treatment of stage Ⅲ Kümmell's disease without nerve injury.Methods From September 2012 to September 2016,there were 28 patients with stage Ⅲ Kümmell's disease recruited to study,of which 16 patients were treated with PKP and the other 12 cases with PVP.with a mean age of 78,ranging from 67 to 95,consisted of 3 males and 29 females.All patients had single vertebral body lesions without symptom of spinal cord injury.Visual analogue scores (VAS) and oswestry dysfunction index (ODI) were recorded before surgery,on the 7 d after surgery and at the last follow-up.Meanwhile,Cobb angles,anterior and posterior heights of the injured vertebral body were measured by X-ray lateral radiography at these three time points.Furthermore,the condition of bone cement in the injured vertebral body was observed with the postoperative CT examination.Results All patients completed the operation safely.Twenty-eight patients were followed up for an average of 18 months (ranging from 12 to 36 months),and 4 patients who failed to be followed up were not included in the statistic analysis.There was no vessel or nerve injury in the operation.Thirteen out of 28 individuals who suffered from bone cement leakage showed no clinical symptom,and recovered walking ability between 12 and 24h after operation.Other types of vertebral body fractures due to compression occurred in 3 cases between 6 and 12 months after surgery,and the symptoms were relieved after another PKP.The rates of improvement at the last follow-up in VAS and ODI were 71.4％ (20/28) and 67.9％ (19/28),respectively.There was statistical difference in VAS between before surgery and 7d after surgery (t=16.68,P＜0.01).However,no statistical difference was found in the comparison of VAS between the last follow-up and 7d after surgery (t=0.598,P ＞ 0.05).The difference of ODI between before surgery and 7d after surgery (t=36.830,P＜0.01) and that of ODI between the last follow-up and 7d after surgery (t=7.375,P＜0.01) showed statistical significance.There were statistical differences in both Cobb angle and anterior heights of the diseased vertebral body between before surgery and 7d after surgery (t=2.52,2.29,both P＜0.05).Besides,significant differences were also observed in them between the last follow-up and 7d after surgery (t=2.58,2.24,both P＜0.05).However,there was no statistical difference of the posterior height of the diseased vertebral body before surgery,7d after surgery and at the last follow-up (t=0.935,0.795,P＞0.05).Conclusions PKP/PVP may relieve the clinical symptoms safely and effectively of stage Ⅲ Kümmell's disease without nerve injury,and may correct heights of kyphosis and vertebral.Nevertheless,it may lead to loss of correction and high rate of bone cement leakage.Further observation is needed for the long-term effectiveness.

Objective To examine the feasibility and early effects of unilateral pedicle screw fixation in combination with contralateral translaminar facet screw fixation plus interbody fusion through the channel-assisted muscle-splitting approach for the treatment of degenerative lumbar spine diseases in elderly patients.Methods A total of 82 elderly patients with degenerative lumbar spine diseases received treatment between January 2015 and June 2016.Of these patients,25 had lumbar spinal stenosis,42 had degenerative lumbar instability,13 had giant lumbar disc herniation,and two had recurrent lumbar disc herniation;There were 69 cases of single segment and 13 cases of double segment lesions.Perioperative evaluation,imaging evaluation,and clinical evaluation were performed,and surgical complications were analyzed.Results The average length of incision was (2.6 ± 0.4) cm in cases of single segment lesions and (4.4±0.5) cm in cases of two segment lesions.The mean operation time was (98.3±19.6) minutes and peri-operation blood loss was (232.2±25.8) ml.The post-operation height of the intervertebral disc space significantly increased at the last follow-up(P ＜ 0.05);the height of the intervertebral disc space was restored and well maintained with internal fixation showing no loosening,breakage or Cage shift.The post-operation lumbar coronal Cobb angle decreased(P＜0.05)while the sagittal Cobb angle increased(P＜0.05)at the last follow-up.There was no significant difference in the area and grade of the multifidus muscle on MRI 12 months after operation.Seventy-two patients were followed up for 12-18 months (mean =16.8 months),and there were 67 cases of intervertebral fusion (93.1％).The last follow-up showed a Japanese Orthopaedic Association(JOA) score of (25.8 ± 1.7),which was significantly higher than the pre-operation score (10.6±1.3),with an excellence rate of 88.9 ％.The Oswestry Disability Index score was significantly reduced,from (50.9±21.6) at pre-operation to (9.6± 4.8) at the last follow-up.There were 78 patients with primary wound healing,three cases of superficial wound necrosis,one case of dural tear,and one case of nerve root injury.No cardiovascular or cerebrovascular incident was observed during or after operation.Conclusions Combined pedicle/facet screw fixation plus interbody fusion through the channel-assisted muscle-splitting approach shows satisfactory short-term effects when used for the treatment of degenerative lumbar spine diseases in the elderly and possesses advantages such as minimal invasiveness,limited bleeding,quick recovery,high fusion rates and significantly improved clinical outcomes.However,further clinical studies are required to assess its medium-and long-term efficacy.

UL48 plays essential role in replication of MDV genome and interacts with UL36 as well as other MDV tegument proteins.To investigate the interaction between UL48 and UL36 during MDV oncogenisis,antibody against UL48 was prepared and characterized in current study.UL48 gene was amplified from MDV-Ⅰ genome and then subcloned into pTYB1 and pGEX-4T3 vectors for UL48 expression with induction of IPTG in BL21(DE3) E..coli cells.Chitin-sepharose and Glutathion-sepharose were,respectively,used to purify fusion protein intein-UL48 and GST-UL48.Four subcutaneous injections of intein-UL48 fusion protein were done on the lower back and the thigh of rabbit and then other three injections with an interval 10 days.The titer of antibody was measured by the sandwich ELISA with UL48 protein isolated from GST-UL48 after cleavage of thrombin.Western blot was carried out for specificity analysis of antibody against UL48 protein.The results suggested that UL48 antibody was succesfully prepared,and its titer was 1 ∶ 512 000.

Objective To evaluate the effect of electric vagal stimulation on postoperative cognitive dysfunction in aged rats.Methods Thirty healthy Sprague-Dawley rats of both sexes,aged 18-20 months,weighing 390-550 g,were randomly divided into 3 groups (n=10 each) using a random number table:control group (group C),surgery group (group S),and electric vagal stimulation group (group V).Incision of the right carotid sheath was performed,and the vagal nerve was exposed after anesthesia in S and V groups.The right vagus nerve was stimulated for 30 min with continuous electric rectangular pulses (1 ms,10 Hz,1-2 V) after surgery in group V.The Morris water maze place navigation test was performed at 4,3,2 and 1 days before surgery and 2 days after surgery.The cognitive function was assessed using spatial probe and open field tests conducted at 2 days after surgery.The escape latency,the number of crossing the platform,the number of crossing the grid,the number of standing on the back legs,and the time animals spent in the central square were recorded.After the end of behavioral testing,venous blood samples were collected from the jugular vein for determination of concentrations of serum tumor necrosis factor-alpha (TNF-α),interleukin (IL)-1β and IL-6 using enzyme-linked immunosorbent assay.Results Compared with group C,the number of crossing the platform,the number of crossing the grid,and the number of standing on the back legs were significantly decreased,the escape latency and the time animals spent in the central square were significantly prolonged,and the concentrations of serum TNF-α,IL-1β and IL-6 were significantly increased at 2 days after surgery in group S (P＜0.05).Compared with group S,the number of crossing the platform,the number of crossing the grid,and the number of standing on the back legs were significantly increased,the escape latency and the time animals spent in the central square were significantly shortened,and the concentrations of serum TNF-α,IL-1β and IL-6 were significantly decreased at 2 days after surgery in group V (P＜0.05).Conclusion Electric vagal stimulation can improve the postoperative cognitive dysfunction in aged rats.

Angioplasty, Balloon, Coronary ; Heart Injuries ; drug therapy ; etiology ; Humans ; Thrombin ; administration & dosage