Objective:To summarize the clinical characteristics, diagnosis and treatment of caspase recruitment domain-containing protein 9 (CARD9) gene deficiency associated invasive candidiasis, and report a novel mutation in CARD9 gene.Methods:The clinical characteristics, laboratory tests, treatment and the outcome of follow-up in a boy with invasive candidiasis were described. The boy′s main clinical manifestations were central nervous system infection and retroperitoneal mass. Whole-exome sequencing was performed and Sanger sequencing was verified to identify the CARD9 gene mutations in the patient and his parents. A literature search for “CARD9”and “invasive candidiasis”was conducted in PubMed, Wanfang and CNKI databases from their establishment to May 2020.Results:A 10-year-old boy suffered onset symptom of chronic diarrhea, which lasted for two months. The symptom was followed by progressive neurological symptoms such as headache, vomiting, seizures and disorder of consciousness. His unusual medical history was absent. Candida albicans were cultured several times in cerebrospinal fluid and blood, and yeast-like fungi were found in the stool high power field of vision. Cerebral magnetic resonance imaging indicated obstructive hydrocephalus and abdominal CT scan showed retroperitoneal mass and thickening of the intestinal wall. The whole-exome sequencing analyses of blood samples from the boy and his parents were performed. The results showed that there was a homozygous mutation of c.952-12_956delinsAG in the CARD9 gene, which was an unreported pathogenic mutation. This was confirmed by Sanger sequencing. There was no significant relief from intravenous combined antifungal medications. After lateral ventricular drainage surgery and injection of amphotericin B into the lateral ventricle, improvement of clinical symptoms and cerebral spinal fluid abnormalities was observed after nine weeks, and the retroperitoneal mass shrank. At follow-up after four-month oral combined antifungal medications, the child had no complaint except fatigue. However, cerebral spinal fluid analysis showed increased protein level and decreased glucose. Persistent hydrocephalus and periventricular white matter abnormal signals were revealed on the brain magnetic resonance imaging and the smaller retroperitoneal mass than before on the abdominal CT scan. In addition to this case, totally 21 cases with CARD9 gene deficiency associated invasive candidiasis have been reported worldwide, most of which featured central nervous system infections.Conclusions:CARD9 gene deficiency is an autosomal recessive primary immunodeficiency that confers human susceptibility to fungal disease. The associated invasive candidiasis often affects the central nervous system and makes the patient severely ill. Adequate systemic antifungal therapies should be given, and patients with hydrocephalus need surgical treatment. A novel mutation is reported that expands the variant diversity of CARD9 gene. For patients with unexplained invasive candidiasis, including those without a history of previous recurrent infection, genetic testing is recommended for primary immunodeficiency including CARD9 gene deficiency.

Objective To investigate the clinical outcomes of pedicle screw fixation assisted with the 3D printing positioning guide template for treatment of unstable atlas fractures.Methods A retrospective case series review was made on 10 patients with unstable atlas fractures undergone direct posterior C1 pedicle screw fixation assisted with the 3D printing drill guide template from September 2012 to May 2015.There were 7 males and 3 females,with a mean age of 52.6 years (range,23-75 years).All patients complained of neck pain,stiffness and decreased range of motion without neurologic deficit.Preoperative skull traction was used routinely.After the three-dimension reconstruction of cervical vertebrae,ideal trajectory for C1 pedicle screws was designed with a complementary basal template for posterior surface of atlas corresponding anatomical structure.Then the drill guide template was materialized in a rapid prototyping machine and used during operation.Start point and direction of the ideal and actual trajectories were measured after matching the position of the pre-and post-operative patients' cervical spine.Safety of pedicle screw fixation was assessed in the transverse and sagittal planes of CT scan.Operation time and blood loss were recorded.Visual Analogue Scale (VAS) of neck pain was recorded before operation and 3 months after operation.Clinical efficacy,fracture reduction,stability and surgical complications were reviewed at the follow-up.Results A total of 20 screws were inserted safely.No significant differences existed in deviation of entry point and direction between ideal and actual trajectories (P ＞0.05).Operation time was 60-90 min (mean,75 min) and intraoperative blood loss was 110-300 ml (mean,160 ml).No spinal cord or vertebral artery injury was noted during operation.All patients were followed up for 12-36 months (mean,20.5 months).VAS was improved from preoperative 7.3 (6.3-9.5) points to 1.4 (0.3-2.5) points 3 months after operation (P ＜ 0.05).All patients had normal range of motion of the cervical spine 3 months after operation.Bony fusion was achieved 6 months after operation.At the follow-up,good cervical alignment was maintained with no instrument failure and C1.2 instability.Conclusion For treatment of unstable atlas fractures,direct posterior C1 pedicle screw fixation assisted with the 3D printing drill guide template can improve the precision of screw placement,reduce complications,and preserve the function of the occipital-atlantoaxial junction.

Objective To explore an ideal screw insertion point and optimal trajectory for anterior axis pedicle screw (AAPS) so as to provide an anatomical basis for AAPS placement.Methods CT scan of the cervical spine was performed for 40 healthy Chinese adults.Then,the CT data were imported into the Mimics software to reconstruct the three-dimensional images of the axes.The data were divided into two groups according to the gender.The following data were measured:pedicle centerline minimal diameter on both left and right sides,pedicle axial length,the distance between entrance point and upper endplate,the distance between entrance point and median sagittal plane,the distance between entrance point and peak of crista lambdoidalis of C2 vertebral body,extraversion angle and sagittal angle.The screw fixation parameters for AAPS were measured using the Mimics software.Results There was no statistical difference between the left and right sides as well as between the genders (P ＞ 0.05).The entrance point for insertion of AAPS was recommended to be on (4.39 ± 0.67) mm from the upper endplate,and on (3.95 ± 0.44) mm from the median sagittal plane.The ideal pedicle axial length was (34.15 ± 2.93) mm,and the pedicle centerline minimal diameter was (7.04 ± 0.87) mm.The distance between the entrance point and the peak of crista lambdoidalis of C2 vertebral body was (1.45 ± 0.19) mm.The ideal extraversion angle was (30.80 ± 2.79) °,and the ideal sagittal angle was (36.35 ± 3.26) ° . Conclusion The ideal insertion pathway of AAPS placement can avoid spinal canal,foramen intervertebrale and other important anatomical structure,which is feasible in regard of anatomy.The insertion point can refer to the peak of crista lambdoidalis of C2 vertebral body.However,AAPS placement should be individualized in term of its anatomy variability.

Objective To determine the treatment options for teardrop fracture of the axis and discuss the treatment efficacy.Methods Nineteen patients with teardrop fracture of the axis treated from March 2003 to June 2013 were retrospectively reviewed.Teardrop fracture of the axis accounted for 3.9％ of the cervical injuries and 11.4％ of the axis fractures over the same period.There were 15 males and 4 females,at age range of 21-56 years (mean,37.8 years).Injury was caused by traffic accidents in 12 patients,falls in 6,and hit from heavy objects in 1.Cervical imaging examinations (X-ray,CT and MRI) were performed on admission.Thirteen patients were immobilized for 3 to 6 months with the Halovest device,and six patients underwent anterior cervical surgery.No patients had neurologic deficit [American Spinal Injury Association (ASIA) grade E].Visual analogue scale (VAS),implant failure and bone fusion were recorded after operation.Results All patients were followed up for 12-18 months (mean,15.6 months).At the final follow-up,no implant loosening or breakage happened and 18 patients achieved bone union.Neck mobility returned to normal,which showed VAS improved from (7.5 ± 1.2) points to (3.1 ± 1.5) points.ASIA grade E remained in 18 patients,and one patient were progressed to grade D.Conclusions Teardrop fracture of the axis is rare cervical injury,and can be treated conservatively in most cases.However,surgery is often necessary when imaging findings suggest the existence of instability.

Objective To compare the clinical efficacy and fusion rate of unilateral and bilateral C1 and C2 pedicle screw fixation of unstable Jefferson fractures.Methods This retrospective casecontrol study enrolled 22 patients with unstable Jefferson fractures admitted between April 2012 and May 2015.There were 18 males and four females,with the mean age of 52.9 years (range,35-67 years).Mean preoperative visual analogue scale (VAS) was 6.09 points (range,4-8 points).According to the American spinal injury association (ASIA) classification,two patients were rated grade D and one patient grade C.Mean Japanese orthopedic association (JOA) score was 12.3 points.Bilateral C1 and C2 pedicle screw fixation was performed for 15 patients (bilateral group).Advantage side unilateral C1 and C2 pedicle screw fixation was performed for seven patients with extremely unstable fracture or narrow pedicle (unilateral group).Operation time,blood loss and surgical complications were recorded.VAS was used to evaluate the improvement of neck pain after operation.ASIA classification and JOA score were used to assess nerve function recovery.Atlanto-dental interval (ADI),srew position and bone fusion were evaluated after operation.Results All patients successfully completed the operation.Operation time was (119.5 ±21.2)min,and blood loss was (280.1 ±83.1)ml.A total of 74 screws were placed and CT scan showed satisfactory position of the screws.No complications were noted either during the operation or after surgery.All patients were followed up for mean 20.7 months (range,13-33 months).VAS was improved in both groups after operation (P ＜ 0.01),and there was no significant difference between the two groups (P ＞ 0.05).Two patients with ASIA grade D in bilateral group were improved to ASIA grade E after operation.One patient with ASIA grade C in unilateral group was improved to ASIA grade D after operation.JOA score increased to mean 15.7 points at last follow-up.ADI were decreased in both groups after operation(P ＜0.05),but there was no significant difference between the two groups (P ＞ 0.05).All patients had bony fusion 6 months after operation,with similar fusion rate between the two groups (P ＞ 0.05).Conclusion Advantage side unilateral screw fixation can be used for the patients with bilateral C1 and C2 pedicle screw fixation failure,for the technique can improve cervical pain and provide relatively high stability and fusion rate.

Objective To compare the clinical effects of posterior pedicle screw fixation combined with anterior monosegmental or bisegmental fusion reconstruction in patients with unstable Denis type B thoracolumbar burst fractures.Methods A retrospective case-control analysis was made on 62 cases of Denis type B thoracolumbar burst fractures treated from June 2010 to June 2014.There were 51 males and 11 females,aged 19-55 years (mean,35.1 years).The injury causes included fall from height in 32 cases,traffic accidents in 24,hit by heavy objects in 6.Fifty cases were with monosegmental burst fractures,and 12 with monosegmental burst fractures combined with other vertebral compressive fractures.The burst fracture levels were at T~in 8 cases,T12in 20,L1 in 24,L2 in 6,and L3 in 4.According to the different surgical methods,the patients were divided into two groups:Group A (n =30,treated with posterior pedicle screw fixation combined with anterior monosegmental fusion reconstruction) and Group B (n =30,treated with posterior pedicle screw fixation combined with anterior bisegmental fusion construction).The operation time and intraoperative blood loss were compared between the two groups.Visual analogue scale (VAS),Oswestry disability index (ODI),and Frankel scale of neurologic function were compared at last follow-up.The changes of anterior height of fracture vertebrae and Cobb angle of the two groups were also compared preoperatively,postoperatively and at last follow-up.Implant looseness and breakage,titanium mesh tilt,and bone fusion were recorded postoperatively.Results All patients were followed up for 18-24 months (mean,20.8 months).The operation time and blood loss in Group A was (208.2 ± 15.6) min and (598.3 ± 55.3) ml,respectively.The operative time and blood loss in Group B was (260.1 ± 17.4)min and (662.2± 58.3)ml,respectively.There were significantly statistical differences between two groups in operation time and blood loss (P ＜0.05).There were no statistical differences between two groups in terms of Cobb angle restoration and fracture height restoration rate after surgery,Cobb angle loss and fracture vertebral body front height loss rate at final follow-up (P ＞ 0.05).At the final follow-up,VAS in Group A was (2.5 ± 0.8) points,less than (3.2 ± 1.1) points in Group B (P ＜ 0.05);ODI in Group A was (20.3 ± 5.8) points,less than (28.2 ± 5.1) points in Group B (P ＜ 0.05).Frankel scale was improved to some degree after operation (P ＜ 0.05).One case did not achieve bone fusion in Group A versus three cases in Group B (P＜0.05).No implant Loosening,titanium mesh tilt or settlement was found in Group A,while there were eight cases of titanium mesh tilt or settlement in Group B (P ＜0.05).Conclusions For unstable Denis type B thoracolumbar burst fractures,posterior pedicular fixation combined with anterior monosegmental fusion or bisegmental fusion can achieve equal clinical effects.However,posterior pedicular fixation combined with anterior monosegmental fusion can have less injury,higher bone fusion rate,better function restoration,and less incidence of complication.

Objective:To evaluate the medium and long-term clinical efficacy of the treatment of lumbar degenerative diseases in Dynesys dynamic internal fixation combined with decompression.Methods:From March 2008 to March 2015, 145 patients (84 males and 61 females, mean age 55.9±7.1 years old) with symptoms of lumbar degenerative diseases (69 lumbar disc herniation, 53 lumbar spinal stenosis and 23 I grade lumbar degenerative spondylolisthesis) were treated by the lumbar discectomy using Dynesys dynamic internal fixation combined with decompression. The clinical symptoms before and after surgery were assessed by visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI). Lumbar lateral radiographs were used to measure the height of intervertebral space between the surgical segment and the adjacent segment. The range of motion (ROM) between the surgical segment and the adjacent segment was measured by lumbar dynamic position X-ray. Surgical and adjacent segments degenerative were classified according to the Pfirrmann grade classification.Results:The VAS score, ODI and JOA score of lower back and lower limbs in patients with lumbar disc herniation were improved from 6.6±1.7, 7.1±1.4, 63.1%±10.2%, 12.5±2.4 preoperatively to 2.6±1.0, 2.8±0.9, 30.9%±9.8%, 22.4±2.1 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with lumbar spinal stenosis were improved from 6.3±2.2, 6.9±1.3, 63.4%±8.5%, 12.8±2.7 preoperatively to 2.4±1.2, 2.8±1.0, 35.1%±12.0%, 22.2±2.2 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with I degree lumbar degenerative spondylolisthesis were improved from 5.7±2.3, 6.7±0.9, 65.7%±10.0%, 12.5±2.7 preoperatively to 2.2±1.2, 2.7±1.1, 37.0%±11.8%, 22.4±2.6 at the latest follow-up. The differences were statistically significant. Comparing to preoperational value, the height of the operative segment and caudal intervertebral space were decreased at the 1 year postoperatively and last follow-up. But the difference was not significant. As for cranial adjacent segment, the height of intervertebral space preoperatively was decreased from 12.1±1.9 mm preoperatively to 11.7±1.6 mm at 1 year postoperatively, and to 11.3±1.8 mm at the latest follow-up. The difference between them was statistically significant ( F=6.46, P=0.001). The ROM of surgical segments was decreased from 7.6°±2.2° preoperatively to 5.5°±1.6° at 1 year postoperatively, and to 2.9°±1.4° at the latest follow-up. The difference between them was statistically significant ( F=267.9, P<0.001). Conversely, the ROM of cranial and caudal segments was increased from 8.2°±2.4°, 6.5°±1.6° preoperatively to 9.1°±2.1°, 7.1°±1.9° at 1 year postoperatively, and to 10.6°±2.5°, 7.2°±1.8° at the latest follow-up. The difference between them was statistically significant ( F=38.66, 3.81, P<0.001, 0.023). At the latest follow-up, 120 (51.9%) adjacent segments were to be defined adjacent segment degeneration which includes 103 radiological adjacent segment degeneration and 17 symptomatic adjacent segment degenerations. Conclusion:Dynesys dynamic internal fixation combined with decompression could achieve satisfying mid- and long-term therapeutic effect in the treatment of lumbar degenerative diseases. The ROM of surgical segments decreased with time, although part of the ROM was still retained at the latest follow-up. However, it does not seem to avoid the degeneration of adjacent segment.

Apoptosis Regulatory Proteins ; Apoptosis ; Antiviral Agents/pharmacology* ; Mitochondrial Proteins ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*