Objective:To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants.Methods:A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed.Results:Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score).Conclusions:Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.

Objective:To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants.Methods:A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed.Results:Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score).Conclusions:Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.

Objective:To explore the factors affecting changes of disc angle (ΔDA) during oblique lateral interbody fusion (OLIF) and establish a predictive model of ΔDA.Methods:This retrospective study included 119 patients with 174 segments undergoing OLIF procedures between July 2017 and August 2019 in Beijing Jishuitan Hospital. 45 males and 74 females with an average age of 62.1±9.8 years (33-86 years) were included. The lordotic cages were all 6 degrees. Radiographic parameters included preoperative and postoperative disc angle (DA), disc height (DH), ΔDA on flexion-extension views (ΔDA-FE), cage location and cage inclination. Pearson correlation coefficient and machine-learning techniques were utilized to identify factors related to ΔDA. Based on machine leaning techniques, ten-fold cross-validation for model training and validation were used to develop a predictive linear model for ΔDA.Results:The average ΔDA was 3.9°±4.8° with preoperative disc angle (preoperative DA) of 5.3°±5.0°. The average change of posterior DH (ΔPDH) was 3.1±2.1 mm with preoperative posterior DH of 6.6±1.9 mm. The average change of anterior DH was 6.1±3.2 mm. Pearson correlation analysis showed a significant negative correlation between ΔDA and preoperative DA ( r=-0.713, P<0.001), cage location ( r=-0.183, P=0.016), and ΔDA-FE ( r=-0.153, P=0.044). PDH changes were significantly negatively correlated with preoperative PDH ( r=-0.444, P<0.001) and positively correlated with cage location ( r=0.218, P=0.004). ΔDA was 10.8°±3.2° for negative preoperative DA (indicating kyphotic), 5.0°±3.7° for preoperative DA between 0° and 6°, and 1.0°±4.1° for preoperative DA>6°. A predictive model was developed using ten-fold cross-validation, resulting in the formula ΔDA=7.9°-0.8×preoperative DA ( R=0.707, MAE=2.837). Conclusion:Disc angle changes in OLIF primarily depend on the preoperative disc angle, secondly on cage location. The predicting model based on machine-learning techniques using preoperative disc angle facilitates preoperative planning for OLIF procedures.

Objective To compare the clinical outcomes between oblique lumbar interbody fusion(OLIF)and transforaminal lumbar interbody fusion(TLIF)for patients with degenerative spondylolisthesis during 2-year follow-ups.Methods Patients with symptomatic degenerative spondylolisthesis who underwent OLIF(46 cases)and TLIF(45 cases)between July 2017 and September 2020 with 2-year follow-ups were retrospectively reviewed.One level or two-level lumbar fusion were included.The primary outcomes were Visual Analogue Scale(VAS)and Oswestry Disability Index(ODI)at 2 years after surgery.The secondary outcomes included radiographic parameters,fusion rate,cage subsidence rate,and permanent nerve injury rate.Results No significantly different changes were noted in VAS-back[2(2,3)vs.2(2,2),P=0.943],VAS-leg[2(2,2)vs.2(2,2),P=0.988],and ODI[17％(10％,22％)vs.14％(10％,22％),P=0.417]between the OLIF group and the TLIF group,respectively.Greater restoration of disc height and segmental lordosis were obtained in the OLIF group[mean,(11.9±1.5)mm and 15.7°±7.2°]than in the TLIF group[mean,(9.2±2.0)mm and 12.5°±5.9°]at postoperative 2-year(P＜0.001 and P=0.029).The subsidence rate was lower in the OLIF group than in the TLIF group[19.6％(9/46)vs.40.0％(16/40),P=0.037].The fusion rates at postoperative 2-year were 93.5％(43/46)in the OLIF group and 87.5％(35/40)in the TLIF group,having no significant difference(P=0.562).The rates of permanent nerve injury were similar between the two groups[4.3％(2/46)vs.6.7％(3/45),P=0.980]at postoperative 2-year.Conclusion Short segment OLIF doesn't show better clinical outcomes and fusion rate than TLIF for degenerative spondylolisthesis,except for greater disc height restoration,greater segmental lordosis,and lower subsidence rate at postoperative 2-year.

Objective:To evaluate the effect of oblique lateral interbody fusion (OLIF) combined with posterior fixation on segmental alignment in the treatment of degenerative spondylolisthesis (DS).Methods:The clinical data of 40 patients with DS who underwent OLIF combined with posterior fixation from July 2017 to December 2019 were retrospectively analyzed. There were 7 males and 33 females, aged 45-81 years, with an average age of 65.7±9.06 years. The total number of slip segments was 43, including 37 levels at L 4, 5, 5 levels at L 3, 4, and 1 level at L 2, 3. According to the decompression methods, the patients were divided into two groups. 22 patients with 23 levels were treated with direct decompression combined with laminectomy, and 18 patients with 20 levels were treated with indirect decompression without laminectomy. All patients underwent preoperative and intraoperative imaging examination. The disc height (DH), slip ratio (SR) and segmental lordosis (SL) were measured by preoperative CT and intraoperative fluoroscopy images. One-way repeated measures ANOVA was used to compare the radiographic parameters of the segmental alignment prior to cage implantation, following cage insertion and posterior fixation. Bonferroni test was used to compare the radiographic parameters between groups. Results:In the OLIF combined with the posterior fixation, there were statistically significant differences in the radiographic parameters of segmental alignment at different stages of operation [DH ( F=147.786, P<0.001) , SR ( F=83.754, P<0.001) , SL ( F=38.296, P<0.001) ]. DH increased from 7.99±1.39 mm to 11.69±1.72 mm ( P<0.001), SR decreased from 10.67%±4.67% to 8.66%±4.50% ( P=0.001) and SL increased from 7.26°±2.73° to 7.85°±2.30° ( P=0.425). After combined posterior fixation, SR further decreased from 8.66%±4.50% to 2.07%±4.00% ( P<0.001), SL further increased from 7.85°±2.30° to 10.72°±3.08° ( P<0.001), and DH had no significant change ( P=1.000). There was no significant difference in radiographic parameters between the direct decompression group and the indirect decompression group when prior to cage implantation, following cage insertion and following posterior fixation, respectively. Conclusion:OLIF combined with posterior fixation in the treatment of DS can further reduce the slip rate of patients with lumbar degenerative spondylolisthesis and increase the lordosis angle of the surgical segment. At the same time, the direct decompression combined with laminectomy has no significant effect on the segmental alignment.

Objective:To investigate the clinical characteristics of R403C variant in DNM1L gene caused encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (EMPF1).Methods:The clinical data of three patients, who carried R403C variant in the DNM1L gene, diagnosed at Xiangya Hospital from February 2018 to February 2020 were retrospectively summarized. Literature reviewing was performed by taking "DNM1L" or "encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1" as keywords for searching in online Mendelian inheritance in man (OMIM), PubMed, China national knowledge infrastructure (CNKI), and Wanfang data knowledge service platform up to July 2020. And the clinical manifestation, laboratory examination, imaging, treatment, and prognosis were reviewed.Results:Case 1, a 7-year-old boy, developed seizures after a 9-day course of cough without fever. The seizures manifested as generalized tonic-clonic seizures (GTCS) and soon converted to focal status epilepticus (EPC) or focal myoclonus, which were resistant to multi-anti-epileptic drugs combined with sedative drugs. The boy died at the 2 nd week after seizure onset. Case 2, also a 7-year-old boy, developed seizures after a 10-day history of amygdalitis. The seizures manifested as focal to generalized tonic-clonic seizure and then converted to EPC or focal myoclonus. And all seizures showed poor responses to multi-anti-epileptic drugs combined with sedative drugs, ketogenic diet, and methylprednisolone treatment. The boy died after 1 month′s treatment. Case 3, a 3-year and 5-month old girl, had seizures onset after a 2-week course of viral pneumonia. The seizures onset manifested as focal clonic seizure and converted to EPC, shortly. She was resistant to multi-anti-epiletic drugs combined with sedative drugs and ketogenic treatment. The girl died 3 months afte seizure onset. All of their images showed multifocal T1 low, T2, fluid attenuated inversion recovery, and diffusion-weighted imaging high signal lesions among the brain, and diffuse brain atrophy in case 3. The blood metabolic and cerebrospinal-fluid immunological assays were normal. Genetic analysis suggested a de novo, heterozygous, NM_012062.4: c.1207C>T, p.R403C variant in the DNM1L gene. According to their clinical manifestations, all of them were diagnosed with EMPF1. Literature review included 11 patients carrying this variant in the world. Summarizing the 14 cases, 8 cases had an infectious history before seizure onset, 8 cases had mild or moderate development delay. All of 14 cases had seizures, and the forms mainly included EPC ( n=9), focal myoclonus ( n=6), GTCS ( n=5) and focal clonic seizures ( n=4). All of them were refractory, and no effective anti-epileptic drugs were recommended. Early-stage cranial magnetic resonance imaging results showed multiple intracranial focal lesions ( n=10), including thalamus ( n=7), hippocampus ( n=5), basal ganglia ( n=4), frontal lobe ( n=3), and temporal lobe ( n=2). As the disease progressed, the brain manifested as diffused progressive atrophy ( n=10). Five of the 14 cases died at reported age. Conclusions:R403C variant in the DNM1L gene can cause mitochondrial fission dysfunction. Patients carrying this variant may manifest as refractory status epilepticus with or without mild-infection indction, development regression and brain atrophy.

More than 150 different human proteins are anchored to the outer leaflet of the plasma membrane via glycosylphosphatidylinositol (GPI). From the synthesis of GPI anchors, binding to proteins to localization on cell membranes, these processes are regulated by a wide range of genes, including PIG genes such as PIGA, PIGB, PIGC, and PGAP genes such as PGAP1, PGAP2, etc.Recently, the number of reports about PIG/PGAP gene related diseases is increasing but rarely reported in China.Now, the inheritance and clinical features, treatment and genotype/phenotype associated with PIG/PGAP gene related diseases, were reviewed.

Objective: To investigate the clinical features of childhood epilepsy with occipital paroxysms. Methods: The clinical data of 33 children admitted to our hospital from 2015 to 2019 were retrospectively analyzed. Results: The children were divided into three groups: idiopathic group (n=20), structural group (n=10) and genetic group (n=3). Among the structural etiology group, there were 1 case of megagyrus malformation, 1 case of focal cortical dysplasia type Ⅱ (FCDⅡ), 1 case of gestational age infant with enlarged ventricle, and 7 cases of perinatal ischemic-hypoxic encephalopathy (HIE). In the genetic group, there were 1 case of PCDH19 gene mutation, 1 case of cyclin-dependent kinase like 5 (CDKL5) deficiency disorder and 1 case of Wolf-Hirschhorn syndrome. All three groups had ocular motor symptoms and secondary motor symptoms. Compared with the structural group, patients of the idiopathic group had more autonomic symptoms, less visual symptoms, longer ictal duration, less episodes, less abnormal background rhythm, and more epileptic discharges in the frontal lobe or Rolandic area. The genetic group had frequent seizures and the CDKL5 deficiency disorder patient had slowed background and spasms. Compared with the other two groups, patients of the idiopathic group had fewer MRI abnormalities, better seizure control effect, and better prognosis. Conclusions There are many causes of childhood epilepsy with occipital paroxysms. The idiopathic group accounts for a large proportion. The visual symptoms and autonomic symptoms are different between groups. Background abnormalities are detected more often in the structural group and the genetic group, which is also helpful for differential diagnosis. The treatment options and prognosis of different groups vary greatly. The overall therapeutic effect and prognosis of the idiopathic group are better than those of the structural group and the genetic group.

Objective: To explore clinical features and prognosis factors of surgical complications after intersphincteric resection (ISR) for low rectal cancer following neoadjuvant chemoradiotherapy. Methods: The clinical data of 132 patients with low rectal cancer who underwent ISR following neoadjuvant chemoradiotherapy from September 2010 to June 2017 at Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University were retrospectively reviewed. There were 100 males and 32 females, with the age of (52.9±11.4) years and distance to anal verge of 3.9 cm. Records of perioperative complication (POC) within 30 days after surgery, anastomotic leakage (AL), and anastomotic stenosis (AS) were analyzed. POC was recorded according to the Clavien-Dindo classification. AL was graded by ISREC system and classified into the early AL within 30 days after surgery and delayed AL beyond 30 days. AS was defined as narrowing of the bowel lumen at the anastomosis that prevented passage through a colonoscope with a 12 mm diameter. According to the shape of narrowing, AS was recorded as the stenosis in situ or stenosis with long-segment bowel above. Univariate and multivariate analysis were used to identify risk factors of anastomotic complications. Results: Among the 132 patients, full-dose radiotherapy and diverting stoma were performed in 128 (97.0%) patients, respectively. In entire cohort, AL was found in 41 (31.1%) patients, including 32 patients with clinical leakage (24.2%). The median time for diagnosis of AL was 37 days (2 to 214 days) after surgery. There were 25 patients (18.9%) who were diagnosed with delayed AL beyond 30 days. Chronic presacral sinus formation was detected in 22 of 129 (17.1%) patients at 12 months from surgery. Among the 128 eligible patients, 36 (28.1%) were diagnosed as AS, including 24 (18.8%) patients with stenosis in situ and 12 (9.4%) patients with bowel stenosis above. After a median follow-up of 26 months, 7(5.3%) patients received permanent colostomy and the other 20(15.2%) patients retained a persistent ileostomy, owing to anastomotic complications. Results of multivariate analysis showed that radiation colitis was an independent prognosis factor of AL after ISR (OR=5.04, 95% CI: 2.05 to 12.43, P=0.000); male gender (OR=5.19, 95% CI: 1.24 to 21.75, P=0.024) and AL (OR=8.49, 95% CI: 3.32 to 21.70, P=0.000) were independent prognosis factors of AS after ISR. Conclusions Surgical complications are common after ISR for low rectal cancer patients with neoadjuvant chemoradiotherapy. A high rate of AL is observed after long-term follow-up, which is associated with AS. Increasing awareness of anastomotic complications after ISR should be raised, especially for male patients with radiation colitis.

OBJECTIVETo evaluate the short-term outcomes and perioperative safety of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy.

METHODSFrom colorectal cancer database in The Sixth Affiliated Hospital of Sun Yat-sen University, a cohort of patients who underwent neoadjuvant chemoradiotherapy(1.8-2.0 Gy per day, 25-28 fractions, concurrent fluorouracil-based chemotherapy) followed by curative sphincter-preserving surgery for locally advanced rectal cancer between May 2016 and June 2017 were retrospectively identified. Exclusion criteria were synchronous colon cancer, intraoperatively confirmed distal metastasis, multiple visceral resection, and emergency operation. Thirty-one patients underwent proximal extended resection and two were excluded for incomplete extended resection, then 29 patients were enrolled as the extended group. Using propensity scores matching with 1/1 ration, 29 locally advanced rectal cancer patients who underwent conventional resection after neoadjuvant chemoradiotherapy at the same time were matched as the conventional group. Clinical data of two groups were analyzed, and the baseline characteristics and short-term outcomes were compared using the t test, χtest, or Mann-Whitney U test.

RESULTSTwo groups were well balanced with respect to the baseline characteristics after propensity score matching. As compared with conventional group, patients in extended group had longer surgical specimen [(18.8±5.1) cm vs.(11.6±3.4) cm, t=6.314, P=0.000] and longer proximal resection margin [(14.8±5.5) cm vs.(8.2±3.0) cm, t=5.725, P=0.000], but also had longer total operating time [(322.4±100.7) min vs.(254.6±70.3) min, t=2.975, P=0.004] and more intraoperative blood loss [100(225) ml vs. 100(50) ml, Z=-2.403, P=0.016]. No significant differences were observed in the length of distal resection margin, ratio of positive resection margin, number of retrieved lymph node, time of analgesic use, time of draining tube use, time to first flatus, time to first oral diet, and postoperative hospital stay. During the perioperative period of 30 days, the morbidity of complication in extended group and conventional group was 17.2%(5/29) and 34.5% (10/29), respectively (P=0.134).

CONCLUSIONProximally extended resection is a radical and safe surgical alternative for locally advanced rectal cancer after neoadjuvant chemoradiotherapy, which can potentially reduce the risk of anastomosis complication.