Objective:To determine the genetic causes of dystonic cerebral palsy (DCP) of unknown etiology by using whole exome and mitochondrial gene detection methods, and to analyze clues for early identification of DCP.Methods:This was a retrospective analysis of clinical data describing 21 children with unknown etiology and DCP-like phenotypes. It involved collecting a detailed medical history, biochemical testing, neuroimaging, electroencephalography and hematuria metabolic screening. Peripheral blood was collected from the children, their parents and their siblings. Genomic DNA was extracted, and whole exome and/or mitochondrial gene sequencing was performed to obtain variant sites and annotations. The candidate variants were verified by Sanger sequencing.Results:No clear perinatal risk factors were found in the 21 cases, though there was 1 case of family history. Laboratory tests found increased lactic acid in 3 and abnormal thyroid function in 2 cases. The neuroimaging showed lesions in the basal ganglia in 2 cases, delayed myelination in 6 cases, sometimes with cortical dysplasia, a wide extracerebral space and/or a thin corpus callosum. The images of 11 of the children were normal. Later follow-up showed changes in the brain magnetic resonance images (MRIs) of 2 of the children. Pathogenic or likely pathogenic candidate variants were identified in 15 of the 21 children (71%) within 12 genes: TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MT- ATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 or NACC1. Fifteen of the children received a precise diagnosis. Genetic testing found heterozygous variants of ATP1 A2, SPR, ATP1 A3, MED13 L or NR4 A2 genes in the remaining six children, all of which were non-pathogenic variants. Conclusions:The absence of perinatal high-risk factors, a positive family history, and a normal or progressive brain MRI can be used as early clues to identify atypical DCP cases. TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MTATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 and NACC1 variants belong to the spectrum of DCP-related pathogenic genes, and attention should be paid to the interpretation of genomic analysis results.

Objective:To determine the genetic causes of dystonic cerebral palsy (DCP) of unknown etiology by using whole exome and mitochondrial gene detection methods, and to analyze clues for early identification of DCP.Methods:This was a retrospective analysis of clinical data describing 21 children with unknown etiology and DCP-like phenotypes. It involved collecting a detailed medical history, biochemical testing, neuroimaging, electroencephalography and hematuria metabolic screening. Peripheral blood was collected from the children, their parents and their siblings. Genomic DNA was extracted, and whole exome and/or mitochondrial gene sequencing was performed to obtain variant sites and annotations. The candidate variants were verified by Sanger sequencing.Results:No clear perinatal risk factors were found in the 21 cases, though there was 1 case of family history. Laboratory tests found increased lactic acid in 3 and abnormal thyroid function in 2 cases. The neuroimaging showed lesions in the basal ganglia in 2 cases, delayed myelination in 6 cases, sometimes with cortical dysplasia, a wide extracerebral space and/or a thin corpus callosum. The images of 11 of the children were normal. Later follow-up showed changes in the brain magnetic resonance images (MRIs) of 2 of the children. Pathogenic or likely pathogenic candidate variants were identified in 15 of the 21 children (71%) within 12 genes: TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MT- ATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 or NACC1. Fifteen of the children received a precise diagnosis. Genetic testing found heterozygous variants of ATP1 A2, SPR, ATP1 A3, MED13 L or NR4 A2 genes in the remaining six children, all of which were non-pathogenic variants. Conclusions:The absence of perinatal high-risk factors, a positive family history, and a normal or progressive brain MRI can be used as early clues to identify atypical DCP cases. TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MTATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 and NACC1 variants belong to the spectrum of DCP-related pathogenic genes, and attention should be paid to the interpretation of genomic analysis results.

Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.

Objective:To explore any effect of the single- and dual-task treadmill training on the functioning of children with bilateral spastic cerebral palsy.Methods:Fifty children with bilateral spastic cerebral palsy were randomly divided into a single-task treadmill training group (the control group, n=25) and a dual-task treadmill training group (the observation group, n=25). All of the children also received routine rehabilitation training, and the control and observation groups also conducted single- and dual-task treadmill training in addition to the routine rehabilitation training, respectively. Before and after 2 months of treatment, each child′s gross motor functioning was quantified using sections D (standing) and E (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument. Balance was quantified using the Pediatric Balance Scale (PBS) and walking mobility was quantified using a 1 minute walking test (1MWT). Modified and dual task Timed Up and Go (mTUG) tests and dual-task effects (DTE) tests were also administered. Results:There were no significant differences in average test scores between the two groups before the treatment. After the treatment significant improvement was observed in both groups. There was no significant difference between the two groups in terms of average GMFM-88, PBS and 1MWT scores, but significantly greater improvement was observed in the average dual-task mTUG and DTE results of the observation group.Conclusion:Both single- and dual-task treadmill training are effective supplements to routine rehabilitation training for children with bilateral spastic cerebral palsy. Dual-task treadmill training is more effective than the single-task version.

Objective:To study the detection rates of using different MRI sequences and enhanced CT in colorectal cancer liver metastasis (CRLM).Methods:The imaging data of CRLM patients who were treated at Peking University Third Hospital from March 2018 to September 2021 were retrospectively analyzed. Sixty-six CRLM lesions with a maximum diameter ≤10 mm were selected. Different MRI sequences such as T 1 weighted imaging (T 1WI), T 2 weighted imaging (T 2WI), diffusion weighted imaging (DWI), dynamic enhanced phase of MRI (MR-Dyn), gadolinium-etoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), enhanced hepatobiliary phase of MRI (HBP) and CT enhancement phase (CT-Dyn) were reviewed independently to determine whether the target lesions were detected. The pathological results were used as the gold standard. Paired chi-square test was used to compare the detection rate of CRLM in each group. Results:Among the 66 liver metastases, 15, 31, 55, 21, 56 and 20 were detected by T 1WI, T 2WI, DWI, MR-Dyn, HBP and CT-Dyn, respectively. Their detection rates were 22.7%, 47.0%, 83.3%, 31.8%, 84.8% and 30.3%, respectively. The detection rates of HBP and DWI were higher than those of T 2WI, MR-Dyn, CT-Dyn and T 1WI, respectively (all P<0.05). The detection rate of T 2WI was higher than that of MR-Dyn, CT-Dyn and T 1WI (all P<0.05). The detection efficiencies of non-contrast MRI and Gd-EOB-DTPA enhanced MRI for CRLM were highly consistent ( Kappa=0.745). Conclusions:The detection rates of HBP, DWI and T 2WI for CRLM were high. Non-contrast MRI could replace Gd-EOB-DTPA enhanced MRI for detection of large CRLM.

Objective:To investigate the gross motor function, manual ability and language communication of children with cerebral palsy (CP) and their correlation.Methods:A total of 318 children with CP (132 with spastic diplegia, 27 with spastic quadriplegia, 32 with spastic hemiplegia, 54 with dyskinesia, 41 with ataxia and 32 children with multiple difficulties) aged 4 to 12 years were classified according to the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), and the Communication Function Classification System (CFCS). Spearman correlation coefficients were used to analyze the correlation among the three ratings.Results:Only 125 of the 318 children (39%) had the same classification level according to all three scales, showing moderate correlation and different levels for patients with different types of disability. The GMFCS and MACS levels of the subjects with spastic quadriplegia and those with dyskinesia were highly correlated. The GMFCS and CFCS levels of the hemiplegic children and those with spastic quadriplegia were also highly correlated. The MACS and CFCS levels were strongly correlated for children with spastic quadriplegia and multiple disabilities.Conclusions:The functioning of children with CP differs with their CP subtype. Correlations among the three functional assessments also differ for children with different subtypes. Combining the three classification systems provides a more comprehensive picture of the children′s ability to function in daily life.

Objective:This research was designed to investigate the safety and efficiency of laparoscopic simultaneous resection in the treatment of synchronous colorectal cancer liver metastases (sCRLM).Methods:From January 2009 to December 2019, 121 patients diagnosed as sCRLM received radical resection in Peking University Third Hospital were included in the research. According to the surgery approaches, the patients were divided into laparoscopic surgery group and open surgery group. Statistical analysis of general patient data, surgical data, postoperative complications and follow-up of the two groups of patients.Results:There were 79 cases in the laparoscopic surgery group including 30 females and 49 males, and the average age was 61.5 years. There were 42 cases in the open surgery group including 15 females and 27 males, and the average age was 63.2 years. There were no significant differences in the preoperative demographic characteristics, the location of primary tumor, gene status, the size of liver metastases, the proportion of multiple liver metastases, the level of tumor markers and the proportion of neoadjuvant chemotherapy between laparoscopic surgery group and the open surgery group ( P>0.05). The complication rate was 15.2% (12/79) in the laparoscopic surgery group and 23.8% (10/42) in the open surgery group. There were no significant differences between the two groups ( P>0.05). The 3-year and 5-year survival rates in laparoscopic surgery group were 52.9% and 44.4%, which were 42.5% and 23.0% respectively in open surgery group. There were no significant differences between the two groups ( P>0.05). The 1-year and 3-year disease-free survival rate in laparoscopic surgery group were 50.6% and 41.2%, which were 44.7% and 19.4% respectively in open surgery group. There were no significant differences between the two groups ( P>0.05). Conclusions:Laparoscopic simultaneous resection was safe and feasible for patients with sCRLM. Comparing with the open surgery, the laparoscopic surgeries had similar incidence of perioperative complications and long-term oncological efficiency.

Infantile spasms (IS) is an age dependent epileptic encephalopathy in early infancy. Early diagnosis and treatment (within 4 weeks of onset) are beneficial to the termination of seizures and long-term cognitive protection. This paper reviewed the related literatures in the treatment of infantile spasms, mainly including the first-line and second-line drugs, the ketogenic diet and surgical treatment, to discuss the recent advances in the treatment of infantile spasms.

Objective To evaluate the efficacy of laparoscopic radical resection for rectal cancer by collecting and analyzing long-term outcomes of patients and to investigate prognostic factors of overall survival and disease free survival.Methods The clinicopathological data of 235 patients who underwent laparoscopic radical resection for rectal cancer from Jan 2007 to Dec 2010 were retrospectively analyzed.COX proportional hazards regression model was used to determine the risk factors for overall survival and disease free survival.Results A total of 235 patients were included in this analysis.Local recurrence rate were 8.1％ at 3 years and 9.8％ at 5 years.Overall and disease free survival were 85.2％ and 75.1％ at 3 years,77.1％ and 69.6％ at 5 years,respectively.Factors found to significantly and independently predict a poor overall and disease free survival were laparoscopic Hartmann,postoperative complications,stage Ⅲ tumor and ulcerative type tumor.Neural invasion was also an adverse prognostic factor of overall survival.Conclusions Laparoscopic Hartmann,postoperative complications,stage Ⅲ tumor and ulcerative type tumor were independently associated with overall and disease free survival.In addition to this,neural invasion was also an adverse prognostic factor of overall survival.

Objective To explore the clinical effect of laparoscopic colorectal radical resection combined with simultaneous laparoscopic or open major hepatectomy for synchronous colorectal liver metastases (SCRLM).Methods The retrospective cohort study was adopted.The clinical data of 14 patients with SCRLM who were admitted to the Peking University Third Hospital from July 2010 to September 2015 were collected.Seven patients undergoing total laparoscopic colorectal radical resection combined with major hepatectomy (TLCRMH) were allocated into the TLCRMH group and 7 patients undergoing laparoscopic colorectal radical resection combined with open major hepatectomy (LCROMH) were allocated into the LCROMH group.The statuses of colorectal cancer and metastatic lesions were detected by endoscopy and imaging examination,and diagnostic and therapeutic plans were confirmed through the consultation of muhidisciplinary team.During the hepatectomy,total liver ultrasonography was performed and the extent of liver resection was above 3 hepatic segments.The follow-up of outpatient reexamination was applied to all the patients once every 3 months within postoperative year 2 and once every 6 months after 2 years till December 2015.(1) During operation,method of liver resection,radiofrequency ablation (RFA),operation time,volumes of intraoperative blood loss and blood transfusion,pathological results of primary lesions (T stage,N stage,nerve invasion and canalis haemalis invasion) were collected.(2) After operation,duration of intensive care unit (ICU) care,time for fluid diet intake,postoperative alanine transaminase (ALT),total bilirubin (TBil),complications and duration of hospital stay were collected.(3) Survival of patients and recurrence of tumor were followed up.Count data were analyzed by the chi-sqaure test.Measurement data with normal distribution were presented as x ± s and analyzed using the t test.Measurement data with skewed distribution were described as M(Qn) and M(range) and analyzed using the Mann-Whitney U test.The survival curve was drawn by the Kaplan-Meier method,and overall survival rate and tumor-free survival rate were calculated.The survival analysis was done using the Log-rank test.Results (1) The status of operation:1 and 6 patients in the TLCRMH group underwent respectively left and right hemihepatectomies and 7 patients in the LCROMH group underwent right hemihepatectomy.Four and 6 patients in the TLCRMH and LCROMH groups received local resection of liver metastatic lesions or RFA at segment Ⅱ,Ⅲ or Ⅳ of liver,respectively.The operation time,volumes of intraoperative blood loss and blood transfusion were (651 ± 218)minutes,(1 387 ± 871)mL,(914 ±641)mL in the TLCRMH group and (535 ± 83) minutes,(1 357 ±991)mL,(857 ± 360) mL in the LCROMH group,respectively,with no significant difference between the 2 groups (t =1.320,0.060,0.206,P ＞ 0.05).The numbers of patients in T2,T3,T4,N0,N1,N2 stages,with nerve invasion and canalis haemalis invasion were 1,5,1,3,4,0,3,2 in the TLCRMH group and 0,4,3,1,4,2,2,3 in the LCROMH group,respectively,showing no significant difference between the 2 groups (x2=2.111,3.000,0.311,0.311,P ＞ 0.05).(2) After operation,time for fluid diet intake,ALT,TBil,number of patients with complications and duration of hospital stay were (4.3 ± 1.0) days,(105 ± 47) U/L,(34 ± 25) μmol/L,3 (Ⅲ a,Ⅲ b and Ⅳ a grades of Dindo-Clavien grade),(27 ± 21)days in the TLCRMH group and (4.3 ± 1.1)days,(113 ± 57)U/L,(26 ± 11) μmol/L,4 (Ⅰ,Ⅰ,Ⅱ and Ⅳ a grades of Dindo-Clavien grade),(19 ± 9)days,respectively,showing no significant difference between the 2 groups (t =0.079,-0.286,0.806,X2 =0.286,t =0.856,P ＞ 0.05).The duration of ICU care in the TLCRMH and LCROMH groups were (2.1 ± 1.6) days and (1.0 ± 0.6) days,with a significant difference between the 2 groups (t =1.804,P ＜ 0.05).(3) The status of follow-up:all the patients were followed up for 3-54 months,and the median follow-up time was 15 months (range,3-39 months) in the TLCRMH group and 30 months (range,11-54 months) in the LCROMH group.The 1-,3-year overall survival rates were 100.0％ and 100.0％ in the TLCRMH group and 85.7％ and 64.3％ in the LCROMH group,respectively,showing no significant difference between the 2 groups (x2 =0.676,P ＞ 0.05).The postoperative 1-,2-year cumulative tumor-free survival rates and overage cumulative tumor-free survival time were 64.3％,64.3％ and 20.5 months in the TLCRMH group and 42.9％,14.3％ and 10.9 months in the LCROMH group,respectively,showing no significant difference between the 2 groups (x2=3.160,P ＞ 0.05).Conclusion TLCRMH is safe and feasible for patients with SCLM,and it is comparable with LCROMH in the incidence of postoperative complication and long-term outcomes.