Application of 99Tc m-MIBI SPECT/CT imaging in patients with primary cervical dystonia / 中华核医学与分子影像杂志

Objective:To evaluate the value of 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT imaging for the identification of dystonic muscles in patients with primary cervical dystonia (PCD). Methods:A total of 10 patients with PCD (3 males, 7 females, age (47.3±9.9) years) and 10 healthy subjects (4 males, 6 females, age (43.5±9.4) years; control group) between August 2019 and October 2021 in China-Japan Friendship Hospital were enrolled prospectively. All subjects underwent 99Tc m-MIBI SPECT/CT scan. The SUV max of 8 bilateral representative muscles, including rectus capitis posterior major, obliquus capitis inferior, splenius capitis, semispinalis, sternocleidomastoid, trapezius, musculus scalenus muscle and levator scapulae were evaluated in control group. In PCD group, muscles with abnormal uptake were determined. ROI was drawn and SUV max was measured. Independent-sample t test was used to analyze the differences of SUV max between normal and abnormal muscles. The detecting rates of neck MRI and SPECT/CT for abnormal muscles were analyzed by χ2 test. Results:Normal muscles of healthy subjects showed mild symmetrical radioactivity distribution, with the SUV max of 1.10±0.19. A total of 60 muscles with abnormal uptake in 10 patients were found, including 7 rectus capitis posterior major, 10 obliquus capitis inferior, 8 splenius capitis, 8 semispinalis, 10 sternocleidomastoid, 5 trapezius, 3 musculus scalenus muscle and 9 levator scapulae. The SUV max of muscles with abnormal uptake was 1.81±0.43, which was higher than that of normal muscles ( t=17.05, P<0.001). Only 30 pieces abnormal hypertrophy muscle were found by neck MRI, and the detecting rate was much lower than that of SPECT/CT (18.75%(30/160) vs 37.50%(60/160); χ2=28.03, P<0.001). Conclusion:99Tc m-MIBI SPECT/CT may be a useful method for identifying dystonic muscles and a guide to precision therapy in patients with PCD.

Role of quadrate lobe hepatectomy in the management of complex iatrogenic high biliary tract injury / 中华普通外科杂志

Objective:To evaluate partial ventral hepatectomy in the treatment of patients with complicated iatrogenic high bile duct injury.Methods:The clinical data of 8 cases of complicated iatrogenic high bile duct injury treated with the assistance of hepatic ventral segmentectomy from Mar 2013 to May 2020 at Hunan Provincial People's Hospital was retrospectively analyzed.Results:Among the 8 patients, 5 patients underwent partial Ⅳb lobectomy, and 3 patients received partial Ⅳb and Ⅴ segmentectomy of the liver. All the operation was successful without death in hospital. One case developed subphrenic infection and seroperitoneum, which was healed by anti-infection treatment and abdominocentesis. The postoperative follow-up time was 5-90 months, and all of patients are doing well. There was no stenosis in intrahepatic bile duct by postoperative cholangiography or MRI.Conclusions:Quadrate lobe hepatectomy provides a wide view for the treatment of complicated iatrogenic high bile duct injury by fully opening the first porta hepatis and exposing the primary and secondary bile duct branch helping establish a wide patent tension free bile duct-jejunostomy.

The genetic distribution in Chinese patients with Charcot-Marie-Tooth diseases: a 14-year cohort study / 中华神经科杂志

Objective:To investigate the genetic distribution of pathogenic genes of Charcot-Marie-Tooth diseases (CMT) in Chinese Han population, and compare the similarity and difference with the data in Peking University Third Hospital in 2013.Methods:Five hundred and twenty families with CMT and related diseases in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to March 2021 were collected. After peripheral myelin protein 22 (PMP22) gene duplication and deletion mutations were initially detected by multiple ligation probe amplification, the probands of these families were sequenced by next-generation sequencing (NGS) gene panel or whole exome sequencing, and validated by Sanger sequencing.Results:Among the 520 families, 336 CMT families were genetically confirmed, and the mutation detection rate increased from 48.6% (51/105) in 2013 to 64.6% (336/520) in 2021 (χ 2=9.54, P=0.003). Among them, 139 families had PMP22 gene duplication mutation (139/520, 26.7%), 46 families had gap junction beta-1 (GJB1) gene mutation (46/520, 8.8%), 26 families had mitofusin-2 (MFN2) gene mutation (26/520, 5.0%), 12 families had myelin protein zero (MPZ) gene mutation (12/520, 2.3%), 11 families had PMP22 gene point mutation (11/520, 2.1%), and 10 families had heat shock protein B1 gene mutation (10/520, 1.9%). There were 10 families with ganglioside induced differentiation associated protein 1 (GDAP1) gene mutation (10/520, 1.9%), 8 families with SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene mutation (8/520, 1.5%), 7 families with immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene mutation (7/520, 1.3%), 6 families with MORC family CW-type zinc finger 2 (MORC2) gene mutation (6/520, 1.2%), 5 families with sorbitol dehydrogenase (SORD) gene mutation (5/520, 1.0%), 16 families with very rare gene mutation (16/520, 3.1%) and 184 families without genetic diagnosis (184/520, 35.4%). Conclusions:Compared with the results in 2013, the 3 most common genes affecting CMT were still PMP22, GJB1 and MFN2 genes, but the proportion difference of patients with MPZ gene mutation gradually decreased with other genes such as SH3TC2 and GDAP1 genes. The proportion of newly discovered CMT genes, such as MORC2 and SORD genes, was similar with IGHMBP2 gene, which should be paid more attention. NGS greatly improved the detection rate of CMT, especially for patients with autosomal recessive-CMT.

Phenotype and genetic studies of the cases with ATXN2 intermediate-length CAG-repeat expansion in spinocerebellar ataxia type 2 pedigree / 中华神经科杂志

Objective:To explore the phenotype and molecular genetic features of spinocerebellar ataxia type 2 (SCA2) cases with ATXN2 intermediate-length CAG-repeat expansion.Methods:Fragment analysis by capillary electrophoresis was performed to detect the dynamic mutations in the samples of the probands in 1 383 pedigrees with autosomal dominant inherited ataxia in Research Center for Motor Disorders and Neurogenetic Diseases, Department of Neurology, China-Japan Friendship Hospital from 2005 to 2018. The clinical and genetic features of individuals carrying the ATXN2 intermediate-length CAG-repeat expansion were carefully analyzed.Results:Two hundred and three individuals (including the probands and members of their families) in 163 families carried the expanded CAG repeats in ATXN2 gene, among which 107 individuals in 93 families carried the intermediate-length CAG-repeats. Within 20 parent-child pairs, the CAG repeats increased 0-28 copies in 16 pairs with paternal inheritance, and 0-4 copies in 4 pairs with maternal inheritance.Conclusions:For suspected SCA2 cases, ATXN2 gene testing should be performed on the parental members and adult offspring members in the family. Dynamic mutations testing is essential to identify the individuals with ATXN2 intermediate-length repeat expansion, which is very important for genetic counseling.

Surgical therapy for hepatocellular carcinoma patients with biliary tract tumor thrombus / 中华普通外科杂志

Objective:To evaluate surgical therapy for patients of hepatocellular carcinoma(HCC) with bile duct tumor thrombi(BDTT).Methods:A retrospective analysis was made on 66 patients with HCC and BDTT undergoing surgical treatment at the First Affiliated Hospital of Hunan Normal University from Jan 2011 to Dec 2016.Results:The overall median survival time of the patients was 31 months. The 1, 3, and 5-year survival rates were 87.9%, 45.5%, and 13.6%, respectively. Univariate analysis showed hepatitis B virus, liver cirrhosis and history of drinking, AFP≥200 ng/ml, tumor resection combined with biliary incision to remove tumor thrombus, tumor undifferentiated/poorly differentiated, tumor diameter ≥50 mm, AJCC 8th stage Ⅲ/Ⅳ and number of lesions ≥ 2 were risk factors for postoperative survival (all P<0.05). Multivariate analysis showed that drinking history, undifferentiated/poorly differentiated tumor, tumor diameter ≥50 mm, and AJCC 8th Ⅲ/Ⅳ stage were independent risk factors (all P<0.05). Conclusion:Surgical resection of HCC combined with BDTT can achieve a satisfactory survival and prognosis.

The application of ventral-combined-dorsal exposure of middle hepatic vein via caudal approach in liver cancer laparoscopic anatomic hemihepatectomy / 中华肝胆外科杂志

Objective:To investigate the feasibility of ventral-combined-dorsal exposure of middle hepatic vein via caudal approach in laparoscopic anatomic hemihepatectomy of liver cancer.Methods:A retrospective analysis was performed on the clinical data of 44 patients undergoing laparoscopic antecedent hemihepatectomy with the ventral-combined-dorsal exposure of middle hepatic vein via caudal approach in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) from January 2021 to September 2021. Among the 44 patients, there were 24 male and 20 female patients, aged 56-66 (61±5) years. The operative time, intraoperative blood loss, occlusion time of the first hilum hepatis, postoperative complications and postoperative hospital stay were analyzed.Results:All 44 patients underwent the surgery successfully. The average operation time was (259.3±33.4) min. Intraoperative blood loss was (113.8±31.0) ml, and no intraoperative blood transfusion was performed. The mean intraoperative occlusion time of the first hilum was (56.1±7.1) min. No postoperative hemorrhage and biliary fistula and other complications occurred. The mean postoperative hospital stay is (9.3±1.4) days. Pathological examination confirmed hepatocellular carcinoma in 36 cases and intrahepatic cholangiocarcinoma in 8 cases.Conclusion:The ventral-combined-dorsal exposure of middle hepatic vein via caudal approach benefits exposure of middle hepatic vein in laparoscopic anatomic hemihepatectomy, reducing intraoperative accidental bleeding and ensuring surgical safety.

Phenotype analysis of the families with Gerstmann-Str?ussler-Scheinker syndrome caused by prion protein gene mutations / 中华神经科杂志

Objective:To explore the clinical, imaging features and pathogenic mutations in three cases of Gerstmann-Str?ussler-Scheinker syndrome (GSS) with ataxia.Methods:Since 2014, totally 137 probands with autosomal dominant or sporadic ataxia were treated in the Department of Neurology, China-Japan Friendship Hospital. They were screened for mutations in prion protein (PRNP) gene using next-generation sequencing. Spinocerebellar ataxia 1, 2, 3, 6, 7, 8, 12, 17 and dentatorubral-pallidoluysian atrophy were excluded by capillary electrophoresis. Potential pathogenic variants were confirmed by Sanger sequencing. Pathogenicity assessment was interpreted according to the American College of Medical Genetics standards and guidelines. Clinical phenotypes and imaging features of patients were analyzed in detail.Results:Three pedigrees of GSS caused by PRNP gene variants were found. The probands of three pedigrees carried reported heterozygous missense mutation c.305C>T (p.P102L), all onset in adults. All of the three probands showed walking instability and dysarthria, additionally, the proband of pedigree 1 showed parkinsonian signs, the proband of pedigree 2 had cognitive impairment. Brain magnetic resonance imaging showed cerebellar atrophy of different degrees in probands 2 and 3, while pallidum hyperintense signal in proband 1.Conclusions:GSS as a rare subtype of prion disease, could be characterized by cerebellar ataxia. For patients with ataxia, attention should be paid to GSS disease-causing gene mutations in genetic testing. Early diagnosis based on genetic testing will be instrumental in genetic counseling and birth defect intervention in pedigree members.

Phenotype analysis of patients of spinocerebellar ataxia with trinucleotide repeat expansion of ATXN8OS gene / 中华神经科杂志

Objective:To investigate the clinical and genetic characteristics of patients with CTA/CTG trinucleotide repeat expansion of ATXN8OS gene.Methods:The CTA/CTG trinucleotide repeats of ATXN8OS gene were detected in 1 689 spinocerebellar ataxia cases from Research Center for Movement Disorders and Neurogenetics, Department of Neurology, China-Japan Friendship Hospital in 2005—2017. The correlation between clinical phenotypes and expanded CTA/CTG repeats in the ATXN8OS gene of patients was studied carefully, and compared with 100 healthy controls.Results:Twenty-one patients with pathological CTA/CTG repeat expansion of ATXN8OS gene were collected. Eighteen of them carried the alleles with more than 80 repeats, whose common initial symptom was gait instability, followed by dysarthria and dysphagia with disease progression. Four of the 18 patients presented with head or truncal tremor. The other three patients carried the alleles with the repeats ranging from 70 to 79, whose initial symptom was walking instability, gradually appeared dysarthria, with no dysphagia or tremor. The repeat lengths ranged from 19 to 42 in the 100 healthy controls. The brain magnatic resonance imaging of almost all the patients showed moderate to severe cerebellar atrophy, and some patients with mild atrophy of the brainstem except one case with corpus callosum dysplasia.Conclusions:Most of the patients with CTA/CTG repeat expansion presented with ataxia and dysarthria. Brain magnetic resonance imaging showed significant cerebellar atrophy, suggesting that the mutation is related to SCA8 gene.

Complications after laparoscopic pancreaticoduodenectomy and establishment of predicting model for postoperative pancreatic fistula / 中华普通外科杂志

Objective:To explore the risk factors for overall complications after laparoscopic pancreaticoduodenectomy(LPD) and to establish postoperative pancreatic fistula prediction model for LPD.Methods:The clinical data of 176 patients undergoing LPD from Jan 2014 to Mar 2018 were retrospectively analyzed.Results:One died within 30 days. Five patients underwent reoperation. Seventy-three patients (41%) had complications including pancreatic fistula in 30 cases(17.0%), postoperative hemorrhage in 16 (9.1%); bile leakage in 10 (5.7%); abdominal infection in 6 (3.4%); wound infection in 4 (2.2%); pulmonary infection in 4 (2.2%); gastric emptying disorder in 3 (1.7%). Age, intraoperative blood loss, diabetes mellitus were risk factors for overall postoperative complications of LPD(all P<0.05); Age, male gender, pancreatic duct diameter, pancreas texture, lesion size were risk factors for pancreatic fistula after LPD(all P<0.05). Conclusions:Age, intraoperative blood loss, diabetes mellitus were risk factors for overall postoperative complications of LPD; Age, male gender, pancreatic duct diameter, pancreas texture, and lesion size were risk factors for pancreatic fistula after LPD.

Characteristics of cerebral blood flow in patients with psychiatric symptoms caused by nitrous oxide abuse / 中华行为医学与脑科学杂志

Objective:To investigate the clinical, neuropsychological and regional cerebral blood flow (rCBF) characteristics in patients with psychiatric symptoms caused by nitrous oxide abuse.Methods:Twelve patients with psychiatric symptoms caused by nitrous oxide abuse were enrolled from February 2018 to February 2020 in the Department of Neurology, China-Japan Friendship Hospital and the First Hospital of Tsinghua University.All patients were scored with the brief psychiatric rating scale (BPRS), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). The SPECT/CT images were collected with low-energy and high-resolution collimator.After the pictures were reconstructed, 18 brain regions were automatically sketched and calculated by Database Comparison software.The statistical value of the difference between the general mean value of each brain region and that of the corresponding region of interest in the same age group was estimated.Results:(1)The clinical manifestations of 12 patients were anxiety, depression, hallucination, delusion, and 7 patients were accompanied by cognitive decline.(2)Neuropsychological examination: BPRS score was 57.83±11.15 (anxiety depression factor was 3.94±0.47; lacking active factor was 3.25±0.85; thinking disturbance factor was 3.21±1.27; activity factor was 2.28±0.56; hostility factor was 3.14±1.24). The score of self-knowledge impairment was 2.92±1.08, the score of inability to work was 4.50±1.17, the score of HAMD was 32.75±10.13, the score of HAMA was 18.67±5.80, the score of MMSE was 27.67±2.50, and the score of MoCA was 24.58±3.78.(3)SPECT showed that compared with the general mean value of the corresponding regions of interest of normal people, the patients showed hypoperfusion in the frontal lobe (7 patients, 58.30%) and the temporal lobe (8 patients, 66.70%).Conclusion:Nitrous oxide abuse has an obvious effect on rCBF.The psychiatric symptoms include anxiety, depression, hallucination, delusion and so on, which affect the ability to work and learn.SPECT has important value in the diagnosis of nitrous oxide abuse, and indicates changes in local brain functional activity.

Lymphadenectomy in laparoscopic radical resection of distal cholangiocarcinoma / 中华消化外科杂志

Lymph node metastasis is the important survival predictor in patients with distal cholangiocarcinoma.With the application of laparoscopic pancreaticoduodenectomy in radical resection of distal cholangiocarcinoma,it is of great clinical significance to explore lymphadenectomy in laparoscopic radical resection of distal cholangiocarcinoma.The American Joint Committee on Cancer (AJCC) Cancer Staging Manual (8th ed) has became the new global guideline for cancer diagnosis and treatment since January 2018,which provides a new recommendation for lymphadenectomy of distal cholangiocarcinoma.This review provides an overview of the clinical significance of total lymph node count and number of involved lymph nodes,"en-block" procedure in lymphadenectomy,membrane anatomy for lymphadenectomy,experience and skills in lymph node dissection,lymph node sorting after surgery,adjuvant therapy in the treatment of distal cholangiocarcinoma.

Reoperation after laparoscopic pancreatoduodenectomy: an analysis of ten patients / 中华肝胆外科杂志

Objective To investigate the causes and countermeasures of reoperation following laparoscopic pancreatoduodenectomy.Methods The causes,approaches and outcome of reoperation were retrospectively analyzed in 10(4.0％,10/250) patients undergoing reoperations following pancreaticoduodenectomy with various complications in Hunan Provincial People's Hospital from April 2014 to April 2018.Results The causes of the 10 patients including intra-abdominal bleeding of seven cases (2 cases combined with pancreatic fistula,1 case with pancreatic and biliary fistula),1 patient with gastrointestinal anastomosis output perforation,1 patient with intra-abdominal abscess,and 1 case with postoperative pancreatitis.The time of reoperation was one day to 82 day after the first operation.The main methods of reoperation including suture and hemostasis,rebuilding the digestive tract,gastrostomy and enterostomy combined with abdominal cavity drainage.The mortality of reoperation following laparoscopic pancreatoduodenectomy was 20.0％ (2/10).Conclusions Intra-abdominal hemorrhage,pancreatic fistula and intra-abdominal abscess are the major causes of reoperation after laparoscopic pancreatoduodenectomy.Timely and decisive reoperation is an effective means to reduce postoperative morbidity and mortality after LPD.

Clinical phenotypes study of autosomal recessive cerebellar ataxia type 1 caused by SYNE 1 gene mutations / 中华神经科杂志

Objective@#To investigate the clinical features of autosomal recessive cerebellar ataxia type 1 (ARCA1) and analyze the pathogenic variants in SYNE 1 gene.@*Methods@#A cohort of 80 probands of autosomal recessive cerebellar ataxia pedigrees excluding Friedreich ataxia were detected by whole-exome sequencing technology. Potential pathogenic variants were confirmed by Sanger sequencing. Clinical phenotypes of positive patients were analyzed in detail.@*Results@#Three pedigrees of ARCA1 caused by SYNE 1 gene variants were found. The proband of pedigree 1 carried homozygous frameshift mutation c.12670dupC(p.L4224fs), presented as pure cerebellar ataxia. The proband of pedigree 2 carried compound heterozygous mutations c.20826+1G>T and c.25954C>T(p.R8652X), presented as cerebellar ataxia plus upper motor neuron dysfunction. The proband of pedigree 3 carried compound heterozygous mutations c.21955C>T(p.Q7319X) and c.23777C>A(p.T7926K), presented as mental behavior and cognitive impairment, cerebellar ataxia and upper motor neuron dysfunction. Brain MRI showed obvious cerebellar atrophy in all patients, and the fronto-temporal lobes were also found slight atrophy in proband of pedigree 3.@*Conclusions@#The phenotype of ARCA1 caused by SYNE 1 gene mutations is characterized by cerebellar ataxia, maybe accompanied with motor neuron damage and cognitive dysfunction. ARCA1 is a rare form of autosomal recessive cerebellar ataxia in Chinese population, with a complex phenotype. The use of next generation sequencing allows the rapid analysis of ARCA1, and will likely further expand genotype-phenotype correlations.

Coordination and function of a laparoscopic assistant in laparoscopic pancreaticoduodenectomy / 中华肝胆外科杂志

Objective To study the coordination and function of a laparoscopic assistant in laparoscopic pancreaticoduodenectomy (LPD).Methods A retrospective analysis was conducted on 101 patients who underwent LPD at the Department of Hepatobiliary Surgery,Hunan Provincial People's Hospital,from January 2014 to March 2017.The study aimed to study the coordination and function of a laparoscopic assistant.Results LPD was successfully completed in all the 101 patients.There was no conversion to open surgery.The operation time was (326.0 ± 55.6) min,and the resection time was (174.4 ± 42.5) min.The digestive tract reconstruction time was (101.0 ± 21.4) min.The time of pancreaticojejunostomy was (40.5 ± 8.7) min.The time of gastrointestinal anastomosis was:(26.3 ± 5.5) min.The time of biliary anastomosis was (24.4 ± 6.5) min.The intraoperative bleeding was (175.6 ± 41.1) ml.Postoperative pathological data showed that 27 patients (26.7％) had distal common bile duct cancer,23 patients (22.8％)ampullary carcinoma,39 patients (38.6％) duodenal papillary carcinoma,and 12 patients (11.9％) pancreatic ductal adenocarcinoma.The tumor diameter was (2.3 ± 1.3) cm,and the number of resected lymph nodes was (16.7 ±4.2).The number of positive lymph nodes was 1.3 ± 1.1.The length of postoperative hospital stay was 14.8 (8 ～ 29) d.Twenty-three patients developed postoperative pancreatic fistula,including 17 patients (16.8％) with a biochemical fistula,5 patients (5.0％) with a grade B pancreatic fistula,and 1 patient (1.0％) with a grade C pancreatic fistula.There were 2 patients (3.0％) with bile leakage,7 patients (6.9％) with intra-abdominal bleeding,4 patients (4.0％) with delayed gastric emptying,6 patients (5.9％) with abdominal infection,3 patients (3.0％) with pulmonary infection,2 patients (2.0％)with intestinal obstruction,3 patients (3.0％) required a repeated operation,and 1 patient (1.0％) with death in hospital within 30 days after surgery.Conclusions The laparoscopic assistant should have the perspective of "one axis,two sides and four regions" in LPD,and warn the operator to ensure the safety and fluency of the operation by clearly exposing important blood vessels and organs when performing the Kocher incision and when dissecting the key parts such as the dangerous triangle of the uncinate process.During anastomosis,the laparoscopic assistant should appropriately adjust the distance of vision,clearly reveal the surgical field of the anastomotic area,and help the surgeon in improving the precision of the suture and the quality of the anastomosis.

Clinical and genetic analysis of a patient with Perrault syndrome and additional neurological features / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical, neuropathological and genetic characteristics of a patient with Perrault syndrome caused by TWNK mutation.@*METHODS@#Potential variation of the TWNK gene was detected by next-generation sequencing (NGS) and verified by Sanger sequencing.@*RESULTS@#The patient has featured primary amenorrhoea and progressive sensorineural hearing loss since childhood. She also had gait anormaly, distal limb atrophy and weakness, and nystagmus. Further study confirmed sensory neuronopathy accompanied with upper and lower motor neuron involvement as well as cerebellum atrophy. NGS has identified two heterozygous variants of the TWNK gene, namely c.794G>A (p.Arg265His) and c.1181G>A (p.Arg394His). Sanger sequencing confirmed that c.1181G>A (p.Arg394His), a known pathogenic variant, was derived from her farther, while c.794G>A(p.Arg265His), a novel variant, was derived from her mother and likely pathogenic according to the ACMG guidelines.@*CONCLUSION@#Perrault syndrome is a group of disorders with a high phenotypic heterogeneity. The compound heterozygous variation of c.794G>A (p.Arg265His) and c.1181G>A(p.Arg394His) of the TWNK gene may underlie Perrault syndrome in the patient.

Clinical phenotypes study of autosomal recessive cerebellar ataxia type 1 caused by SYNE 1 gene mutations / 中华神经科杂志

Objective To investigate the clinical features of autosomal recessive cerebellar ataxia type 1 (ARCA1) and analyze the pathogenic variants in SYNE 1 gene. Methods A cohort of 80 probands of autosomal recessive cerebellar ataxia pedigrees excluding Friedreich ataxia were detected by whole?exome sequencing technology. Potential pathogenic variants were confirmed by Sanger sequencing. Clinical phenotypes of positive patients were analyzed in detail. Results Three pedigrees of ARCA1 caused by SYNE 1 gene variants were found. The proband of pedigree 1 carried homozygous frameshift mutation c.12670dupC(p.L4224fs), presented as pure cerebellar ataxia. The proband of pedigree 2 carried compound heterozygous mutations c. 20826+1G>T and c. 25954C>T(p. R8652X), presented as cerebellar ataxia plus upper motor neuron dysfunction. The proband of pedigree 3 carried compound heterozygous mutations c.21955C>T(p.Q7319X) and c.23777C>A(p.T7926K), presented as mental behavior and cognitive impairment, cerebellar ataxia and upper motor neuron dysfunction. Brain MRI showed obvious cerebellar atrophy in all patients, and the fronto?temporal lobes were also found slight atrophy in proband of pedigree 3. Conclusions The phenotype of ARCA1 caused by SYNE 1 gene mutations is characterized by cerebellar ataxia, maybe accompanied with motor neuron damage and cognitive dysfunction. ARCA1 is a rare form of autosomal recessive cerebellar ataxia in Chinese population, with a complex phenotype. The use of next generation sequencing allows the rapid analysis of ARCA1, and will likely further expand genotype?phenotype correlations.

Clinical effects of laparoscopic pancreaticoduodenectomy for distal cholangiocarcinoma / 中华消化外科杂志

Objective To investigate the clinical effects of laparoscopic pancreaticoduodenectomy (LPD) for distal cholangiocarcinoma.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 37 patients who underwent LPD for distal cholangiocarcinoma in the Hunan Provincial People's Hospital between January 2013 and November 2016 were collected.LPD for distal cholangiocarcinoma was performed using the "en-block" procedure.According to the principle of "one axis,two planes and four zones",anatomy used posterior approach,anterior approach and medial approach,lymph node dissection was performed from carotid sheath outside,and en bloc specimens were resected.Observation indicators:(1) surgical and postoperative recovery situations;(2) postoperative pathological examination;(3) follow-up and survival situations.Follow-up using outpatient examination was performed to detect the patients' recurrence-free survival up to November 2017.Measurement data with normal distribution were represented as (x)±s.The survival curve and rate were drawn and calculated by the Kaplan-Meier method.Results (1) Surgical and postoperative recovery situations:all the 37 patients underwent successful LPD,without conversion to open surgery and perioperative death.The operation time,volume of blood loss and case with intraoperative blood transfusion were (326 ± 55) minutes,(176± 39)mL and 1,respectively.The time to initial exsufflation and time for diet intake were respectively (4.5± 1.6)days and (5.3±2.7)days.Of 37 patients,14 had postoperative complications,including 8 with pancreatic fistula (6 with biochemical fistula and 2 with grade B pancreatic fistula),1 with biliary fistula,3 with postoperative bleeding (2 with intra-abdominal bleeding and 1 with gastrointestinal anastomosis bleeding),2 with delayed gastric emptying (grage A),2 with intra-abdominal infection and 2 with pulmonary infection;the same patients can merge multiple complications.Three patients were in Clavien-Dindo classification ≥ Ⅲ.One patient received reoperation and other patients were improved by symptomatic treatment.Duration of hospital stay of 37 patients was 13.5 days (range,8.0-33.0 days).Eight patients underwent adjuvant chemotherapy of 4-6 cycles by taking orally tegafur or gemcitabine with cisplatin.(2) Postoperative pathological examination:tumor diameter and pancreatic duct diameter of 37 patients were (2.1±1.1)cm and (2.5±1.2) mm,respectively.Of 37 patients,9,13 and 15 were respectively detected in high-differentiated,moderate-differentiated and lowdifferentiated adenocarcinoma.Surgical margins:35 patients received R0 resection and 2 received R1 resection.Number of lymph node dissected,cases with lymph node metastasis and number of positive lymph nodes were respectively 18.5±4.9,16 and 1.7± 1.4.Analysis of lymph node metastasis location showed that the positive rates in 8a,12,13,14 and 17 groups lymph nodes were respectively 5.4％ (2/37),18.9％ (7/37),21.6％ (8/37),8.1％ (3/37) and 10.8％ (4/37);Perineural invasion (PNI),lymphovascular invasion (LVI),pancreatic invasion and duodenal invasion were identified in 14,9,16 and 6 patients,respectively.TNM stage:stage 0,Ⅰ A,Ⅰ B,ⅡA and Ⅱ B were respectively detected in 1,3,5,12 and 16 patients.(3) Follow-up situation:of 37 patients,36 were followed up for 6-45 months,with a median time of 26 months.The median recurrence-free survival time,1-and 3-year recurrence-free survival rates were respectively 28 months,80.6％ and 42.2％.Conclusion LPD is safe and effective for distal cholangiocarcinoma,and "en-block" resection not only helps to optimize the process of LPD for distal cholangiocarcinoma,but also has a significant effect on R0 resection and lymph node dissection.

Effects of Isopimaric Acid on cognitive handicap and synaptic plasticity in APP/PS1 mice / 中华行为医学与脑科学杂志

Objective To investigate the protective effects of isopimaric acid ( ISO), the BKCa channel activator, on cognitive function and synaptic plasticity in APP/PS1 mice. Methods Alzet osmotic pump was loaded with ISO or DMSO only and assembled with ALZET Brain Infusion Kit III. The cannula was implanted into the lateral ventricle of 4-month-old male APP/PS1 mice or matched wild type ( WT) mice. Two weeks later, open field test and Morris water maze were conducted. Paired-pulse facilitation ( PPF) and TBS-induced long-term potentiation ( LTP ) were recorded in CA1 region of hippocampus. Results The open field test showed that there was no significant difference among the four groups in spontaneous activities and vertical plane movement distance within 30 minutes. Floor plane movement distance was significantly greater in APP/PS1+DMSO group than that in WT+DMSO group(P<0.05) . Compared with the WT+DMSO group, APP/PS1+DMSO group had significantly longer escape latency from the third to fifth day and lower percentage of time spent in the target quadrant ((43.27±3.24)% vs (34.19±2.56)%) and the number of crossing through the platform ((4.25±0.66)times vs (1.93±0.33)times)(P<0.05). Compared with the APP/PS1+DMSO group, the APP/PS1+ISO group had significantly shorter escape latency from the fourth to fifth day and higher percentage of time spent in the target quadrant ((46.16±3.51)%) and the number of crossing through the platform ((3.41±0.34) times) (P<0.05). PPF in APP/PS1+DMSO group significantly reduced compared with that in WT+DMSO group at 30-50ms interstimulus interval(P<0.05). PPF in APP/PS1+ISO group((224.50±13.79)%) was significantly augment compared with APP/PS1+DMSO ((174.99 ±6.68)%) group at 40 ms interstimulus interval (P<0.05). The LTP at 60 min post-TBS was significantly smaller in the APP/PS1+DMSO group ((135.19±1.32)%) than that in the WT+DMSO group ((172.17± 4.15)%)(P<0.001). The LTP of the APP/PS1+ISO group((160.48±1.19)%) became significantly in-creased compared with that in the APP/PS1+DMSO group(P<0.001).Conclusion BKCa channel activator ISO improve the learning and memory function of APP/PS1 mice by promoting PPF and increasing LTP to recover synaptic plasticity in the hippocampus.

Molecular and clinical study of spinocerebellar ataxia type 17 / 中华神经科杂志

Objective To investigate the clinical features and genetic mutations of spinocerebellar ataxia type 17 (SCA17).Methods The pathological CAG triplet repeat expansions of the SCA3,SCA1,SCA2,SCA6,SCA7,SCA8,SCA12,SCA17 and dentatorubral pallidoluysian atrophy genes were analyzed in 708 probands of autosomal dominant familial SCA and 1 19 sporadic SCA cases.The CAG repeats of TATA-binding protein (TBP) gene were amplified by means of polymerase chain reaction and agarose gel electrophoresis.For the samples with two alleles,fragment analysis based on CEQ8000 sequencer was applied to analyze the CAG repeat numbers.Furthermore,the correlation between clinical features and CAG repeat in the TBP gene was studied carefully.Results The expanded CAG repeats in the TBP gene was detected in 5 cases with 37/50,36/45,38/52,38/53,36/54 separately.And the main clinical manifestations were ataxia and memory impairment.Conclusion These findings indicate that SCA17 might be a rare subtype of SCA in the Chinese population and the clinical features of SCA17 cover a wider spectrum than previously reviewed.

Effect of high-dose vitamin C on MMP2 expression and invasive ability in human pancreatic cancer cell line PANC-1 / 中国医师杂志

Objective To observe the effect of high-dose vitamin C on MMP2 expression and invasive ability in PANC-1. Methods Transwell invasion assay was used to compare the invasive ability of PANC-1 cells in different concentrations of vitamin C treated groups. RT-PCR and Western blot were used to detect and compare the levels of MMP2 mRNA and protein expression in each group. Results Compared with the 0mM vitamin C treated group, the mRNA expression of MMP2 was significantly decreased in 1.0,5.0,10. 0mM group(0. 510 ±0. 004 vs 0. 792 ±0. 006, 0. 391 ±0. 007 vs 0. 792 ±0. 006, 0. 282 ±0. 008vs 0. 792 ± 0. 006, P ＜ 0. 05 ). Compared with the 0mM vitamin C treated group, the protein expression of MMP2 was significantly decreased in 1.0,5.0,10. 0mM group(0. 519 ±0. 004 vs 0. 761 ±0. 014,0. 310 ±0. 007 vs 0. 761 ±0. 014,0. 297 ±0. 008 vs 0. 761 ±0. 014, P ＜0. 05). Compared with the 0mM vitamin C treated group, the invaded cell number was significantly decreased in 1.0,5.0,10. 0mM groups ( 452 ± 22 vs653 ± 28,340 ± 32 vs 653 ± 28,409 ± 33 vs 653 ± 28, P ＜ 0. 05 ). Conclusion High-dose vitamin C can decrease the expression of MMP2 in PANC-1 cells, and weaken its invasive ability.