Objective:To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy (HCM) families.Methods:A retrospective cohort study was conducted on 527 unrelated HCM probands who were first diagnosed at the First Affiliated Hospital of Air Force Medical University (Xijing Hospital) from February 2014 to July 2018, and the high-throughput whole exome targeted sequencing of 96 genes related to hereditary cardiovascular disease was performed on the probands. The probands carrying the MYH7-R453C mutation were screened out, and their family members carrying the mutation were verified using Sanger sequencing. Healthy individuals without family history of genetic diseases from the same period and ethnicity were recruited as controls. Clinical data such as echocardiography, 12-lead electrocardiogram, and cardiac magnetic resonance imaging of the probands and their family members were collected, and the correlation between patient genotype and clinical phenotype was analyzed. Endpoint or key events were recorded through hospital re-examination or telephone follow-up.Results:The MYH7-R453C mutation was detected in 5 HCM probands, and clinical data and genetic results of 20 family members, including probands, were collected. Among them, 13 carried the MYH7-R453C mutation, of which 12 were diagnosed with HCM, and one child (F1Ⅲ 5) experienced early changes of HCM. The seven family members who did not carry the MYH7-R453C mutation had normal echocardiograms and 12-lead electrocardiograms. Among the 12 patients diagnosed with HCM, 2 experienced (F2Ⅱ 7, F5Ⅰ 2) sudden cardiac death, 2 experienced (F1Ⅲ 1, F3Ⅲ 3) events of sudden cardiac death survival, 2(F1Ⅱ 2, F3Ⅱ 1) died from heart failure during the follow-up period. Combined with the initial visit and follow-up, 4 families (F1, F2, F3, F5) had a family history of sudden death, among which 3 families probands or multiple family members experiencing sudden death before the age of 30 and adverse outcomes such as implantation of implantable cardioverter-defibrillators after sudden death survival. Conclusions:In the five families with HCM carrying MYH7-R453C mutations, genotype is highly correlated with clinical phenotype, and patients have a high risk of sudden death and poor prognosis. Early diagnosis of individuals carrying the MYH7-R453C gene mutation, both within the patient′s family and in the patients themselves, is crucial for initiating early treatment, preventing sudden death, and assessing prognosis.

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.

Objective:To investigate the correlation between decline of intrinsic capacity and falls in the elderly, in order to provide a new method and basis for fall risk assessment.Methods:A total of 125 elderly inpatients were selected between March 2019 and December 2019 for the survey.The intrinsic capacity of elderly inpatients was evaluated, and the history of falls in the past year were obtained through interviewing.The impact of intrinsic capacity on the risk of falls was analyzed by using logistics regression analysis.Results:Of 125 elderly patients, 37 had experienced falls in the past year, with an incidence of 29.6%(37/125). A decline of intrinsic capacity in varying degrees was found in 92.0%(115/125)of elderly patients and the average score of decline was 2.2(1.0, 3.0). The more intrinsic capacity decreased, the greater the risk of falls( OR=2.425, 95% CI: 1.132-4.848, P=0.016). After taking demographics into consideration, age( OR=1.786, 95% CI: 1.034-2.023)and decline of intrinsic capacity( OR=2.425, 95% CI: 1.132-4.848)were independent risk factors for falls. Conclusions:Decline of intrinsic capacity is closely related to the occurrence of falls.The five-dimension framework of intrinsic capacity provides new ideas and directions for predicting the risk of falls.

Objective: To assess the association of single nucleotide polymorphisms (SNPs) CHRNA4 gene with response to selective serotonin re-uptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD). Methods: For 304 patients receiving drug treatment for major depression, 2 SNPs, namely rs4522666 and rs4603829, of the CHRNA4 gene were determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th weeks treatment. Results: The frequency of GG genotype/G allele for rs4522666 differed significantly from that of TT and GT genotypes/T allele between responders and non-responders (P =0.015 and P=0.006, respectively). No significant difference was found in genotypic and allelic frequencies of rs4603829 between the two groups (P > 0.05). Conclusion SNPs of the CHRNA4 gene may play an important role in the response to antidepressant drugs among ethnic Han Chinese with MDD.

In the original publication the grant number is incorrectly published. The correct grant number should be read as "17140901600". The corrected contents are provided in this correction article. This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 81670470 and 81600149), a grant from the Shanghai Municipal Commission for Science and Technology (17140901600, 18411953500 and 15JC1400201) and a grant from National Key Research and Development Program (2016YFC0905100).

Adenosine ; genetics ; Adenosine Deaminase ; genetics ; metabolism ; Animals ; CRISPR-Associated Protein 9 ; genetics ; metabolism ; CRISPR-Cas Systems ; genetics ; Embryo, Mammalian ; metabolism ; Gene Editing ; Genetic Variation ; genetics ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley

Objective To explore the diagnosis,treatment,risk factors and prognosis factors of postpancreaticoduodenectomy hemorrhage (PPH).Methods The retrospective case-control study was adopted.The clinical data of 703 patients who underwent pancreatoduodenectomy at Hospital 401 of the People's Liberation Army from January 2008 to July 2013 were collected.Standard pancreatoduodenectomy was carried out for the malignant tumors of the head of pancreas or ampulla,pylorus-preserving pancreatoduodenectomy was operated for the benign tumor or the duodenal papilla tumor.The corresponding treatment was adopted for PPH.The observation indicators included:(1) the surgical situation (surgical method,operation time and the volume of intraoperative blood loss),(2) diagnosis of PPH,(3) treatment of PPH,(4) univariate and multivariate analyses for the risk factors affecting the occurrence of PPH,(5) univariate and multivariate analyses for the risk factors affecting prognosis of PPH patients.The measurement data with normal distribution were represented as x ± s.The measurement data with skewed distribution were represented as M (range).The chi-square test or Fisher exact probability was used for univariate analysis.Logistic regression model was used for multivariate analysis.Results (1) The surgical situation:among 703 patients,409 patients underwent standard pancreatoduodenectomy and 294 underwent pylorus-preserving pancreatoduodenectomy,including 1 combined with right hemihepatectomy,27 with portal vein reconstruction and 2 with hepatic artery reconstruction.Pancreaticojejunostomy was applied to 658 patients using mucosa anastomosis of the pancreatic duct to jejunum and 45 patients using invagination anastomosis.Supporting tube was routinely deposed in the pancreatic duct,598 patients had internal drainage and 105 patients had external drainage.The end-to-side anastomosis between common bile duct and jejunum was used for choledochojejunostomy.The 409 patients received the gastrojejunostomy using side-to-side anastomosis of gastric part and jejunum and 294 patients using end-to-side anastomosis of duodenum and jejunum.Operation time and volume of intraoperative blood loss were (324 ± 54) minutes and (428 ± 118) mL.(2) The diagnosis of PPH:among 703 patients after pancreatoduodenectomy,62 patients had PPH,the hemorrhage reasons of 38 patients had been identified,and the hemorrhage reasons of 24 patients had not been identified (A level in 5 patients,B level in 17 patients,C level in 2 patients).① The site of hemorrhage:the hemorrhage outside the cavity were detect in 27 patients,the hemorrhage inside the cavity in 28 patients,and the hemorrhage from both outside and inside part of the cavity in 7 patients.② The time of hemorrhage:early-stage hemorrhage were detected in 5 patients and the delayed hemorrhage in 57 patients.③The volume of postoperative blood loss was (885 ± 253)mL,30 patients had mild hemorrhage and 32 patients had severe hemorrhage.④ The clinical classification of PPH:5,32 and 25 patients were detected in level A,B,C,and 19 patients combined with sentinel hemorrhage.(3) The treatment of PPH:①5 patients with PPH in A level were given clinical observation,blood volume supplement and other treatment,then the symptoms gradually turned better.② Among 32 patients with PPH in B level,15 patients became better after symptomatic and supportive treatments,6 patients received successful hemostasis after guglielmi detachable colis embolization,4 patients received successful hemostasis under gastroscopic hemostasis,7 patients received emergency exploratory laparotomy.Thirty-two patients were improved and then out of hospital after treatment,without occurrence of death.③ Among 25 patients with PPH in C level,4 patients received successful hemostasis after guglielmi detachable colis embolization,17 patients received hemostasis by emergency exploratory laparotomy,4 patients with undiscovered bleeding points received the treatment of fluid infusion,blood volume supplement and antacid.Among 25 patients after corresponding treatment,10 patients were improved and 15 patients were dead.(4) The result of univariate analysis showed that the combined hypertension,vascular resection and reconstruction,postoperative pancreatic leakage and postoperative intraabdominal infection were risk factors affecting the occurrence of PPH (x2 =4.950,5.300,7.568,5.505,P ＜ 0.05).The results of multivariate analysis showed that the combined pancreatic leakage and postoperative intraabdominal infection were independent risk factors affecting the occurrence of PPH [OR =2.761,2.216,95％ confidence interval (CI):1.389-5.489,1.198-4.101,P ＜ 0.05].(5) The risk factors affecting the prognosis of PPH patients:the results of univariate analysis showed that postoperative sentinel hemorrhage,postoperative pancreatic leakage,site,degree and level of hemorrhage were risk factors affecting the prognosis of PPH patients (x2 =8.022,4.448,11.853,18.551,28.285,P ＜ 0.05).The results of multivariate analysis showed that postoperative sentinel hemorrhage and site of hemorrhage (outside and inside part of the cavity) were independent risk factors affecting the prognosis of PPH patients (OR =5.550,0.233,95％ CI:1.595-19.314,0.086-0.635,P ＜ 0.05).Conclusions Pancreatic leakage and intraabdominal infection are independent risk factors after pancreatoduodenectomy.The treatment effect of the early-stage hemorrhage is better than that of the delayed hemorrhage,and angiographic embolization is the first choice of diagnosis and treatment for the delayed hemorrhage.Sentinel hemorrhage could result from aneurysm or continuous arterial hemorrhage of vascular erosion,it is the independent risk factor affecting the death of hemorrhage after pancreatoduodenectomy.

Objective To investigate the efficacy of modified VDLP (vincristine + daunorubicin + L-asparaginase + prednisone) for acute lymphoblastic leukemia (ALL) in elderly patients and its adverse reactions.Methods 31 elderly patients diagnosed as ALL at the initial visit from Jan.2009 to Dec.2014 were randomly divided into the experiment group (n=16) and the control group (n=15).Patients in the control group received traditional VDLP chemotherapy (vincristine 2 mg at 1,8,15 days;daunorubicin 30-40 mg/m2 at 1,2,15,16 days;L-asparaginase 6 000-10 000 U at 11,14,17,20 days;prednisone 1 mg/kg at 1 to 14 days),whereafter underwent a gradual dose reduction and drug withdrawal within 1-2 weeks.Patients in the experiment group received the modified VDLP chemotherapy (vincristine 2mg at 1,8,15 days;daunorubicin 30-40 mg/m2 at 1-3 days;L-asparaginase 6 000-10 000 U at 11,14,17,20 days;prednisone 1 mg/kg at 1 to 14 days),whereafter underwent a gradual dose reduction and drug withdrawal within 1-2 weeks.The complete response (CR) rate and complications were recorded.Results The CR rates were 53.3％ in modified VDLP group and 58.3％ in VDLP group,and there was no statistically significant difference between two groups (P ＞ 0.05).The treatment-related mortality and the incidence of severe infection had significant differences between the modified VDLP and VDLP groups (6.3％ vs.46.3％,31.3％ vs.66.7％,both P＜0.05).Conclusions Compared with VDLP,the modified VDLP is more tolerable and suitable for the elderly patients with ALL.

Objective To assess the role of the different pancreatic islet β cell function index in the evaluation of glucose metabolism in different duration of type 2 diabetes mellitus (T2DM).Methods Normal glucose tolerance subjects without diabetes family history (NC group,48 cases) and T2DM patients (182 cases) were enrolled.The T2DM patients were divided into three groups:less than 5 years group (DM ＜5 group,74 cases),5-10 years group (DM5-10 group,51 cases) and more than 10 years group ( DM ＞10 group,57 cases).Oral glucose tolerance test (OGTT) and insulin release test were taken in all groups.Insulin resistance index (HOMA-IR) and whole body insulin sensitivity index [ISI(Matsuda)] were used to estimate insulin sensitivity,and early insulin secretion index ( △ I30/ △ G30) and glucose disposition index (DI) were used to evaluate the function of pancreatic islet β cell.Results HOMA-IR was increased and ISI (Matsuda) was decreased in DM ＜5 group,DM5-10 group and DM ＞10 group compared with those in NC group [HOMA-IR:8.78 ± 7.12,8.08 ± 3.67,7.84 ± 5.08 vs.4.76 ± 3.43;ISI(Matsuda):46.78 ± 29.00,36.71 ± 16.67,38.86 ±21.72 vs.61.13 ± 32.08,P ＜ 0.05],however,there was no significant difference among DM ＜5 group,DM5-10 group and DM ＞10 group.△ I30/ △ G30 and DI were decreased in DM ＜5 group,DM5-10 group and DM ＞10 group compared with those in NC group [ △ I30 △ G30:( 68.41 ± 361.52 ),(4.31 ± 3.42 ),(7.70 ± 5.78 ) mU/mmol vs.(92.65 ± 309.29) mU/mmol;DI:0.0421 ± 0.0123,0.0412 ± 0.0123,0.0363 ± 0.0116 vs.0.1151 ± 0.0236,P ＜ 0.05 ],and there was no significant difference in △ I30 / △ G30 among DM ＜5 group,DM5-10 group and DM ＞10 group,however,DI was decreased in DM＞10 group compared with that in DM＜5 group and DM5-10 group (P＜0.05).ConclusionsHOMA-IR,ISI (Matsuda),△I30/△G30 are not sensitive to evaluate the insulin resistance of different duration.DI can reflect the glucose utilization of pancreatic islet β cell earlier and the ability to regulate blood sugar steady state changes.

Objective To analyse the etiology,clinical characteristics and risk factors of central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The clinical features of CNS complications in patients who underwent allo-HSCT were observed,and analysis its causes and risk factors.Results 8 cases of CNS complications occured in 69 patients within 6 months after allo-HSCT and the incidence was 11.6 ％,the occurrence rate of CNS complications was 21.4 ％ (6/28) in HLA mismatched group,higher than HLA matehed group [49 ％ (2/41)] (P ＜ 0.05).Analogously,the incidence was 44.4 ％ (4/60) in patients with graft-versus-host disease (GVIID) (＞grade 2),which was significantly higher than patients with 2 or below grade 2 GVHD [6.7 ％ (4/9)] (P ＜ 0.01).But there was no significant difference in the incidence of CNS complications between ≤14 years old and ＞14 years old,with or without ATG,different stages of diseases,whether pretreatment with maryland respectively (P ＞0.05),either.Epilepsy and intracranial infection were the most common CNS complications in allo-HSCT,followed by intracranial hemorrhage.Conclusion HLA mismatched and above grade 2 GVHD are the risk factors of CNS complications in allo-HSCT.Epilepsy,intracranial infection and bleeding are common CNS complications in allo-HSCT.