Background:CDK14 is a novel cyclin-dependent kinase,which is overexpressed in a variety of cancer and related to their malignant behavior. Aims:To investigate the effect of CDK14 on proliferation of human esophageal carcinoma cells and its possible mechanism. Methods:Expressions of CDK14 and two cell proliferation markers,PCNA and Ki-67 were estimated in 8 fresh-frozen specimens of esophageal squamous cell carcinoma(ESCC),96 paraffin-embedded specimens of ESCC,and human ESCC cell line Eca-109 by Western blotting and immunohistochemistry. Correlations of CDK14 expression with the clinicopathological characteristics and prognosis of ESCC were analyzed. Serum starvation and release assay was performed to evaluate the relationship between CDK14 expression and cell cycle progression in Eca-109 cells. Furthermore,Eca-109 cells were transiently transfected with shRNA-CDK14 to reduce CDK14 protein level,and then the phosphorylation of tumor suppressor protein Rb,cell cycle progression and proliferation capability of Eca-109 cells were determined. Results:CDK14 was highly expressed in both ESCC tissue and cell line,which was paralleled with the expressions of PCNA and Ki-67 and correlated significantly with the tumor size,histological grade,invasiveness and metastasis of ESCC(P < 0. 05). The overall survival was poor in patients with high CDK14 expression than those with low CDK14 expression(P < 0. 05). Serum starvation and release assay showed that the expression of CDK14 was cell cycle-dependent. Knockdown of CDK14 reduced the expression level of phosphorylated Rb,induced significant G1 phase arrest and resulted in less colony formation in Eca-109 cells(P all < 0. 05). Conclusions:CDK14 is highly expressed in ESCC. It may promote cell cycle progression by phosphorylating downstream Rb protein,thus enhancing the proliferation of tumor cells,and ultimately participating in the occurrence and development of ESCC.

Objective To establish the method of gene mutation screening for HME and investigate the relationship between genotype and clinical phenotype in HME patients. Methods Fifteen cases of HME probands were divided into the following four subgroups: mild (M) and severe ( Ⅰ S, Ⅱ S, Ⅲ S) according to the clinical diagnosis. DNA samples were obtained from the probands and family members. All of the EXT1 and EXT2 gene exons and their boundary sequences were amplified by PCR, and sequenced by directsequencing. Then the relationship between the genotypes and clinical phenotype was analyzed. Results Among the fifteen cases of HME probands, nine harbored EXT1 gene mutation, while the other 6 were positive for EXT2 gene mutation. Moreover, six novel mutations in EXT1 gene, including I8 + 2T ＞ G, c. 1182delG,c. 1108G ＞T(p. E370X) ,c. 335delA,c. 361C ＞T(p. Q121X) and c. 1879_1881delCAC were identified. In 9 patients with EXT1 gene mutation, 2 (22. 2% ) were M-type, 2 (22. 2% ) were Ⅰ S -type, 4 (44. 4% )were Ⅱ S-type,and 1 ( 11.1% ) was ⅢS-type. Whereas, 5 cases (83.3%) were M-type and only one case was Ⅱ S-type( 16. 7% ) in 6 patients with EXT2 gene mutation. Conclusions An accurate and simple gene diagnostic method for HME was established. Six novel EXT1 gene mutations, including I8 + 2T ＞ G,c. 1182delG, c. 1108G ＞T(p. E370X), c. 335delA, c. 361C ＞T(p. Q121X)and c. 1879_1881delCAC were identified as well. The clinical phenotype of the patients with EXT1 gene mutation was more severe compared to those with EXT2 gene mutations.

Aim To observe the neuroprotective effect of sinomenine on hippocampal neurons from injury in-duced by oxygen glucose deprivation ( OGD ) and its underlying mechanism. Methods Hippocampal neu-rons were exposed to OGD for 4 h followed by 24 h re-oxygenation ( OGD-R) . Then cell viability was detec-ted by MTT. LDH release was detected by LDH kit. Cell apoptosis was detected by Hoechst stain. The ex-pression of Bax, Bcl-2 and caspase-3 were detected by Western blot. [ Ca2+] i of hippocampal neurons was detected by calcium imaging. Acid-sensing ion chan-nels ( ASICs ) current was detected by patch clamp technique. Results SN increased cell viability and reduced LDH release. SN also inhibited neuron apop-tosis and increased ratio of Bcl-2/Bax and reduced the expression of caspase-3 . OGD-induced increase of [ Ca2+] i was inhibited by SN. Furthermore, SN inhib-ited ASIC1 a current and also inhibited OGD induced increase of ASICs current in hippocampal neurons. Conclusion SN protects hippocampal neurons against OGD-R-induced injury. The inhibitory effect of SN on ASIC1 a and calcium overload was involved in the pro-tective effect of SN.

Objective To compare the effect of L-T4 taken in the morning vs bedtime on serum thyroid hormone in patients with hypothyroidism.Methods Seventeen patients with primary hypothyroidism were prospectively included.They took L-T4 in the morning for 2 months followed by L-T4 taken during the bedtime for 2 months.Thyroid hormone levels and cholesterol,triglyceride,albumin,creatinine and heart rate were measured.Wilcoxon test and paired t test were used to compare the data.The correlation between the changes of TSH and FT3,FT4 was analyzed respectively by Pearson correlation analysis.Results TSH,FT3,FT4 were:(12.10±7.19) vs (3.90±3.47) mU/L,(4.14±0.86) vs (5.24±1.11) pmol/L,(12.72± 4.40) vs (18.48±2.87) pmoL/L for L-T4 taken in the morning and during the bedtime respectively (t value:6.371,-3.166,-5.435,all P＜0.01).There was no correlation between the changes of TSH and FT3,FT4(r=O.12,0.22,both P＞0.05),respectively.The averaged changes were (8.20±5.31) mU/L,(1.09± 1.42) pmol/L and (5.76±4.37) pmol/L.Triglyceride,cholesterol,albumin,creatinine levels and heart rate were not significantly different with L-T4 taken in the morning and during bedtime (t=0.240,0.017;z=0;t=-0.610,1.588,all P＞0.05).Conclusions L-T4 taken during the bedtime by patients with hypothyroidism would reduce TSH and increase FT3,FT4 levels.This method can maintain the stability of TSH level with no need to increase the dose.

Objective To examine the efficacy and safety of 125Iseed implantation for treating neuroblastoma (NB) in animal models.Methods A total of 45 nude mice models of neuroblastoma were constructed and divided into the 125Igroup.control group.and blank group at 15 mice per group.The long and short diameters of the tumor were measured every 3 days.and the tumor inhibition rate was calculated every 9 days.Apoptotic and proliferative protein expression levels in tumor tissue and peritumoral tissue.as well as endocrine markers and bone marrow of the nude mice.were analyzed.The independent sample t test was used to compare the mean scores.and ANOVA was used for comparison between multiple groups.Results Tumor volume inhibition rate was significantly higher in the 125Igroup than in the control group and blank group on days 9.18.and 27(all P<0.05).Caspase-3 expression in tumor tissues was significantly higher in the 125Igroup than in the control group and blank group (all P<0.05).whereas proliferating cell nuclear antigen (PCNA) expression was significantly lower in the 125Igroup than in the control group and blank group (all P<0.05).There was no significant difference in Caspase-3 and PCNA expression between the control group and blank group (all P>0.05).In addition.no significant difference in the expression of Caspase-3 and PCNA in peritumoral tissue was observed between the 125Igroup.control group.and blank group (all P>0.05).Cell apoptosis in tumor tissue was significantly lower in the blank group and control group than in the 125Igroup (all P<0.05).while there was no significant difference between the blank group and the control group (P>0.05).There was no significant difference in endocrine markers between the three groups (P>0.05).There was no significant bone marrow suppression in the 125Igroup.and this observation was similar to those in the control group and blank group (all P>0.05).Conclusions 125Iseeds have significant toxicity to NB.125Iseed implantation is safe in nude mice with NB within the therapeutic doses.

Objective To investigate the clinical efficacy and feasibility of 125I seeds implantation combined with high intensity focused ultrasound (HIFU) for portal vein tumor thrombus (PVTF) from HCC.Methods Nineteen cases of PVTT from HCC (17 males,2 females;average age:50 years,stage:Ⅰ-Ⅲ)undergoing 125I seeds implantation combined with HIFU from March 2011 to October 2013 were retrospectively studied.The radioactivity of each 125I seed was 18.5 MBq and the matched peripheral dose was 90-120 Gy.HIFU parameters were set as follows:ultrasound wave frequency,0.85 mHz;output power,300-400 W;total treatment duration,33-70 min.During the follow-up of 3-24 months,the change of PVTT size,postoperative complications and survival rate were recorded.Kaplan-Meier method was used to analyze the survival rate.Results The treatment was successfully completed in all patients and no serious complications were observed.After 1 month of follow-up,the tumor thrombi shrank in all patients.Among 19 patients,9 achieved PR,4 SD,6 PD.The one-year and two-year survival rates were 47.4％ and 7.9％,respectively.The mean survival was 11.6±3.0 months (range:3-24 months).The median postoperative survival for stages Ⅰ,Ⅱ,Ⅲ was 13.5,7.0,4.0 months,respectively.Conclusion 125I seeds implantation combined with HIFU could be a safe and effective therapy for PVTT from HCC.

Objective To investigate the functional and radiographic outcomes of pre-bent elastic stable intramedullary nail in treatment of distal radial shaft fractures in children. Methods From January 2006 to December 2008, 18 children with distal radial shaft fracture were treated by close reduction and internal fixation with a pre-bent elastic stable intramedullary nail. The age range was from 5 years to 15 years,with an average of 9 years and 8 months. All the cases were closed fractures, and followed up at least 12 months. The time interval from injury to surgery were 1 to 9 days. Fracture sites were located at the distal radial shaft. Among them, 15 cases suffered ipsilateral ulnar fracture, and the others for solitery radial fracture. Closed reductions were performed under C-arm fluoroscopy. All affected arms were immobilized in the functional position postoperatively by the plaster cast beyond elbows. Results The average time of fracture complete union was 5 months (ranged from 3 months to 7 months). The average preoperative angulation of the fractures: anteroposterior view 16.2±7.5 degrees, lateral view 26.2±13.1 degrees. The average postoperative angulation of the fractures: anteroposterior view 2.7±1.5 degrees, lateral view 1.4±1.2 degrees. All fractures maintained good alignment postoperatively, and 94.4% (17/18) of the patients regained a full range of rotation of the forearm. One patient suffered limitation of rotation in forearm less than 10°, and this had improved by final follow-up. Complications included soft tissue irritation at the site of nail insertion in one patient and transient scar hypersensitivity in another. Conclusion Fixation with a pre-bent elastic stable intramedullary nail is an effective, safe and convenient method for treating distal radial shaft fractures in children.

Objective:To investigate the correlation between serum uric acid/high density lipoprotein cholesterol (URH) and diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM) .Methods:According to urinary albumin creatinine ratio, 171 patients with T2DM were divided into simple T2DM group (group A1), microalbuminuria group (group A2) and macroalbuminuria group (group A3). The general data, HbA1c, biochemical indices were compared, and URH was calculated.Results:The systolic blood pressure, diastolic blood pressure, SUA, TG and URH of A1 group were lower than those of the other two groups [ (129.7±15.78) vs (141.65±16.04) vs (147.31±17.01) mmHg, (78.9±10.71) vs (83.79±10.67) vs (84.61±12.19) mmHg, 291.5 (253.75, 351.25) vs 346 (280, 409) vs 344.5 (274.75, 425.75) μmol/L, 26.12 (19.71,32.96) vs 33.45 (26.55,42.2) vs 33.45 (26.55,42.2) ] ( P<0.05). HDL-C was higher than those of the other two groups [1.19 (1.02,1.29) vs1.02 (0.87,1.21) vs 1.07 (0.93,1.25) mmol/L] ( P<0.05), the course of disease and SCr of group A3 were higher than those of the other two groups [10.5 (7.25, 15) vs 8.5 (4,12) vs 8 (3,11) years; 82.5 (70.57,101.75) vs 66 (52.75,73.75) vs 64 (51, 84) μmol/L ] ( P<0.05), and eGFR was lower than those of the other two groups [91.63 (67.09, 112.21) vs 116.7 (96.6, 142.53) vs 109.85 (85.64, 152.39) ml/min/1.73 m 2] ( P<0.05). There were no significant differences in gender, smoking history, drinking history, age, BMI, TC, LDL-C, BUN, FPG or HbA1c among different groups (P> 0.05). Correlation analysis showed that the course of disease, systolic blood pressure, diastolic blood pressure, TG, SUA, URH were positively correlated with UACR, while HDL-C was negatively correlated with UACR. Logistic regression analysis showed that course of disease was a risk factor for macroproteinuria, while systolic blood pressure and URH were risk factors for microproteinuria and macroproteinuria. ROC curve showed that the AUC value of URH was the highest, and the accuracy rate was 69.3%. Conclusions:URH is closely related to the occurrence of DKD and is a risk factor of DKD. Dynamic monitoring of URH in T2DM patients is helpful for early screening of DKD, which is superior to SUA and HDL-C.

Objective To explore the risk factors of postoperative pulmonary infection in patients with craniocerebral injury and establish a nomogram model to predict the risk of postoperative pulmonary infection after craniocerebral injury.Methods The clinical data of 169 patients with craniocerebral injury,admitted to and underwent craniotomy in our hospital from January 2013 to December 2018,were retrospectively analyzed.The clinical data of patients with postoperative pulmonary infection and without postoperative pulmonary infection were compared.The risk factors of postoperative pulmonary infection were analyzed by multivariate Logistic regression.R language was used to establish a nomogram model to predict the risk of postoperative pulmonary infection after craniocerebral injury.Receiver operating characteristic (ROC) curve was used to explore the prediction efficiency of the nomogram model for pulmonary infection after craniocerebral injury.Results Among the 169 patients,74 (43.8％) were complicated with pulmonary infection and 95 (56.2％) were not complicated with pulmonary infection.As compared with non-pulmonary infection group,pulmonary infection group had significantly higher percentages of patients with open craniocerebral injury and Glasgow coma scale (GCS) scores＜7,significantly higher American Society of Anesthesiologists (ASA) grading,lower albumin level one week after surgery,statistically longer operation time,and significantly higher percentages of patients with conscious disorder,patients accepted intraoperative blood transfusion,patients used breathing machine,and patients stayed in bed for 4 weeks or more (P＜0.05).Multivariate Logistic regression analysis showed that GCS scores (OR=0.243,95％CI:0.122-0.497,P=0.000),ASA grading (OR=3.349,95％CI:2.233-5.021,P=0.000),disturbance of consciousness (OR=3.185,95％CI:1.217-8.334,P=0.018),and useofventilator (OR=3.376,95％CI:1.590-7.167,P=0.002) were independent risk factors for postoperative pulmonary infection in patients with craniocerebral injury.The scores of the nomograrn model were 13.7,100.0,38.0 and 27.5 in GCS scores,ASA grading,disturbance of consciousness and use of ventilator,respectively.The consistency index of the nomogram model for predicting postoperative pulmonary infection in patients with craniocerebral injury was 0.835.ROC curve showed that the area under the curve predicted by nomogram model for postoperative pulmonary infection in patients with craniocranial injury was 0.840 (95％CI:0.778-0.901).Conclusion Based on the risk factors for pulmonary infection after craniocerebral injury,a nomogram model for predicting the risk of pulmonary infection is established,which has a good differentiation degree and prediction effect,and can provide a reference for medical staffto identify high-risk patients at an early stage,so as to take more targeted intervention measures.

Objective:To explore the method of ultrasonography for detecting the fetal umbilical vein diameter, blood flow volume and normalized volume blood flow and establish normal reference ranges with umbilical vein diameter, blood flow volume and normalized blood flow and Z-scores for umbilical vein diameter and blood volume flow.Methods:This was a prospective study on 907 normal fetuses in the Second Xiangya Hospital, Central South University and Women and Children Healthcare Hospital of Zhuzhou from March 2019 to December 2020. The umbilical vein diameter (Duv), umbilical vein blood flow volume (Quv) and normalized volume blood flow (nQ = Quv/estimated fetal weight) of the free loop of umbilical vein (FUV) and fetal intra-abdominal umbilical vein (IUV) were collected. And the mean values and 90% confidence intervals of Duv, Quv and nQ in two segments of umbilical veins at different gestational ages were calculated. Regression analysis of Duv, Quv and nQ were performed with gestational age (GA), and the parameters of umbilical vein in different segments were compared. Finally, with gestational age (GA) as the independent variable, Z-scores of the Duv and Quv were built.Results:The mean values and 90% confidence intervals of Duv, Quv, and nQ in 858 (94.6%) normal fetal umbilical veins were successfully obtained. The Duv, Quv of the FUV and IUV increased as pregnancy progressed. The Quadratic curve of Duv and Linear curve of Quv were of the highest fitnesses, respectively( r=0.951, 0.941, 0.986, 0.982; all P<0.001). While nQ increased with GA followed by a decreased trend, and the Quadratic curve was the highest fitting curve of nQ( r=0.610, 0.611; all P<0.001). Duv-FUV was greater than Duv-IUV( P<0.001), nQ-FUV was bigger than Quv-IUV( P=0.001), and he difference was not statistically significant between Quv-FUV and Quv-IUV( P=0.133). Z-scores models of Duv and Quv were successfully established, and all Z-scores were Gaussian distribution. Conclusions:The normal ranges and Z-scores of umbilical vein parameters are useful to improve the evaluation of placental circulation and provide a strong basis for the monitoring of fetus-related diseases and the evaluation of pregnancy prognosis. The choice of FUV or IUV umbilical vein to evaluate placental circulation may depend on the actual situation in clinical application.