Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial.

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. PATIENTS AND METHODS: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. CLINICALTRIALS: gov identifier: NCT02578641. RESULTS: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. CONCLUSIONS: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

[Evaluation of the anatomical morphology of the adrenal veins in patients with primary aldosteronism by adrenal venous sampling].

Objective: To analyze the anatomical characteristics of the adrenal veins through adrenal venography to improve the success rate of adrenal venography (AVS). Methods: This study was a cross-sectional study. Patients who were diagnosed with primary aldosteronism and underwent AVS from January 2019 to October 2023 at the First Affiliated Hospital of Dalian Medical University were included. Adrenal vein imaging was collected from the enrolled patients. We performed statistical analysis on the adrenal vein orifice position, inflow angle, and adrenal venography morphology. The adrenal venous orifice was defined as the location where the catheter was placed at the end of the calm inhalation. Spearman correlation analysis was used to explore the relationship between the positions of bilateral adrenal vein orifices and body mass index (BMI). Results: A total of 282 patients with successful bilateral AVS and complete bilateral adrenal vein imaging were enrolled, of whom 57.1% (161/282) were male and the age was (53.3±10.7) years old. The orifice of the left adrenal vein was located between the middle segment of the 11th thoracic vertebra and the upper segment of the 2nd lumbar vertebra. The inflow angle relative to the position of the orifice was all leftward and upward. The orifice of the right adrenal vein was located between the upper segment of the 11th thoracic vertebra and the lower segment of the 1st lumbar vertebra, and 91.1% (257/282) had a rightward and downward angle of inflow relative to the position of the orifice. The position of the adrenal vein orifices on both the left (r=0.211, P<0.001) and right (r=0.196, P=0.001) showed positive correlation with BMI. The position of the right adrenal vein orifice also increased with the position of the left adrenal orifice (r=0.530, P<0.001). The most common adrenal venography morphology on the right side was triangular (36.5%, 103/282), while the most common venography morphology on the left side was glandular (66.3%, 187/282). Conclusions: The anatomical morphology of adrenal veins are diverse. Being familiar with the morphological characteristics of the adrenal vein and identifying the adrenal vein accurately during surgery has important clinical value in improving the success rate of AVS.

[The expression of clock gene CLOCK and its clinical significance in nasopharyngeal carcinoma].

Objective: To explore the relationship between expression levels of CLOCK mRNA and protein and the clinical characteristics of patients with nasopharyngeal carcinoma. Methods: The frozen tissue specimens from 33 patients with nasopharyngeal carcinoma in the Affiliated Tumor Hospital of Guizhou Medical University from 2018 to 2019 were collected. Seventeen cases of tissue specimens from patients with nasopharyngeal chronic inflammation in the Affiliated Hospital of Guizhou Medical University in 2019 were collected. From 2008 to 2014, 68 cases of formalin-fixed paraffin-embedding (FFPE) nasopharyngeal carcinoma tissue and 37 cases of FFPE nasopharyngeal chronic inflammation tissue were collected from the Affiliated Tumor Hospital of Guizhou Medical University. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to detect the mRNA and protein expression levels of CLOCK. The nasopharyngeal carcinoma cells including CNE1, CNE2, 5-8F and the normal nasopharyngeal epithelial cell NP69 were cultured. qRT-PCR was used to detect the expression level of CLOCK mRNA in each cell line at the time points of ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22. The cosine method was used to fit the rhythm of CLOCK gene in nasopharyngeal carcinoma. The protein expression of CLOCK protein was detected by using immunohistochemical method in 68 cases of nasopharyngeal carcinoma and 37 cases of nasopharyngeal chronic inflammation tissue. Survival was analyzed by Kaplan-Meier method and Log rank test, and the influencing factors was analyzed by Cox regression model. Results: The expression levels of CLOCK mRNA in CNE1, CNE2 and 5-8F cells (0.63±0.07, 0.91±0.02 and 0.33±0.04, respectively) were lower than that in NP69 cell (1.00±0.00, P<0.05). The expression levels of CLOCK protein in CNE1, CNE2 and 5-8F cells (0.79±0.06, 0.57±0.05 and 0.74±0.10, respectively) were lower than that of NP69 cells (1.00±0.00, P<0.05). The expressions of CLOCK mRNA in nasopharyngeal carcinoma cells including CEN1, CNE2, 5-8F and normal nasopharyngeal epithelial cell NP69 were different at different time points, with temporal fluctuations. The fluctuation periods of CLOCK mRNA in CNE1, CNE2, 5-8F, and NP69 cells were 16, 14, 22 and 24 hours, respectively. The peak and trough times were ZT10: 40 and ZT18: 40, ZT10 and ZT3, ZT14: 30 and ZT3: 30, ZT12: 39 and ZT0: 39, respectively. CLOCK mRNA and protein expression levels in nasopharyngeal carcinoma tissues (0.37±0.20 and 0.20±0.26, respectively) were lower than those in nasopharyngeal chronic inflammation tissues (1.00±0.00 and 0.51±0.41, respectively, P<0.05). The 1, 3, and 5-year survival rates of patients in the CLOCK protein high expression group (CLOCK protein expression level ≥ 0.178) were 96.2%, 92.1%, and 80.1%, respectively, which were higher than those in the low expression group (CLOCK protein expression level <0.178, 92.9% , 78.6% and 57.1%, respectively, P=0.009). The 1, 3, and 5-year progression-free survival (PFS) rates of patients in the CLOCK protein high expression group were 96.2%, 87.8%, and 87.7%, respectively, which were higher than those in the low expression group (92.7%, 82.2%, and 70.8%, respectively, P=0.105). Compared with the low-expression group (100.0%, 96.9%, and 90.0%, respectively), the 1, 3, and 5-year recurrence-free survival rates of patients in the CLOCK protein high expression group (100.0%, 95.7%, and 95.7%, respectively) were not statistically significant (P=0.514). Compared with the low-expression group (92.7%, 82.2%, and 79.3%), the 1, 3, and 5-year survival rates without metastasis in the CLOCK protein high expression group (96.2%, 92.0%, and 92.0%, respectively) were not statistically significant (P=0.136). CLOCK protein expression and T stage were independent prognostic factors of overall survival (P<0.05). Conclusions: The expression of CLCOK is downregulated in the nasopharyngeal carcinoma cell and nasopharyngeal carcinoma tissues. Clock gene CLOCK is rhythmically expressed in the nasopharyngeal carcinoma cells and normal nasopharyngeal epithelial cells. Compared with normal nasopharyngeal epithelial cells, the fluctuation period of CLOCK in nasopharyngeal carcinoma cells is shortened. The overall survival of patients in the CLOCK protein high expression group is better than that of low expression group. The expression of CLOCK protein is an independent influencing factor for overall survival. CLOCK gene may be a potential tumor suppressor gene in the nasopharyngeal carcinoma.

[Postoperative distal tibiofibular synostosis: radiographic characteristics and the influence on ankle mobility].

Objective: To investigate the clinical and imaging characteristics of distal tibiofibular synostosis in postoperative ankle fractures and its effects on the ankle mobility. Methods: The clinical and imaging data of 47 patients with distal tibiofibular synostosis treated surgically from October 1991 to June 2013 were analyzed retrospectively. There were 30 males and 17 females, aged from 15 to 68 years with a mean age of (39±13) years. The original fracture types, internal fixation profiles, imaging features of distal tibiofibular synostosis were recorded. Ankle range of motion (ROM) and complications at the last follow-up were also evaluated.The ROMs of healthy and fractured sides were compared with paired sample rank test. Results: The patients were followed up for 3 to 204 months (mean 25.4 months). Of the patients, 34(72.4%) were ankle fractures, 7(14.9%) were distal tibiofibular fractures, 1(2.1%) was tibiofibular shaft fracture, 2(4.3%) were tibial shaft fractures associated with lateral malleolus fracture and the resting 3(6.4%) were Pilon fractures. In patients with ankle fractures, 76.5%(26/34) of the synostosis occurred at the distal tibiofibular syndesmosis, while 23.5%(8/34) at the proximal of the tibiofibular sydesmosis; in patients with distal tibiofibular fracture, 85.7%(6/7) of the tibiofibular synostoses occurred at the fracture sites. The synostosis occurred at the level of syndesmotic screws in 8 patients (88.9%, 8/9) fixed with distal tibiofibular syndesmotic screws. And synostosis occurred at the sites of the distal locking screws in all (3/3) of the patients fixed with intramedullary nails. At the last follow-up, the active plantarflexion, active dorsiflexion and passive dorsiflexion in the affected side was 0°(0°, 5°), 2°(0°, 5°), 5°(0°, 10°) less than those in the healthy side, respectively (Z=-3.493, -4.491, -5.130, all P<0.05).During the follow-up, 4 patients complained of lateral ankle discomfort with no impact on daily life. Conclusions: Post-operative distal tibiofibular synostosis mainly occurs at the sites of fractures, distal tibiofibular syndesmotic screw sites and the sites of the distal locking screws of tibial intramedullary nails. ROM of the injured ankle decreases in comparison with that at the contralateral side, although no obvious symptoms are observed and no intervention needed.

Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence.

OBJECTIVES: Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis. METHODS: CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method. RESULTS: CK13 was predominately expressed in non-cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10-year follow-up. CONCLUSION: Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis.

[Deltoid ligament augmentation and repairing in ankle fracture associated with deltoid ligament injury and syndesmosis diastasis].

Objective: To evaluate the outcome of the deep component augmentation and superficial component repairing and syndesmosis screw fixation in treating ankle fracture associated with deltoid ligament injury and syndesmosis diastasis. Methods: From January 2014 to December 2017, 16 patients with ankle fracture combined with deltoid ligament injury and syndesmosis diastasis were treated with the deep component augmentation and superficial component repairing in Beijing Jishuitan Hospital.Of the patients, 13 were males and 3 were females, with an average age of (38±10) years (21-57 years). Nine cases were athletic injuries, 4 cases were daily-life injuries and 3 cases were traffic injuries.According to the Weber classification, 6 cases were type B, 10 cases were type C. According to the Lauge-Hansen classification, 6 cases were supination external rotation Ⅳ injury, 9 cases were pronation external rotation Ⅳ injury, 1 case was pronation abduction Ⅲ injury.The surgical treatment method was rigid fixation of the lateral malleolus and deep deltoid ligament augamentation instead of syndesmosis screw fixation.The effect of the surgical method was observed. Results: The average follow up was (24±12) months (6-40 months). The mean degree of dorsiflexion was 17.8°±6.8° (5°-30°), with 3.8°±6.0° (0°-15°) less than that in normal side, the mean degree of plantar flexion was 46.9°±7.9°, with 1.9°±3.9° (0°-10°) less than that in normal side.The mean Philips and Schwartz score was 96.8±5.1 (82-100), the American Orthopaedic Foot and Ankle Society (AOFAS) Score was 97.4±4.6 (84-100). Conclusion: In the treatment of ankle fracture associated with deltoid ligament injury and syndesmosis diastasis, the deep component augmentation and superficial component repairing and proper rehabilitation can benefit the functional recovery.

[Value of four-dimensional echocardiography combined with speckle tracking technique on the assessment of right heart function and prognosis in patients with pulmonary arterial hypertension].

Objective: To investigate the value of four-dimensional echocardiography combined with speckle tracking technique on the assessment of right heart function and prognosis in patients with pulmonary arterial hypertension (PAH). Methods: In this prospective study, 51 patients with PAH diagnosed by right heart catheterization in east hospital and south hospital of Renji hospital affiliated to school of medicine of Shanghai Jiaotong University from September 2015 to July 2017 were enrolled as PAH group from July to November 2017. Meanwhile, 26 healthy volunteers with age and sex matched with pulmonary hypertension patients were recruited as control group. The patients were aged (45.8±15.5) years old in PAH group, and there were 6 males and 45 females. The healthy volunteers were aged (45.4±14.6) years old in control group, and there were 4 males and 22 females. Two-dimensional and four-dimensional echocardiographic images were obtained to measure the structure and function of the right heart. The myocardial strain of each ventricle and atrium was measured by sparkle tracking. The patients in PAH group were followed up from July 2017 to August 2018 to observe the endpoint events including all-cause death, re-hospitalization, and clinical deterioration. Results: There were significant differences in two-dimensional echocardiographic parameters(including tricuspid annular plane systolic excursion (TAPSE), right ventricular area change fraction (FAC), and right ventricular systolic pressure (RVSP)), speckle tracking parameters (including global longitudinal systolic peak strain of left ventricle (LVGLS), global longitudinal systolic peak strain of right ventricle (RVGLS),left atrial reservoir function(LASr), left atrial conduit function (LASc), left atrial pump function (LASp), right atrial reservoir function (RASr), right atrial conduit function (RASc), and right atrial pump function (RASp)), and four-dimensional echocardiographic parameters(including right ventricular end diastolic volume (RVEDV) , right ventricular end systolic volume(RVESV), right ventricular stroke volume(RVSV), right ventricular freewall longitudinal strain(RVLSf), interventricular septum longitudinal strain(IVSLS), right ventricular ejection fraction(RVEF)) between control group and PAH group (all P<0.01 or 0.05).Spearman correlation analysis showed that RVEF was correlated with 6-minute walking distance (r=0.540, P<0.001), B-type natriuretic peptide (r=-0.545,P<0.001), New York Heart Association (NYHA) cardiac function classification(r=-0.583, P<0.001), TAPSE(r=0.595, P<0.001), LVGLS (r=-0.461, P=0.001) ,LASc (r=0.453, P=0.002) ,RASc (r=0.532, P<0.001) ,RVESV (r=-0.418, P=0.004) , RVSV (r=0.351, P=0.017) , and IVSLS (r=-0.450, P=0.002) . Pearson correlation analysis also showed that RVEF was correlated with FAC(r=0.579, P<0.001),RVSP (r=-0.442, P=0.002) ,RVGLS (r=-0.521, P<0.001) , LASr (r=0.483, P=0.001) , RASr (r=0.617, P<0.001) , RASp (r=0.513, P<0.001) , and RVLSf (r=-0.592, P<0.001) .After a follow-up of (10.4±2.7) months, there were 4 all-cause deaths, 5 re-hospitalizations and 5 clinical deterioration. Multivariate Cox regression analysis showed that increased RVEF was independent protective factor for end-point events in PAH patients (HR=0.702, P=0.043), and increased RVSP was independent risk factor for end-point events in PAH patients (HR=1.083, P=0.017). The receiver operating characteristic (ROC) curve showed that RVEF and RVSP could be used to predict the end-point events in PAH patients. The area under the curve (AUC) was 0.835(P=0.001) and 0.820(P=0.001), respectively. Conclusions: RVEF measured by four-dimensional echocardiography is correlated with right ventricular function parameters measured by two-dimensional echocardiography and can be used to estimate the prognosis of PAH patients. The right atrial and left atrial function assessed by speckle tracking can also reflect the right ventricular function to a certain extent.

The fractal correlation between relaxation dynamics and atomic-level structures observed in metallic glasses by computer simulation.

In the present study, atomistic simulation reveals that the microscopic mechanism of the relaxation dynamics in amorphous materials is governed by the activating atoms that jump more than half of the average nearest neighbor distance within a given time. Based on the unsupervised machine-learning algorithm, hierarchical clustering analysis shows that the activating atoms are excited in a cooperative and avalanche-like model to form activating units. Correlation analysis suggests that large free volumes facilitate the formation of activating atoms. Interestingly, a fractal correlation is found between the number and size of the activating units, indicating that when the maturation temperature, i.e. percolation threshold, is reached the activating units form a complicated and connected body in space.

[Evaluation of the proximal femur geometry in patients with elderly osteoporotic hip fractures].

Objective: To investigate the relationship between the proximal femur geometry and elderly osteoporotic hip fractures. Methods: From May 2015 to December 2015, 137 patients with elderly osteoporotic hip fractures were involved.69 cases were in the fracture group and 68 cases were in the control group.CT scan were performed on all patients and the proximal femur geometry parameters were measured, including the neck width (NW), neck length (NL), neck shaft angle (NSA), femur head diameter (FHD), head height (HH) and Offset.Statistical analysis was performed between two groups. Results: The results of single factor analysis showed that age, sex, NL, FHD, NSA and Offset had significantly differences between two groups (P<0.05). The multiple Logistic regression analysis showed that age, sex, NL and NSA were independent risk factor for the hip fractures.The ROC curve analysis showed that area under curve (AUC) were 0.818, 0.818 and 0.725, respectively. Conclusions: The patients with older age, longer NL and larger NSA might be prone to hip fracture and it was an effective and feasible method to reconstruct and measure the CT data of the proximal femur with Mimics software.

[Outcome of vaginal birth after cesarean section in women with advanced maternal age].

Objective: To explore the perinatal outcome of vaginal birth after cesarean (VBAC) in women with advanced age. Methods: Totally 2 587 women delivered after one or two prior cesarean sections (gestational age≥28 weeks) in the First Affiliated Hospital of Kunming Medical University from July 2013 to February 2017. 909 trial of labor after cesarean(TOLAC) cases of singleton pregnancy with one prior cesarean section were studied retrospectively. According to the age, of the 909 TOLAC cases, 237 were the advanced age group, and 672 cases were the low age group. The maternal and neonatal outcomes between the two groups were compared. Results: The percentage of TOLAC in women with advanced age was 32.4% (237/731), and VBAC rate was 88.2% (209/237). The percentage of TOLAC in younger women was 36.2% (672/1 856), and VBAC rate was 82.4% (554/672). The difference of the TOLAC rate between the two groups was not significant (P>0.05), and the VBAC rate of the advanced age group was higher than the low age group (P<0.05). In the comparison of the two groups, the proportion of bachelor degree or above(55.7%,132/237), the prepregnancy BMI (22.4±3.0) kg/m(2), pregnant interval time (68.5±38.3) months, the proportion of gestational hypertension (8.4%,20/237), the proportion of gestational diabetes(34.6%,82/237) and the rate of the neonatal ICU admission (18.1%,43/237) in the advanced age group were higher than those of the low age group (P<0.05), respectively. And there were no significant differences in the rate of postpartum hemorrhage, the rate of postpartum hemorrhage≥1 500 ml, the rate of postpartum transfusion, puerperal morbidity, neonatal birth weight, neonatal 5 min Apgar score<7 score, umbilical artery blood pH<7.0, neonatal tracheal intubation and respiratory distress syndrome (all P>0.05). In all TOLAC cases, the rate of uterine rupture was 0.11%(1/909) and there was no maternal and neonatal death. Conclusion: VBAC is a safe and feasible way of delivery for singleton pregnancy after one prior cesarean section in women with advanced age.

Atomic-scale simulation to study the dynamical properties and local structure of Cu-Zr and Ni-Zr metallic glass-forming alloys.

Molecular dynamics simulation with well-developed EAM potentials was carried out to investigate the transport properties and local atomic structure of Cu-Zr and Ni-Zr metallic glasses and supercooled liquids. It is found that Cu or Ni atoms have much faster dynamics than Zr atoms in relaxation timescales, while Zr atoms display faster dynamics in the Cu-Zr system than in the Ni-Zr system. A dynamical crossover phenomenon from Arrhenius to super-Arrhenius behavior in the transport properties was observed for the Cu65Zr35 system at Tx ≈ 1250 K and the Ni65Zr35 system at Tx ≈ 1500 K, respectively. Further structural analysis suggests that the dominant interconnected clusters in Cu65Zr35 and Ni65Zr35 systems are 〈0, 0, 12, 0〉, 〈0, 1, 10, 2〉, 〈0, 2, 8, 2〉 and 〈0, 3, 6, 4〉. To directly characterize and visualize the correlated dynamics, we regard the full icosahedra as the microscopic origin responsible for the formation of metallic glasses in the Cu65Zr35 system, while the metallic glass formation in the Ni65Zr35 system can be attributed to the slow dynamics of 〈0, 3, 6, 4〉, 〈0, 2, 8, 2〉 and 〈0, 1, 10, 2〉 Ni-centered Voronoi polyhedra. The local atomic order and dynamics for Cu65Zr35 and Ni65Zr35 systems are remarkably different, and these differences are presumed to hinder crystal nucleation and growth, hence promoting the largely different bulk glass-forming ability.

Retraction: Atomic-scale simulation to study the dynamical properties and local structure of Cu-Zr and Ni-Zr metallic glass-forming alloys.

Retraction of 'Atomic-scale simulation to study the dynamical properties and local structure of Cu-Zr and Ni-Zr metallic glass-forming alloys' by M. H. Yang et al., Phys. Chem. Chem. Phys., 2016, 18, 7169-7183.

Development and characterization of microsatellite loci in Excentrodendron hsienmu (Chun & How) H.T. Chang& R.H. Miau.

Microsatellite markers were isolated using dual-suppression-PCR for the endangered species Excentrodendron hsienmu (Tiliaceae) to evaluate the genetic diversity and population structure of this species. A total of 11 polymorphic microsatellite loci were characterized in E. hsienmu. The number of alleles per locus ranged from 2 to 9, with an average of 5.27. The expected heterozygosity value ranged from 0.053 to 0.780, with an average of 0.568 and the observed heterozygosity value ranged from 0 to 0.595, with an average of 0.268. The polymorphic information content value ranged from 0.051 to 0.740, with an average of 0.521. These newly designed markers will be of great potential significance and profound influence in future research related to the genetic diversity, population structure, and patterns of gene flow of this species, which will contribute to the implementation of conservation and management strategies for this species.

[The outcome of trial of labor after cesarean section].

Objective: To explore the outcome of trial of labor after cesarean section(TOLAC). Methods: Totally 614 TOLAC were conducted in the First Affiliated Hospital of Kunming Medical University from July 2013 to June 2016. Among them, 586 cases of singleton pregnancy with one prior cesarean section(gestational age≥28 weeks)were studied retrospectively. The maternal and neonatal outcomes among the vaginal birth after cesarean(VBAC)group(481 cases), failed TOLAC group(105 cases)and the elective repeat cesarean section(ERCS)group(1 145 cases)were compared. Multiple logistic regression was used to determine the risk factors of admission to neonatal intensive care unit(NICU). Results: (1)The TOLAC rate was 29.62%(614/2 073)from July 2013 to June 2016, and the VBAC rate was 82.6%(507/614). The cesarean section rate was reduced by VBAC by 3.147%(507/16 112).(2)The comparison of adverse maternal outcomes: in the VBAC group, the postpartum hemorrhage volume was(431±299)ml, the rate of postpartum fever was 6.4%(31/481), the birth weight of the neonates was(3 085± 561)g, and the rate of large for gestational age was 2.9%(14/481). All were significantly lower than those in the failed TOLAC group and the ERCS group(P<0.05). There was no significant difference in other adverse maternal outcomes[the uterine rupture rate(0.2% ,1/481), the bladder injury rate(0), the proportion of postpartum hemorrhage volume≥1 500 ml(1.0%, 5/481), the blood transfusion rate(3.7%, 18/481)]and adverse perinatal outcomes[the rate of neonatal 5-minute Apgar score<7(0.4%, 21/481), the rate of umbilical arterial pH<7.0(0.6% , 3/481), the rate of the NICU admission and the perinatal mortality rate(12.3%, 59/481)]among the 3 groups(P>0.05). Multiple logistic regression showed no association between VBAC and admission to the NICU(OR=0.84, 95%CI: 0.58-1.21). The isolated risk factors for admission to the NICU were preterm birth(OR=16.71, 95% CI: 11.44-24.40), hypertensive disorder complicating pregnamcy(OR=3.89, 95% CI: 2.39-6.35), meconium stained amniotic fluid(OR=2.48, 95% CI: 1.62-3.80), small for gestational age(OR=2.00, 95% CI: 1.19-3.36)and diabetes mellitus(OR=1.69, 95% CI: 1.14-2.50). Conclusions: VBAC reduces cesarean section rate, with good outcomes in both mother and neonate. It is a safe and feasible way of labor in women with only one cesarean section history.

Atomistic modeling to optimize composition and characterize structure of Ni-Zr-Mo metallic glasses.

An interatomic potential was constructed for the Ni-Zr-Mo ternary metal system with the newly proposed long-range empirical formulism, which has been verified to be applicable for fcc, hcp and bcc transition metals and their alloys. Applying the constructed potential, molecular dynamics simulations predict a hexagonal composition region within which metallic glass formation is energetically favored. Based on the simulation results, the driving force for amorphous phase formation is derived, and thus an optimized composition is pinpointed to Ni45Zr40Mo15, of which the metallic glass could be most stable or easiest to obtain. Further structural analysis indicates that the dominant interconnected clusters for Ni64Zr36-xMox MGs are 〈0, 0, 12, 0〉, 〈0, 1, 10, 2〉, 〈0, 2, 8, 2〉 and 〈0, 3, 6, 4〉. In addition, it is found that the appropriate addition of Mo content could not only make a more ordered structure with a higher atomic packing density and a lower energy state, but also improve the glass formation ability of Ni-Zr-Mo alloys. Moreover, inherent hierarchical atomic configurations for ternary Ni-Zr-Mo metallic glasses are clarified via the short-range, medium-range and further in the extended scale of the icosahedral network.

Anti-prostate cancer effects of CTL cell induction in vitro by recombinant adenovirus mediated PSMA/4-1BBL dendritic cells: an immunotherapy study.

This study aimed to examine anti-prostate cancer immune response induced by dendritic cells (DCs) transduced with PSMA/4-1BBL recombinant adenoviruses in vitro. Ad-PSMA, Ad-4-1BBL, and Ad-GFP were transfected into DCs derived from peripheral blood of healthy volunteers. Ad-PSMA/4-1BBL-DC, Ad-PSMA-DC, Ad-4-1BBL-DC, Ad-GFP-DC, and normal-DC, PSMA and 4-1BBL protein levels in DCs were detected by western blot. IL-12, IFN-γ and IL-10 were measured by ELISA. Mixed lymphocyte reaction and the cytotoxicity of each group targeted to LNCap, Du145, and 22RV prostate cancer cells were determined by CCK-8 assay. PSMA and 4-1BBL protein could express on DC successfully, the IL-12 supernatant content (134.29 ± 2.22 pg) was higher than others (P < 0.05). The ability to stimulate autologous T lymphocyte proliferation in the co-transfection group was higher than others (P < 0.05). When the DCs were co-cultured with CTLs, the PSMA/4-1BBL-DC-CTL group showed the highest content of IFN-γ (1176.10 ± 14.37pg/5 x 10(6) cells), but the lowest IL-10 content (75.14 ± 2.01 pg/5 x 10(6) cells) (P < 0.05), and the strongest anti-tumor effect when the effector to target ratio was 40:1, along with a higher killing ratio of LNCap cells than others (P < 0.05). Overall, Mature DCs transfected with Ad-PSMA/4- 1BBL not only showed high secretion of IL-12, but also induced CTLs to stimulate and enhance the killing effect of PSMA specific effector cells to PSMA positively expressing prostate cancer cells. Furthermore, the DCs infected with two kinds of tumor-associated antigens would induce more effective tumor-specific CTL induction.

[Management of pelvic injury associated with complete anterior sacroiliac joint dislocation].

OBJECTIVE: To investigate the management of pelvic injury associated with complete anterior sacroiliac joint dislocation. METHODS: In the study, 6 cases of pelvic injury associated with complete anterior sacroiliac joint dislocation treated in Beijing Jishuitan Hospital from February 2008 to June 2014 were analyzed. We described the history and severity of injury, emergency treatment, and fracture radiology. In all the cases, the surgical treatment and postoperative functional exercise were performed. We followed up all the cases on an average of 1.6 years, assessed the postoperative recovery and summed up the treatment experience. RESULTS: All the 6 patients with fractures recovered without infection and nerve symptoms after surgery. Their X-rays showed good reduction of sacroiliac joints. All the cases were followed up on an average of 1.6 years. Six months after surgery, the Majeed scores were perfect in 2 cases, good in 2, fair in 1, and poor in 1. The patients with poor scores suffered persistent pain, and decreased physical activity, and when walking long distances, they needed a walking stick. The 2 patients with low scores could not resume the original work. CONCLUSION: Pelvic injury associated with complete anterior sacroiliac joint dislocation is a special type of the pelvic injury since the managements during the emergency phase are difficult.The surgery should be done as early as possible, and the anterior approach is available for the reduction and fixation.

[Pregnancy-related pelvic ring disease and its treatment].

Pregnancy-related pelvic ring disease brings great suffering to pregnant women, including the separation of the pubic symphysis and sacroiliac joint pain. Hormonal changes leading to ligamentous laxity is the main reason for Pregnancy-related pelvic ring disease. In normal pregnant cases, and the physiologic widening at the symphysis is about 3-7 mm. When the widening of the symphysis is more than 10 mm, it may lead to symptoms and need active treatment. Currently the diagnosis of the pubic symphysis separation is based on the clinical symptoms and signs. The treatment of acute pubic symphysis separation bases on conservative therapy, includes bed rest and physical therapy. But when the widening of the symphysis is more than 4 cm, the surgery intervention may be a good treatment. If the conservative treatment is not obviously effective, the surgery consists of plate fixation in the pubic symphysis and sacroiliac screw fixation. Other indications for the surgical intervention include inadequate reduction, recurrent diastasis, intractable symptoms, and open rupture.

Paediatric head CT scan and subsequent risk of malignancy and benign brain tumour: a nation-wide population-based cohort study.

BACKGROUND: To evaluate the possible association between paediatric head computed tomography (CT) examination and increased subsequent risk of malignancy and benign brain tumour. METHODS: In the exposed cohort, 24 418 participants under 18 years of age, who underwent head CT examination between 1998 and 2006, were identified from the Taiwan National Health Insurance Research Database (NHIRD). Patients were followed up until a diagnosis of malignant disease or benign brain tumour, withdrawal from the National Health Insurance (NHI) system, or at the end of 2008. RESULTS: The overall risk was not significantly different in the two cohorts (incidence rate=36.72 per 100 000 person-years in the exposed cohort, 28.48 per 100 000 person-years in the unexposed cohort, hazard ratio (HR)=1.29, 95% confidence interval (CI)=0.90-1.85). The risk of benign brain tumour was significantly higher in the exposed cohort than in the unexposed cohort (HR=2.97, 95% CI=1.49-5.93). The frequency of CT examination showed strong correlation with the subsequent overall risk of malignancy and benign brain tumour. CONCLUSIONS: We found that paediatric head CT examination was associated with an increased incidence of benign brain tumour. A large-scale study with longer follow-up is necessary to confirm this result.

Anti-erythropoietin receptor antibodies in systemic lupus erythematosus patients with anemia.

Anemia is a common hematologic abnormality in systemic lupus erythematosus (SLE). An inadequate erythropoietin (EPO) response in SLE patients with anemia has been described that may be due to the presence of antibodies to EPO in SLE patients. However, whether anemia in patients with SLE is related to antibodies to EPO receptor (EPOR) has not yet been investigated. We enlisted 169 consecutive patients with SLE and 45 normal individuals to investigate the existence and importance of circulating autoantibodies to EPOR in sera from patients with SLE. In all patients with SLE, the disease activity was evaluated by using the SLE disease activity index SLEDAI. Anti-EPOR antibodies were detected by using an enzyme-linked immunosorbent assay (ELISA). A higher frequency of anti-EPOR antibodies was observed in SLE patients than in healthy controls (18.3% vs 2.2%, p = 0.007). Moreover, anti-EPOR antibodies were detected in 22 of 69 (31.9%) SLE patients with anemia and in only nine of 100 (9.0%, p < 0.001) in those without. Furthermore, the patients with anti-EPOR antibodies exhibited more severe anemia and often presented as microcytic anemia (p = 0.001). Finally, anti-EPOR antibodies seemed more likely to occur in patients with rash (p = 0.008), lower levels of C(3) component (p = 0.01), higher titer of anti-dsDNA antibodies (p < 0.001) and higher disease activity scores (p = 0.024). The results of this study suggest that anti-EPOR antibodies might play a vital role in SLE patients developing anemia because of the higher incidence of antibodies to EPOR found in SLE patients with anemia. Thus, there might be clinical value in detecting anti-EPOR antibodies in SLE patients with anemia. Therefore, the pathologic role of the antibodies in inducing anemia needs to be established in future studies.