[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.

Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia.

[Clinical analysis of 14 cases with childhood acute lymphoblastic leukemia complicated with tropical candidemia].

Objective: To investigate the clinical feature, diagnosis, treatment and prognosis of childhood acute lymphoblastic leukemia (ALL) complicated with candida tropicalis bloodstream infection (CTBI), so as to improve the understanding of this disease. Methods: The general information, clinical manifestation, auxiliary examination, treatment and outcome of 14 childhood ALL who were diagnosed with tropical candidemia between January 2015 and December 2018 in 6 hospitals were analyzed retrospectively. Clinical data of non invasive fungal disease (IFD) ALL (28 cases) and other IFD children (9 cases) admitted in the same period were collected as control group. Logistic regression model was used to analyze the risk factor of CTBI. Results: Among 14 cases, there were 7 males and 7 females, with the age ranged from 17 months to 13 years. All the cases had fever, 9 cases had digestive system symptoms and stool fungal culture were positive in 3 of them; 7 cases had respiratory system symptoms and sputum fungal culture was positive in 1 of them; 2 cases had central nervous system symptoms and 10 cases progressed into septic shock. All 14 cases had neutropenia and the neutropenia duration was 1 to 53 days. Among 14 cases, the C-reactive protein was>50 mg/L in 8 cases, in which the proportion was significantly higher than that in other invasive fungal disease(IFD) (8/14 vs. 1/9, P<0.05), meanwhile the 1, 3-ß-D-glucan detection, galactomannan detection and pulmonary imaging were not remarkable in all 14 cases. The blood culture results of 14 cases were all candida tropicalis, among which 13 cases finished drug susceptibility tests, the isolates of all cases were sensitive to flucytosine and amphotericin B, and the isolates of 4 cases were sensitive to fluconazole, voriconazole and itraconazole. Among 14 cases, 1 case lost to follow-up after giving up treatment, 1 case died before antifungal therapy and the remaining 12 cases received antifungal therapy; 7 of the 14 cases died. Univariate analysis showed that between ALL with CTBI group (14 cases) and ALL without invasive fungal disease (IFD) group (28 cases), the differences in variables such as ALL not in remission (χ²=37.847, P<0.01), length of hospital stay>15 days (χ2=8.351, P=0.004), neutropenia (χ²=14.280, P<0.01), neutropenia duration>10 days (χ²=10.254, P=0.001), use of broad-spectrum antibiotics (χ²=13.888, P<0.01), skin and mucous membrane damage (χ²= 5.923, P=0.015) were statistically significant. Conclusions: In childhood ALL complicated with tropical candidemia, the drug resistance rate and mortality rate were high. For azole-resistant tropical candida, amphotericin B liposome or echinocandins(caspofungin) -fluorocytosine combined therapy was recommended to reduce treatment-related deaths.

[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.

Correction to: CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. α-Tubulin image of rCCN2 treatment  (upper panel in CL1-5) only showed eight lanes, when there should be nine.

[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.

[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.

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.

[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.

EZH2-mediated upregulation of ROS1 oncogene promotes oral cancer metastasis.

Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers. Our data further reveal a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower trimethylation of histone H3 lysine 27 suppressive modification, relaxes chromatin, and promotes the accessibility of the transcription factor STAT1 to the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions. Down-regulation of ROS1 in highly invasive OSCC cells, nevertheless, reduces cell proliferation and inhibits metastasis to lung in the tail-vein injection and the oral cavity xenograft models. Our findings highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Finally, we demonstrate that co-targeting of ROS1 and EGFR could potentially offer an effective oral cancer therapy.

[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.

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.

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.

Proposed correlation of structure network inherited from producing techniques and deformation behavior for Ni-Ti-Mo metallic glasses via atomistic simulations.

Based on the newly constructed n-body potential of Ni-Ti-Mo system, Molecular Dynamics and Monte Carlo simulations predict an energetically favored glass formation region and an optimal composition sub-region with the highest glass-forming ability. In order to compare the producing techniques between liquid melt quenching (LMQ) and solid-state amorphization (SSA), inherent hierarchical structure and its effect on mechanical property were clarified via atomistic simulations. It is revealed that both producing techniques exhibit no pronounced differences in the local atomic structure and mechanical behavior, while the LMQ method makes a relatively more ordered structure and a higher intrinsic strength. Meanwhile, it is found that the dominant short-order clusters of Ni-Ti-Mo metallic glasses obtained by LMQ and SSA are similar. By analyzing the structural evolution upon uniaxial tensile deformation, it is concluded that the gradual collapse of the spatial structure network is intimately correlated to the mechanical response of metallic glasses and acts as a structural signature of the initiation and propagation of shear bands.

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.

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.

Imipramine blue halts head and neck cancer invasion through promoting F-box and leucine-rich repeat protein 14-mediated Twist1 degradation.

The unique characteristic of head and neck squamous cell carcinoma (HNSCC) is that local invasion rather than distant metastasis is the major route for dissemination. Therefore, targeting the locally invasive cancer cells is more important than preventing systemic metastasis in HNSCC and other invasive-predominant cancers. We previously demonstrate a specific mechanism for HNSCC local invasion: the epithelial-mesenchymal transition (EMT) regulator Twist1 represses microRNA let-7i expression, leading to the activation of the small GTPase Rac1 and engendering the mesenchymal-mode movement in three-dimensional (3D) culture. However, targeting the EMT regulator is relatively difficult because of its transcription factor nature and the strategy for confining HNSCC invasion to facilitate local treatment is limited. Imipramine blue (IB) is a newly identified anti-invasive compound that effectively inhibits glioma invasion. Here we demonstrate that in HNSCC cells, a noncytotoxic dose of IB represses mesenchymal-mode migration in two-and-a-half-dimensional/3D culture system. IB suppresses EMT and stemness of HNSCC cells through inhibition of Twist1-mediated let-7i downregulation and Rac1 activation and the EMT signalling. Mechanistically, IB inhibits reactive oxygen species-induced nuclear factor-κB pathway activation. Importantly, IB promotes degradation of the EMT inducer Twist1 by enhancing F-box and leucine-rich repeat protein 14 (FBXL14)-mediated polyubiquitination of Twist1. Together, this study demonstrates the potent anti-invasion and EMT-inhibition effect of IB, suggesting the potential of IB in treating local invasion-predominant cancers.

Maternal gestational diabetes mellitus and overweight and obesity in offspring: a study in Chinese children.

The purpose of this study was to investigate the effects of maternal gestational diabetes mellitus (GDM) and breast feeding on childhood overweight and obesity in a mainland Chinese population. The incidence of and factors associated with overweight and obesity were compared between children of mothers with (n=1068) and without (n=1756) GDM. The independent roles of the associated factors were examined by multiple logistic regression analysis. The incidence of overweight was higher (16.6 v. 12.6%, P=0.002) in the GDM group, but that of obesity was not different (10.7 v. 12.0%, P=0.315). At age 1-2 and 2-5 years, no difference in overweight (11.0 v. 12.0%, P=0.917, and 15.7 v. 14.6%, P=0.693, respectively) was found, while obesity (8.0 v. 13.6%, P=0.019, and 8.4 v. 13.4%, P=0.014, respectively) was less frequent in the GDM offspring. At age 5-10 years, increased overweight (22.2 v. 12.1%, P<0.001) and obesity (15.9 v. 9.0%, P=0.001) were found in the GDM group, which was associated with maternal obesity, being born large-for-gestational age, male gender and formula feeding. After adjusting for confounding factors, GDM remained an independent determinant of offspring overweight and obesity (aOR 2.28, 95% CI 1.61-3.22), suggesting that the effects of GDM were independent of breast feeding, as well as of maternal obesity and birth size.

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.