Associations of dietary linoleic acid and alpha linolenic acid intake with cardiovascular, cancer and all-cause mortalities in patients with diabetes: NHANES 1999-2008.

Objective: To investigate the association between the dietary intake of linoleic acid (LA) and alpha linolenic acid (ALA) with mortality outcomes in patients with diabetes. Participants: 3,112 U.S. adults aged≥20 years. Setting: Basic information was collected at baseline of the National Health and Nutrition Examination Survey (NHANES). Serum CRP (mg/dL), total protein (g/L), waist circumference (cm), fasting blood glucose (mmol/L), white blood cell count, serum LDL-C, and serum HDL-C were also measured. Daily diets were also recorded using a 24-hour dietary review to produce the individuals' intake of LA and ALA. The association between tertiles of LA and ALA intake with mortality was analyzed by weighted Cox models adjusted for the main confounders. Main outcome measures: The study included 3,112 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. Death outcomes were ascertained by linkage to the database records through 31 December 2015. Results: Subjects with a high intake of LA (T3) had 17% [hazard ratio (HR) 0.83, 95% CI 0.70 to 0.99) and 48% (HR=0.52, 0.35 to 0.80)] reductions in all-cause mortality and cardiovascular mortality, respectively, compared with subjects with lowest intake (T1). Similar results were observed for ALA, HR of cardiovascular mortality was 0.55 (0.38 to 0.81) and for all-cause mortality was 0.85 (0.69 to 1.04) comparing the highest to lowest intake tertiles. Conclusion: Higher intakes of LA and ALA were inversely associated with CVD and all-cause deaths in patients with diabetes. Proper dietary intakes of LA and ALA could contribute to the cardiovascular health and the long-term survival of patients with diabetes.

Metal Ion Coordination Improves Graphite Nitride Carbon Microwave Therapy in Antibacterial and Osteomyelitis Treatment.

The ability to effectively treat deep bacterial infections while promoting osteogenesis is the biggest treatment demand for diseases such as osteomyelitis. Microwave therapy is widely studied due to its remarkable ability to penetrate deep tissue. This paper focuses on the development of a microwave-responsive system, namely, a zinc ion (Zn2+ ) doped graphite carbon nitride (CN) system (BZCN), achieved through two high-temperature burning processes. By subjecting composite materials to microwave irradiation, an impressive 99.81% eradication of Staphylococcus aureus is observed within 15 min. Moreover, this treatment enhances the growth of bone marrow stromal cells. The Zn2+ doping effectively alters the electronic structure of CN, resulting in the generation of a substantial number of free electrons on the material's surface. Under microwave stimulation, sodium ions collide and ionize with the free electrons generated by BZCN, generating a large amount of energy, which reacts with water and oxygen, producing reactive oxygen species. In addition, Zn2+ doping improves the conductivity of CN and increases the number of unsaturated electrons. Under microwave irradiation, polar molecules undergo movement and generate frictional heat. Finally, the released Zn2+ promotes macrophages to polarize toward the M2 phenotype, which is beneficial for tibial repair.

Association between android fat mass, gynoid fat mass and cardiovascular and all-cause mortality in adults: NHANES 2003-2007.

Objectives: Evidence of the relationship between android fat mass and gynoid fat mass with the mortality prediction is still limited. Current study analyzed the NHANES database to investigate the relationship between android fat mass, gynoid fat mass and CVD, with all-cause mortality. Method: The study subjects were NHANES participants over 20 years old, two indicators of regional body composition, android fat and gynoid fat were measured by Dual Energy x-ray Absorptiometry (DEXA). The other various covariates data obtained from the NHANES questionnaire and laboratory measurements, including age, gender, education, race/ethnicity, uric acid, total serum cholesterol, albumin, Vitamin C, folate, alcohol drinking, smoking status, history of diabetes, and hypertension. Mortality status was ascertained from a linked mortality file prepared by the National Center for Health Statistics. The study population was divided quartiles based on the distribution of android fat mass and gynoid fat mass. The relationship between these two indicators with cardiovascular and all-cause mortality was investigated by using Cox regression. The covariates age, gender, smoking status, drinking status, history of diabetes, and history of hypertension were stratified. Results: In the fully adjusted model, Q3 had the lowest HR in android fat mass and gynoid fat mass. When examining the relationship between android fat mass and CVD mortality, current smokers and drinkers had the lowest CVD risk in Q2 [smoking: 0.21 (0.08, 0.52), drinking: 0.14 (0.04, 0.50)]. In diabetic patients, compared with Q1, other groups with increased android fat mass can significantly reduce the risk of CVD [Q4: 0.17 (0.04, 0.75), Q3: 0.18 (0.03, 1.09), Q2: 0.27 (0.09, 0.83)]. In ≥60 years old and female, the greater the gynoid fat mass, the smaller the HR of all-cause mortality [Q4 for ≥60 years old: 0.57 (0.33, 0.96), Q4 for female: 0.37 (0.23, 0.58)]. People <60 years old had a lower risk of all-cause mortality with gynoid fat mass in Q3 than those ≥60 years old [<60 years: 0.50 (0.27, 0.91), ≥60 years: 0.65 (0.45, 0.95)]. Among subjects without hypertension, the group with the largest android fat mass had the lowest risk of CVD mortality, and the group with the largest gynoid fat mass had the lowest risk of all-cause mortality [Android fat mass: 0.36 (0.16, 0.81), gynoid fat mass: 0.57 (0.39, 0.85)]. Conclusion: Moderate android fat mass and gynoid fat mass (Q3) had the most protective effect. Smokers and drinkers need to control their body fat. Being too thin is harmful to people with diabetes. Increased gynoid fat mass is a protective factor for all-cause mortality in older adults and females. Young people's gynoid fat mass is more protective in the moderate range than older people's. If no high blood pressure exists, people with more android and gynoid fat mass have a lower risk of CVD or all-cause mortality.

Associations between seminal plasma triclosan and low sperm quality: A case-control study.

OBJECTIVE: Triclosan (TCS), a novel endocrine disrupter, has induced widespread human exposure due to its widespread use in personal care products. Environmental TCS exposure was suggested to be associated with human semen quality. However, little is known about seminal plasma TCS concentration and the risk of low sperm quality. This case-control study is established to examine the relationship between seminal plasma TCS and the risk of low sperm quality. STUDY DESIGN: One hundred men with low sperm quality as cases and one hundred normal men as controls were recruited a fertility clinic in Shijiazhuang, China, during 2018-2019. Seminal plasma TCS concentration was determined using an ultrahigh-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). Sperm concentration, sperm count, sperm motility and sperm progressive motility were evaluated according to World Health Organization (WHO) guidelines to assess the sperm quality. We used the Mann-Whitney rank-sum test and Kruskal-Wallis test to assess the differences of seminal plasma TCS concentration between the cases and the controls. In addition, logistic regression analysis was used to estimate the associations between seminal plasma TCS concentrations and low sperm quality risk adjusting for age, body mass index (BMI), abstinence time, smoking, and drinking RESULTS AND CONCLUSIONS: The level of seminal plasma TCS was observed slightly but not significantly higher in the case group than the control group. We also observed significant association between seminal plasma TCS concentrations and semen parameters in both control and case groups. Moreover, the seminal plasma TCS levels at the fourth quartile were found to be more likely to exhibit low sperm quality risk with increased adjusted odds ratios of 2.36 (95% confidence interval 1.03-5.39) compared to the first quartile. Our results reveal that seminal plasma TCS concentration was positively associated with low sperm quality risk.

Association of Blood Urea Nitrogen with Cardiovascular Diseases and All-Cause Mortality in USA Adults: Results from NHANES 1999-2006.

In the general population, there is little evidence of a link between blood urea nitrogen (BUN) and long-term mortality. The goal of this study was to explore whether higher BUN concentration is a predictor of cardiovascular disease (CVD) and all-cause mortality. From 1999 to 2006, the National Health and Nutrition Examination Survey (NHANES) included 17,719 adult individuals. Death outcomes were ascertained by linkage to the database records through 31 December 2015. The Cox proportional hazard regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause mortality in individuals. We also performed stratified analyses based on age, gender, drinking, smoking, history of hypertension and diabetes. During a mean follow-up 11.65 years, a total of 3628 deaths were documented, of which 859 were due to CVD. Participants with higher BUN had a higher risk of CVD and all-cause death compared to those with lower BUN. After multifactor adjustment for demographics, major lifestyle factors, and hypertension and diabetes history, higher BUN levels compared with lower levels were significantly associated with higher risk of CVD (HR: 1.48 [1.08, 2.02], P-trend < 0.001) and all-cause mortality (HR: 1.48 [1.28, 1.72], P-trend < 0.001). In subgroup analyses, we found that the trend in the association of BUN with the risk of death remained strong in female subjects. Greater BUN levels were linked to higher CVD and all-cause mortality in the NHANES of American adults. The importance of BUN in predicting death is supported by our research.

Ultra-Strong Comprehensive Radiation Effect Tolerance in Carbon Nanotube Electronics.

Carbon nanotube (CNT) field-effect transistors (FETs) have been considered ideal building blocks for radiation-hard integrated circuits (ICs), the demand for which is exponentially growing, especially in outer space exploration and the nuclear industry. Many studies on the radiation tolerance of CNT-based electronics have focused on the total ionizing dose (TID) effect, while few works have considered the single event effects (SEEs) and displacement damage (DD) effect, which are more difficult to measure but may be more important in practical applications. Measurements of the SEEs and DD effect of CNT FETs and ICs are first executed and then presented a comprehensive radiation effect analysis of CNT electronics. The CNT ICs without special irradiation reinforcement technology exhibit a comprehensive radiation tolerance, including a 1 × 104 MeVcm2 mg-1 level of the laser-equivalent threshold linear energy transfer (LET) for SEEs, 2.8 × 1013 MeV g-1 for DD and 2 Mrad (Si) for TID, which are at least four times higher than those in conventional radiation-hardened ICs. The ultrahigh intrinsic comprehensive radiation tolerance will promote the applications of CNT ICs in high-energy solar and cosmic radiation environments.

Early-Adulthood Weight Change and Later Physical Activity in Relation to Cardiovascular and All-Cause Mortality: NHANES 1999-2014.

Limited evidence investigated the combined influence of early-adulthood weight change and later physical activity on the risk of cardiovascular (CVD) and all-cause mortality. The aim of this study is to explore the associations of early-adulthood weight change and later physical activity with CVD and all-cause mortality. This is a cohort study of 23,193 US adults aged 40 to 85 years from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2014. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) of CVD and all-cause mortality associated with early-adulthood weight change and later physical activity. During a median follow-up of 9.2 years, there were 533 and 2734 cases of CVD and all-cause deaths. Compared with being physically inactive, the HRs of the CVD mortality of being physically active were 0.44 (0.26 to 0.73), 0.58 (0.19 to 1.82), 0.38 (0.17 to 0.86) and 0.46 (0.21 to 1.02) among individuals with stable normal, stable obese, non-obese to obese and maximum overweight early-adulthood weight change patterns. Using stable normal patterns that were physically active later as the reference, other early-adulthood weight change patterns did not show a significantly higher risk of CVD mortality when participants were physically active in later life; later physically inactive participants had a significantly increased risk of CVD mortality, with HRs of 2.17 (1.30 to 3.63), 5.32 (2.51 to 11.28), 2.59 (1.29 to 5.18) and 2.63 (1.32 to 5.26) in the stable normal, stable obese, non-obese to obese and maximum overweight groups, respectively. Similar results can be seen in the analyses for all-cause mortality. Our findings suggest that inadequate physical activity worsens the negative impact of unhealthy early-adulthood weight change patterns, which is worthy of being noted in the improvement of public health.

Interfacial Mo, W-Conjugated Polarization, and Oxygen Vacancies of MoO2/WO3 in Enhanced Microwave Therapy for MRSA-Induced Osteomyelitis.

Deep tissue infection, such as osteomyelitis, caused by methicillin-resistant Staphylococcus aureus (MRSA) infection, poses a serious threat to public health and cannot be effectively treated by antibiotics. In this study, we report a microwave (MW)-responsive MoO2/WO3 heterojunction that can be utilized to effectively treat MRSA-infected osteomyelitis under MW irradiation because of the enhanced MW thermal effect and MW catalysis of the composite. The underlying mechanism is as follows: A myriad of oxygen vacancies forms on the surface of MoO2 and WO3 by deoxidization effect with hydrogen from the decomposition of sodium borohydride, which induces a mass of free electrons on the surface of the composite and consequently promotes a localized surface plasmon resonance effect (LSPR) under MW irradiation. Furthermore, the conjugation of Mo and W at the interface enhances the LSPR effect. Thus, the LSPR effect not only induces the formation of radical oxygen species, thereby enhancing MW catalysis, but also results in the formation of an interfacial electrical field, which strengthens dipole polarization through synergistic action with oxygen vacancies and contributes to better MW thermal effects. The characteristics of MoO2/WO3 prove to be promising for the treatment of deep-tissue infections under MW irradiation.

Radiotherapy Combined With Concurrent Nedaplatin-Based Chemotherapy for Stage II-III Esophageal Squamous Cell Carcinoma.

Objective: This study was conducted to explore the appropriate radical radiation dose in concurrent chemoradiotherapy (CCRT) for patients with inoperable stage II-III esophageal squamous cell carcinoma (ESCC). Methods: This retrospective study included patients with esophageal cancer (EC) from the database of patients treated at the Affiliated Zhangjiagang Hospital of Soochow University (1/2015-12/2019). Overall survival (OS), progression-free survival (PFS), objective remission rate (ORR), first failure pattern, and toxicities were collected. Results: 112 patients treated with intensity-modulated radiation therapy (IMRT) combined with concurrent chemotherapy of nedaplatin-based regimens were included. Fifty-eight (51.8%) and 54 (48.2%) patients received 60 (HD) and 50.4 (LD) Gy of radiotherapy, respectively. The HD group showed superior OS and a trend for longer PFS compared with the LD group (median OS: 25.5 vs 17.5 months, P = .021; median PFS: 14.0 vs 10.5 months, P = .076). There were more patients with a complete remission (CR) in the HD group than in the LD group (P=.016). The treatment-related toxicities were generally acceptable, but HD radiotherapy would increase the incidence of grade ≥3 late radiotoxicity (22.4% vs 5.6%, P = .011). Conclusion: In nedaplatin-based CCRT for stage II-III ESCC, the radiotherapy dose of 60 Gy achieved a better prognosis. Strengths and limitations of this study: A comparative study of 50.4 Gy and 60 Gy was conducted to evaluate whether 50.4 Gy can be used as a radical radiotherapy dose for inoperable stage II-III esophageal squamous cell carcinoma from a real-world perspective.The highly consistent selection criteria in our study make analysis results highly reliable and scientific.The existing research results support that nedaplatin can be used in concurrent chemoradiotherapy for esophageal squamous cell carcinoma, and this study focuses on the discovery of a better nedaplatin-based combination regimen.The findings of this study are limited to a single-center study with a non-large sample size.Inevitably, recall bias may exist in this retrospective study.Surgery was not involved in the follow-up treatment after concurrent chemoradiotherapy, which may worsen the prognosis of some patients.

Arbutin ameliorated ulcerative colitis of mice induced by dextran sodium sulfate (DSS).

Accumulating evidence has revealed the anti-inflammatory effects of arbutin against various diseases. However, the effects of arbutin are not clarified in ulcerative colitis. This study was intended to investigate the protective effects and mechanisms of arbutin on DSS-induced colitis. Hematoxylin eosin staining was performed to determine the pathological damage of intestinal tissue in mice. Inflammatory factors levels in intestinal tissue were detected by enzyme linked immunosorbent assay (ELISA) assay. TUNEL staining showed the apoptosis levels of cells. Intestinal permeability was analyzed using the application of Fluorescein isothiocyanate Dextran (FD) 4. The levels of Zona Occludens 1 (ZO-1), occluding and claudin-1, and the related proteins in MAPK/ELK1 pathway were analyzed by Western blot. DSS promotes pathological injury, the levels of pro-inflammatory factors containing tumor necrosis factor alpha (TNF-α), Interleukin- 6 (IL-6) and myeloperoxidase (MPO), and cell apoptosis in the mouse colon. Additionally, intestinal permeability was increased and the levels of tight function-related proteins were increased following DSS induction. Its effects could be greatly improved by arbutin. Arbutin exerted effects by eliciting anti-inflammatory effects and maintaining normal intestinal mucosal barrier function, the action mechanism of which could be associated with MAPK/ELK1 pathway.

Radiation damage and abnormal photoluminescence enhancement of multilayer MoS2under neutron irradiation.

In this work, neutron irradiation effects on the optical property of multilayer MoS2have been investigated in depth. Our results display that the intensity of the photoluminescence (PL) spectra of MoS2flakes tends to slightly decrease after exposed to neutron irradiation with low fluence of 4.0 × 108n/cm2. An unexpected improvement of PL intensity, however, is observed when the irradiation fluence accumulates to 3.2 × 109n/cm2. Combined with the experimental results and first-principles calculations, neutron irradiation damage effects of multilayer MoS2are analyzed deeply. Sulfur vacancy (VS) is found to be responsible for the attenuation of the PL intensity as a major defect. In addition, our results reveal that the adsorbed hydroxyl groups (OH) and oxygen atoms (O) on the surface of MoS2flakes not only promote the transition from trion excitons to neutral excitons, but also repair theVSin MoS2, both of which contribute to the enhancement of luminescence properties. The detailed evolution process of irradiation-induced defects is discussed to reveal the microscopic mechanism of the significantly difference in luminescence intensity of MoS2under different irradiation stages. This work has great significance for evaluating the neutron radiation hardness of multilayer MoS2, which is helpful to enrich the fundamental research on neutron irradiation effects.

CIC de novo loss of function variants contribute to cerebral folate deficiency by downregulating FOLR1 expression.

Background Cerebral folate deficiency (CFD) syndrome is characterised by a low concentration of 5-methyltetrahydrofolate in cerebrospinal fluid, while folate levels in plasma and red blood cells are in the low normal range. Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha, FRα), DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter) have been previously identified in patients with CFD. Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios. Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Using 48 sporadic CFD samples as a validation cohort, we identified three additional rare variants in CIC that are putatively deleterious mutations. Functional analysis indicates that CIC binds to an octameric sequence in the promoter regions of folate transport genes: FOLR1, PCFT and reduced folate carrier (Slc19A1; RFC1). The CIC nonsense variant (p.R353X) downregulated FOLR1 expression in HeLa cells as well as in the induced pluripotent stem cell (iPSCs) derived from the original CFD proband. Folate binding assay demonstrated that the p.R353X variant decreased cellular binding of folic acid in cells. Conclusion This study indicates that CIC loss of function variants can contribute to the genetic aetiology of CFD through regulating FOLR1 expression. Our study described the first mutations in a non-folate pathway gene that can contribute to the aetiology of CFD.

Responses of metastatic primary fallopian tube carcinoma to pembrolizumab and nab-paclitaxel: A case report.

RATIONALE: Primary fallopian tube carcinoma (PFTC) is an extremely rare but invasive malignancy with a dismal prognosis. Very few data exist on the salvage treatment for patients with PFTC. Here we report a case showing an impressive response to immunotherapy combined with chemotherapy, which have never been reported before on patients with metastatic PFTC. PATIENT CONCERNS: A 42-year-old woman, who was diagnosed with PFTC in 2010, had been failed of multiple systemic therapies and antiangiogenic therapy because of the disease recurrence and progression. DIAGNOSIS: Metastatic primary fallopian tube carcinoma. INTERVENTIONS: The patient underwent surgery in May 2010 and had multi-line chemotherapies plus an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody for about 9 years. Due to treatment failure the patient accepted the immunotherapy with the checkpoint inhibitor, pembrolizumab, combined with nab-paclitaxel from December 2018 to April 2019. OUTCOMES: The patient showed a complete response after 6 cycles treatment. Thus far, the patient is taking pembrolizumab as maintenance and remains in good health. LESSONS: Pembrolizumab combined with chemotherapy for treatment of PFTC may provide a positive antitumor effect in multiple metastatic lesions, but more clinical evidence is needed to confirm the efficacy and safety.

What Is the Optimal Radiotherapy Target Size for Non-Operable Esophageal Cancer? A Meta-Analysis.

Definitive radiotherapy has an affirmative role in treating non-operable esophageal cancer; however, the controversy between elective lymph node irradiation (ENI) and involved-field irradiation (IFI) still remains. To ascertain the benefits and disadvantages of the two radiation target volumes, we performed a meta-analysis with 7 related publications. According to our findings, patients treated with ENI and IFI had nearly identical 1, 2, and 3-year survival rates (pooled odds ratio [OR] = 1.004, p = 0.980, and pooled OR = 1.15, p = 0.594, and pooled OR = 0.918, p = 0.679, respectively). Likewise, no significant differences were detected in local recurrence rates (pooled OR = 1.04, p = 0.883), regional recurrence rates (pooled OR = 0.65, p = 0.555), and distant metastasis rates (pooled OR = 1.29, p = 0.309) between the two treatment groups. However, IFI could significantly decrease the incidences of acute radiation esophagitis (pooled OR = 2.30, p = 0.001) and late pneumonia (pooled OR = 2.52, p = 0.04) compared with ENI. This meta-analysis provides evidence that IFI is more feasible for non-operable esophageal cancer than ENI.

Knockdown of TUG1 by shRNA inhibited renal cell carcinoma formation by miR-299-3p/VEGF axis in vitro and in vivo.

Renal cell carcinoma (RCC) is one of the top ten deadly malignancies in the world. The long non-coding RNA taurine up-regulated gene 1 (TUG1) is a transcript that is up-regulated by taurine. There is ample evidence that TUG1 plays a crucial role in the progression of various cancers. This study aimed to investigate the role of TUG1 in RCC and its underlying molecular mechanisms. In the current study, knockdown of TUG1 by shRNA (sh-TUG1) significantly inhibited proliferation, invasion, migration and EMT processes of ACHN cells and OS-RC-2 cells, and induced apoptosis. Besides, bioinformatics analysis revealed that miR-299-3p is a target of TUG1. TUG1 overexpression (LV-TUG1) significantly inhibited the expression of miR-299-3p, whereas sh-TUG1 showed the opposite effect. Dual luciferase reporter assay further confirmed the targeting relationship between TUG1 and miR-299-3p. In addition, vascular endothelial growth factor (VEGFA) is a target of miR-299-3p. Knockdown of VEGFA (si-VEGFA) significantly inhibited the proliferation and motility of ACHN cells, and induced apoptosis. RT-qPCR results showed that sh-TUG1 similarly inhibited VEGFA expression. Further functional analysis indicated that sh-TUG1 inhibited tumorigenesis by down-regulating VEGFA levels. However, LV-TUG1 showed the opposite effects. Furthermore, animal experiments have shown that sh-TUG1 inhibited tumor growth and metastasis and induces apoptosis in vivo. These results indicate that sh-TUG1 inhibited renal cell carcinoma formation by miR-299-3p/VEGF axis in vitro and in vivo. Taken together, all of these results reveal a novel mechanism of TUG1 in RCC tumorigenesis, suggesting that targeted drugs for TUG1 provides a new direction for the treatment of RCC.

Nedaplatin-based chemotherapy regimens combined with concurrent radiotherapy as first-line treatment for stage II-III esophageal squamous cell carcinoma.

Concurrent chemoradiotherapy (CCRT) is an effective first-line treatment for esophageal squamous cell carcinoma (ESCC). The present study aimed to compare clinical outcomes between three nedaplatin-based regimens for CCRT of ESCC. Patients with stage II-III thoracic ESCC in China between January 2012 and May 2016 were included. Patients received esophageal ultrasonography prior to treatment. Chemotherapy was as follows: i) 100 mg/m2 nedaplatin intravenously on day 1 and 70 mg/m2 tegafur-gimeracil-oteracil potassium (S-1) orally twice daily for 2 weeks; ii) 50 mg/m2 nedaplatin intravenously on days 1 and 2 and 35 mg/m2 docetaxel intravenously on days 1 and 8; or iii) 60 mg/m2 nedaplatin intravenously on days 1 and 2. Intensity-modulated radiotherapy was used to administer a total dose of 60-66 Gy (1.8-2.0 Gy per fraction) to the primary tumor and 45-50 Gy to the subclinical region. A total of 70 patients were enrolled (median age, 66 years; range, 50-81 years). T4 disease was identified in 45 (64.3%) patients. All patients completed radiotherapy and received ≥2 chemotherapy cycles. Estimated 1-, 2- and 3-year overall survival (OS) rates were 82.9, 53.9 and 31.4%, respectively. OS and progression-free survival were similar between the three treatment groups. Grade 3/4 hematological toxicities were observed in 35 (50%) patients. The incidence of serious treatment-associated toxicities was numerically highest for the nedaplatin/docetaxel combination. Patients with thoracic ESCC had good clinical outcomes following CCRT. With similar survival rates and disease responses yet lower hematological toxicities, nedaplatin/S-1 and single-agent nedaplatin may be preferable to nedaplatin/docetaxel. Poor control of distant metastasis may be a disadvantage of single-agent chemotherapy use in CCRT, and a further study with larger cohorts is required to confirm this.

The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation.

Mutations in IRF6, TFAP2A and GRHL3 cause orofacial clefting syndromes in humans. However, Tfap2a and Grhl3 are also required for neurulation in mice. Here, we found that homeostasis of Irf6 is also required for development of the neural tube and associated structures. Over-expression of Irf6 caused exencephaly, a rostral neural tube defect, through suppression of Tfap2a and Grhl3 expression. Conversely, loss of Irf6 function caused a curly tail and coincided with a reduction of Tfap2a and Grhl3 expression in tail tissues. To test whether Irf6 function in neurulation was conserved, we sequenced samples obtained from human cases of spina bifida and anencephaly. We found two likely disease-causing variants in two samples from patients with spina bifida. Overall, these data suggest that the Tfap2a-Irf6-Grhl3 genetic pathway is shared by two embryologically distinct morphogenetic events that previously were considered independent during mammalian development. In addition, these data suggest new candidates to delineate the genetic architecture of neural tube defects and new therapeutic targets to prevent this common birth defect.

Deliberate self-harm among children with disabilities in China: a matched case-control study.

BACKGROUND: Study about deliberate self-harm (DSH) in children with different types of disabilities was scarce. This study compared the incidence and patterns of DSH between children with and without disabilities aged 6-17 years using a matched case-control study in Beijing. METHODS: A total of 650 pairs of children with and without disabilities were surveyed. Characteristics of latest episode of self-harm within the 12 months were compared. Associations between disability status, sociodemographic factors, smoking, drinking, sleep problems, and self-harm were examined. RESULTS: Children with disabilities showed significant higher incidence of DSH than children without disabilities. Two groups differed significantly in terms of self-harm methods, body parts injured, premeditation, wishing to be known by others and help-seeking behavior. The adjusted OR for self-harm was 4.76 (2.99-7.55) for children with disabilities compared with children without disabilities. Children who slept fewer than 6 h per night, had difficulty falling asleep at night sometimes/often, and went to sleep after midnight 1 to 3 nights per month or at least once a week were at elevated risk of self-harm. CONCLUSION: This study highlights a strong relationship between disability, sleep problems, and DSH. Interventions to reduce self-harm should target disability and sleep problems as important risk factors.

What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis.

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

Clinical Practice Experiences in Diagnosis and Treatment of Traumatic Brain Injury in Children: A Survey among Clinicians at 9 Large Hospitals in China.

Proper diagnosis and treatment of traumatic brain injury (TBI) in children is becoming an increasingly problematic issue in China. This study investigated Chinese clinicians to provide information about their knowledge and experiences in diagnosis and treatment of pediatric TBI. We conducted a questionnaire survey among clinicians in the emergency departments and neurosurgery departments at 9 major hospitals in China. The questionnaire included demographic information, and knowledge and experiences regarding the diagnosis and treatment of pediatric TBI. A total of 235 clinicians completed questionnaires. 43.8% of the surveyed clinicians reported children with only scalp hematoma without any other signs and symptoms of concussion as TBI cases. Most clinicians (85.1%) reported no existing uniform diagnostic criteria for children with TBI in China. The majority of clinicians (91.9%) reported that CT scans were performed in all patients with suspected head injury as a routine procedure in their hospitals. Only 20.9% of clinicians believed that radiation from CT scanning may increase cancer risk in children. About 33.6% of the clinicians reported that they ordered CT scans to investigate suspected head injury due to the poor doctor-patient relationship in China, and to protect themselves against any medical lawsuits in the future. About 80% of the clinicians reported that there are no existing pediatric TBI treatment guidelines in China. Instead a senior doctor's advice is the most reported guidelines regarding treating pediatric TBI (66.0%). All of the surveyed clinicians reported that the lack of diagnosis and/or treatment standard is the biggest problem in effectively diagnosing and treating pediatric TBI in China. Developing guidelines for the diagnosis and treatment of children with TBI is a high priority in China. The extremely high usage of CT for pediatric TBI in China suggests that it is important to establish evidence-based clinical decision rules to help Chinese clinicians make diagnostic and therapeutic decisions during their practice in order to identify children unlikely to have a clinically-important TBI who can be safely discharged without a CT scan.