Echolocation in soft-furred tree mice.

Echolocation is the use of reflected sound to sense features of the environment. Here, we show that soft-furred tree mice (Typhlomys) echolocate based on multiple independent lines of evidence. Behavioral experiments show that these mice can locate and avoid obstacles in darkness using hearing and ultrasonic pulses. The proximal portion of their stylohyal bone fuses with the tympanic bone, a form previously only seen in laryngeally echolocating bats. Further, we found convergence of hearing-related genes across the genome and of the echolocation-related gene prestin between soft-furred tree mice and echolocating mammals. Together, our findings suggest that soft-furred tree mice are capable of echolocation, and thus are a new lineage of echolocating mammals.

Isolated alpine habitats reveal disparate ecological drivers of taxonomic and functional beta-diversity of small mammal assemblages.

The interpretation of patterns of biodiversity requires the disentanglement of geographical and environmental variables. Disjunct alpine communities are geographically isolated from one another but experience similar environmental impacts. Isolated homogenous habitats may promote speciation but constrain functional trait variation. In this study, we examined the hypothesis that dispersal limitation promotes taxonomic divergence, whereas habitat similarity in alpine mountains leads to functional convergence. We performed standardized field investigation to sample non-volant small mammals from 18 prominent alpine sites in the Three Parallel Rivers area. We estimated indices quantifying taxonomic and functional alpha- and beta-diversity, as well as beta-diversity components. We then assessed the respective importance of geographical and environmental predictors in explaining taxonomic and functional compositions. No evidence was found to show that species were more functionally similar than expected in local assemblages. However, the taxonomic turnover components were higher than functional ones (0.471±0.230 vs. 0.243±0.215), with nestedness components showing the opposite pattern (0.063±0.054 vs. 0.269±0.225). This indicated that differences in taxonomic compositions between sites occurred from replacement of functionally similar species. Geographical barriers were the key factor influencing both taxonomic total dissimilarity and turnover components, whereas functional beta-diversity was primarily explained by climatic factors such as minimum temperature of the coldest month. Our findings provide empirical evidence that taxonomic and functional diversity patterns can be independently driven by different ecological processes. Our results point to the importance of clarifying different components of beta-diversity to understand the underlying mechanisms of community assembly. These results also shed light on the assembly rules and ecological processes of terrestrial mammal communities in extreme environments.

Increased risk of metabolic dysfunction in children conceived by assisted reproductive technology.

AIMS/HYPOTHESIS: Assisted reproductive technology (ART) is the most widely used treatment for infertility and has resulted in millions of births worldwide. The safety of the offspring has been of the utmost concern. Previous studies suggested an increase in metabolic disorders in offspring later in life. The aim of the present study was to investigate metabolic changes at age 6-10 years in offspring conceived as a result of in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). METHODS: A total of 380 children born from IVF/ICSI and a matched control group of 380 naturally conceived children, all aged 6-10 years, were recruited. Anthropometric measures, ultrasound and serum tests were performed for body mass, glucose metabolism and lipid profiles, and examination of vasculature structure. RESULTS: The children conceived by ART showed significantly higher fasting blood glucose and serum insulin levels and HOMA-IR (adjusted ß [95% CI]: fasting blood glucose 0.49 [0.42, 0.55]; loge-transformed insulin 0.28 [0.20, 0.35]; loge-transformed HOMA-IR 0.38 [0.30, 0.46]), as well as a lower HOMA-B and serum apolipoprotein A (ApoA) levels (adjusted ß [95% CI]: loge-transformed HOMA-B -0.19 [-0.27, -0.11]; ApoA -0.17 [-0.21, -0.13]), when compared with the control group. Furthermore, the ultrasound scan indicated elevated carotid intima-media thickness in children conceived by ART (ß 0.13 [95% CI 0.12, 0.13]). CONCLUSIONS/INTERPRETATION: Children conceived by IVF/ICSI have a less favourable glucose and cardiovascular metabolic profile in childhood when compared with naturally conceived children. The underlying mechanisms and potential long-term consequences need to be elucidated in future studies. Graphical abstract.

Use of Static Cutoffs of Hypertension to Determine High cIMT in Children and Adolescents: An International Collaboration Study.

BACKGROUND: Pediatric hypertension is typically defined as blood pressure ≥ sex-, age-, and height-specific 95th percentile (high) cutoffs. Given the number of strata, there are hundreds of cutoffs for defining elevated and high blood pressure that make it cumbersome to use in clinical practice. This study aimed to evaluate the utility of the static cutoffs for pediatric hypertension (120/80 mm Hg for children and 130/80 mm Hg for adolescents) in determining high carotid intimamedia thickness (cIMT) in children and adolescents. METHODS: Data were from 6 population-based cross-sectional studies in Brazil, China, Greece, Italy, Spain, and the United Kingdom. A total of 4280 children and adolescents, aged 6 to 17 years, were included. High cIMT was defined as cIMT ≥ sex-, age- and cohort-specific 90th percentile cutoffs. RESULTS: Compared with normal blood pressure, hypertension defined using the percentile-based cutoffs from 2017 American Academy of Pediatrics guideline, and the static cutoffs were associated with similar higher odds for high cIMT (percentile-based cutoffs: odds ratio [OR], 1.46, 95% confidence interval [CI], 1.15-1.86; static cutoffs: OR, 1.65, 95% CI, 1.25-2.17), after adjustment for sex, age, race/ethnicity, body mass index, high-density lipoprotein-cholesterol, triglyceride, and fasting blood glucose. The similar utility of 2 definitions in determining high cIMT was further confirmed by area under the receiver operating characteristic curve and net reclassification improvement methods (P for difference > 0.05). CONCLUSION: Static cutoffs (120/80 mm Hg for children, 130/80 mm Hg for adolescents) performed similarly compared with percentile-based cutoffs in determining high cIMT, supporting the use of static cutoffs in identifying pediatric hypertension in clinical practice.

Metabolic syndrome, clustering of cardiovascular risk factors and high carotid intima-media thickness in children and adolescents.

OBJECTIVE: The clinical utility of screening for pediatric metabolic syndrome (MetS) in children and adolescents is still controversial. We examined the performance of pediatric MetS vs. clustering of cardiovascular risk factors (which are the components of MetS) for predicting high carotid intima-media thickness (cIMT) in children and adolescents. METHODS: Participants included 2427 children and adolescents aged 6-17 years from population-based studies in three countries (Brazil, China and Italy). Pediatric MetS was defined using either the modified National Cholesterol Education Program Adult Treatment Panel III criteria or the modified International Diabetes Federation criteria. Clustering of cardiovascular risk factors was calculated as the sum of five components of MetS (i.e. central obesity, elevated blood pressure, elevated triglycerides, reduced HDL-cholesterol and elevated fasting blood glucose). High cIMT was defined as cIMT at least 95th percentile values for sex and age developed from European children. RESULTS: Presence of one, two or at least three cardiovascular risk factors (using the National Cholesterol Education Program Adult Treatment Panel III criteria), as compared with none, was associated with gradually increasing odds of high cIMT [odds ratios (95% confidence intervals): 1.60 (1.29-1.99), 2.89 (2.21-3.78) and 4.24 (2.81-6.39), respectively]. High cIMT was also associated with presence (vs. absence) of MetS (odds ratio = 2.88, 95% confidence interval = 1.95-4.26). However, clustering of cardiovascular risk factors predicted high cIMT markedly better than MetS (area under the curve of 0.66 vs. 0.54, respectively). Findings were similar using the International Diabetes Federation criteria for pediatric MetS. CONCLUSION: In children and adolescents, a graded score based on five cardiovascular risk factors (used to define MetS) predicted high cIMT markedly better than MetS. These findings do not support the clinical utility of MetS for screening youth at increased cardiovascular risk, as expressed in this study by high cIMT.

Long-term outcome of percutaneous balloon aortic valvuloplasty for children with congenital aortic valve stenosis / 中华心血管病杂志

Objective: To assess the efficacy and long-term outcome of percutaneous balloon aortic valvuloplasty (PBAV) for children with congenital aortic stenosis (CAS) and to explore risk factors for significant aortic regurgitation (AR) and reintervention after PBAV during follow up. Methods: This was a retrospective study. Children (≤18 years old) with CAS, who underwent PBAV in Guangdong Provincial Hospital from January 2004 to December 2018, were included in this study. Demographic, preoperative transthoracic echocardiography (TTE) and surgical data were collected. Postoperative complications were closely observed, and the patients were followed up at 1, 6, 12 months after the operation, and then at one year interval thereafter. Endpoint events included significant AR and reintervention. Reintervention was defined as any intervention that needed to be performed on the valve for various reasons, including re-PBAV, surgical valvuloplasty and valve replacement. Significant AR was defined as AR grade≥3 by TTE criteria. The results of the last TTE examination before the end of the study were collected. The Kaplan-Meier curve for long-term AR-free and intervention-free survival was plotted. Cox regression model was used to further analyze the risk factors for significant AR and reintervention after PBAV in CAS patients. Results: A total of 55 patients were enrolled in this study, and the age was 4.6(1.6, 6.5) years, with 37(67.3%) males. The peak systolic valve gradient fell from (80.3±30.6)mmHg to (38.5±18.5)mmHg(P<0.001, 1 mmHg=0.133 kPa). Surgical success rate was 89% (49/55). Acute post-PBAV AR occurred in 18 patients, including 3 patients with RA≥3 grade. In-hospital complications occurred in 6 patients (2 deaths, 2 cases of transient arrhythmia, and 2 cases of femoral artery embolization). Fifty patients accomplished the follow-up and the follow-up time was 6.2(3.4, 8.5) years. Significant AR was found in 20 patients. Significant AR-free survival rate was 53% at 5 years and 19% at 10 years. Reintervention was performed in 11 patients (4 with valvuloplasty and 7 with valve replacement), and the 5-year and 10-year intervention-free survival rates were 87% and 62%, respectively. Multivariate Cox regression analysis showed that acute post-PBAV AR was a risk factor for long-term significant AR (HR=2.398, 95%CI 1.007-5.712, P=0.048). Post-PBAV residual pressure gradient ≥ 35 mmHg (HR=4.747, 95%CI 1.116-19.329, P=0.030)and acute post-PBAV AR (HR=5.104, 95%CI 1.083-24.065, P=0.039)were risk factors for re-intervention. Conclusions: PBAV is safe and effective in the treatment of CAS in children, but attention should be paid on significant AR post procedure. Acute post-PBAV AR is a risk factor for re-intervention and significant AR post PBAV, and high post-PBAV residual pressure gradient is a risk factor for re-intervention.

Potential urine biomarkers for gestational hypertension and preeclampsia.

Differential proteomic technology was used to identify urine proteomic profile of gestational hypertension and preeclampsia. Urine samples were collected from 10 patients with gestational hypertension, 10 patients with mild preeclampsia, 10 patients with severe preeclampsia and 10 normal pregnancies and analyzed by 2­D difference gel electrophoresis, then matrix assisted laser desorption ionization mass spectrometry was used to identify differential proteins. Subsequently, ELISA was used to verify the content variation of the identified proteins in 200 urine samples. In total, 30 differential proteins were identified. For prostaglandin­H2 D­isomerase (L­PGDS), perlecan and other 15 proteins, the contents in patients with gestational hypertension were higher than that of normal pregnancies, but lower in mild and severe preeclampsia. By contrast, serum albumin and α­1­antitrypsin was lower in samples from patients with gestational hypertension and higher in patients with mild and severe preeclampsia compared with normal pregnancies. ELISA verified that the urinary concentration of L­PGDS and perlecan were significantly lower in patients with preeclampsia than in normal pregnancies (P<0.05). Urine proteomics is a useful tool to identify potential biomarkers to distinguish between different types of hypertensive disorders in pregnancy. L­PGDS and perlecan could potentially be used as markers to reflect the state of renal function, and may participate in the genesis and development of renal injury during preeclampsia.

Metabolically Healthy Obesity and High Carotid Intima-Media Thickness in Children and Adolescents: International Childhood Vascular Structure Evaluation Consortium.

OBJECTIVE: It has been argued that metabolically healthy obesity (MHO) does not increase cardiovascular disease (CVD) risk. This study examines the association of MHO with carotid intima-media thickness (cIMT), a proxy of CVD risk, in children and adolescents. RESEARCH DESIGN AND METHODS: Data were available for 3,497 children and adolescents aged 6-17 years from five population-based cross-sectional studies in Brazil, China, Greece, Italy, and Spain. Weight status categories (normal, overweight, and obese) were defined using BMI cutoffs from the International Obesity Task Force. Metabolic status (defined as "healthy" [no risk factors] or "unhealthy" [one or more risk factors]) was based on four CVD risk factors: elevated blood pressure, elevated triglyceride levels, reduced HDL cholesterol, and elevated fasting glucose. High cIMT was defined as cIMT ≥90th percentile for sex, age, and study population. Logistic regression model was used to examine the association of weight and metabolic status with high cIMT, with adjustment for sex, age, race/ethnicity, and study center. RESULTS: In comparison with metabolically healthy normal weight, odds ratios (ORs) for high cIMT were 2.29 (95% CI 1.58-3.32) for metabolically healthy overweight and 3.91 (2.46-6.21) for MHO. ORs for high cIMT were 1.44 (1.03-2.02) for unhealthy normal weight, 3.49 (2.51-4.85) for unhealthy overweight, and 6.96 (5.05-9.61) for unhealthy obesity. CONCLUSIONS: Among children and adolescents, cIMT was higher for both MHO and metabolically healthy overweight compared with metabolically healthy normal weight. Our findings reinforce the need for weight control in children and adolescents irrespective of their metabolic status.

Diversity and distribution patterns of non-volant small mammals along different elevation gradients on Mt. Kenya, Kenya.

The distribution of small mammals in mountainous environments across different elevations can provide important information on the effects of climate change on the dispersal of species. However, few studies conducted on Afromontane ecosystems have compared the altitudinal patterns of small mammal diversity. We investigated the species diversity and abundance of non-volant small mammals (hereafter 'small mammals') on Mt. Kenya, the second tallest mountain in Africa, using a standard sampling scheme. Nine sampling transects were established at intervals of 200 m on the eastern (Chogoria) and western (Sirimon) slopes. A total of 1 905 individuals representing 25 species of small mammals were trapped after 12 240 trap-nights. Abundance was highest at mid-elevations on both slopes. However, species richness and distribution patterns differed between the two slopes. More species were recorded on Chogoria (24) than on Sirimon (17). On Chogoria, species richness was higher at mid-high elevations, with a peak at mid-elevation (2 800 m a.s.l.), whereas species richness showed little variation on the Sirimon slope. These results indicate that patterns of species diversity can differ between slopes on the same mountain. In addition, we extensively reviewed literature on Mt. Kenya's mammals and compiled a comprehensive checklist of 76 mammalian species. However, additional research is required to improve our understanding of small mammal diversity in mountain habitats in Africa.

Relationship between clustering of metabolic disorders and left ventricular hypertrophy in hypertensive children and adolescents / 中国学校卫生

Objective@#To examine the relationship between clustering of metabolic disorders and left ventricular hypertrophy (LVH) in hypertensive children and adolescents, and to provide the reference for preventing the damage to their heart structure.@*Methods@#Based on the data from the Twelfth Five-year National Science and Technology Support Program “Early Warning, Diagnosis and Treatment of Cardiovascular Disease in Children” from September 2012 to September 2014 in Jinan, 261 children and adolescents aged 6-17 years whose hypertensive status was confirmed based on appearance of elevated blood pressure across three different occasions were included. Covariance analysis was used to analyze the relationship of clustering of metabolic disorders with left ventricular mass index levels. Multivariable logistic regression model was used to examine the relationship of clustering of metabolic disorders with LVH.@*Results@#After adjustment for sex, age and blood pressure, LVMI levels were (33.21±1.85) (38.57±1.19) and (43.00±1.63)g/m2.7, respectively, for hypertensive children and adolescents carrying 0, 1 and ≥2 metabolic disorders; LVMI levels increased with the number of metabolic disorders in hypertensive children and adolescents (P<0.01). Compared with the hypertensive children and adolescents without any metabolic disorders, the risk for LVH increased in ones carrying 1 and ≥2 metabolic disorders, the odds ratios and 95% confidence intervals were 2.41(1.11-5.23) and 4.69(2.05-10.74), respectively.@*Conclusion@#The clustering of metabolic disorders was positively correlated with the LVMI levels and risk of LVH in hypertensive children and adolescents. Therefore, to prevent cardiac damage such as LVH in hypertensive children and adolescents, it is important to prevent and control metabolic disorders comprehensively.

Research progress in the role of small RNA fragments derived from tRNA in malignant tumors / 医学研究生学报

Noncoding small RNAs are the important regulators of vital processes. Through the high-throughput sequencing and analyses of small RNA fragments, a new class of non-coding small RNAs has been presented, which can be matched to the known tRNA gene. The different sources of tRFs are classified into various types depending on where they match on the parental tRNA. The tRFs can be expressed in a variety of organisms. Recent studies have found that the tRFs have a variety of biological functions in the regulation of gene expression, epigenetics，tumor suppression, neurodegeneration and so on. As a regulatory RNA, the tRFs play an important role in development and progression of tumors, and are known to play regulatory roles in the proliferation and metastasis of tumor cells. This article reviews the research progress on the classification，biological function and role of tRFs in malignant tumors.

Predictors of operability in children with severe pulmonary hypertension associated with congenital heart disease / 中华医学杂志(英文版)

BACKGROUND@#Pulmonary artery hypertension associated with congenital heart disease (PAH-CHD) occurs predominantly among patients with uncorrected CHD. Treatment of severe pediatric PAH-CHD remains a major intractability. This study evaluated the predictors and prognoses of children with PAH-CHD who underwent surgical correction.@*METHODS@#The data for 59 children with severe PAH-CHD who underwent surgical correction, with or without postoperative medication, between May 2011 and June 2015 at the Guangdong Provincial People's Hospital were analyzed retrospectively. A regression analysis, receiver-operating characteristic (ROC) curves, and Kaplan-Meier curves were used for survival analysis.@*RESULTS@#Fifty-nine children with severe PAH-CHD underwent heart catheterization and correction, with or without specific anti-PAH drugs postoperatively, were included in this study. The pulmonary pressure, heart function, and ending events were observed and median observation period was 49 ± 20 months. Twenty-eight patients (50%) received at least one additional anti-PAH drug after correction. The survival rate after 2 years was 91.5% (54/59); two patients were in a critical condition, and three were lost to follow-up. Twelve patients (29%) still received over one additional PAH-specific therapy at follow-up, whereas 42 (75%) had successfully stopped drug treatment. Two patients (3.5%) died and one underwent a second thoracotomy to remove the ventricular septal defect patch. Acute vasoreactivity test (AVT) criteria had limited efficacy in predicting pediatric PAH-CHD, whereas pulmonary vascular resistance (PVR) ≤ 6.65 Wood units (WU)/m or PVR/systemic vascular resistance (SVR) ≤ 0.39 during AVT indicated a good prognosis after surgical correction with an AUC of 98.3% (95% confidence interval [CI]: 96.0-100%), 98.4% (95% CI: 96.0-100%) sensitivity of 100%, 100% and specificity of 82.1%, 92.9%, respectively.@*CONCLUSIONS@#Although the criteria for positive AVT currently used are unsuitable for pediatric patients with PAH-CHD, PVR and PVR/SVR during AVT are excellent predictors of outcome in pediatric PAH-CHD. Surgery aided by anti-PAH drugs is an effective strategy and should be recommended for severe pediatric PAH-CHD with PVR ≤ 6.65 WU/m and PVR/SVR ≤ 0.39 after iloprost aerosol inhalation.

A new genus of Asiatic short-tailed shrew (Soricidae, Eulipotyphla) based on molecular and morphological comparisons.

Blarinellini is a tribe of soricine shrews comprised of nine fossil genera and one extant genus. Blarinelline shrews were once widely distributed throughout Eurasia and North America, though only members of the Asiatic short-tailed shrew genus Blarinella currently persist (mostly in southwestern China and adjacent areas). Only three forms of Blarinella have been recognized as either species or subspecies. However, recent molecular studies indicated a strikingly deep divergence within the genus, implying the existence of a distinct genus-level lineage. We sequenced the complete mitochondrial genomes and one nuclear gene of three Asiatic short-tailed and two North American shrews and analyzed them morphometrically and morphologically. Our molecular analyses revealed that specimens ascribed to B. griselda formed two deeply diverged lineages, one a close relative to B. quadraticauda, whereas the other - comprised of topotype specimens from southern Gansu - diverged from other Blarinella in the middle Miocene (ca. 18.2 million years ago (Ma), 95% confidence interval=13.4-23.6 Ma). Although the skulls were similarly shaped in both lineages, we observed several diagnostic characteristics, including the shape of the upper P4. In consideration of the molecular and morphological evidence, we recognize B. griselda as the sole species of a new genus, namely, Pantherina gen. nov. Interestingly, some characteristics of Pantherina griselda are more similar to fossil genera, suggesting it represents an evolutionarily more primitive form than Blarinella. Recognition of this new genus sheds light on the systematics and evolutionary history of the tribe Blarinellini throughout Eurasia and North America.

Species identification of crested gibbons (Nomascus) in captivity in China using karyotyping- and PCR-based approaches.

Gibbons and siamangs (Hylobatidae) are well-known for their rapid chromosomal evolution, which has resulted in high speciation rate within the family. On the other hand, distinct karyotypes do not prevent speciation, allowing interbreeding between individuals in captivity, and the unwanted hybrids are ethically problematic as all gibbon species are endangered or critically endangered. Thus, accurate species identification is crucial for captive breeding, particularly in China where studbooks are unavailable. Identification based on external morphology is difficult, especially for hybrids, because species are usually similar in appearance. In this study, we employed G-banding karyotyping and fluorescence in situ hybridization (FISH) as well as a PCR-based approach to examine karyotypic characteristics and identify crested gibbons of the genus Nomascus from zoos and nature reserves in China. We characterized and identified five karyotypes from 21 individuals of Nomascus. Using karyotypes and mitochondrial and nuclear genes, we identified three purebred species and three hybrids, including one F2 hybrid between N. gabriellae and N. siki. Our results also supported that N. leucogenys and N. siki shared the same inversion on chromosome 7, which resolves arguments from previous studies. Our results demonstrated that both karyotyping and DNA-based approaches were suitable for identifying purebred species, though neither was ideal for hybrid identification. The advantages and disadvantages of both approaches are discussed. Our results further highlight the importance of animal ethics and welfare, which are critical for endangered species in captivity.

Diagnosis and treatment of anomalous aortic origin of a coronary artery from the opposite sinus / 中华实用儿科临床杂志

Anomalous aortic origin of a coronary artery from the opposite sinus (AAOCA)is one of the con-genital coronary artery malformations that might cause syncope,myocardial ischemia and sudden cardiac death (SCD), particularly in adolescents and young people.The most important inducing factor of myocardial ischemia and syncope is strenuous exercise.In recent years,more and more young athletes SCD events have been reported,and SCD related to AAOCA is now becoming the hot issue of common concern. Now,the concept,classification,clinical manifestations, diagnosis,and treatment strategies of AAOCA were introduced.

[Screening and verification of plasma biomarkers for stable angina pectoris: a differential proteomic analysis].

OBJECTIVE: To compare and analyze the differentially expressed plasma proteome between patients with stable angina pectoris (SAP) and healthy donors to identify the biomarkers for early diagnosis of SAP. METHODS: Plasma samples from 60 patients with SAP and 60 healthy controls were collected. Twenty samples (100 mL each) randomly selected from each group were pooled and after removing high-abundance proteins from the pooled plasma, two-dimensional gel electrophoresis (2DE) was performed to isolate the total proteins. The protein spots with more than 2 fold changes were selected after 2D analysis using software, and the differentially expressed proteins were identified by MALDI TOF/TOF mass spectrometer. ELISA was performed to detect hemoglobin subunit delta (HBD) levels in 40 randomly selected samples from each group for verification of the results of 2DE. RESULTS: A total of 7 differentially expressed proteins were found in plasma samples from patients with SAP, including 3 up regulated proteins (serum albumin, hemoglobin subunit alpha and hemoglobin subunit delta,) and 4 down?regulated ones (apolipoprotein L1, apolipoprotein C3, apolipoprotein E and complement C4B). ELISA results showed that HBD level was increased in SAP plasma, which was consistent with the results of 2DE. CONCLUSION: Patients with SAP have different plasma protein profiles from those of healthy controls, and HBD may serve as a potential specific biomarker for early diagnosis of SAP.

Dose escalation of Stereotactic Body Radiotherapy (SBRT) for locally advanced unresectable pancreatic cancer patients with CyberKnife: protocol of a phase I study.

BACKGROUND: Dose escalation of SBRT for locally advanced pancreatic cancer patients had been reported in several studies in one or three fractions, and phase I protocol was developed to investigate the maximum tolerated dose with CyberKnife for locally advanced unresectable pancreatic cancer patients in five fractions. METHODS: The study is designed as a mono-center phase I study. The primary endpoint is to determine the maximum tolerated dose by frequency of III/IV GI (gastrointestinal) toxicity. Adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Doses of 7 Gy, 7.5 Gy, 8 Gy, 8.5 Gy, 9 Gy, 9.5Gy x 5 respectively would be delivered while meeting with normal tissue constraints. A minimum of three patients will be included for each dosage level. And an interval is 4 weeks from the first patient treatment to the next patient treatment at each dose level. The maximal tolerated dose will be defined as the dose for which at least two patients in three, or at least three patients in nine, will present with a limiting toxicity. DISCUSSION: Since the dose and fractions of SBRT treatment for locally advanced pancreatic cancer patients are still unknown, we propose to conduct a Phase I study determining the maximum tolerated dose of CyberKnife SBRT for the treatment of locally advanced pancreatic tumor based on a 5 fractions treatment regimen. This trial protocol has been approved by the Ethics committee of Changhai hospital. The ethics number is 2016-030-01. TRIAL REGISTRATION: Clinical trials number: NCT02716207 . Date of registration: 20 March 2016.

Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study.

The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples. Benzo(a)pyrene exposure induced multiple alterations in DNA methylation and in mRNA expressions of DNA methyltransferases and ten-11 translocation proteins; these alterations partially occurred in Xuanwei lung cancer. Furthermore, benzo(a)pyrene-induced DKK2 and EN1 promoter hypermethylation and LPAR2 promoter hypomethylation led to down-regulation and up-regulation of the genes, respectively; the down-regulation of DKK2 and EN1 promoted the cellular proliferation. Thus, DNA methylation alterations induced by benzo(a)pyrene contribute partially to abnormal DNA methylation in air pollution-related lung cancer, and these DNA methylation alterations may affect the development and progression of lung cancer. Additionally, vitamin C and B6 can reduce benzo(a)pyrene-induced DNA methylation alterations and may be used as chemopreventive agents for air pollution-related lung cancer.

Initial experience of using improved motion sensitized driven equilibrium prepared balanced steady-state free precession / 实用医学杂志

Objective To assess the application value of NCE-MRA using iMSDE prepared bSSFP sequence in lower limb in patients with diabetes. Methods This prospective study included a total of 35 patients with type II diabetes who underwent CE-MRA on the 1.5T MR scanner after the NCE-MRA. The obtained MIP images were independently rated by two radiologist with a four score table and using CE-MRA as a reference standard to evaluate the diagnostic accuracy of NCE-MRA for the narrowed arteries. The difference of the percent age of diagnostic arterial segments between NCE-MRA and CE-MRA on diabetic patients was evaluated by the χ2 test. Results Compared with CE-MRA, the diagnostic-value arterial segment ratio of pelvic arteries on NCE-MRA is decreased significantly. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of two readers in NCE-MRA were 95%/87%, 96%/95%, 57%/72%, 99%/99%, and 96%/95%(k=0.76), respectively. Conclusions The NCE-MRA using iMSDE prepared bSSFP sequence is capable of depicting vascu-lar lesions for the lower extremities in diabetic patients with the advantages of contrast agent free, short scan times and good diagnostic value in the thigh and calves.

Anti-tumor immunity and mechanism of microwave ablation / 国际外科学杂志

Microwave ablation,as a minimally invasive therapy,causes focal hyperthermic injury to ablated tumors.It also induces anti-tumor immunity which could contribute to another mechanism of tumor destruction.Combination with immunotherapy could further enhance the tumor-specific immunity,lead to stronger inhibitory effects on both primary and metastatic lesions and decrease recurrence and metastasis.Thus,combination of microwave ablation and immunotherapy is a promising approach in the treatment of solid tumors,especially for advanced cancers.This article reviews recent advances in the mechanism and application of immune effect induced by microwave ablation.