Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes.The etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and multistage.However,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic studies.Herein,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle conditions.Advanced symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in mice.In-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene detections.Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the model.Based on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to HCC.Collectively,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism status.METHODS We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were nondiabetic.Patients were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,respectively.The primary endpoint was in-hospital mortality.RESULTS Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,respectively.Compared with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not changed.Further-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status.Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts.CONCLUSIONS This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without diabetes.FPG might be useful to stratify patients with AMI.

Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions:a systematic review and meta-analysis

Background Globally,populations afflicted by armed conflict are known to have high rates of mental health disorders.Aims This meta-analysis aims to estimate the prevalence of post-traumatic stress disorder(PTSD)and depressive symptoms among civilians residing in armed conflictaffected regions.Methods This meta-analysis was conducted in accordance with the Preferred Reporting Items forSystematic Reviews and Meta-Analyses.A literature search employing MEDLINE(R),Embase Classic+Embase,APA PsyclNFO,Ovid Healthstar,Journal@Ovid Full Text,Cochrane,PTSDpubs and CINAHL was conducted from inception until 19 March 2024 to identify relevant studies.Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies,and a Comprehensive Meta-Analysiswas usedto conduct the statistical analysis.Results The search yielded 38595 articles,of which 57 were considered eligible for inclusion.The included studies comprised data from 64596 participants.We estimated a prevalence of 23.70%(95%CI 19.50%to28.40%)forPTSD symptomsand 25.60%(95%Cl 20.70%to 31.10%)for depressive features among war-afflicted civilians.The subgroup analysis based on time since the war and the country's economic status revealed the highest prevalence for both PTSD and depressive symptoms was present during the years of war and in low/middle-incomecountries.Conclusions The results of this study provide conclusive evidence of the detrimental impacts of armed conflict on mental health outcomes.Hence,it is crucial to emphasise the significance of both physical and mental health in the aftermath of war and take appropriate humanistic measures to overcome challenges in the management of psychiatric illnesses.

2020版肺癌多学科团队诊疗中国专家共识解读

肺癌是一类异质性较高的恶性肿瘤,诊疗有争议、预后不确定的现象屡见不鲜。目前,肺癌的管理呈现个性化、精准化、多学科、综合治疗的发展趋势。基于循证医学的多学科团队(multidisciplinary team,MDT)诊疗融合了最佳证据、专家经验和个人意愿,减少专科医生的选择偏倚,强调对患者诊疗决策的改变,可有效提高患者的临床获益,优化医疗资源使用,提升诊疗的合理性,拓展科研思路,最终使医患双方在多方面获益。为规范中国肺癌MDT诊疗的开展,中国胸部肿瘤研究协作组、中国抗癌协会肺癌专业委员会、中华医学会肿瘤学分会肺癌学组和中国医师协会肿瘤多学科诊疗专业委员会于2020年共同制定了《肺癌多学科团队诊疗中国专家共识》。本文将从MDT的准备、实施、后期、实战应用4个方面对该共识进行解读。

Clinical significance of diabetes on symptom and patient delay among patients with acute myocardial infarction——an analysis from China Acute Myocardial Infarction(CAMI) registry

Background Diabetes is frequently associated with poor prognosis among acute myocardial infarction(AMI)patients.Patients with these comorbidities often have atypical symptoms and subsequent delay in treatment.Few studies have reported detailed AMI symptoms in patients with diabetes.This study compared AMI symptoms and presentation characteristics between diabetics and non-diabetics.Methods We included patients from the China AMI registry diagnosed with AMI between January 2013 and September 2014.Baseline characteristics,symptomology,and delay in treatment were compared between diabetics and non-diabetics.Multivariable logistic regression analysis was used to explore independent predictors of atypical symptoms.Results A total of 4450(20.2%)patients had diabetes.They were older,more often women,higher in body mass index,and more likely to have non-ST segment elevation myocardial infarction.Fewer diabetic patients presented with persistent precordial chest pain(63.1%vs.68%,P<0.0001),diaphoresis(60.1%vs.65.6%,P<0.0001),fatigue(16.7%vs.18.3%,P=0.0123),and incontinence(0.4%vs.0.7%,P=0.0093).Time to hospital presentation was longer among patients with diabetes than those without.In multivariable analysis,diabetes was identified as an independent predictor of atypical symptoms(OR:1.112,95%CI:1.034?1.196).Conclusions Our study is the first large-scale study providing evidence that diabetics are less likely to present with typical chest pain and more likely to experience treatment delay when suffering from an AMI.Our results may increase clinician awareness of recognizing AMI patients rapidly to reduce diagnosis and treatment delay,particularly in the context of diabetes.

Triglyceride glucose index predicts in-hospital mortality in patients with ST-segment elevation myocardial infarction who underwent primary angiography

OBJECTIVES To assess the correlation between triglyceride glucose(TyG)index and in-hospital mortality in patients with ST-segment elevation myocardial infarction(STEMI).METHODS A total of 2190 patients with STEMI who underwent primary angiography within 12 h from symptom onset were selected from the prospective,nationwide,multicenter CAMI registry.TyG index was calculated with the formula:Ln[fasting triglycerides(mmol/L)×fasting glucose(mmol/L)/2].Patients were divided into three groups according to the tertiles of TyG index.The primary endpoint was in-hospital mortality.RESULTS Overall,46 patients died during hospitalization,in-hospital mortality was 1.5%,2.2%,2.6%for tertile 1,tertile 2,and tertile 3,respectively.However,TyG index was not significantly correlated with in-hospital mortality in single-variable logistic regression analysis.Nonetheless,after adjusting for age and sex,TyG index was significantly associated with higher mortality when regarded as a continuous variable(adjusted OR=1.75,95%CI:1.16-2.63)or categorical variable(tertile 3 vs.tertile 1:adjus-ted OR=2.50,95%CI:1.14-5.49).Furthermore,TyG index,either as a continuous variable(adjusted OR=2.54,95%CI:1.42-4.54)or categorical variable(tertile 3 vs.tertile 1:adjusted OR=3.57,95%CI:1.24-10.29),was an independent predictor of in-hospital mortality after adjusting for multiple confounders in multivariable logistic regression analysis.In subgroup analysis,the pro-gnostic effect of high TyG index was more significant in patients with body mass index<18.5 kg/m2(P interaction=0.006).CONCLUSIONS This study showed that TyG index was positively correlated with in-hospital mortality in STEMI patients who underwent primary angiography,especially in underweight patients.

Did the MS 7.0 Lushan earthquake dynamically trigger earthquakes in the Datong volcanic region(Shanxi Province)?

Immediately following the Ms7.0 Lushan earthquake on April 20, 2013, using high-pass and low- pass filtering on the digital seismic stations in the Shanxi Province, located about 870-1,452 km from the earthquake epicenter, we detected some earthquakes at a time corre- sponding to the first arrival of surface waves in high-pass filtering waveform. The earthquakes were especially noticed at stations in Youyu （YUY）, Shanzizao （SZZ）, Shanghuangzhuang （SHZ）, and Zhenchuan （ZCH）, which are located in a volcanic region in the Shanxi Province,but they were not listed in the Shanxi seismic observation report. These earthquakes occurred 4-50 rain after the passage of the maximum amplitude Rayleigh wave, and the periods of the surface waves were mainly between 15 and 20 s following. The Coulomb stresses caused by the Ray- leigh waves that acted on the four stations was about 0.001 MPa, which is a little lower than the threshold value of dynamic triggering, therefore, we may conclude that the Datong volcanic region is more sensitive to the Coulomb stress change. To verify, if the similar phenomena are widespread, we used the same filtering to observecontrastively continuous waveform data before, and 5 h after, the Ms7.0 Lushan earthquake and Ms9.0 Tohoku earthquake in 2011. The results show that the similar phenomena occur before the earthquakes, but the seis- micity rates after the earthquakes are remarkably increased. Since these weak earthquakes are quite small, it is hard to get clear phase arrival time from three or more stations to locate them. In addition, the travel time differences between P waves and S waves （S-P） are all less than 4 s, that means the events should occur in 34 km around the stations in the volcanic region. The stress of initial dynamic triggering of the Ms9.0 Tohoku earthquake was about 0.09 MPa, which is much higher than the threshold value of dynamic triggering stress. The earthquakes after the Ms9.0 Tohoku earthquake are related to dynamic triggering stress, but the events before the earthquake cannot be linked to seismic events, but may be related to the back- ground seismicity or from other kinds of local sources, such as anthropogenic sources （i.e., explosions）. Using two teleseismic filtering, the small background earthquakes in the Datong volcanic region occur frequently, thus we postulate that previous catalog does not apply bandpass filter to pick out the weak earthquakes, and some of the observed weak events were not triggered by changes in the dynamic stress field.

Case report of a patient with suspected COVID-19 with depression and fever in an epidemic stress environment

During the COVID-19 pandemic,the number of suspected cases,confirmed cases and those who passed away from the virus has been reported in major media and the internet,and has caused a high degree of tension.In addition,people's outdoor activities have been limited,making it more difficult to find outlets for releasing stress.Under this situation,some people began to experience emotions of anxiety and depression.This article reports a case of depression with fever caused by the stress tension of the pandemic.The patient was highly suspected to have contracted COVID-19.The reported patient,who had a history of depression and had been to Wuhan to attend an exam,showed obvious pre-exam anxiety under the epidemic situation,which gradually increased the patient's pressure and then caused some adverse symptoms,such as insomnia,anxiety,sweating and a reoccurrent fever.Local community authorities paid close attention to him and later sent him to a general hospital in Jingmen for quarantine and treatment,as he was suspected of having COVID-19.After being hospitalised for half a month,he was ruled out from having‘COVID-19'and was cured of depression and discharged from the hospital.From this case,we can realise that,under the situation of the epidemic,people are easily prone to insomnia,anxiety and even depression.As clinicians in general hospitals,especially when encountering large emergencies,we must carefully inquire about the patient's medical history while strengthening our understanding of psychiatric knowledge to improve the recognition rate for depression.

Case of catatonia misdiagnosed with coma

Catatonia is a state of high-degree psychomotor inhibition in which patients often maintain a constant fixed posture,and generally have unconscious obstacles and various reflex preservation.Patients suffering from severe catatonia will become stiff.Catatonia generally manifests unconsciousness while various reflexes are preserved.Patients show reticence,no food or drink intake,and immobility as signs of complete suppression of speech and movement,and even incontinence.Patients are often first diagnosed in non-psychiatric departments and are more likely to be misdiagnosed as having‘coma’or‘epilepsy,,thus delaying treatment.This article reports a case of a 19-year-old female patient who was misdiagnosed with'catatonia'.A month ago,she was admitted to a general hospital of our city because of"intermittent attacks of nausea,vomiting,stupor for 15 years,with one week of exacerbation".During her hospitalisation,she suddenly appeared was mute,had no food or drink intake,and showed immobility and incontinence,presenting a'coma state'.She was transferred to a general hospital in Wuhan to further investigate the cause of her"coma".After 7 days in the hospital,no abnormal examination results were found and the symptoms were not alleviated.Later,she was transferred to the mental health centre for hospitalisation in this city.The patient was diagnosed as having(1)‘epileptic psychosis’and(2)‘catatonic stupor*.After 3 days of treatment,the patient's recovered consciousness.She was clinically cured and discharged half a month later.We hereby report this case.

Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions,MET exon skipping or de novo MET amplification

Gene fusions and MET alterations are rare and difficult to detect in plasma samples.The clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cell lung cancer(NSCLC)with these mutations remains unknown.This prospective,non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions(ALK,ROS1,RET,and FGFR1),MET exon 14 skipping or de novo MET amplification.We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021-and 338-gene panels,respectively.Detectable MRD correlated with a significantly higher recurrence rate(P<0.001),yielding positive predictive values of 100%and 90.9%,and negative predictive values of 82.4%and 86.4%at landmark and longitudinal time points,respectively.Patients with detectable MRD showed reduced disease-free survival(DFS)compared to those with undetectable MRD(P<0.001).Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not(P=0.05).To our knowledge,this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations.Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.

Single stain hyperspectral imaging for accurate fungal pathogens identification and quantification

The most widely used method of identification of microbial morphology and structure is microscopy,but it can be difficult to distinguish between pathogens with a similar appearance.Existing fluorescent staining methods require a combination of a variety of fluorescent materials to meet this demand.In this study,unique concentration-dependent fluorescent carbon dots(CDs)were synthesized for the identification and quantification of pathogens.The emission wavelength of the CDs could be tuned spanning the full visible region by virtue of aggregation-induced narrowing of bandgaps.This tunable emission wavelength of the specific concentration response to diverse microbes can be used to distinguish microorganisms with a similar appearance,even in a same genus.A hyperspectral microscopy system was demonstrated to distinguish Aspergillus flavus and A.fumigatus based on the results above.The identification accuracy of the two similar-looking pathogens can be close to 100%,and the relative proportions and spatial distributions can also be profiled from the mixture of the pathogens.This technique can provide a solution to the fast detection of microorganisms and is potentially applicable to a wide range of problems in areas such as healthcare,food preparation,biotechnology,and health emergency.

Superior strength-ductility synergy of wire-arc directed energy deposited Mg-Al-Si alloys mediated by sub-rapid solidification

Here we propose to employ wire-arc directed energy deposition(WA-DED) to tune the microstructure and the mechanical property of Mg-Al-Si alloys, on the basis of its sub-rapid solidification effect. According to finite element analysis, WA-DED shows higher cooling rate than conventional casting, reaching 598.3 K/s for Mg-Al-Si alloy, and the lower heat input, the larger cooling rate of WA-DED. Significant microstructure refinement is thus achieved, with reduced grain size and Mg_(2)Si particle diameter. The transition from hypereutectic to fully eutectic microstructure is triggered by reducing the heat input. Compared with the as-cast alloy, WA-DED alloys demonstrate higher ultimate tensile strengths(UTS) at both room-and high-temperature(150°C) properties, increasing by 50.1% and 30.3%, respectively. The superior strength-ductility synergy for Mg-Al-Si alloys results from the microstructure tuning via sub-rapid solidification of WA-DED.

Differences in symptoms and pre-hospital delay among acute myocardial infarction patients according to ST-segment elevation on electrocardiogram: an analysis of China Acute Myocardial Infarction (CAMI) registry

Background: Approximately 70% patients with acute myocardial infarction (AMI) presented without ST-segment elevation on electrocardiogram. Patients with non-ST segment elevation myocardial infarction (NSTEMI) often presented with atypical symptoms, which may be related to pre-hospital delay and increased risk of mortality. However, up to date few studies reported detailed symptomatology of NSTEMI, particularly among Asian patients. The objective of this study was to describe and compare symptoms and presenting characteristics of NSTEMI vs. STEMI patients. Methods: We enrolled 21,994 patients diagnosed with AMI from China Acute Myocardial Infarction (CAMI) Registry between January 2013 and September 2014. Patients were divided into 2 groups according to ST-segment elevation: ST-segment elevation (STEMI) group and NSTEMI group. We extracted data on patients' characteristics and detailed symptomatology and compared these variables between two groups. Results: Compared with patients with STEMI (N=16,315), those with NSTEMI (N=5679) were older, more often females and more often have comorbidities. Patients with NSTEMI were less likely to present with persistent chest pain (54.3% vs.71.4%), diaphoresis (48.6% vs.70.0%), radiation pain (26.4% vs.33.8%), and more likely to have chest distress (42.4% vs.38.3%) than STEMI patients (all P<0.0001). Patients with NSTEMI were also had longer time to hospital. In multivariable analysis, NSTEMI was independent predictor of presentation without chest pain (odds ratio: 1.974, 95% confidence interval:1.849-2.107). Conclusions: Patients with NSTEMI were more likely to present with chest distress and pre-hospital patient delay compared with patients with STEMI. It is necessary for both clinicians and patients to learn more about atypical symptoms of NSTEMI in order to rapidly recognize myocardial infarction.

Angiographic characteristics and in-hospital mortality among patients with ST-segment elevation myocardial infarction presenting without typical chest pain: an analysis of China Acute Myocardial Infarction registry

Background:Patients with ST-segment elevation myocardial infarction(STEMI)who present without typical chest pain are associated with a poor outcome.However,whether angiographic characteristics are related to a higher risk of mortality in this population is unclear.This study aimed to investigate whether the higher mortality risk in patients with STEMI without chest pain could be explained by their"high-risk"angiographic characteristics.Methods:We used data of 12,145 patients with STEMI who was registered in China Acute Myocardial Infarction registry from January 2013 to September 2014.We compared the infarct-related artery(IRA),thrombolysis in myocardial infarction(TIMI)flow grade in the IRA,and other angiographic characteristics between patients without and those with chest pain.Multivariable logistic regression model was used to identify independent risk factor of in-hospital mortality.Results:The 2922(24.1%)patients with STEMI presented without typical chest pain.These patients had a higher TIMI flow grade(mean TIMI flow grade:1.00 vs.0.94,P=0.02)and a lower rate of IRA disease of the left anterior descending artery(44.6%vs.51.2%,χ^2=35.63,P<0.01)than did those with typical chest pain.Patients without chest pain were older,more likely to have diabetes,longer time to hospital and higher Killip classification,and less likely to receive optimal medication treatment and primary percutaneous coronary intervention and higher In-hospital mortality(3.3%vs.2.2%,χ^2=10.57,P<0.01).After adjusting for multi-variables,presentation without chest pain was still an independent predictor of in-hospital death among patients with STEMI(adjusted odds ratio:1.36,95%confidence interval:1.02–1.83).Conclusions:Presentation without chest pain is common and associated with a higher in-hospital mortality risk in patients with acute myocardial infarction.Our results indicate that their poor prognosis is associated with baseline patient characteristics and delayed treatment,but not angiographic lesion characteristics.Clinical trial registration:NCT01874691,https://clinicaltrials.gov.

Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs

Blastocyst complementation by pluripotent stem cell(PSC)injection is believed to be the most promising method to generate xenogeneic organs.However,ethical issues prevent the study of human chimeras in the late embryonic stage of development.Primate embryonic stem cells(ESCs),which have similar pluripotency to human ESCs,are a good model for studying interspecies chimerism and organ generation.However,whether primate ESCs can be used in xenogenous grafts remains unclear.In this study,we evaluated the chimeric ability of cynomolgus monkey(Macaca fascicularis)ESCs(cmESCs)in pigs,which are excellent hosts because of their many similarities to humans.We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos,in which domesticated cmESCs(D-ESCs)injected into pig blastocysts differentiated into cells of all three germ layers.In addition,we obtained two neonatal interspecies chimeras,in which we observed tissue-specific D-ESC differentiation.Taken together,the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model,with a chimeric ratio of 0.001-0.0001 in different neonate tissues.We believe this work will facilitate future developments in xenogeneic organogenesis,bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.

Hot workability characteristics of Rene88DT superalloy with directionally solidified microstructure

The hot deformation characteristics of Rene88DT superalloy with directionally solidified micro- structure produced by electroslag remelting continuous directionally solidification （ESR-CDS） were studied in the temperature range of 1,040-1,140 ℃ and strain rate range of 0.001-1.000 s-1 by hot compression tests. Flow curves for Rene88DT alloy with initial directionally solidified （DS） microstructure exhibit pronounced peak stresses at the early stage of deformation followed by the occurrence of dynamic softening phenomenon. Rene88DT alloy with DS micro- structure shows higher flow peak stresses compared with HIPed P/M superalloy FGH4096, but the disparities in peak stresses between ESR-CDSed Rene88DT and HIPed P/M superalloy FGH4096 reduce as temperature increases. The improvement of hot workability of DS alloy with columnar grains avoiding the maximum shear stress comes true. A hot deformation constitutive equation as a function of strain that describes the dependence of flow stress on strain rate and temperature is established. Hot deformation apparent acti- vation energy （Q） varies not only with the strain rate and temperature but also with strain. The strain rate sensitivity exponent （m） map is established at the strain of 0.8, which reveals that global dynamic recrystallization （DRX） shows a relatively high m value in a large strain compression. Optimum parameters are predicted in two regions： T = 1,100-1,130 ℃, ε = 0.100-1.000 s-1 and T = 1,080- 1,100 ℃, ε = 0.010-100 s-1, which is based on pro- cessing maps and deformation microstructure observations.

Disulfide Crosslinking-Induced Aggregation:Towards Solid-State Fluorescent Carbon Dots with Vastly Different Emission Colors

Solid-state fluorescent multi-color carbon dots(SFM-CDs),prepared using the same precursor(s)without the need for dispersion in a solid matrix,are highly demanded for a wide range of applications.Herein,we report a microwave-assisted strategy for the prepara-tion of SFM-CDs with blue,yellow and red emissions within 5 min from the same precursors.The as-prepared B-CDs,Y-CDs,and R-CDs possessed bright fluorescence at 425 nm,550 nm,and 640 nm,and photoluminescence quantum yields(PLQYs)of 54.68%,17.93%,and 2.88%,respectively.The structure of SFM-CDs consisted of 5-oxo-3,5-dihydro-2H-thiazolo[3,2-a]pyridine-7-carboxylic acid(TPCA)immobilized on the surface of a carbon core,with the size of the carbon core and degree of disulfide crosslinking between CDs both increasing on going from the B-CDs to the R-CDs,as verified by mechanochromic experiments.The excellent solid-state fluorescence performance of the SFM-CDs allowed their utilization as the fluorescent converter layer in multi-color LEDs and white LEDs with a high color rendering index.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis:a prospective,comparative study

Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

Derivation of Non-Integration Induced Pluripotent Stem Cells from Fibroblast of Severe Deafness Patients with GJB2 Mutation

In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 （gap junction protein β2, also called connexin 26, Cx26） gene link with nonsyndromic or syndromic senso- rineural hearing loss and were shown to account for a large proportion of congenital deaf cases in many studied populations （del Castillo and del Castillo, 2011）. For example, the 235de1C mutation in GJB2 shows the frequency of approximately 1% and is the most frequent mutation in East Asian population （Yan et al., 2003）. Many efforts have been put to study the function of Gjb2 gene in both mouse model and human. In mouse, extensive deletion of Gjb2 causes embryo lethal due to the decreased transplacental glucose uptake, which was not found in human （Takata and Hirano, 1997; Gabriel et al., 1998）. In human, GJB2 deficiency is not able to cause embryo lethal （D＇Andrea et al., 2002）. However, the study of GJB2-associated hearing loss is hampered by many difficulties, such as unobtainable human cochlea and acoustic nerve tissues, and therefore the GJB2-associated hearing loss are underlying mechanisms of still remaining unclear.

Genomic Evolution of Lung Cancer Metastasis:Current Status and Perspectives

INTRODUCTION Lung cancer is one of the cancers with the highest morbidity and mortality worldwide.Over the two past decades,although the treatment of non-small cell lung cancer(NSCLC)has been revolutionized by the use of tyrosine kinase inhibitor(TKI)and immune treatments,metastatic disease remains largely incurable and presents a 5-year survival rate of approximately 10%[1].