A 36-year-old unmarried woman with no sexual history presented with 12 days of uncontrollable yellowish vaginal discharge,bloating,lower back pain,frequent urination,and urgency.Her menstrual cycles were regular with ...A 36-year-old unmarried woman with no sexual history presented with 12 days of uncontrollable yellowish vaginal discharge,bloating,lower back pain,frequent urination,and urgency.Her menstrual cycles were regular with moderate flow and worsening dysmenorrhea.Ultrasound and magnetic resonance imaging identified uterine and cervical masses.Laparoscopic surgery and postoperative gonadotropin-releasing hormone agonist injections led to significant lesion reduction.The patient is currently on oral dienogest acetate with ongoing follow-up.展开更多
Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia(MPP),quantitative polymerase chain reaction(qPCR)has become a useful diagn...Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia(MPP),quantitative polymerase chain reaction(qPCR)has become a useful diagnostic method.This study was performed to explore the relationship between the qPCR findings,clinical symptoms,and inflammatory markers in children with MPP.Four hundred children with MPP have been enrolled in this retrospective analysis.All clinical and analytical information,including mycoplasma pneumoniae(MP)PCR results,has been collected.Based on the PCR results,the patients were divided into groups with load values(copy number)<105(54 cases),2105 and<106(71 cases),2106 and<107(112 cases),>107 and<108(114 cases),and>108(49 cases).The clinical features(including symptoms and signs)and inflammatory indicators were compared among the groups.The incidence of high fever(above 39℃),thermal peak during the entire hospitalization period,fever duration,days of hospitalization,and plasma lactate dehydrogenase(LDH)levels were statistically correlated with the MP PCR load value in children with MPP.The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization>duration of fever>period of hospitalization>LDH value>C-reactive protein value.The host immune response was significantly greater in the complication group than in the non-complication group.展开更多
AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancr...AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P = 0.020), pancreatic invasion (P = 0.016), duodenal invasion (P = 0.034), and advanced stage of TNM clinical classification (P = 0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P = 0.029). CONCLUSION: The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of cardnoma of the ampulla of Vater.展开更多
New samples returned by China Chang’e-5(CE-5)mission offer an opportunity for studying the lunar geologic longevity,space weathering,and regolith evolution.The age determination of the CE-5 samples was among the firs...New samples returned by China Chang’e-5(CE-5)mission offer an opportunity for studying the lunar geologic longevity,space weathering,and regolith evolution.The age determination of the CE-5 samples was among the first scientific questions to be answered.However,the precious samples,most in the micrometer size range,challenge many traditional analyses on large single crystals of zircon developed for massive bulk samples.Here,we developed a non-destructive rapid screening of individual zirconium-containing particle for isotope geochronology based on a Micro X-ray fluorescence analysis(μXRF).The selected particles were verified via scanning electron microscopy(SEM),3D X-ray microscopy(XRM),and focused ion beam scanning electron microscopy(FIB-SEM)techniques,which showed that zirconium-bearing minerals with several microns were precisely positioned and readily suitable for site-specific isotopic dating by second ion mass spectrometry(SIMS).Such protocol could be also appli-cable in non-destructively screening other types of particles for different scientific purposes.We there-fore proposed a correlative workflow for comprehensively studying the CE-5 lunar samples from single particles on nanometer to atomic scales.Linking various microscopic and spectromicroscopic instru-ments together,this workflow consists of six steps:(1)single-particle selection with non-destructive μXRF technique,(2)2D/3D morphological and structural characterization with a correlative submicron 3D XRM and nanoscale resolution FIB-SEM imaging methods,(3)SEM analysis of the surface morphology and chemistry of the selected particle,(4)a series of microscopic and microbeam analyses(e.g.,SEM,electron probe microanalysis,and SIMS)on the cross-section of the selected particle to obtain structural,mineralogical,chemical,and isotopic features from the micron to nanometer scale,(5)advanced 2D/3D characterization and site-specific sample preparation of thin foil/tip specimens on a microregion of inter-est in the selected particle with FIB-SEM technique,and(6)comprehensive analyses on the FIB-milled specimens at nanometer to atomic scale with synchrotron-based scanning transmission X-ray micro-scopy,analytic transmission electron microscopy,and atom probe tomography.Following this technical roadmap,one can integrate multiple modalities into a uniform frame of multimodal and multiscale cor-related datasets to acquire high-throughput information on the limited or precious terrestrial and extraterrestrial samples.展开更多
AIM: To assess subcellular localization of KL-6 mucin and its clinicopathological significance in colorectal carcinoma as well as metastatic lymph node and liver tissues. METHODS: Colorectal carcinoma tissues as wel...AIM: To assess subcellular localization of KL-6 mucin and its clinicopathological significance in colorectal carcinoma as well as metastatic lymph node and liver tissues. METHODS: Colorectal carcinoma tissues as well as metastatic lymph node and liver tissues were collected from 82 patients who underwent colorectomy or hepatectomy. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Of the 82 colorectal carcinoma patients, 6 showed no staining, 29 showed positive staining only in the apical membrane, and 47 showed positive staining in the circumferential membrane and/or cytoplasm. Positive staining was not observed in non-cancerous colorectal epithelial cells surrounding the tumor tissues. The five-year survival rate was significantly lower in cases showing positive staining in the circumferential membrane and/or cytoplasm (63.0%) than those showing positive staining only in the apical membrane (85.7%) and those showing no staining (100%). Statistical analysis between clinicopathological factors and subcellular localization of KL-6 mucin showed that KL-6 localization in the circumferential membrane and/or cytoplasm was significantly associated with the presence of venous invasion (P = 0.0003), lymphatic invasion (P 〈 0.0001), lymph node metastasis (P〈0.0001), liver metastasis (P = 0.058), and advanced histological stage (P〈 0.0001). Positive staining was observed in all metastatic lesions tested as well as in the primary colorectal carcinoma tissues. CONCLUSION: The subcellular staining pattern of KL-6 in colorectal adenocarcinoma may be an important indicator for unfavorable behaviors such as lymph node and liver metastasis, as well as for the prognosis of patients.展开更多
Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative researc...Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.展开更多
Detecting, real-time monitoring and early warning of underground water-bearing structures are critically important issues in prevention and mitigation of water inrush hazards in underground engineering. Direct current...Detecting, real-time monitoring and early warning of underground water-bearing structures are critically important issues in prevention and mitigation of water inrush hazards in underground engineering. Direct current (DC) resistivity method is a widely used method for routine detection, advanced detection and real-time monitoring of water-bearing structures, due to its high sensitivity to groundwater. In this study, the DC resistivity method applied to underground engineering is reviewed and discussed, including the observation mode, multiple inversions, and real-time monitoring. It is shown that a priori information constrained inversion is desirable to reduce the non-uniqueness of inversion, with which the accuracy of detection can be significantly improved. The focused resistivity method is prospective for advanced detection;with this method, the flanking interference can be reduced and the detection dis-tance is increased subsequently. The time-lapse resistivity inversion method is suitable for the regions with continuous conductivity changes, and it can be used to monitor water inrush in those regions. Based on above-mentioned features of various methods in terms of benefits and limitations, we propose a three-dimensional (3D) induced polarization method characterized with multi-electrode array, and introduce it into tunnels and mines combining with real-time monitoring with time-lapse inversion and cross-hole resistivity method. At last, the prospective applications of DC resistivity method are discussed as follows: (1) available advanced detection technology and instrument in tunnel excavated by tunnel boring machine (TBM), (2) high-resolution detection method in holes, (3) four-dimensional (4D) monitoring technology for water inrush sources, and (4) estimation of water volume in water-bearing structures.展开更多
Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of m...Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.展开更多
We present our optical multi-color monitoring of the BL Lac object OJ 287 from January 2006to December 2012 in the V,R and I bands.A relatively active state in OJ 287 has been found over all monitored epochs,among whi...We present our optical multi-color monitoring of the BL Lac object OJ 287 from January 2006to December 2012 in the V,R and I bands.A relatively active state in OJ 287 has been found over all monitored epochs,among which the variations of average magnitude in V/R/I bands were measured with ?V=1.956 mag,?R=2.067 mag and ?I=2.115 mag,respectively.No reliable intraday variability is detected,but possible variability is detected on 16 nights.Their relative variation amplitudes fall into the range between 1% and 8%,with the majority between 2% and 4%.No time lags have been detected,but strong correlations exist among light curves in the three wavebands.The bluer-when-brighter trend is dominant over intraday timescales,which supports the shock-in-jet model.When combining with additional V/R band data obtained from SMARTS and the Steward Observatory,we also find a bluer-when-brighter trend over a long-term timescale.Some possible periods of 513,176,36,30,26,17 and 14 d are found in all time-series data sets from 2006 to 2017.Possible explanations about these periods are given.展开更多
Background Disrupted white matter(WM)microstructure has been commonly identified in youth at clinical high risk(CHR)for psychosis.Several lines of evidence suggest that fatty acids,especially unsaturated fatty acids(U...Background Disrupted white matter(WM)microstructure has been commonly identified in youth at clinical high risk(CHR)for psychosis.Several lines of evidence suggest that fatty acids,especially unsaturated fatty acids(UFAs),might play a crucial role in the WM pathology of early onset psychosis.However,evidence linking UFA and WM microstructure in CHR is quite sparse.Aims We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls(HC).Methods Plasma fatty acids were assessed and diffusion tensor imaging(DTI)data were performed with tract-based spatial statistics(TBSS)analysis for 66 individuals at CHR for psychosis and 70 HC.Results Both the global and regional diffusion measures showed significant between-group differences,with decreased fractional anisotropy(FA)but increased mean diffusivity(MD)and radial diffusivity(RD)found in the CHR group compared with the HC group.On top of that,we found that in the HC group,plasma arachidic acid showed obvious trend-level associations with higher global FA,lower global MD and lower global RD,which regionally spread over the corpus callosum,right anterior and superior corona radiata,bilateral anterior and posterior limb of the internal capsule,and bilateral superior longitudinal fasciculus.However,there were no associations between global WM measures and any UFA in the CHR group.Conversely,we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.Conclusions Compared with the HC group,CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA,with a neuroprotective effect found in the HC group but not in the CHR group.Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group,highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.展开更多
Background Self-reflectiveness,one dimension of cognitive insight,plays a protective role in an individual’s mental state.Both high and low levels of self-reflectiveness have been reported in patients with schizophre...Background Self-reflectiveness,one dimension of cognitive insight,plays a protective role in an individual’s mental state.Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.Aims This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.Methods A total of 181 subjects,including individuals with attenuated positive symptoms(APS,n=122)and patients with first-episode psychosis(FEP,n=59),completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale.All subjects were classified into three groups according to their level of selfreflectiveness:low level(LSR,n=59),medium level(MSR,n=67)and high level(HSR,n=55).Both linear and nonlinear relationships between self-reflectiveness and clinical symptoms were explored.Results More individuals with APS were classified into the MSR group,while more patients with FEP were classified into the LSR group.The LSR group demonstrated less awareness of illness than the MSR and HSR groups,more stereotyped thinking and poorer impulse control but less anxiety than the MSR group,and lower levels of blunted affect and guilt feelings than the HSR group.The MSR group demonstrated lower stereotyped thinking than the HSR group.Compared to the LSR group,the MSR group had increased selfreflectiveness,improved awareness of illness,decreased stereotyped thinking,and better impulse control,but increased feelings of guilt.The HSR group showed increased stereotyped thinking when compared to the MSR group,but the other variables did not change significantly between these two groups.Overall,self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness,a U-shaped relationship with stereotyped thinking and poor impulse control,and an almost linear relationship with anxiety and guilt feelings.Conclusions Self-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.展开更多
Background Eye movement abnormality in schizophrenia has been studied for several decades.However,patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well docume...Background Eye movement abnormality in schizophrenia has been studied for several decades.However,patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.Aims This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia.Methods This study included 78 persons at clinical high risk(CHR)for schizophrenia,68 first-episode(FEZ)patients,and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project(SHARP Extending cohort)as well as 74 healthy controls(HCs).The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication.Type 1 was a scenery picture without people,type 2 was a picture with four people not communicating,and type 3 was a picture with four people communicating.We used two measures:(1)initial fixation duration and(2)total fixation duration.Results A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication.The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients(0.13(0.34))compared with HCs(0.31(0.36)),FEZ patients(0.31(0.46)),and CHR patients(0.36(0.42)).The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants(HCs vs chronically ill patients,t=2.706,p=0.009;CHR patients vs chronically ill patients,t=4.079,p<0.001).In addition,the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants’high-risk symptoms(r=−0.35,p=0.002)among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale(PANSS)among chronically ill patients(r=−0.33,p=0.037).The ratio of initial fixation duration between type 1 and type 3 pictures was associated with PANSS negative symptoms only in female patients with schizophrenia(r=−0.46,p=0.004).Conclusions These findings suggest an altered attentive bias towards pictures with a high degree of interpersonal communication information across different clinical phases in schizophrenia.The ratio of initial attentive orienting was associated with negative symptoms in female patients.展开更多
Background Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks.Abnormal neural oscillations have been discovered in patients with s...Background Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks.Abnormal neural oscillations have been discovered in patients with schizophrenia.However,there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis(CHR-P).The brain signals recorded by the magnetoencephalography(MEG)technique are not to be disrupted by the skull and scalp.Methods In this study,we applied the MEG technique to record the resting-state neural activities in CHR-P.This was followed by a detailed MEG analysis method including three steps:(1)preprocessing,which was band-pass filtering based on the 0.5-60Hz frequency range,removal of 50Hz power frequency interference,and removal of electrocardiography(ECG)and electrooculography(EOG)artefacts by independent component analysis;(2)time-frequency analysis,a multitaper time-frequency transformation based on the Hanning window,and(3)source localisation.an exact low-resolution brain electromagnetic tomography.The method was verified by comparing aparticipant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.Results Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band(4-7Hz)and the delta frequency band(1-3Hz).Also,relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.Conclusions Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups.Further work will validate these characteristics in CHR-P cohorts.展开更多
BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,th...BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.展开更多
基金supported by Foundation for Discipline Construction of Fujian Medical University Union Hospital(2100201).
文摘A 36-year-old unmarried woman with no sexual history presented with 12 days of uncontrollable yellowish vaginal discharge,bloating,lower back pain,frequent urination,and urgency.Her menstrual cycles were regular with moderate flow and worsening dysmenorrhea.Ultrasound and magnetic resonance imaging identified uterine and cervical masses.Laparoscopic surgery and postoperative gonadotropin-releasing hormone agonist injections led to significant lesion reduction.The patient is currently on oral dienogest acetate with ongoing follow-up.
基金This study was supported by the Chongqing Science and Health Joint Medical Research Project(No.8187011078)。
文摘Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia(MPP),quantitative polymerase chain reaction(qPCR)has become a useful diagnostic method.This study was performed to explore the relationship between the qPCR findings,clinical symptoms,and inflammatory markers in children with MPP.Four hundred children with MPP have been enrolled in this retrospective analysis.All clinical and analytical information,including mycoplasma pneumoniae(MP)PCR results,has been collected.Based on the PCR results,the patients were divided into groups with load values(copy number)<105(54 cases),2105 and<106(71 cases),2106 and<107(112 cases),>107 and<108(114 cases),and>108(49 cases).The clinical features(including symptoms and signs)and inflammatory indicators were compared among the groups.The incidence of high fever(above 39℃),thermal peak during the entire hospitalization period,fever duration,days of hospitalization,and plasma lactate dehydrogenase(LDH)levels were statistically correlated with the MP PCR load value in children with MPP.The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization>duration of fever>period of hospitalization>LDH value>C-reactive protein value.The host immune response was significantly greater in the complication group than in the non-complication group.
基金Supported by Grants-in-aid From the Ministry of Education, Science, Sports, and Culture of Japan and a grant for Hi-Tech Research from Tokai University
文摘AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P = 0.020), pancreatic invasion (P = 0.016), duodenal invasion (P = 0.034), and advanced stage of TNM clinical classification (P = 0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P = 0.029). CONCLUSION: The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of cardnoma of the ampulla of Vater.
基金the National Key R&D Program of China(2018YFA0702600)the Key Research program of Chinese Academy of Sciences(ZDBS-SSW-JSC007-13)+1 种基金the institute of Geology and Geophysics,Chinese Academy of Sciences(IGGCAS-202101)the National Natural Science Foundation of China(grants no.41890843,41920104009)。
文摘New samples returned by China Chang’e-5(CE-5)mission offer an opportunity for studying the lunar geologic longevity,space weathering,and regolith evolution.The age determination of the CE-5 samples was among the first scientific questions to be answered.However,the precious samples,most in the micrometer size range,challenge many traditional analyses on large single crystals of zircon developed for massive bulk samples.Here,we developed a non-destructive rapid screening of individual zirconium-containing particle for isotope geochronology based on a Micro X-ray fluorescence analysis(μXRF).The selected particles were verified via scanning electron microscopy(SEM),3D X-ray microscopy(XRM),and focused ion beam scanning electron microscopy(FIB-SEM)techniques,which showed that zirconium-bearing minerals with several microns were precisely positioned and readily suitable for site-specific isotopic dating by second ion mass spectrometry(SIMS).Such protocol could be also appli-cable in non-destructively screening other types of particles for different scientific purposes.We there-fore proposed a correlative workflow for comprehensively studying the CE-5 lunar samples from single particles on nanometer to atomic scales.Linking various microscopic and spectromicroscopic instru-ments together,this workflow consists of six steps:(1)single-particle selection with non-destructive μXRF technique,(2)2D/3D morphological and structural characterization with a correlative submicron 3D XRM and nanoscale resolution FIB-SEM imaging methods,(3)SEM analysis of the surface morphology and chemistry of the selected particle,(4)a series of microscopic and microbeam analyses(e.g.,SEM,electron probe microanalysis,and SIMS)on the cross-section of the selected particle to obtain structural,mineralogical,chemical,and isotopic features from the micron to nanometer scale,(5)advanced 2D/3D characterization and site-specific sample preparation of thin foil/tip specimens on a microregion of inter-est in the selected particle with FIB-SEM technique,and(6)comprehensive analyses on the FIB-milled specimens at nanometer to atomic scale with synchrotron-based scanning transmission X-ray micro-scopy,analytic transmission electron microscopy,and atom probe tomography.Following this technical roadmap,one can integrate multiple modalities into a uniform frame of multimodal and multiscale cor-related datasets to acquire high-throughput information on the limited or precious terrestrial and extraterrestrial samples.
基金Supported by Grants-in-aid from the Ministry of Education,Science,Sports and Culture of Japan and a grant for Hi-Tech Research from Tokai University
文摘AIM: To assess subcellular localization of KL-6 mucin and its clinicopathological significance in colorectal carcinoma as well as metastatic lymph node and liver tissues. METHODS: Colorectal carcinoma tissues as well as metastatic lymph node and liver tissues were collected from 82 patients who underwent colorectomy or hepatectomy. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Of the 82 colorectal carcinoma patients, 6 showed no staining, 29 showed positive staining only in the apical membrane, and 47 showed positive staining in the circumferential membrane and/or cytoplasm. Positive staining was not observed in non-cancerous colorectal epithelial cells surrounding the tumor tissues. The five-year survival rate was significantly lower in cases showing positive staining in the circumferential membrane and/or cytoplasm (63.0%) than those showing positive staining only in the apical membrane (85.7%) and those showing no staining (100%). Statistical analysis between clinicopathological factors and subcellular localization of KL-6 mucin showed that KL-6 localization in the circumferential membrane and/or cytoplasm was significantly associated with the presence of venous invasion (P = 0.0003), lymphatic invasion (P 〈 0.0001), lymph node metastasis (P〈0.0001), liver metastasis (P = 0.058), and advanced histological stage (P〈 0.0001). Positive staining was observed in all metastatic lesions tested as well as in the primary colorectal carcinoma tissues. CONCLUSION: The subcellular staining pattern of KL-6 in colorectal adenocarcinoma may be an important indicator for unfavorable behaviors such as lymph node and liver metastasis, as well as for the prognosis of patients.
基金This study was supported by funding from the Science Technology and Innovation Committee of Shenzhen Municipality(Grant No.2019N002)Capital's Funds for Health Improvement and Research(Grant No.Z181100001718075).
文摘Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.
基金supported by the National Program on Key Basic Research Project of China (973 Program) (Nos. 2013CB036002 and 2014CB046901)the National Key Technology R&D Program of the Ministry of Science and Technology of China (No. 2013BAK06B01)the National Natural Science Foundation of China (No. 51139004)
文摘Detecting, real-time monitoring and early warning of underground water-bearing structures are critically important issues in prevention and mitigation of water inrush hazards in underground engineering. Direct current (DC) resistivity method is a widely used method for routine detection, advanced detection and real-time monitoring of water-bearing structures, due to its high sensitivity to groundwater. In this study, the DC resistivity method applied to underground engineering is reviewed and discussed, including the observation mode, multiple inversions, and real-time monitoring. It is shown that a priori information constrained inversion is desirable to reduce the non-uniqueness of inversion, with which the accuracy of detection can be significantly improved. The focused resistivity method is prospective for advanced detection;with this method, the flanking interference can be reduced and the detection dis-tance is increased subsequently. The time-lapse resistivity inversion method is suitable for the regions with continuous conductivity changes, and it can be used to monitor water inrush in those regions. Based on above-mentioned features of various methods in terms of benefits and limitations, we propose a three-dimensional (3D) induced polarization method characterized with multi-electrode array, and introduce it into tunnels and mines combining with real-time monitoring with time-lapse inversion and cross-hole resistivity method. At last, the prospective applications of DC resistivity method are discussed as follows: (1) available advanced detection technology and instrument in tunnel excavated by tunnel boring machine (TBM), (2) high-resolution detection method in holes, (3) four-dimensional (4D) monitoring technology for water inrush sources, and (4) estimation of water volume in water-bearing structures.
基金supported by grants from the National Natural Science Foundation of China(No.92049107 and No.31929002)the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Academic Frontier Youth Team Project to Xiaochuan Wang from Huazhong University of Science and Technology.
文摘Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.
基金supported by Fermi Guest Investigator grants NNX08AW56G, NNX09AU10G, NNX12AO93G and NNX15AU81Gsupported by the Strategic Priority Research Program of the Chinese Academy of Sciences-The Emergence of Cosmological Structures (grant No. XDB09000000)+3 种基金the Key Research Program of the Chinese Academy of Sciences (grant No. KJZD-EWM06)the NSFC through NSFC-11133006 and 11361140347support from Chinese Western Young Scholars ProgramLight of West China Program provided by CAS
文摘We present our optical multi-color monitoring of the BL Lac object OJ 287 from January 2006to December 2012 in the V,R and I bands.A relatively active state in OJ 287 has been found over all monitored epochs,among which the variations of average magnitude in V/R/I bands were measured with ?V=1.956 mag,?R=2.067 mag and ?I=2.115 mag,respectively.No reliable intraday variability is detected,but possible variability is detected on 16 nights.Their relative variation amplitudes fall into the range between 1% and 8%,with the majority between 2% and 4%.No time lags have been detected,but strong correlations exist among light curves in the three wavebands.The bluer-when-brighter trend is dominant over intraday timescales,which supports the shock-in-jet model.When combining with additional V/R band data obtained from SMARTS and the Steward Observatory,we also find a bluer-when-brighter trend over a long-term timescale.Some possible periods of 513,176,36,30,26,17 and 14 d are found in all time-series data sets from 2006 to 2017.Possible explanations about these periods are given.
基金This research was supported by National Natural Science Foundation of China grants(81971251,81671329,81871050,82171497,82101582,82001406)Clinical Research Center at Shanghai Mental Health Center grants(CRC2018ZD01,CRC2018ZD04,CRC2018YB01,CRC2019ZD02)+6 种基金Clinical Research Center at Shanghai Jiao Tong University School of Medicine(DLY201817,20190102)Shanghai Science and Technology Committee Foundations(19411950800,16ZR1430500,19411969100,19410710800,21ZR1481500,20ZR1448600,21S31903100,19ZR14451)Shanghai Clinical Research Center for Mental Health(19MC1911100)Project of the Key Discipline Construction,Shanghai 3-Year Public Health Action Plan(GWV-10.1-XK18)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01,2018SHZDZX05)and ZJ LabFoundation of Shanghai Mental Health Center(2020-FX-02)Excellent Talents Training Project of Shanghai Municipal Commission of Health(GWV-10.2-YQ44).
文摘Background Disrupted white matter(WM)microstructure has been commonly identified in youth at clinical high risk(CHR)for psychosis.Several lines of evidence suggest that fatty acids,especially unsaturated fatty acids(UFAs),might play a crucial role in the WM pathology of early onset psychosis.However,evidence linking UFA and WM microstructure in CHR is quite sparse.Aims We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls(HC).Methods Plasma fatty acids were assessed and diffusion tensor imaging(DTI)data were performed with tract-based spatial statistics(TBSS)analysis for 66 individuals at CHR for psychosis and 70 HC.Results Both the global and regional diffusion measures showed significant between-group differences,with decreased fractional anisotropy(FA)but increased mean diffusivity(MD)and radial diffusivity(RD)found in the CHR group compared with the HC group.On top of that,we found that in the HC group,plasma arachidic acid showed obvious trend-level associations with higher global FA,lower global MD and lower global RD,which regionally spread over the corpus callosum,right anterior and superior corona radiata,bilateral anterior and posterior limb of the internal capsule,and bilateral superior longitudinal fasciculus.However,there were no associations between global WM measures and any UFA in the CHR group.Conversely,we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.Conclusions Compared with the HC group,CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA,with a neuroprotective effect found in the HC group but not in the CHR group.Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group,highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.
基金supported by the Ministry of Science and Technology of China,National Key R&D Program of China(2016YFC1306800)National Natural Science Foundation of China(81671332,81971251,81671329,81871050,81901832,81971251,82001406,82101582,82151314,and 82171497)+9 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01,2018SHZDZX05)and ZJLabScience and Technology Commission of Shanghai Municipality(16JC1420200,16ZR1430500,19410710800,19411950800,19411969100,19441907800,19ZR1445100,19ZR1477800,20ZR1448600,21ZR1481500,and 21S31903100)Shanghai Municipal Health Commission(202040361)Project of the Key Discipline Construction,Shanghai 3-Year Public Health Action Plan(GWV10.1-XK18)Shanghai Clinical Research Center for Mental Health(19MC1911100)Clinical Research Plan of SHDC(SHDC2020CR4066)Clinical Research Center at Shanghai Jiao Tong University School of Medicine(DLY201817,20190102)Shanghai Jiao Tong University Foundation(ZH2018ZDB03,ZH2018QNB19)The Clinical Research Center at Shanghai Mental Health Center(CRC2018ZD01,CRC2018ZD04,CRC2018YB01,CRC2019ZD02,and 2020-FX-02)Shanghai Mental Health Center(2019-zd01).
文摘Background Self-reflectiveness,one dimension of cognitive insight,plays a protective role in an individual’s mental state.Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.Aims This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.Methods A total of 181 subjects,including individuals with attenuated positive symptoms(APS,n=122)and patients with first-episode psychosis(FEP,n=59),completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale.All subjects were classified into three groups according to their level of selfreflectiveness:low level(LSR,n=59),medium level(MSR,n=67)and high level(HSR,n=55).Both linear and nonlinear relationships between self-reflectiveness and clinical symptoms were explored.Results More individuals with APS were classified into the MSR group,while more patients with FEP were classified into the LSR group.The LSR group demonstrated less awareness of illness than the MSR and HSR groups,more stereotyped thinking and poorer impulse control but less anxiety than the MSR group,and lower levels of blunted affect and guilt feelings than the HSR group.The MSR group demonstrated lower stereotyped thinking than the HSR group.Compared to the LSR group,the MSR group had increased selfreflectiveness,improved awareness of illness,decreased stereotyped thinking,and better impulse control,but increased feelings of guilt.The HSR group showed increased stereotyped thinking when compared to the MSR group,but the other variables did not change significantly between these two groups.Overall,self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness,a U-shaped relationship with stereotyped thinking and poor impulse control,and an almost linear relationship with anxiety and guilt feelings.Conclusions Self-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.
文摘Background Eye movement abnormality in schizophrenia has been studied for several decades.However,patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.Aims This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia.Methods This study included 78 persons at clinical high risk(CHR)for schizophrenia,68 first-episode(FEZ)patients,and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project(SHARP Extending cohort)as well as 74 healthy controls(HCs).The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication.Type 1 was a scenery picture without people,type 2 was a picture with four people not communicating,and type 3 was a picture with four people communicating.We used two measures:(1)initial fixation duration and(2)total fixation duration.Results A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication.The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients(0.13(0.34))compared with HCs(0.31(0.36)),FEZ patients(0.31(0.46)),and CHR patients(0.36(0.42)).The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants(HCs vs chronically ill patients,t=2.706,p=0.009;CHR patients vs chronically ill patients,t=4.079,p<0.001).In addition,the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants’high-risk symptoms(r=−0.35,p=0.002)among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale(PANSS)among chronically ill patients(r=−0.33,p=0.037).The ratio of initial fixation duration between type 1 and type 3 pictures was associated with PANSS negative symptoms only in female patients with schizophrenia(r=−0.46,p=0.004).Conclusions These findings suggest an altered attentive bias towards pictures with a high degree of interpersonal communication information across different clinical phases in schizophrenia.The ratio of initial attentive orienting was associated with negative symptoms in female patients.
基金This study was supported by the National Natural Science Foundation of China(81901832,82171544,82171497,62072014)Clinical Research Plan of SHDC(SHDC2020CR4066)+3 种基金Science and Technology Commission of Shanghai Municiality(19ZR1477800,19ZR1445200)Shanghai Key Laboratory of Psychotic Disorders(13d22260500)Clinical Research Center at Shanghai Mental Health Center(CRC2018ZD01,CRC2018ZD04 and CRC2018YB01)Shanghai Mental Health Center Foundation(2020-FX-01,2019-zd01).
文摘Background Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks.Abnormal neural oscillations have been discovered in patients with schizophrenia.However,there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis(CHR-P).The brain signals recorded by the magnetoencephalography(MEG)technique are not to be disrupted by the skull and scalp.Methods In this study,we applied the MEG technique to record the resting-state neural activities in CHR-P.This was followed by a detailed MEG analysis method including three steps:(1)preprocessing,which was band-pass filtering based on the 0.5-60Hz frequency range,removal of 50Hz power frequency interference,and removal of electrocardiography(ECG)and electrooculography(EOG)artefacts by independent component analysis;(2)time-frequency analysis,a multitaper time-frequency transformation based on the Hanning window,and(3)source localisation.an exact low-resolution brain electromagnetic tomography.The method was verified by comparing aparticipant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.Results Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band(4-7Hz)and the delta frequency band(1-3Hz).Also,relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.Conclusions Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups.Further work will validate these characteristics in CHR-P cohorts.
文摘BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.