Objective： Diffuse large B-cell lymphoma （DLBCL） is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance o...Objective： Diffuse large B-cell lymphoma （DLBCL） is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods： Thirty-two patients with DLBCL underwent baseline, interim and post-treatment lSF-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results： Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival （PFS） rates were significantly different between the groups above and below SUVmax CUt-Off value of 2.5 （P=0.039）. No significant differences were found in the 2-year PFS rates if SUVm, cut-offvalues were set as 2.0 and 3.0, respectively （P=0.360; P=0.113）. Conclusions： Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.展开更多
Objective: The present study investigated the prognosis value of preoperative fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT) in patients with local advanced gastric cancer(LAGC).Method...Objective: The present study investigated the prognosis value of preoperative fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT) in patients with local advanced gastric cancer(LAGC).Methods: In total, 144 patients [median age 63(range: 48-80) years old] with LAGC underwent 18 F-FDG PET/CT prior to any treatment. The maximum standardized uptake values(SUVmax), mean standardized uptake values(SUVmean), metabolic tumor volume(MTV) and total lesion glycolysis(TLG) of the primary lesion were measured on PET/CT and correlated with clinicopathological features and survival.Results: Significant differences in SUVmean, SUVmax, MTV and TLG were found according to Lauren’s classification, histologic grade and T category(P<0.05). During the 26.5-month follow-up, 51(35.4%) patients died and 70(48.6%) exhibited disease progression. The optimal thresholds of MTV and TLG were 15.1 cm^3 and 47.3 cm^3, respectively. The 3-year progression-free survival(PFS) and overall survival(OS) for patients with high TLG values were 30% and 38% compared to 38% and 47% for low TLG values, respectively(P<0.05). Univariate and multifactor analyses demonstrated that lymph node metastasis and T stage were independent prognostic factors for PFS;T stage, histologic grade and TLG were independent prognostic factors for OS(P<0.05). Molecular markers had no relationship with patient’s outcomes.Conclusions: Metabolic activity of primary gastric tumors from 18 F-FDG PET/CT is a prognostic factor in patients with LAGC.展开更多
Objective： High-dose chemotherapy （HDC） followed by autologous stem cell transplantation （ASCT） is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma （...Objective： High-dose chemotherapy （HDC） followed by autologous stem cell transplantation （ASCT） is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma （NHL）. However, a proportion of patients do not respond to ASCT. lSF-fluorodeoxyglueose （FDG） positron emission tomography （PET）/computed tomography （CT） has been widely used for staging, response evaluation, and prognosis prediction. Here, we investigated the prognostic role of PET/CT in NHL patients before and after ASCT. Methods： A retrospective study was conducted at Peking University Cancer Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016 were identified. Patients who had PET/CT scan before and after ASCT were included. Deauville criteria （5-point scale） were used to interpret PET scans. Univariate and multivariate survival analyses were performed using Cox regression. The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic （ROC） curve. Results： In total, 79 patients were enrolled in this study. In univariate analysis, pre- and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival （PFS） and overall survival （OS）. Patients with negative pre-ASCT PET result demonstrated significantly better PFS （84.2% vs. 54.2%） and OS （89.2% vs. 63.6%） than patients with positive pre-ASCT PET result. PFS （91.6% vs. 25.3%） and OS （96.5% vs. 36.8%） were also significantly different between patients with negative and positive post-ASCT PET result. Multivariate analysis also showed a significant association between survival and post-ASCT PET result. ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation. Deauville criteria score 〉3 was identified as the best cutoffvalue for post-ASCT PET. Conclusions： Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT. The prognostic significance can be improved when combining pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.展开更多
Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluo...Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.展开更多
Objective： The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was ...Objective： The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was to synthesize and optimize a dual-labeled trastuzumab-based imaging agent that can be used to validate an optical imaging agent with potential use in identifying tumor metastases in human epidermal growth factor receptor 2 （HER2） positive breast cancer patients. Methods： [111In]-DTPA-trastuzumab-IRDye 800 was synthesized by a three-step procedure. Purity, stability, immunoreactivity, internalization and biodistribution were explored in HER2＋ SKBR-3 cells. Biodistribution of [111In]-DTPA-trastuzumab-IRDye 800 was performed in a SKBR-3 xenograft model. Results： [111In]-DTPA-trastuzumab-IRDye 800 demonstrated high purity by both chemical and fluorometric determinations. Both flow cytometry and the Lindmo assay demonstrated a high binding affinity of [111In]-DTPA-trastuzumab-IRDye 800 to HER2-overexpressing cells. The dual-labeled conjugate was stable in PBS, but not in serum after 24 h at 37 ℃. Larger molecules （〉150 kD） were seen after a 24 h-incubation in human serum. Biodistribution studies revealed tumor-specific accumulation of [111In]-DTPA- trastuzumab-IRDye 800 in SKBR-3 tumors, and tumor uptakes at 24 and 48 h were （12.42±1.72）% and （9.96±1.05） %, respectively, following intravenous administration. The tumor-to-muscle ratio was 9.13±1.68 at 24 h, and increased to 12.79±2.13 at 48 h. Liver and kidney showed marked uptake of the dual-labeled imaging agent. Conclusions： [111In]-DTPA-trastuzumab-IRDye 800 is an effective diagnostic biomarker that can be used to validate dual-labeled, molecularly targeted imaging agents and can allow these agents to be translated into clinical practice for identifying HER2＋ lesions.展开更多
Atmospheric electricity is composed of a series of electric phenomena in the atmosphere.Significant advances in atmospheric electricity research conducted in China have been achieved in recent years.In this paper,the ...Atmospheric electricity is composed of a series of electric phenomena in the atmosphere.Significant advances in atmospheric electricity research conducted in China have been achieved in recent years.In this paper,the research progress on atmospheric electricity achieved in China during 2019-22 is reviewed focusing on the following aspects:(1)lightning detection and location techniques,(2)thunderstorm electricity,(3)lightning forecasting methods and techniques,(4)physical processes of lightning discharge,(5)high energy emissions and effects of thunderstorms on the upper atmosphere,and(6)the effect of aerosol on lightning.展开更多
Objective： To investigate the effect of fluorescent dye labeling on the targeting capabilities of 111 In- （DTPA）.-trastuzumab-（IRDye 800）m. Methods： Trastuzumab-based conjugates were synthesized and conjugated w...Objective： To investigate the effect of fluorescent dye labeling on the targeting capabilities of 111 In- （DTPA）.-trastuzumab-（IRDye 800）m. Methods： Trastuzumab-based conjugates were synthesized and conjugated with diethylenetriaminepentaacetic acid （DTPA） at molar ratios of I, 2, 3 and 5 and with a fluorescent dye （IRDye 800CW） at molar ratios of 1, 3 and 5. Immunoreactivity and internalization were assessed on SKBR-3 cells, overexpressing human epidermal growth factor receptor 2. The stability in human serum and phosphate-buffered saline （PBS） was evaluated. The biodistribution of dual-labeled conjugates was compared with that of 111In-（DTPA）2-trastuzumab in a SKBR-3 xenograft model to evaluate the effect of dye-to-protein ratio. Results： All trastuzumab-based conjugates exhibited a high level of chemical and optical purity. Flow cytometry results showed that increasing dye-to-protein ratios were associated with decreased immunoreactivity. Stability studies revealed that the conjugate was stable in PBS, while in human serum, increased degradation and protein precipitation were observed with increasing dye-to-protein ratios. At 4 h, the percentages of internalization of dual-labeled conjugates normalized by dye-to-protein ratio （m） were 24.88%±2.10%, 19.99%±0.59%, and 17.47%±1.26% for ＂m＂ equal to 1, 3, and 5, respectively. A biodistribution study revealed a progressive decrease in tumor uptake with an increase in the dye-to-protein ratios. The liver, spleen and kidney showed a marked uptake with increased dye-to-protein ratios, particularly in the latter. Conclusions： With non-specific-site conjugation of the fluorescent dye with a protein based on imaging agent, the increase in dye-to-protein ratios negatively impacted the immunoreactivity and stability, indicating a reduced tumor uptake.展开更多
Purpose To investigate the influence of different reconstruction techniques on the quantitative accuracy and image quality of PET/CT.Methods The NEMA NU2-2018 image quality phantom was scanned on a GE Discovery Elite ...Purpose To investigate the influence of different reconstruction techniques on the quantitative accuracy and image quality of PET/CT.Methods The NEMA NU2-2018 image quality phantom was scanned on a GE Discovery Elite PET/CT scanner and the spatial resolution was measured based on NEMA NU2 standard.The same raw data were reconstructed using five different algorithms:ordered subset expectation maximization(OSEM),OSEM with point spread function(PSF)modeling,OSEM with time-of-flight(TOF),OSEM with TOF and PSF,and filtered back-projection(FBP).The recovery coefficient(RC),contrast recovery coefficient(CRC),and contrast-to-noise ratio(CNR)were calculated for the six hot spheres,the percent background variability(PBV)and coefficient of variation(COV)were calculated for the background,and the residual error(RE)was calculated for lung insert in different image slices.Results The incorporation of PSF modeling showed the smallest transverse FWHM and FWTM at both 1 and 10 cm radical offsets.The combination of PSF modeling and TOF improved RC_(mean) and CRC for all spheres and resulted in the highest ratings for the detectability of 10 mm spheres in human observer assessment.PSF modeling played a role in reducing the COV within the background region of interest and increasing the CNR of the spheres,and decreased background noise ratings in human observer assessment.Besides,TOF significantly reduced the RE in lung insert.Neither PSF modeling nor TOF had a significant effect on PBV.Compared to FBP,the OSEM algorithm showed significant advantages in PBV,COV,CNR and RE and human observer ratings of image quality,but worse results for RC_(max),RC_(mean) and CRC.Conclusions The integration of TOF and PSF modeling into the OSEM algorithm achieves improvements in both quantitative accuracy and image quality,providing distinct advantages.PSF modeling improves the spatial resolution and decreases the visual appearance of background noise.The OSEM algorithm shows significantly better image quality than the FBP algorithm but no distinct advantages concerning quantitative accuracy.展开更多
The presence and functions of nuclear actin have been controversial due to the lack of molecular mechanisms.Nuclear actin and actin?『elated proteins (Arps) are subunits of several chromatin remodelers, including the ...The presence and functions of nuclear actin have been controversial due to the lack of molecular mechanisms.Nuclear actin and actin?『elated proteins (Arps) are subunits of several chromatin remodelers, including the evolutionarily conserved IN080 chromatin-remodeling complex. Here, we present an improved cryo-EM structure of the yeast IN080 complex and the first 3D reconstruction of the IN080 actin/Arp module.The modular and subunit architecture is defined using a combination of subunit deletion analysis and published crosslinking-mass spectrometry. The functional interactions of the IN080 actin/Arp module with a nucleosome is 3D EM reconstructed in two different binding states. Nucleosomes initially bind to the Arp8 subunit and the substantial conformational changes maximize nucleosome contacts of the actin/Arp module, which could promote the bound nucleosome to be engaged onto the IN080 ATPase domain. Our findings suggest that the conserved nuclear actin/Arp module acts a conformational switch of the IN080 for nucleosome binding.展开更多
Fatty acid synthase (FAS) is the key enzyme for de novo fatty acid synthesis and exists widely from bacteria to mammalian cells (Schweizer and Hofmann, 2004). It is involved in membrane organization, metabolism regula...Fatty acid synthase (FAS) is the key enzyme for de novo fatty acid synthesis and exists widely from bacteria to mammalian cells (Schweizer and Hofmann, 2004). It is involved in membrane organization, metabolism regulation, energy storage, and many other processes (Maier et al., 2010). The ataxia telangiectasia-mutated and Rad3-related kinase (ATR) is a master regulator of DNA damage response (DDR) and is highly conserved. ATR is activated by DNA double-strand breaks and various types of DNA replication stresses (Cortez et al., 2001). Recent researches have reported that FAS seems closely related to genome stability (Wu et al., 2016). It has been proved that palmitic acid, the product of FAS, can inhibit ATR phosphorylation and kinase activity in mouse fibroblast (Zeng et al., 2008). These studies suggest that there is a crosstalk between fatty acid metabolism and DDR pathway, but the mechanism remains unknown.展开更多
Mediator is a highly conserved large protein complex(25 proteins,>1000 kD a)and preeminently responsible for eu-karyotic transcription,which contains a dissociable‘Cdk8 module’.Although increasing evidence demons...Mediator is a highly conserved large protein complex(25 proteins,>1000 kD a)and preeminently responsible for eu-karyotic transcription,which contains a dissociable‘Cdk8 module’.Although increasing evidence demonstrates that Cdk8 module plays both positive and negative roles in transcription regulation,the detailed structure,and subu-nit organization,molecular mechanism how it regulates transcription remain elusive.Here we used single-particle electron microscopy to characterize the structure and subunit organization of the Cdk8 module and illuminated the substantial mobility of the Med13 subunit results in the structural fl exibility.The Cdk8 module interaction with core Mediator is concurrent with active transcription in vivo.An interaction with the Cdk8 module induces core Mediator into very extended conformation in vitro,which is presumed to be an active functional state of Mediator.Taken together,our results illuminated the detailed archi-tecture of Cdk8 module,and suggested the Cdk8 module could positively regulate transcription by modulating Me-diator conformation.展开更多
Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supporte...Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supported by high-quality evidence.However,the TB indications and strategies are controversial.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,invited a panel of recognized urology experts in PCa to address these topics at the Panjiayuan Consensus Conference 2022.The conference results on prostate TB are presented herein.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences identified 10 key areas of prostate biopsy:(1)selection of imaging examination;(2)indications of TB;(3)transperineal and transrectal prostate biopsy;(4)TB pathways;(5)TB and SB;(6)three techniques of TB;(7)the number of TB cores needed for one lesion;(8)core number for SB;(9)free-hand TB;(10)future development of TB/prostate diagnosis.Thus,a panel of 25 recognized urologists and 2 radiologists from China were invited to attend this conference.The panel voted anonymously on 14 predetermined questions.Voting was based on the panelists'clinical practice and opinion,rather than high-level evidence.The voting outcomes were supported by the panel unequally,and details of the voting results were reported.The voting results can help clinicians to decide on biopsy timing and proper strategies,for which guidelines are sparse.We also focused on the future development of TB and SB,such as the combined pathway of TB and SB,techniques of TB,biopsy cores,free-hand TB,and prostate-specific membrane antigen positron emission tomography/computed tomography.展开更多
Excitation wavelength dependent(Ex-De) luminescent materials have attracted intense attention due to their great potential in multicolor bioimaging,dynamic anti-counterfeiting,and light emitting devices.However,it rem...Excitation wavelength dependent(Ex-De) luminescent materials have attracted intense attention due to their great potential in multicolor bioimaging,dynamic anti-counterfeiting,and light emitting devices.However,it remains a formidable challenge to construct an Ex-De luminescent biomaterial with green starting materials,excellent biocompatibility,good water solubility,and multiple color emission for dynamic cell imaging.In this work,nanocomposites based on the facile self-assembly strategy of bovine serum albumin(BSA) and Au(Ⅰ)-complex are rationally designed and synthesized to simultaneously present Ex-De fluorescence(429–516 nm) and decent phosphorescence(~615 nm) in a dilute aqueous solution.Combinatory analyses of spectroscopic and microscopic results reveal that the luminescent mechanism of Au(Ⅰ)-BSA nanocomposites is cluster-induced Ex-De fluorescence and metal-to-ligand charge transition(MLCT) based phosphorescence.Importantly,based on the excellent biocompatibility,water-solubility and color-tunable emission over the entire visible region(360–800 nm),the Au(Ⅰ)-BSA nanocomposites are successfully used for cell imaging with multiple and switchable colors on demand.What is more,the solid tablets of Au(Ⅰ)-BSA nanoparticles showed pressure-responsive luminescence and decent room temperature phosphorescence.This work provides an assembling-induced emission strategy for the design of water-soluble,non-cytotoxic,and color-tunable luminescent biomaterials based on the composite of protein and Au nanoparticles.展开更多
Using the optical images of a cloud-to-ground lightning flash with multiple grounding points obtained by a highspeed video system in the Qinghai Province of China along with synchronous radiated electric field informa...Using the optical images of a cloud-to-ground lightning flash with multiple grounding points obtained by a highspeed video system in the Qinghai Province of China along with synchronous radiated electric field information, the propagation characteristic and the electric field change features of the leaders and the grounding behavior of discharge channels are analyzed.In addition, the two-dimensional velocity of the leader was estimated and its correlation with the time interval of the corresponding subsequent return stroke, and that with the peak current of return stroke are investigated. The results show that the average distance between the three obvious grounded points of the first return stroke channel is about 512.7 m, and the average time interval between the pulses of the corresponding electric field fast changes is 3.8 μs. Further, the average time interval between electric field pulses from the stepped leader is smaller than that of normal single grounding lightning. The observed lightning in our study has two main channels, namely the left and right channels. Based on our observations, it is clear that the dart leader comes close to the ground in case of the left channel after the first return stroke, but it fails to form a return stroke.However, the right channel exhibits a relatively rare phenomenon in that the subsequent return stroke R2 occurred about 2.1 ms after the dart leader arrived at the ground, which was unusually long; this phenomenon might be attributed to the strong discharge of the first return stroke and insufficient charge accumulation near the grounded point in a timely manner. The two-dimensional velocities for the stepped leader of the two main channels are about 1.23×105 and 1.16×105 m s-1, respectively. A sub-branch of stepped leader for the left channel fails to reach the ground and develops into an attempt leader eventually; this might be attributed to the fact that the main branch connects considerably many sub-branches, which leads to the instantaneous decline of the potential difference between the sub-branch and ground. Furthermore, it might also be because the propagation direction of this sub-branch is almost perpendicular to the atmospheric electric field direction, which is not conducive to charge transfer. The two-dimensional velocities for the dart leaders of five subsequent return strokes are all in the normal range, and they positively correlate with the peak current of the subsequent return stroke.展开更多
文摘Objective： Diffuse large B-cell lymphoma （DLBCL） is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods： Thirty-two patients with DLBCL underwent baseline, interim and post-treatment lSF-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results： Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival （PFS） rates were significantly different between the groups above and below SUVmax CUt-Off value of 2.5 （P=0.039）. No significant differences were found in the 2-year PFS rates if SUVm, cut-offvalues were set as 2.0 and 3.0, respectively （P=0.360; P=0.113）. Conclusions： Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.
基金supported by a grant from Beijing Municipal Natural Science Foundation (No. 7172043)
文摘Objective: The present study investigated the prognosis value of preoperative fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT) in patients with local advanced gastric cancer(LAGC).Methods: In total, 144 patients [median age 63(range: 48-80) years old] with LAGC underwent 18 F-FDG PET/CT prior to any treatment. The maximum standardized uptake values(SUVmax), mean standardized uptake values(SUVmean), metabolic tumor volume(MTV) and total lesion glycolysis(TLG) of the primary lesion were measured on PET/CT and correlated with clinicopathological features and survival.Results: Significant differences in SUVmean, SUVmax, MTV and TLG were found according to Lauren’s classification, histologic grade and T category(P<0.05). During the 26.5-month follow-up, 51(35.4%) patients died and 70(48.6%) exhibited disease progression. The optimal thresholds of MTV and TLG were 15.1 cm^3 and 47.3 cm^3, respectively. The 3-year progression-free survival(PFS) and overall survival(OS) for patients with high TLG values were 30% and 38% compared to 38% and 47% for low TLG values, respectively(P<0.05). Univariate and multifactor analyses demonstrated that lymph node metastasis and T stage were independent prognostic factors for PFS;T stage, histologic grade and TLG were independent prognostic factors for OS(P<0.05). Molecular markers had no relationship with patient’s outcomes.Conclusions: Metabolic activity of primary gastric tumors from 18 F-FDG PET/CT is a prognostic factor in patients with LAGC.
基金sponsored by Scientific Research Foundation for the Returned Overseas Chinese ScholarsMinistry of Human Resources and Social SecurityBeijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.XMLX201502)
文摘Objective： High-dose chemotherapy （HDC） followed by autologous stem cell transplantation （ASCT） is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma （NHL）. However, a proportion of patients do not respond to ASCT. lSF-fluorodeoxyglueose （FDG） positron emission tomography （PET）/computed tomography （CT） has been widely used for staging, response evaluation, and prognosis prediction. Here, we investigated the prognostic role of PET/CT in NHL patients before and after ASCT. Methods： A retrospective study was conducted at Peking University Cancer Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016 were identified. Patients who had PET/CT scan before and after ASCT were included. Deauville criteria （5-point scale） were used to interpret PET scans. Univariate and multivariate survival analyses were performed using Cox regression. The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic （ROC） curve. Results： In total, 79 patients were enrolled in this study. In univariate analysis, pre- and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival （PFS） and overall survival （OS）. Patients with negative pre-ASCT PET result demonstrated significantly better PFS （84.2% vs. 54.2%） and OS （89.2% vs. 63.6%） than patients with positive pre-ASCT PET result. PFS （91.6% vs. 25.3%） and OS （96.5% vs. 36.8%） were also significantly different between patients with negative and positive post-ASCT PET result. Multivariate analysis also showed a significant association between survival and post-ASCT PET result. ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation. Deauville criteria score 〉3 was identified as the best cutoffvalue for post-ASCT PET. Conclusions： Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT. The prognostic significance can be improved when combining pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.
基金supported by the National Natural Science Foundation of China (No. 81600164)
文摘Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.
基金supported by Beijing Natural Science Foundation (No. 7132037)NIH R01
文摘Objective： The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was to synthesize and optimize a dual-labeled trastuzumab-based imaging agent that can be used to validate an optical imaging agent with potential use in identifying tumor metastases in human epidermal growth factor receptor 2 （HER2） positive breast cancer patients. Methods： [111In]-DTPA-trastuzumab-IRDye 800 was synthesized by a three-step procedure. Purity, stability, immunoreactivity, internalization and biodistribution were explored in HER2＋ SKBR-3 cells. Biodistribution of [111In]-DTPA-trastuzumab-IRDye 800 was performed in a SKBR-3 xenograft model. Results： [111In]-DTPA-trastuzumab-IRDye 800 demonstrated high purity by both chemical and fluorometric determinations. Both flow cytometry and the Lindmo assay demonstrated a high binding affinity of [111In]-DTPA-trastuzumab-IRDye 800 to HER2-overexpressing cells. The dual-labeled conjugate was stable in PBS, but not in serum after 24 h at 37 ℃. Larger molecules （〉150 kD） were seen after a 24 h-incubation in human serum. Biodistribution studies revealed tumor-specific accumulation of [111In]-DTPA- trastuzumab-IRDye 800 in SKBR-3 tumors, and tumor uptakes at 24 and 48 h were （12.42±1.72）% and （9.96±1.05） %, respectively, following intravenous administration. The tumor-to-muscle ratio was 9.13±1.68 at 24 h, and increased to 12.79±2.13 at 48 h. Liver and kidney showed marked uptake of the dual-labeled imaging agent. Conclusions： [111In]-DTPA-trastuzumab-IRDye 800 is an effective diagnostic biomarker that can be used to validate dual-labeled, molecularly targeted imaging agents and can allow these agents to be translated into clinical practice for identifying HER2＋ lesions.
基金supported by the National Key Research and Development Program of China(Grant No.2017YFC1501500).
文摘Atmospheric electricity is composed of a series of electric phenomena in the atmosphere.Significant advances in atmospheric electricity research conducted in China have been achieved in recent years.In this paper,the research progress on atmospheric electricity achieved in China during 2019-22 is reviewed focusing on the following aspects:(1)lightning detection and location techniques,(2)thunderstorm electricity,(3)lightning forecasting methods and techniques,(4)physical processes of lightning discharge,(5)high energy emissions and effects of thunderstorms on the upper atmosphere,and(6)the effect of aerosol on lightning.
基金supported by Beijing Natural Science Foundation(No.7132037)the National Cancer Institute Network for Translational Research U54 CA136404-01
文摘Objective： To investigate the effect of fluorescent dye labeling on the targeting capabilities of 111 In- （DTPA）.-trastuzumab-（IRDye 800）m. Methods： Trastuzumab-based conjugates were synthesized and conjugated with diethylenetriaminepentaacetic acid （DTPA） at molar ratios of I, 2, 3 and 5 and with a fluorescent dye （IRDye 800CW） at molar ratios of 1, 3 and 5. Immunoreactivity and internalization were assessed on SKBR-3 cells, overexpressing human epidermal growth factor receptor 2. The stability in human serum and phosphate-buffered saline （PBS） was evaluated. The biodistribution of dual-labeled conjugates was compared with that of 111In-（DTPA）2-trastuzumab in a SKBR-3 xenograft model to evaluate the effect of dye-to-protein ratio. Results： All trastuzumab-based conjugates exhibited a high level of chemical and optical purity. Flow cytometry results showed that increasing dye-to-protein ratios were associated with decreased immunoreactivity. Stability studies revealed that the conjugate was stable in PBS, while in human serum, increased degradation and protein precipitation were observed with increasing dye-to-protein ratios. At 4 h, the percentages of internalization of dual-labeled conjugates normalized by dye-to-protein ratio （m） were 24.88%±2.10%, 19.99%±0.59%, and 17.47%±1.26% for ＂m＂ equal to 1, 3, and 5, respectively. A biodistribution study revealed a progressive decrease in tumor uptake with an increase in the dye-to-protein ratios. The liver, spleen and kidney showed a marked uptake with increased dye-to-protein ratios, particularly in the latter. Conclusions： With non-specific-site conjugation of the fluorescent dye with a protein based on imaging agent, the increase in dye-to-protein ratios negatively impacted the immunoreactivity and stability, indicating a reduced tumor uptake.
文摘Purpose To investigate the influence of different reconstruction techniques on the quantitative accuracy and image quality of PET/CT.Methods The NEMA NU2-2018 image quality phantom was scanned on a GE Discovery Elite PET/CT scanner and the spatial resolution was measured based on NEMA NU2 standard.The same raw data were reconstructed using five different algorithms:ordered subset expectation maximization(OSEM),OSEM with point spread function(PSF)modeling,OSEM with time-of-flight(TOF),OSEM with TOF and PSF,and filtered back-projection(FBP).The recovery coefficient(RC),contrast recovery coefficient(CRC),and contrast-to-noise ratio(CNR)were calculated for the six hot spheres,the percent background variability(PBV)and coefficient of variation(COV)were calculated for the background,and the residual error(RE)was calculated for lung insert in different image slices.Results The incorporation of PSF modeling showed the smallest transverse FWHM and FWTM at both 1 and 10 cm radical offsets.The combination of PSF modeling and TOF improved RC_(mean) and CRC for all spheres and resulted in the highest ratings for the detectability of 10 mm spheres in human observer assessment.PSF modeling played a role in reducing the COV within the background region of interest and increasing the CNR of the spheres,and decreased background noise ratings in human observer assessment.Besides,TOF significantly reduced the RE in lung insert.Neither PSF modeling nor TOF had a significant effect on PBV.Compared to FBP,the OSEM algorithm showed significant advantages in PBV,COV,CNR and RE and human observer ratings of image quality,but worse results for RC_(max),RC_(mean) and CRC.Conclusions The integration of TOF and PSF modeling into the OSEM algorithm achieves improvements in both quantitative accuracy and image quality,providing distinct advantages.PSF modeling improves the spatial resolution and decreases the visual appearance of background noise.The OSEM algorithm shows significantly better image quality than the FBP algorithm but no distinct advantages concerning quantitative accuracy.
基金the National Natural Science Foundation of China (31570726 and 31170694)the National Basic Research Program (2014CB910700).
文摘The presence and functions of nuclear actin have been controversial due to the lack of molecular mechanisms.Nuclear actin and actin?『elated proteins (Arps) are subunits of several chromatin remodelers, including the evolutionarily conserved IN080 chromatin-remodeling complex. Here, we present an improved cryo-EM structure of the yeast IN080 complex and the first 3D reconstruction of the IN080 actin/Arp module.The modular and subunit architecture is defined using a combination of subunit deletion analysis and published crosslinking-mass spectrometry. The functional interactions of the IN080 actin/Arp module with a nucleosome is 3D EM reconstructed in two different binding states. Nucleosomes initially bind to the Arp8 subunit and the substantial conformational changes maximize nucleosome contacts of the actin/Arp module, which could promote the bound nucleosome to be engaged onto the IN080 ATPase domain. Our findings suggest that the conserved nuclear actin/Arp module acts a conformational switch of the IN080 for nucleosome binding.
文摘Fatty acid synthase (FAS) is the key enzyme for de novo fatty acid synthesis and exists widely from bacteria to mammalian cells (Schweizer and Hofmann, 2004). It is involved in membrane organization, metabolism regulation, energy storage, and many other processes (Maier et al., 2010). The ataxia telangiectasia-mutated and Rad3-related kinase (ATR) is a master regulator of DNA damage response (DDR) and is highly conserved. ATR is activated by DNA double-strand breaks and various types of DNA replication stresses (Cortez et al., 2001). Recent researches have reported that FAS seems closely related to genome stability (Wu et al., 2016). It has been proved that palmitic acid, the product of FAS, can inhibit ATR phosphorylation and kinase activity in mouse fibroblast (Zeng et al., 2008). These studies suggest that there is a crosstalk between fatty acid metabolism and DDR pathway, but the mechanism remains unknown.
基金This work was supported by grants from the National Basic Research Program(973 Program)(No.2013CB910200)the National Natural Science Foundation of China(Grant Nos.31170694 and 31222017)+1 种基金Ministry of Education of PRC(NCET-11-0874)Chinese Academy Of Sciences(48500108-6).
文摘Mediator is a highly conserved large protein complex(25 proteins,>1000 kD a)and preeminently responsible for eu-karyotic transcription,which contains a dissociable‘Cdk8 module’.Although increasing evidence demonstrates that Cdk8 module plays both positive and negative roles in transcription regulation,the detailed structure,and subu-nit organization,molecular mechanism how it regulates transcription remain elusive.Here we used single-particle electron microscopy to characterize the structure and subunit organization of the Cdk8 module and illuminated the substantial mobility of the Med13 subunit results in the structural fl exibility.The Cdk8 module interaction with core Mediator is concurrent with active transcription in vivo.An interaction with the Cdk8 module induces core Mediator into very extended conformation in vitro,which is presumed to be an active functional state of Mediator.Taken together,our results illuminated the detailed archi-tecture of Cdk8 module,and suggested the Cdk8 module could positively regulate transcription by modulating Me-diator conformation.
基金Capital's Funds for Health Improvement and Research,Grant/Award Number:2022-3-40714。
文摘Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supported by high-quality evidence.However,the TB indications and strategies are controversial.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,invited a panel of recognized urology experts in PCa to address these topics at the Panjiayuan Consensus Conference 2022.The conference results on prostate TB are presented herein.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences identified 10 key areas of prostate biopsy:(1)selection of imaging examination;(2)indications of TB;(3)transperineal and transrectal prostate biopsy;(4)TB pathways;(5)TB and SB;(6)three techniques of TB;(7)the number of TB cores needed for one lesion;(8)core number for SB;(9)free-hand TB;(10)future development of TB/prostate diagnosis.Thus,a panel of 25 recognized urologists and 2 radiologists from China were invited to attend this conference.The panel voted anonymously on 14 predetermined questions.Voting was based on the panelists'clinical practice and opinion,rather than high-level evidence.The voting outcomes were supported by the panel unequally,and details of the voting results were reported.The voting results can help clinicians to decide on biopsy timing and proper strategies,for which guidelines are sparse.We also focused on the future development of TB and SB,such as the combined pathway of TB and SB,techniques of TB,biopsy cores,free-hand TB,and prostate-specific membrane antigen positron emission tomography/computed tomography.
基金supported by the National Natural Science Foundation of China(22101208,22125803,22020102006)the Fundamental Research Funds for the Central Universitiesthe Program for Professors of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning。
文摘Excitation wavelength dependent(Ex-De) luminescent materials have attracted intense attention due to their great potential in multicolor bioimaging,dynamic anti-counterfeiting,and light emitting devices.However,it remains a formidable challenge to construct an Ex-De luminescent biomaterial with green starting materials,excellent biocompatibility,good water solubility,and multiple color emission for dynamic cell imaging.In this work,nanocomposites based on the facile self-assembly strategy of bovine serum albumin(BSA) and Au(Ⅰ)-complex are rationally designed and synthesized to simultaneously present Ex-De fluorescence(429–516 nm) and decent phosphorescence(~615 nm) in a dilute aqueous solution.Combinatory analyses of spectroscopic and microscopic results reveal that the luminescent mechanism of Au(Ⅰ)-BSA nanocomposites is cluster-induced Ex-De fluorescence and metal-to-ligand charge transition(MLCT) based phosphorescence.Importantly,based on the excellent biocompatibility,water-solubility and color-tunable emission over the entire visible region(360–800 nm),the Au(Ⅰ)-BSA nanocomposites are successfully used for cell imaging with multiple and switchable colors on demand.What is more,the solid tablets of Au(Ⅰ)-BSA nanoparticles showed pressure-responsive luminescence and decent room temperature phosphorescence.This work provides an assembling-induced emission strategy for the design of water-soluble,non-cytotoxic,and color-tunable luminescent biomaterials based on the composite of protein and Au nanoparticles.
基金supported by the National Natural Science Foundations of China (Grants Nos. 11475139, 11365019 & 11605108)the Gansu Provincial Science and Technology Program (Grant No. 1506RJZA119)
文摘Using the optical images of a cloud-to-ground lightning flash with multiple grounding points obtained by a highspeed video system in the Qinghai Province of China along with synchronous radiated electric field information, the propagation characteristic and the electric field change features of the leaders and the grounding behavior of discharge channels are analyzed.In addition, the two-dimensional velocity of the leader was estimated and its correlation with the time interval of the corresponding subsequent return stroke, and that with the peak current of return stroke are investigated. The results show that the average distance between the three obvious grounded points of the first return stroke channel is about 512.7 m, and the average time interval between the pulses of the corresponding electric field fast changes is 3.8 μs. Further, the average time interval between electric field pulses from the stepped leader is smaller than that of normal single grounding lightning. The observed lightning in our study has two main channels, namely the left and right channels. Based on our observations, it is clear that the dart leader comes close to the ground in case of the left channel after the first return stroke, but it fails to form a return stroke.However, the right channel exhibits a relatively rare phenomenon in that the subsequent return stroke R2 occurred about 2.1 ms after the dart leader arrived at the ground, which was unusually long; this phenomenon might be attributed to the strong discharge of the first return stroke and insufficient charge accumulation near the grounded point in a timely manner. The two-dimensional velocities for the stepped leader of the two main channels are about 1.23×105 and 1.16×105 m s-1, respectively. A sub-branch of stepped leader for the left channel fails to reach the ground and develops into an attempt leader eventually; this might be attributed to the fact that the main branch connects considerably many sub-branches, which leads to the instantaneous decline of the potential difference between the sub-branch and ground. Furthermore, it might also be because the propagation direction of this sub-branch is almost perpendicular to the atmospheric electric field direction, which is not conducive to charge transfer. The two-dimensional velocities for the dart leaders of five subsequent return strokes are all in the normal range, and they positively correlate with the peak current of the subsequent return stroke.
