AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric cancer, who underwent radical gastrectomy with D2 dissecti...AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric cancer, who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011, were analyzed retrospectively. Among these patients, 131 patients underwent laparoscopyassisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG). The parameters analyzed included operative time, blood loss, blood transfusion, morbidity, mortality, the number of harvested lymph nodes (HLNs), and pathological stage.RESULTS: There were no significant differences in sex, age, types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)], and stages between the LAG and OG groups (P > 0.05). Among the two groups, 127 cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs, respectively. The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P = 0.233). In the same type of radical resection, there were no signifi cant differences in the number of HLNs between the two groups (PG + D2: 21.7 ± 7.5 vs 22.4 ± 9.3; DG + D2: 25.7 ± 11.0 vs 22.3 ± 7.9; TG + D2: 30.9 ± 13.4 vs 29.3 ± 10.4; P > 0.05 for all comparisons). Tumor free margins were obtained in all cases. Compared with OG group, the LAG group had signifi cantly less blood loss, but a longer operation time (P < 0.001). The morbidity of the LAG group was 9.9%, which was not signifi cantly different from the OG group (7.7%) (P = 0.587). The mortality was zero in both groups. CONCLUSION: Laparoscopic D2 dissection is equivalent to OG in the number of HLNs, regardless of tumor location. Thus, this procedure can achieve the same radicalness as OG.展开更多
microRNAs （miRNAs） are a class of endogenous, single-stranded non-coding RNAs of 20- 23 nucleotides in length, functioning as negative regulators of gene expression at the post-transcriptional level. The dysregulati...microRNAs （miRNAs） are a class of endogenous, single-stranded non-coding RNAs of 20- 23 nucleotides in length, functioning as negative regulators of gene expression at the post-transcriptional level. The dysregulation of miRNAs has been demonstrated to play critical roles in tumorigenesis, either through inhibiting tumor suppressor genes or activating oncogenes inappropriately. Besides their promising clinical applications in cancer diagnosis and treatment, recent studies have uncovered that miRNAs could act as a regulatory language, through which messenger RNAs, transcribed pseudogenes, and long noncoding RNAs crosstalk with each other and form a novel regulatory network. RNA transcripts involved in this network have been termed as competing endogenous RNAs （ceRNAs）, since they influence each other＇s level by competing for the same pool of miRNAs through miRNA response elements （MREs） on their target transcripts. The discovery of miRNA-ceRNA network not only provides the possibility of an additional level of post-transcriptional regulation, but also dictates a reassessment of the existing regulatory pathways involved in cancer initiation and progression.展开更多
Background： We investigated the effect of a small molecular inhibitor of heat shock protein （HSP）, qnercetin, on tumor radiofrequency （RF） ablation, and explored the underlying molecular mechanisms. Methods： In ...Background： We investigated the effect of a small molecular inhibitor of heat shock protein （HSP）, qnercetin, on tumor radiofrequency （RF） ablation, and explored the underlying molecular mechanisms. Methods： In in vivo study, rats with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross coagulation areas were compared, and next, randomized into four treatment arms （control, quercetin alone, RF alone, and combination） for Kaplan-Meier analysis of defined endpoint survival. Then the distribution and expression levels of heat shock protein 70 （HSP70）, cleaved caspase-3 and heat shock factor 1 （HSF1） were analyzed after different treatments. In in vitro study, we used quercetin to promote SK- HEP-I （hepatic） and MCF-7 （breast） cancer cell apoptosis in heat shock cell model, and siRNA was used to block c-Jun and to explore the role of activating protein-1 （AP-1） signaling pathways. Results： We found the effects of quercetin plus RFA resulted in increase on the tumor destruction/ endpoint survival （26.5±3.4 d） in vivo, compared with RF alone （17.6±2.5 d） and quercetin alone （15.7±3.1 d）. Most importantly, quercetin-induced cancer cell death required the presence of HSF1 in animal model. Furthermore, quercetin directly down-regulated expression of HSF1 in vitro, which our findings have revealed, required the activation of AP-1 signaling pathways by loss-of-function analysis using siRNA mediated targeting of c-Jun. Conclusions： These results indicated a protective role of quercetin in tumor ablation and highlighted a novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid tumors.展开更多
The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body,including the mouth,lung,intestines,skin,and vagina.These micr...The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body,including the mouth,lung,intestines,skin,and vagina.These microbial communities are involved in many essential functions,such as metabolism,immunity,host nutrition,and diseases.Recent studies have focused on the microbiota associated with cancers,particularly the oral and intestinal microbiota.Radiotherapy,the most effective cytotoxic modality available for solid tumors,contributes to the treatment of cancer patients.Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy.Here,we review current research on the microbiota and cancer development,and describe knowledge gaps in the study of radiotherapy and the microbiota.Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.展开更多
Background With the rapid increase in ageing population,China is confronted with the daunting challenge of a growing number of patients with neurocognitive disorders(NCDs).This trend makes the maintenance of self-heal...Background With the rapid increase in ageing population,China is confronted with the daunting challenge of a growing number of patients with neurocognitive disorders(NCDs).This trend makes the maintenance of self-health and early intervention essential,highlighting the need for a tool that assesses self-efficacy of older adults in maintaining brain health or cognitive function.Aim This study aimed to design the Brain Health Self-Efficacy Scale(BHSES)to measure elderly individuals'attitudes to NCDs,motivations and future plans for controlling risks.The psychometric properties of BHSES have been validated.Methods Based on the current literature and relevant models,a 19-item scale was created during the first stage.A total of 660 older adults in the Yinhang community of Shanghai were included.The statistical approaches of item analysis,exploratory factor analysis(EFA),confirmatory factor analysis(CFA),criterion-related validity and reliability test were used to evaluate the quality of BHSES.In addition,the Geriatric Depression Scale(GDS)and the Self-Rating Anxiety Scale(SAS)were used as criteria to test the criterion-related validity.Results To test item differentiation,the study adopted item analysis and excluded item 8.Selecting a random half of the sample for EFA,the BHSES was refined to 16 items,which were categorised into the following three dimensions:'memory belief efficacy','self-care efficacy'and'future planning efficacy'.These were highly consistent with the hypothesis model.Its cumulative variance contribution rate reached 61.14%,with factor loads of all items above 0.5.The three-factor model was confirmed by the remaining data through CFA.All fit indices reached the acceptable level(x2=3.045,Goodness of Fit Index=0.898,adjusted Goodness of Fit Index=0.863,Comparative Fit Index=0.916,Incremental Fit Index=0.917,Tucker-Lewis Index=0.900,root mean square error of approximation=0.079 and root mean residual=0.068).The GDS and SAS scores revealed significant correlations with the BHSES score,indicating a high criterion-related validity.The overall Cronbach'sαcoefficient was 0.793,with theαcoefficients'distribution of subdimensions ranging from 0.748 to 0.883.Conclusions The 16-item,self-compiled BHSES is a reliable and valid measurement.It could help identify older adults with potential risks for developing NCDs or with high suspicion of cognitive impairment onset in recent periods and also offer insight into tracking brain health self-efficacy in association with cognition status.展开更多
A modified weak Galerkin(MWG)finite element method is developed for solving the biharmonic equation.This method uses the same finite element space as that of the discontinuous Galerkin method,the space of discontinuou...A modified weak Galerkin(MWG)finite element method is developed for solving the biharmonic equation.This method uses the same finite element space as that of the discontinuous Galerkin method,the space of discontinuous polynomials on polytopal meshes.But its formulation is simple,symmetric,positive definite,and parameter independent,without any of six inter-element face-integral terms in the formulation of the discontinuous Galerkin method.Optimal order error estimates in a discrete H2 norm are established for the corresponding finite element solutions.Error estimates in the L^(2)norm are also derived with a sub-optimal order of convergence for the lowest-order element and an optimal order of convergence for all high-order of elements.The numerical results are presented to confirm the theory of convergence.展开更多
The traditional human comfort meter has the following defects: the interface is not uniform;the operation is cumbersome and complicated;the interface is unfriendly, and the stability and adaptability are poor. This pa...The traditional human comfort meter has the following defects: the interface is not uniform;the operation is cumbersome and complicated;the interface is unfriendly, and the stability and adaptability are poor. This paper presents a design scheme for human comfort instrument based on embedded system, using S3C2440 embedded development board and the sensors to collect the real-time temperature, relative humidity and wind speed data and to process the collecting data;then obtaining the human body comfort value according to the basic algorithm of human body comfort instrument;giving the human comfort conclusion according to the diastolic index range of human comfort, and showing the temperature and humidity, wind speed, comfort value and conclusion through writing the Qt graphical user interface program. At the same time, the human comfort instrument has the data storage function. The human comfort instrument is high in integration, strong in real time, high in sensitivity, stable and reliable, and it meets the development goals of the intelligent meteorological service, and meets the demand of the meteorological service that is closer to life, and it has broad development prospect.展开更多
Background:The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer,but the effects on safety and survival are still controversial.The objective of this meta-analysis was to compare the overall sur...Background:The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer,but the effects on safety and survival are still controversial.The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery(NACS)and surgery alone(SA)for locally advanced gastric cancer.Methods:Databases(PubMed,Embase,Web of Science,Cochrane Library,and Google Scholar)were explored for relative studies from January 2000 to January 2021.The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale,respectively.The Review Manager software(version 5.3)was used to perform this meta-analysis.The overall survival was evaluated as the primary outcome,while perioperative indicators and post-operative complications were evaluated as the secondary outcomes.Results:Twenty studies,including 1420 NACS cases and 1942 SA cases,were enrolled.The results showed that there were no significant differences in overall survival(P=0.240),harvested lymph nodes(P=0.200),total complications(P=0.080),and 30-day post-operative mortality(P=0.490)between the NACS and SA groups.However,the NACS group was associated with a longer operation time(P<0.0001),a higher R0 resection rate(P=0.003),less reoperation(P=0.030),and less anastomotic leakage(P=0.007)compared with SA group.Conclusions:Compared with SA,NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage.While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.展开更多
Background:Extralevator abdominoperineal excision (ELAPE) has become a popular procedure for low rectal cancer as compared with abdominoperineal excision (APE). No definitive answer has been achieved whether one is su...Background:Extralevator abdominoperineal excision (ELAPE) has become a popular procedure for low rectal cancer as compared with abdominoperineal excision (APE). No definitive answer has been achieved whether one is superior to the other. This study aimed to evaluate the safety and efficacy of ELAPE for low rectal cancer with meta-analysis.Methods:The Web of Science, Cochrane Library, Embase, and PubMed databases before September 2019 were comprehensively searched to retrieve comparative trials of ELAPE and APE for low rectal cancer. Pooled analyses of the perioperative variables, surgical complications, and oncological variables were performed. Odds ratio (OR) and mean differences (MD) from each trial were pooled using random or fixed effects model depending on the heterogeneity of the included studies. A subgroup analysis or a sensitivity analysis was conducted to explore the potential source of heterogeneity when necessary.Results:This meta-analysis included 17 studies with 4049 patients, of whom 2248 (55.5%) underwent ELAPE and 1801 (44.5%) underwent APE. There were no statistical differences regarding the circumferential resection margin positivity (13.0% vs. 16.2%, OR = 0.69, 95% CI = 0.42-1.14, P = 0.15) and post-operative perineal wound complication rate (28.9% vs. 24.1%, OR = 1.21, 95% CI = 0.75-1.94, P= 0.43). The ELAPE was associated with lower rate of intraoperative perforation (6.6% vs. 11.3%, OR = 0.50, 95% CI = 0.39-0.64, P < 0.001) and local recurrence (8.8% vs. 20.5%, OR = 0.29, 95% CI = 0.21-0.41, P < 0.001) when compared with APE.Conclusions:The ELAPE was associated with a reduction in the rate of intra-operative perforation and local recurrence, without any increase in the circumferential resection margin positivity and post-operative perineal wound complication rate when compared with APE in the surgical treatment of low rectal cancer.展开更多
Farnesoid X receptor(FXR)is widely accepted as a promising target for various liver diseases;however,panels of ligands in drug development show limited clinical benefits,without a clear mechanism.Here,we reveal that a...Farnesoid X receptor(FXR)is widely accepted as a promising target for various liver diseases;however,panels of ligands in drug development show limited clinical benefits,without a clear mechanism.Here,we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury,which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases.Upon inflammatory and apoptotic stimulation,enhanced FXR acetylation at K217,closed to the nuclear location signal,blocks its recognition by importin KPNA3,thereby preventing its nuclear import.Concomitantly,reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1,and thereby facilitating FXR export to the cytosol.Acetylation governs nucleocytoplasmic shuttling of FXR,resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP.SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation.More importantly,SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries.In conclusion,these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.展开更多
Pancreatic cancer (PC), a deadly malignancy with an overall 5-year survival rate of 5% to 15%, is ranked as the seventh leading cause of cancer death in the world in spite of its low occurrence rate.[1,2] Early detect...Pancreatic cancer (PC), a deadly malignancy with an overall 5-year survival rate of 5% to 15%, is ranked as the seventh leading cause of cancer death in the world in spite of its low occurrence rate.[1,2] Early detection appears to be the most effective approach to improve the overall survival of patients with PC. However, the difficulty in early detection of PC is a lack of specific symptoms and reliable biomarkers. Currently, carbohydrate antigen 19-9 (CA 19-9) is a serum biomarker that is widely used in PC detection. However, 10% of patients with PC cannot produce CA 19-9 and serum CA 19-9 is frequently absent in patients with early-stage cancer. Furthermore, CA 19-9 is often found to be elevated in benign conditions or in other cancers, making its utility limited. Therefore, it is important to identify new diagnostic biomarkers to improve PC detection.展开更多
Pancreatic cystic neoplasms(PCNs)are recognized as precursor lesions of pancreatic cancer,with a marked increase in prevalence.Early detection of malignant PCNs is crucial for improving prognosis;however,current diagn...Pancreatic cystic neoplasms(PCNs)are recognized as precursor lesions of pancreatic cancer,with a marked increase in prevalence.Early detection of malignant PCNs is crucial for improving prognosis;however,current diagnostic methods are insufficient for accurately identifying malignant PCNs.Here,we utilized mass spectrometry(MS)-based glycosite-and glycoform-specific glycoproteomics,combined with proteomics,to explore potential cyst fluid diagnostic biomarkers for PCN.The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated,and its characteristics during the malignant transformation of PCN were analyzed.Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN,a group of cyst fluid glycoprotein biomarkers was identified.Through parallel reaction monitoring(PRM)-based targeted glycoproteomic analysis,we validated these chosen glycoprotein biomarkers in a second cohort,ultimately confirming N-glycosylated PHKB(Asn-935,H5N2F0S0;Asn-935,H4N4F0S0;Asn-935,H5N4F0S0),CEACAM5(Asn-197,H5N4F0S0)and ATP6V0A4(Asn-367,H6N4F0S0)as promising diagnostic biomarkers for distinguishing malignant PCNs.These glycoprotein biomarkers exhibited robust performance,with an area under the curve ranging from 0.771 to 0.948.In conclusion,we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN.These findings hold significant clinical implications,providing valuable insights for PCN decision-making,and potentially offering therapeutic targets for PCN treatment.展开更多
The scarcity of doctors is common in underdeveloped countries as well as in some developing and developed countries including Japan, Germany, Australia, Korea, and even the United States of America, indicating that th...The scarcity of doctors is common in underdeveloped countries as well as in some developing and developed countries including Japan, Germany, Australia, Korea, and even the United States of America, indicating that this scarcity has become a global issue. Causes vary from country to country. In China, the causes of this shortage are complicated. Due to increasing violence in recent years against medical staff that endangers the personal safety of medical practitioners, the number of Chinese medical school applicants has decreased greatly. Furthermore, the proportion of students who abandon the health sector is very high.展开更多
In this paper,we consider the energy conserving numerical scheme for coupled nonlinear Klein-Gordon equations.We propose energy conserving finite element method and get the unconditional superconvergence resultO(h^(2)...In this paper,we consider the energy conserving numerical scheme for coupled nonlinear Klein-Gordon equations.We propose energy conserving finite element method and get the unconditional superconvergence resultO(h^(2)+Dt^(2))by using the error splitting technique and postprocessing interpolation.Numerical experiments are carried out to support our theoretical results.展开更多
Pancreatic cystic disease is being increasingly identified in patients,and many relevant papers have been published in this field.A bibliometric analysis was previously performed to identify the most influential studi...Pancreatic cystic disease is being increasingly identified in patients,and many relevant papers have been published in this field.A bibliometric analysis was previously performed to identify the most influential studies in many subject areas,and the top 100 most cited papers on pancreatic cystic disease were analyzed in this study.The Web of Science database was searched for all papers related to pancreatic cystic disease on June 9,2018.The top 100 most cited papers were selected and listed in descending order based on the total number of citations(TCs).The author,journal,institution,country of origin,and research focus were further analyzed.The most cited papers were published between 1975 and 2015.Intraductal papillary mucinous neoplasm was the most commonly studied subtype(36%),followed by pancreatic pseudocyst(16%),solid pseudopapillary neoplasm(9%),and mucinous cystic neoplasm(7%).The average number of TCs was 282,and the average citation index value was 21.Thirty-eight journals published the top 100 papers;Annals of Surgery(n=14)and Gastrointestinal Endoscopy(n=11)published the most papers.Most papers were published in the United States of America(59%),with the majority from Johns Hopkins Medical Institution(15%).Canto MI from Johns Hopkins Medical Institution authored the largest number of most cited papers(n=8).This study reviews the significant achievements and developmental trends in pancreatic cystic disease.Abbreviations:CI=citation index,IPMN=intraductal papillary mucinous neoplasm,MCN=mucinous cystic neoplasm,PP=pancreatic pseudocyst,SCN=serous cystic neoplasm,SPN=solid pseudopapillary neoplasm,TC=total number of citation.展开更多
基金Supported by The Capital Medical Development Research Fund, No. 2009-2093
文摘AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric cancer, who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011, were analyzed retrospectively. Among these patients, 131 patients underwent laparoscopyassisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG). The parameters analyzed included operative time, blood loss, blood transfusion, morbidity, mortality, the number of harvested lymph nodes (HLNs), and pathological stage.RESULTS: There were no significant differences in sex, age, types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)], and stages between the LAG and OG groups (P > 0.05). Among the two groups, 127 cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs, respectively. The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P = 0.233). In the same type of radical resection, there were no signifi cant differences in the number of HLNs between the two groups (PG + D2: 21.7 ± 7.5 vs 22.4 ± 9.3; DG + D2: 25.7 ± 11.0 vs 22.3 ± 7.9; TG + D2: 30.9 ± 13.4 vs 29.3 ± 10.4; P > 0.05 for all comparisons). Tumor free margins were obtained in all cases. Compared with OG group, the LAG group had signifi cantly less blood loss, but a longer operation time (P < 0.001). The morbidity of the LAG group was 9.9%, which was not signifi cantly different from the OG group (7.7%) (P = 0.587). The mortality was zero in both groups. CONCLUSION: Laparoscopic D2 dissection is equivalent to OG in the number of HLNs, regardless of tumor location. Thus, this procedure can achieve the same radicalness as OG.
基金supported by the grants from the National Natural Science Foundation of China (No. 81272766)Capital Medical Development and Research Foundation (No. 2009-2093)+2 种基金Clinical Characteristics and Application Research of Capital (No. Z121107001012130)Beijing Natural Science Foundation (No. 7132054)New Star of Science and Technology Program of Beijing (No. 2011060)
文摘microRNAs （miRNAs） are a class of endogenous, single-stranded non-coding RNAs of 20- 23 nucleotides in length, functioning as negative regulators of gene expression at the post-transcriptional level. The dysregulation of miRNAs has been demonstrated to play critical roles in tumorigenesis, either through inhibiting tumor suppressor genes or activating oncogenes inappropriately. Besides their promising clinical applications in cancer diagnosis and treatment, recent studies have uncovered that miRNAs could act as a regulatory language, through which messenger RNAs, transcribed pseudogenes, and long noncoding RNAs crosstalk with each other and form a novel regulatory network. RNA transcripts involved in this network have been termed as competing endogenous RNAs （ceRNAs）, since they influence each other＇s level by competing for the same pool of miRNAs through miRNA response elements （MREs） on their target transcripts. The discovery of miRNA-ceRNA network not only provides the possibility of an additional level of post-transcriptional regulation, but also dictates a reassessment of the existing regulatory pathways involved in cancer initiation and progression.
基金supported by the National Natural Science Foundation of China (Commission No. 81471768)supported by Beijing Municipal Health System Special Funds of High-Level Medical Personnel Construction (No. 2013-3-086)
文摘Background： We investigated the effect of a small molecular inhibitor of heat shock protein （HSP）, qnercetin, on tumor radiofrequency （RF） ablation, and explored the underlying molecular mechanisms. Methods： In in vivo study, rats with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross coagulation areas were compared, and next, randomized into four treatment arms （control, quercetin alone, RF alone, and combination） for Kaplan-Meier analysis of defined endpoint survival. Then the distribution and expression levels of heat shock protein 70 （HSP70）, cleaved caspase-3 and heat shock factor 1 （HSF1） were analyzed after different treatments. In in vitro study, we used quercetin to promote SK- HEP-I （hepatic） and MCF-7 （breast） cancer cell apoptosis in heat shock cell model, and siRNA was used to block c-Jun and to explore the role of activating protein-1 （AP-1） signaling pathways. Results： We found the effects of quercetin plus RFA resulted in increase on the tumor destruction/ endpoint survival （26.5±3.4 d） in vivo, compared with RF alone （17.6±2.5 d） and quercetin alone （15.7±3.1 d）. Most importantly, quercetin-induced cancer cell death required the presence of HSF1 in animal model. Furthermore, quercetin directly down-regulated expression of HSF1 in vitro, which our findings have revealed, required the activation of AP-1 signaling pathways by loss-of-function analysis using siRNA mediated targeting of c-Jun. Conclusions： These results indicated a protective role of quercetin in tumor ablation and highlighted a novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid tumors.
基金supported by grants from the Science Foundation for Distinguished Young Scholars of Tianjin(Grant No.20JCJQJC00100)the National Natural Science Foundation of China(Grant Nos.81572969,81730086 and 81872555)+1 种基金the Drug Innovation Major Project of China(Grant No.2018ZX09711001-007-008)the PUMC Graduate Innovation Fund(Grant No.2018-1001-04 and 2019-1001-06)。
文摘The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body,including the mouth,lung,intestines,skin,and vagina.These microbial communities are involved in many essential functions,such as metabolism,immunity,host nutrition,and diseases.Recent studies have focused on the microbiota associated with cancers,particularly the oral and intestinal microbiota.Radiotherapy,the most effective cytotoxic modality available for solid tumors,contributes to the treatment of cancer patients.Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy.Here,we review current research on the microbiota and cancer development,and describe knowledge gaps in the study of radiotherapy and the microbiota.Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.
基金supported by grants from the National Key R&D Program of China(No.2017YFC1310501)the National Natural Science Foundation Committee(No.81671402).
文摘Background With the rapid increase in ageing population,China is confronted with the daunting challenge of a growing number of patients with neurocognitive disorders(NCDs).This trend makes the maintenance of self-health and early intervention essential,highlighting the need for a tool that assesses self-efficacy of older adults in maintaining brain health or cognitive function.Aim This study aimed to design the Brain Health Self-Efficacy Scale(BHSES)to measure elderly individuals'attitudes to NCDs,motivations and future plans for controlling risks.The psychometric properties of BHSES have been validated.Methods Based on the current literature and relevant models,a 19-item scale was created during the first stage.A total of 660 older adults in the Yinhang community of Shanghai were included.The statistical approaches of item analysis,exploratory factor analysis(EFA),confirmatory factor analysis(CFA),criterion-related validity and reliability test were used to evaluate the quality of BHSES.In addition,the Geriatric Depression Scale(GDS)and the Self-Rating Anxiety Scale(SAS)were used as criteria to test the criterion-related validity.Results To test item differentiation,the study adopted item analysis and excluded item 8.Selecting a random half of the sample for EFA,the BHSES was refined to 16 items,which were categorised into the following three dimensions:'memory belief efficacy','self-care efficacy'and'future planning efficacy'.These were highly consistent with the hypothesis model.Its cumulative variance contribution rate reached 61.14%,with factor loads of all items above 0.5.The three-factor model was confirmed by the remaining data through CFA.All fit indices reached the acceptable level(x2=3.045,Goodness of Fit Index=0.898,adjusted Goodness of Fit Index=0.863,Comparative Fit Index=0.916,Incremental Fit Index=0.917,Tucker-Lewis Index=0.900,root mean square error of approximation=0.079 and root mean residual=0.068).The GDS and SAS scores revealed significant correlations with the BHSES score,indicating a high criterion-related validity.The overall Cronbach'sαcoefficient was 0.793,with theαcoefficients'distribution of subdimensions ranging from 0.748 to 0.883.Conclusions The 16-item,self-compiled BHSES is a reliable and valid measurement.It could help identify older adults with potential risks for developing NCDs or with high suspicion of cognitive impairment onset in recent periods and also offer insight into tracking brain health self-efficacy in association with cognition status.
基金M.Cui was supported in part by the National Natural Science Foundation of China(Grant No.11571026)the Beijing Municipal Natural Science Foundation of China(Grant No.1192003)Xiu Ye was supported in part by the National Science Foundation Grant DMS-1620016.
文摘A modified weak Galerkin(MWG)finite element method is developed for solving the biharmonic equation.This method uses the same finite element space as that of the discontinuous Galerkin method,the space of discontinuous polynomials on polytopal meshes.But its formulation is simple,symmetric,positive definite,and parameter independent,without any of six inter-element face-integral terms in the formulation of the discontinuous Galerkin method.Optimal order error estimates in a discrete H2 norm are established for the corresponding finite element solutions.Error estimates in the L^(2)norm are also derived with a sub-optimal order of convergence for the lowest-order element and an optimal order of convergence for all high-order of elements.The numerical results are presented to confirm the theory of convergence.
文摘The traditional human comfort meter has the following defects: the interface is not uniform;the operation is cumbersome and complicated;the interface is unfriendly, and the stability and adaptability are poor. This paper presents a design scheme for human comfort instrument based on embedded system, using S3C2440 embedded development board and the sensors to collect the real-time temperature, relative humidity and wind speed data and to process the collecting data;then obtaining the human body comfort value according to the basic algorithm of human body comfort instrument;giving the human comfort conclusion according to the diastolic index range of human comfort, and showing the temperature and humidity, wind speed, comfort value and conclusion through writing the Qt graphical user interface program. At the same time, the human comfort instrument has the data storage function. The human comfort instrument is high in integration, strong in real time, high in sensitivity, stable and reliable, and it meets the development goals of the intelligent meteorological service, and meets the demand of the meteorological service that is closer to life, and it has broad development prospect.
基金the Capital Medical Development and Research Foundation(No.2018-2-2153)the National Natural Science Foundation of China(Nos.82073357,81672439,81272766,and 81450028)the Beijing Natural Science Foundation(No.7162039).
文摘Background:The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer,but the effects on safety and survival are still controversial.The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery(NACS)and surgery alone(SA)for locally advanced gastric cancer.Methods:Databases(PubMed,Embase,Web of Science,Cochrane Library,and Google Scholar)were explored for relative studies from January 2000 to January 2021.The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale,respectively.The Review Manager software(version 5.3)was used to perform this meta-analysis.The overall survival was evaluated as the primary outcome,while perioperative indicators and post-operative complications were evaluated as the secondary outcomes.Results:Twenty studies,including 1420 NACS cases and 1942 SA cases,were enrolled.The results showed that there were no significant differences in overall survival(P=0.240),harvested lymph nodes(P=0.200),total complications(P=0.080),and 30-day post-operative mortality(P=0.490)between the NACS and SA groups.However,the NACS group was associated with a longer operation time(P<0.0001),a higher R0 resection rate(P=0.003),less reoperation(P=0.030),and less anastomotic leakage(P=0.007)compared with SA group.Conclusions:Compared with SA,NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage.While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.
基金grants from the National Natural Science Foundation of China(No.81672439)the CapitaPs Funds for Health Improvement and Research(No.CFH 2018-2-2153)Beijing Municipal Administration of Hospitals Incubating Program(No.PX2016018).
文摘Background:Extralevator abdominoperineal excision (ELAPE) has become a popular procedure for low rectal cancer as compared with abdominoperineal excision (APE). No definitive answer has been achieved whether one is superior to the other. This study aimed to evaluate the safety and efficacy of ELAPE for low rectal cancer with meta-analysis.Methods:The Web of Science, Cochrane Library, Embase, and PubMed databases before September 2019 were comprehensively searched to retrieve comparative trials of ELAPE and APE for low rectal cancer. Pooled analyses of the perioperative variables, surgical complications, and oncological variables were performed. Odds ratio (OR) and mean differences (MD) from each trial were pooled using random or fixed effects model depending on the heterogeneity of the included studies. A subgroup analysis or a sensitivity analysis was conducted to explore the potential source of heterogeneity when necessary.Results:This meta-analysis included 17 studies with 4049 patients, of whom 2248 (55.5%) underwent ELAPE and 1801 (44.5%) underwent APE. There were no statistical differences regarding the circumferential resection margin positivity (13.0% vs. 16.2%, OR = 0.69, 95% CI = 0.42-1.14, P = 0.15) and post-operative perineal wound complication rate (28.9% vs. 24.1%, OR = 1.21, 95% CI = 0.75-1.94, P= 0.43). The ELAPE was associated with lower rate of intraoperative perforation (6.6% vs. 11.3%, OR = 0.50, 95% CI = 0.39-0.64, P < 0.001) and local recurrence (8.8% vs. 20.5%, OR = 0.29, 95% CI = 0.21-0.41, P < 0.001) when compared with APE.Conclusions:The ELAPE was associated with a reduction in the rate of intra-operative perforation and local recurrence, without any increase in the circumferential resection margin positivity and post-operative perineal wound complication rate when compared with APE in the surgical treatment of low rectal cancer.
基金supported by the National Natural Science Foundation of China(grants 81720108032 and 81930109 to Haiping Hao,82073926 to Hong Wang,and 82073928 to Guangji Wang)the National Key Research and Development Programme of China(2021YFA1301300 to Haiping Hao)+2 种基金Leading Technology Foundation Research Project of Jiangsu Province(grant BK20192005 to Guangji Wang,China)the Project Program of State Key Laboratory of Natural Medicines(China Pharmaceutical University,SKLNMZZ202202 to Haiping Hao)Sanming Project of Medicine in Shenzhen(SZSM201801060 to Guangji Wang,China)。
文摘Farnesoid X receptor(FXR)is widely accepted as a promising target for various liver diseases;however,panels of ligands in drug development show limited clinical benefits,without a clear mechanism.Here,we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury,which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases.Upon inflammatory and apoptotic stimulation,enhanced FXR acetylation at K217,closed to the nuclear location signal,blocks its recognition by importin KPNA3,thereby preventing its nuclear import.Concomitantly,reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1,and thereby facilitating FXR export to the cytosol.Acetylation governs nucleocytoplasmic shuttling of FXR,resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP.SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation.More importantly,SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries.In conclusion,these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.
文摘Pancreatic cancer (PC), a deadly malignancy with an overall 5-year survival rate of 5% to 15%, is ranked as the seventh leading cause of cancer death in the world in spite of its low occurrence rate.[1,2] Early detection appears to be the most effective approach to improve the overall survival of patients with PC. However, the difficulty in early detection of PC is a lack of specific symptoms and reliable biomarkers. Currently, carbohydrate antigen 19-9 (CA 19-9) is a serum biomarker that is widely used in PC detection. However, 10% of patients with PC cannot produce CA 19-9 and serum CA 19-9 is frequently absent in patients with early-stage cancer. Furthermore, CA 19-9 is often found to be elevated in benign conditions or in other cancers, making its utility limited. Therefore, it is important to identify new diagnostic biomarkers to improve PC detection.
基金This work was supported by grants National Key R&D Program of China(No.2020YFC2002702)National High Level Hospital Clinical Research Funding(2022-PUMCH-D-001)+2 种基金Beijing Natural Science Foundation(No.7224340)the Fundamental Research Funds for the Central Universities(No.3332022006)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT32014).
文摘Pancreatic cystic neoplasms(PCNs)are recognized as precursor lesions of pancreatic cancer,with a marked increase in prevalence.Early detection of malignant PCNs is crucial for improving prognosis;however,current diagnostic methods are insufficient for accurately identifying malignant PCNs.Here,we utilized mass spectrometry(MS)-based glycosite-and glycoform-specific glycoproteomics,combined with proteomics,to explore potential cyst fluid diagnostic biomarkers for PCN.The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated,and its characteristics during the malignant transformation of PCN were analyzed.Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN,a group of cyst fluid glycoprotein biomarkers was identified.Through parallel reaction monitoring(PRM)-based targeted glycoproteomic analysis,we validated these chosen glycoprotein biomarkers in a second cohort,ultimately confirming N-glycosylated PHKB(Asn-935,H5N2F0S0;Asn-935,H4N4F0S0;Asn-935,H5N4F0S0),CEACAM5(Asn-197,H5N4F0S0)and ATP6V0A4(Asn-367,H6N4F0S0)as promising diagnostic biomarkers for distinguishing malignant PCNs.These glycoprotein biomarkers exhibited robust performance,with an area under the curve ranging from 0.771 to 0.948.In conclusion,we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN.These findings hold significant clinical implications,providing valuable insights for PCN decision-making,and potentially offering therapeutic targets for PCN treatment.
文摘The scarcity of doctors is common in underdeveloped countries as well as in some developing and developed countries including Japan, Germany, Australia, Korea, and even the United States of America, indicating that this scarcity has become a global issue. Causes vary from country to country. In China, the causes of this shortage are complicated. Due to increasing violence in recent years against medical staff that endangers the personal safety of medical practitioners, the number of Chinese medical school applicants has decreased greatly. Furthermore, the proportion of students who abandon the health sector is very high.
基金The work is supported by the National Natural Science Foundation of China(No.11871441)Beijing Natural Science Foundation(No.1192003).
文摘In this paper,we consider the energy conserving numerical scheme for coupled nonlinear Klein-Gordon equations.We propose energy conserving finite element method and get the unconditional superconvergence resultO(h^(2)+Dt^(2))by using the error splitting technique and postprocessing interpolation.Numerical experiments are carried out to support our theoretical results.
基金National Natural Science Foundation of China（81071906, 81172127, 81572969, 81402633） Technology and Development and Research Projects for Research Institutes, Ministry of Science and Technology（2014EG150134）+3 种基金 Tianjin Science ＆ Technology Pillar Program（14ZCZDSY00001） Natural Science Foundation of Tianjin（16JCQNJC13600） Peking Union Medical College Youth Innovation Fund（1581） IRM-CAMS Research Fund（1614）
基金National Natural Science Foundation of China（81071906, 81172127, 81572969） Ministry of Science and Technology Researth Institutes Development Project（2014EG150134）+3 种基金 Technology and Development and Research Projects for Research Institutes, Ministry of Science and Technology（2014EG150134） Tianjin Science and Technology Support Plan Project（14ZCZDSY00001） PUMC Youth Fund, the Fundamental Research Funds for the Central Universities（33320140187） Institute of Radiation Medicine, Chinese Academy of Medical Sciences Research Fund （1547,1522）.
基金the Capital’s Funds for Health Improvement and Research(CFH,2018-2-4014).
文摘Pancreatic cystic disease is being increasingly identified in patients,and many relevant papers have been published in this field.A bibliometric analysis was previously performed to identify the most influential studies in many subject areas,and the top 100 most cited papers on pancreatic cystic disease were analyzed in this study.The Web of Science database was searched for all papers related to pancreatic cystic disease on June 9,2018.The top 100 most cited papers were selected and listed in descending order based on the total number of citations(TCs).The author,journal,institution,country of origin,and research focus were further analyzed.The most cited papers were published between 1975 and 2015.Intraductal papillary mucinous neoplasm was the most commonly studied subtype(36%),followed by pancreatic pseudocyst(16%),solid pseudopapillary neoplasm(9%),and mucinous cystic neoplasm(7%).The average number of TCs was 282,and the average citation index value was 21.Thirty-eight journals published the top 100 papers;Annals of Surgery(n=14)and Gastrointestinal Endoscopy(n=11)published the most papers.Most papers were published in the United States of America(59%),with the majority from Johns Hopkins Medical Institution(15%).Canto MI from Johns Hopkins Medical Institution authored the largest number of most cited papers(n=8).This study reviews the significant achievements and developmental trends in pancreatic cystic disease.Abbreviations:CI=citation index,IPMN=intraductal papillary mucinous neoplasm,MCN=mucinous cystic neoplasm,PP=pancreatic pseudocyst,SCN=serous cystic neoplasm,SPN=solid pseudopapillary neoplasm,TC=total number of citation.
