BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems ...BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.展开更多
AIM: To investigate the effect of Qingyi decoction onthe expression of secreted phospholipase A2(s PLA2) in intestinal barrier injury.METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into control, seve...AIM: To investigate the effect of Qingyi decoction onthe expression of secreted phospholipase A2(s PLA2) in intestinal barrier injury.METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into control, severe acute pancreatitis(SAP), Qingyi decoction-treated(QYT), dexamethasonetreated(DEX), and verapamil-treated(VER) groups. The SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into the biliopancreatic duct of the rats. All rats were sacrificed 24 h post-SAP induction. Arterial blood, intestine, and pancreas from each rat were harvested for investigations. The levels of serum amylase(AMY) and diamine oxidase(DAO) were determined using biochemical methods, and serum tumor necrosis factor(TNF)-α level was measured by an enzyme linked immunosorbent assay. Pathologic changes in the harvested tissues were investigated by microscopic examination of hematoxylin and eosinstained tissue sections. The expressions of s PLA2 at m RNA and protein levels were detected by reverse transcriptase PCR and Western blot, respectively. A terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was used to investigate apoptosis of epithelial cells in the intestinal tissues. RESULTS: Compared to the control group, the expression of s PLA2 at both the m RNA and protein levels increased significantly in the SAP group(0.36 ± 0.13 vs 0.90 ± 0.38, and 0.16 ± 0.05 vs 0.64 ± 0.05, respectively; P s < 0.01). The levels of AMY, TNF-α and DAO in serum were also significantly increased(917 ± 62 U/L vs 6870 ± 810 U/L, 59.7 ± 14.3 ng/L vs 180.5 ± 20.1 ng/L, and 10.37 ± 2.44 U/L vs 37.89 ± 5.86 U/L, respectively; P s < 0.01). The apoptosis index of intestinal epithelial cells also differed significantly between the SAP and control rats(0.05 ± 0.02 vs 0.26 ± 0.06; P < 0.01). The serum levels of DAO and TNF-α, and the intestinal apoptosis index significantly correlated with s PLA2 expression in the intestine(r = 0.895, 0.893 and 0.926, respectively; Ps < 0.05). Thelevels of s PLA2, AMY, TNF-α, and DAO in the QYT, VER, and DEX groups were all decreased compared with the SAP group, but not the control group. Qingyi decoction intervention, however, gave the most therapeutic effect against intestinal barrier damage, although the onset of its therapeutic effect was slower. CONCLUSION: Qingyi decoction ameliorates acute pancreatitis-induced intestinal barrier injury by inhibiting the overexpression of intestinal s PLA2. This mechanism may be similar to that of verapamil.展开更多
OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine micr...OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in vitro.METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were observed.The expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 cells.In addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated.RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified morphology.However,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid shape.The expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 antagonist.These results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.展开更多
Single-pixel imaging （SPI） technology has garnered great interest within the last decade because of its ability to record high-resolution images using a single-pixel detector. It has been applied to diverse fields, ...Single-pixel imaging （SPI） technology has garnered great interest within the last decade because of its ability to record high-resolution images using a single-pixel detector. It has been applied to diverse fields, such as magnetic resonance imaging （MRI）, aerospace remote sensing, terahertz photography, and hyperspectral imaging. Compared with conventional silicon-based cameras, single-pixel cameras （SPCs） can achieve image compression and operate over a much broader spectral range. However, the imaging speed of SPCs is governed by the response time of digital mieromirror devices （DMDs） and the amount of com- pression of acquired images, leading to low （ms-level） temporal resolution. Consequently, it is particularly challenging for SPCs to investigate fast dynamic phenomena, which is required commonly in microscopy. Recently, a unique approach based on photonic time stretch （PTS） to achieve high-speed SPI has been reported. It achieves a frame rate far beyond that can be reached with conventional SPCs. In this paper, we first introduce the principles and applications of the PTS technique. Then the basic archi- tecture of the high-speed SPI system is presented, and an imaging flow cytometer with high speed and high throughput is demonstrated experimentally. Finally, the limitations and potential applications of high-speed SPI are discussed.展开更多
Background： Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment a...Background： Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns ofantipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life （QOL）. Methods： A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients＇ socio-demographic and clinical characteristics including psychopathology, medication side effects. satisfaction with treatment and QOL were recorded using a standardized protocol and data collection. Results： The frequency ofantipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively （χ^2 = 90.3, df= 2, P 〈 0.001 ）. Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals （i.e., Level-Ⅲ hospital）. Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups. Conclusions： Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients＇ and relatives＇ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.展开更多
We propose an efficient colocated multiple-input multiple-output radar waveform-design method based on two-step optimizations in the spatial and spectral domains. First, a minimum integrated side-lobe level strategy i...We propose an efficient colocated multiple-input multiple-output radar waveform-design method based on two-step optimizations in the spatial and spectral domains. First, a minimum integrated side-lobe level strategy is adopted to obtain the desired beam pattern with spatial nulling. By recovering the hidden convexity of the resulting fractional quadratically constrained quadratic programming non-convex problem, the global optimal solution can be achieved in polynomial time through a semi- definite relaxation followed by spectral factorization. Second, with the transmit waveforms obtained via spatial optimization, a phase changing diagonal matrix is introduced and optimized via power method-like iterations. Without influencing the shape of the optimized beam pattern, the transmit waveforms are further optimized in the spectral domain, and the desired spectral nulling is formed to avoid radar interference on the overlaid licensed radiators. Finally, the superior performance of the proposed method is demonstrated via numerical results and comparisons with other approaches to waveform design.展开更多
To the Editor： Moderator band （MB） is a part of the septomarginal trabeculation, which not only supports the anterior papillary muscle （APM） of the tricuspid valve but also connects it to the flee wall. Neverthel...To the Editor： Moderator band （MB） is a part of the septomarginal trabeculation, which not only supports the anterior papillary muscle （APM） of the tricuspid valve but also connects it to the flee wall. Nevertheless, with the advent of intracardiac echocardiography （ICE）, electrophysiologists are now aware of the arrhythmogenic role of MB besides its mechanical function. MB-originated ventricular tachycardia or ventricular fibrillation （VT/VF） is a kind of idiopathic malignant arrhythmia in the absence of structural heart disease, which is frequently triggered by a premature ventricular contraction （PVC） from the same site.展开更多
基金Supported by National Natural Science Foundation of China,No.82174363.
文摘BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.
基金financially supported by the Guangdong Basic and Applied Basic Research Foundation(Grant No.2022A1515011485)National Natural Science Foundation of China(Grant No.62104243)SIAT Innovation Program for Excellent Young Researchers and Shenzhen Post-doctoral Funding.
基金Supported by National Natural Science Foundation of China,No.81173452
文摘AIM: To investigate the effect of Qingyi decoction onthe expression of secreted phospholipase A2(s PLA2) in intestinal barrier injury.METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into control, severe acute pancreatitis(SAP), Qingyi decoction-treated(QYT), dexamethasonetreated(DEX), and verapamil-treated(VER) groups. The SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into the biliopancreatic duct of the rats. All rats were sacrificed 24 h post-SAP induction. Arterial blood, intestine, and pancreas from each rat were harvested for investigations. The levels of serum amylase(AMY) and diamine oxidase(DAO) were determined using biochemical methods, and serum tumor necrosis factor(TNF)-α level was measured by an enzyme linked immunosorbent assay. Pathologic changes in the harvested tissues were investigated by microscopic examination of hematoxylin and eosinstained tissue sections. The expressions of s PLA2 at m RNA and protein levels were detected by reverse transcriptase PCR and Western blot, respectively. A terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was used to investigate apoptosis of epithelial cells in the intestinal tissues. RESULTS: Compared to the control group, the expression of s PLA2 at both the m RNA and protein levels increased significantly in the SAP group(0.36 ± 0.13 vs 0.90 ± 0.38, and 0.16 ± 0.05 vs 0.64 ± 0.05, respectively; P s < 0.01). The levels of AMY, TNF-α and DAO in serum were also significantly increased(917 ± 62 U/L vs 6870 ± 810 U/L, 59.7 ± 14.3 ng/L vs 180.5 ± 20.1 ng/L, and 10.37 ± 2.44 U/L vs 37.89 ± 5.86 U/L, respectively; P s < 0.01). The apoptosis index of intestinal epithelial cells also differed significantly between the SAP and control rats(0.05 ± 0.02 vs 0.26 ± 0.06; P < 0.01). The serum levels of DAO and TNF-α, and the intestinal apoptosis index significantly correlated with s PLA2 expression in the intestine(r = 0.895, 0.893 and 0.926, respectively; Ps < 0.05). Thelevels of s PLA2, AMY, TNF-α, and DAO in the QYT, VER, and DEX groups were all decreased compared with the SAP group, but not the control group. Qingyi decoction intervention, however, gave the most therapeutic effect against intestinal barrier damage, although the onset of its therapeutic effect was slower. CONCLUSION: Qingyi decoction ameliorates acute pancreatitis-induced intestinal barrier injury by inhibiting the overexpression of intestinal s PLA2. This mechanism may be similar to that of verapamil.
基金supported by National Natural Science Foundation of China(81671188)Zhejiang Provincial Natural Science Foundation of China(LY12H31010)the Key Laboratory of Hangzhou City Project(20090233T12)
文摘OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in vitro.METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were observed.The expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 cells.In addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated.RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified morphology.However,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid shape.The expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 antagonist.These results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.
基金Project supported by the National Natural Science Foundation of China （Nos. 61771284 and 61322113）
文摘Single-pixel imaging （SPI） technology has garnered great interest within the last decade because of its ability to record high-resolution images using a single-pixel detector. It has been applied to diverse fields, such as magnetic resonance imaging （MRI）, aerospace remote sensing, terahertz photography, and hyperspectral imaging. Compared with conventional silicon-based cameras, single-pixel cameras （SPCs） can achieve image compression and operate over a much broader spectral range. However, the imaging speed of SPCs is governed by the response time of digital mieromirror devices （DMDs） and the amount of com- pression of acquired images, leading to low （ms-level） temporal resolution. Consequently, it is particularly challenging for SPCs to investigate fast dynamic phenomena, which is required commonly in microscopy. Recently, a unique approach based on photonic time stretch （PTS） to achieve high-speed SPI has been reported. It achieves a frame rate far beyond that can be reached with conventional SPCs. In this paper, we first introduce the principles and applications of the PTS technique. Then the basic archi- tecture of the high-speed SPI system is presented, and an imaging flow cytometer with high speed and high throughput is demonstrated experimentally. Finally, the limitations and potential applications of high-speed SPI are discussed.
文摘Background： Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns ofantipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life （QOL）. Methods： A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients＇ socio-demographic and clinical characteristics including psychopathology, medication side effects. satisfaction with treatment and QOL were recorded using a standardized protocol and data collection. Results： The frequency ofantipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively （χ^2 = 90.3, df= 2, P 〈 0.001 ）. Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals （i.e., Level-Ⅲ hospital）. Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups. Conclusions： Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients＇ and relatives＇ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.
基金the National Natural Science Foundation of China （No. 61302153）
文摘We propose an efficient colocated multiple-input multiple-output radar waveform-design method based on two-step optimizations in the spatial and spectral domains. First, a minimum integrated side-lobe level strategy is adopted to obtain the desired beam pattern with spatial nulling. By recovering the hidden convexity of the resulting fractional quadratically constrained quadratic programming non-convex problem, the global optimal solution can be achieved in polynomial time through a semi- definite relaxation followed by spectral factorization. Second, with the transmit waveforms obtained via spatial optimization, a phase changing diagonal matrix is introduced and optimized via power method-like iterations. Without influencing the shape of the optimized beam pattern, the transmit waveforms are further optimized in the spectral domain, and the desired spectral nulling is formed to avoid radar interference on the overlaid licensed radiators. Finally, the superior performance of the proposed method is demonstrated via numerical results and comparisons with other approaches to waveform design.
文摘To the Editor： Moderator band （MB） is a part of the septomarginal trabeculation, which not only supports the anterior papillary muscle （APM） of the tricuspid valve but also connects it to the flee wall. Nevertheless, with the advent of intracardiac echocardiography （ICE）, electrophysiologists are now aware of the arrhythmogenic role of MB besides its mechanical function. MB-originated ventricular tachycardia or ventricular fibrillation （VT/VF） is a kind of idiopathic malignant arrhythmia in the absence of structural heart disease, which is frequently triggered by a premature ventricular contraction （PVC） from the same site.
