Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
AIM:To predict best-corrected visual acuity(BCVA)by machine learning in patients with ocular trauma who were treated for at least 6mo.METHODS:The internal dataset consisted of 850 patients with 1589 eyes and an averag...AIM:To predict best-corrected visual acuity(BCVA)by machine learning in patients with ocular trauma who were treated for at least 6mo.METHODS:The internal dataset consisted of 850 patients with 1589 eyes and an average age of 44.29y.The initial visual acuity was 0.99 log MAR.The test dataset consisted of 60 patients with 100 eyes collected while the model was optimized.Four different machine-learning algorithms(Extreme Gradient Boosting,support vector regression,Bayesian ridge,and random forest regressor)were used to predict BCVA,and four algorithms(Extreme Gradient Boosting,support vector machine,logistic regression,and random forest classifier)were used to classify BCVA in patients with ocular trauma after treatment for 6mo or longer.Clinical features were obtained from outpatient records,and ocular parameters were extracted from optical coherence tomography images and fundus photographs.These features were put into different machine-learning models,and the obtained predicted values were compared with the actual BCVA values.The best-performing model and the best variable selected were further evaluated in the test dataset.RESULTS:There was a significant correlation between the predicted and actual values[all Pearson correlation coefficient(PCC)>0.6].Considering only the data from the traumatic group(group A)into account,the lowest mean absolute error(MAE)and root mean square error(RMSE)were 0.30 and 0.40 log MAR,respectively.In the traumatic and healthy groups(group B),the lowest MAE and RMSE were 0.20 and 0.33 log MAR,respectively.The sensitivity was always higher than the specificity in group A,in contrast to the results in group B.The classification accuracy and precision were above 0.80 in both groups.The MAE,RMSE,and PCC of the test dataset were 0.20,0.29,and 0.96,respectively.The sensitivity,precision,specificity,and accuracy of the test dataset were 0.83,0.92,0.95,and 0.90,respectively.CONCLUSION:Predicting BCVA using machine-learning models in patients with treated ocular trauma is accurate and helpful in the identification of visual dysfunction.展开更多
Objective:To investigate the possible mechanism of microRNA-9-5p(miR-9-5p)and Ras homologous gene family A(RHOA)in aluminum-induced cognitive dysfunction in rats.Methods:According to the principle of randomization,48 ...Objective:To investigate the possible mechanism of microRNA-9-5p(miR-9-5p)and Ras homologous gene family A(RHOA)in aluminum-induced cognitive dysfunction in rats.Methods:According to the principle of randomization,48 Wistar rats were randomly divided into four groups(n=12)of blank control,low dose,medium dose and high dose.The blank control group was gavaged daily saline,and the other three dose groups were given daily gavage AlCl3 aqueous solution at three doses of 25 mg/kg,50 mg/kg,and 100 mg/kg to create a rat model of cognitive impairment for three months.The water maze(MWM)positioning navigation experiment was used to record the time t(s),namely,the incubation period,on the platform of rats,and the incubation period of each group was used to determine whether the rats in the infected group had learning and memory impairment.Hematoxylin-eosin(HE)and Nissl stains observed the pathological changes of nerve cells in the hippocampus of the four groups.Western blot detected the protein expression levels of RHOA and cranial neurotrophic factor(BDNF)in fresh rat hippocampal tissues.RT-qPCR detected the mRNA expression of miR-9-5p,RHOA,and BDNF in rat hippocampal tissues.Results:The results of Morris water maze positioning navigation test showed that the incubation period of each group was calculated on the 1st,3rd and 5th days of the experiment,and the motor incubation period of the infected group was higher than that of the control group.The results of HE staining showed that the rat nerve cells in the control group were morphologically intact,the staining was clear,the nucleus was clearly visible,and the edge of the cell membrane was sharp.The rat neurons in the infected group were damaged to varying degrees,the nucleus gradually dissolved,the cytoplasmic staining became deeper,the edges of the cell membrane were blurred and disordered,and the cells were deformed and arranged disordered.The results of Nissl staining showed that the well-stained Nissl body particles were visible in the nerve cells of rats in the control group,and the dissipation of Nissl bodies in the nerve cells of the infected group was reduced,and the staining was shallow.The results of RT-qPCR showed that compared with the control group,the mRNA expression of miR-9-5p and BDNF was decreased in the infected group,and the mRNA expression of RHOA was increased(P<0.05 or P<0.001).The Western blot results showed that compared with the control group,the relative expression of BDNF in the three infected groups was decreased,and the relative expression of RHOA increased(P<0.05).Conclusion:In aluminum-induced cognitive impairment,miR-9-5p is downregulated and RHOA is upregulatd.展开更多
Background:Postoperative cognitive dysfunction(POCD)can occur in patients with cardiac and non-cardiac surgeries.About 20%to 40%patients develop POCD at hospital discharge(a few days after surgery,acute POCD)and 10%el...Background:Postoperative cognitive dysfunction(POCD)can occur in patients with cardiac and non-cardiac surgeries.About 20%to 40%patients develop POCD at hospital discharge(a few days after surgery,acute POCD)and 10%elderly patients(>60 years old)have POCD at 3 months after surgery(delayed POCD).Age and degree of education are risk factors for delayed POCD.It has been shown that POCD is associated with increased mortality.Patients with POCD have a longer hospital stay and an increased rate of leaving job market.Thus,POCD is a very significant clinical syndrome during the perioperative period,which is recognized only in recent years.We and others have shown that neuroinflammation is a critical neuropathological process for POCD.However,neuroinflammation lasts for a few days after surgery.It is not known how such a short-lived neuropathological process lead to POCD a few months after surgery.To address this issue,a series of experiments were performed in my laboratory.Methods:Rats or mice were subjected to common carotid arterial exposure,a surgical component of carotid endarterectomy that is often performed in elderly patients.Their learning and memory were assessed at least one week after surgery.Their blood and brain tissues were harvested at various time after surgery for biochemical and structural analyses.Results:The surgery induced an increase of proinflammatory cytokines in the blood.The surgery also increased the expression of active matrix metallopeptidase 9(MMP-9)and its activity in the brain.This surgery induced POCD and neuroinflammation in wild-type mice but not in the MMP-9 knockout mice.P2X7 receptors and inflammasome were activated by the surgery.Inhibition of P2X7 receptors and P2X7 receptor knockout abolished POCD and neuroinflammation after surgery.The surgery decreased growth factor production and inhibition of neuroinflammation attenuated this decrease.The decreased growth factor expression occurred at 3 to 5 days after the surgery.Surgery increased histone deacetylase activity and inhibition of histone deacetylase attenuated the decrease of growth factor expression and the development of POCD.The surgery decreased neurogenesis in the hippocampus and application of growth factors to the brain attenuated this decrease and POCD.This decreased neurogenesis was observed 3 weeks after surgery.Finally,surgery impaired dendritic arborization that was assessed 3 weeks after surgery.Inhibition of histone deacetylases attenuated this impairment and POCD.Conclusion:Surgery induces a delayed POCD in rodents.Surgery results in systemic inflammation,which then activates MMP-9 to damage the brain-blood barrier to facilitate the systemic inflammation to be transmitted to the brain.Proinflammatory signals in the blood activate P2X7 receptors to induce neuroinflammation that inhibits growth factor expression through epigenetic regulation.Reduced growth factor expression results in decreased neurogenesis and dendritic arborization that then ultimately lead to the delayed POCD.Thus,surgery activates a series of cascade events to induce the delayed POCD.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13~(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金Supported by National Key R&D Program of China(No.2022YFC3302001)the Human Injury and Disability Degree Classification(No.SF20181312)the National Natural Science Foundation of China(No.62071285)。
文摘AIM:To predict best-corrected visual acuity(BCVA)by machine learning in patients with ocular trauma who were treated for at least 6mo.METHODS:The internal dataset consisted of 850 patients with 1589 eyes and an average age of 44.29y.The initial visual acuity was 0.99 log MAR.The test dataset consisted of 60 patients with 100 eyes collected while the model was optimized.Four different machine-learning algorithms(Extreme Gradient Boosting,support vector regression,Bayesian ridge,and random forest regressor)were used to predict BCVA,and four algorithms(Extreme Gradient Boosting,support vector machine,logistic regression,and random forest classifier)were used to classify BCVA in patients with ocular trauma after treatment for 6mo or longer.Clinical features were obtained from outpatient records,and ocular parameters were extracted from optical coherence tomography images and fundus photographs.These features were put into different machine-learning models,and the obtained predicted values were compared with the actual BCVA values.The best-performing model and the best variable selected were further evaluated in the test dataset.RESULTS:There was a significant correlation between the predicted and actual values[all Pearson correlation coefficient(PCC)>0.6].Considering only the data from the traumatic group(group A)into account,the lowest mean absolute error(MAE)and root mean square error(RMSE)were 0.30 and 0.40 log MAR,respectively.In the traumatic and healthy groups(group B),the lowest MAE and RMSE were 0.20 and 0.33 log MAR,respectively.The sensitivity was always higher than the specificity in group A,in contrast to the results in group B.The classification accuracy and precision were above 0.80 in both groups.The MAE,RMSE,and PCC of the test dataset were 0.20,0.29,and 0.96,respectively.The sensitivity,precision,specificity,and accuracy of the test dataset were 0.83,0.92,0.95,and 0.90,respectively.CONCLUSION:Predicting BCVA using machine-learning models in patients with treated ocular trauma is accurate and helpful in the identification of visual dysfunction.
基金National Natural Science Foundation Project of China(No.31560294)Guangxi Degree and Postgraduate Education Reform Project in 2021(No.JGY2021208)。
文摘Objective:To investigate the possible mechanism of microRNA-9-5p(miR-9-5p)and Ras homologous gene family A(RHOA)in aluminum-induced cognitive dysfunction in rats.Methods:According to the principle of randomization,48 Wistar rats were randomly divided into four groups(n=12)of blank control,low dose,medium dose and high dose.The blank control group was gavaged daily saline,and the other three dose groups were given daily gavage AlCl3 aqueous solution at three doses of 25 mg/kg,50 mg/kg,and 100 mg/kg to create a rat model of cognitive impairment for three months.The water maze(MWM)positioning navigation experiment was used to record the time t(s),namely,the incubation period,on the platform of rats,and the incubation period of each group was used to determine whether the rats in the infected group had learning and memory impairment.Hematoxylin-eosin(HE)and Nissl stains observed the pathological changes of nerve cells in the hippocampus of the four groups.Western blot detected the protein expression levels of RHOA and cranial neurotrophic factor(BDNF)in fresh rat hippocampal tissues.RT-qPCR detected the mRNA expression of miR-9-5p,RHOA,and BDNF in rat hippocampal tissues.Results:The results of Morris water maze positioning navigation test showed that the incubation period of each group was calculated on the 1st,3rd and 5th days of the experiment,and the motor incubation period of the infected group was higher than that of the control group.The results of HE staining showed that the rat nerve cells in the control group were morphologically intact,the staining was clear,the nucleus was clearly visible,and the edge of the cell membrane was sharp.The rat neurons in the infected group were damaged to varying degrees,the nucleus gradually dissolved,the cytoplasmic staining became deeper,the edges of the cell membrane were blurred and disordered,and the cells were deformed and arranged disordered.The results of Nissl staining showed that the well-stained Nissl body particles were visible in the nerve cells of rats in the control group,and the dissipation of Nissl bodies in the nerve cells of the infected group was reduced,and the staining was shallow.The results of RT-qPCR showed that compared with the control group,the mRNA expression of miR-9-5p and BDNF was decreased in the infected group,and the mRNA expression of RHOA was increased(P<0.05 or P<0.001).The Western blot results showed that compared with the control group,the relative expression of BDNF in the three infected groups was decreased,and the relative expression of RHOA increased(P<0.05).Conclusion:In aluminum-induced cognitive impairment,miR-9-5p is downregulated and RHOA is upregulatd.
文摘Background:Postoperative cognitive dysfunction(POCD)can occur in patients with cardiac and non-cardiac surgeries.About 20%to 40%patients develop POCD at hospital discharge(a few days after surgery,acute POCD)and 10%elderly patients(>60 years old)have POCD at 3 months after surgery(delayed POCD).Age and degree of education are risk factors for delayed POCD.It has been shown that POCD is associated with increased mortality.Patients with POCD have a longer hospital stay and an increased rate of leaving job market.Thus,POCD is a very significant clinical syndrome during the perioperative period,which is recognized only in recent years.We and others have shown that neuroinflammation is a critical neuropathological process for POCD.However,neuroinflammation lasts for a few days after surgery.It is not known how such a short-lived neuropathological process lead to POCD a few months after surgery.To address this issue,a series of experiments were performed in my laboratory.Methods:Rats or mice were subjected to common carotid arterial exposure,a surgical component of carotid endarterectomy that is often performed in elderly patients.Their learning and memory were assessed at least one week after surgery.Their blood and brain tissues were harvested at various time after surgery for biochemical and structural analyses.Results:The surgery induced an increase of proinflammatory cytokines in the blood.The surgery also increased the expression of active matrix metallopeptidase 9(MMP-9)and its activity in the brain.This surgery induced POCD and neuroinflammation in wild-type mice but not in the MMP-9 knockout mice.P2X7 receptors and inflammasome were activated by the surgery.Inhibition of P2X7 receptors and P2X7 receptor knockout abolished POCD and neuroinflammation after surgery.The surgery decreased growth factor production and inhibition of neuroinflammation attenuated this decrease.The decreased growth factor expression occurred at 3 to 5 days after the surgery.Surgery increased histone deacetylase activity and inhibition of histone deacetylase attenuated the decrease of growth factor expression and the development of POCD.The surgery decreased neurogenesis in the hippocampus and application of growth factors to the brain attenuated this decrease and POCD.This decreased neurogenesis was observed 3 weeks after surgery.Finally,surgery impaired dendritic arborization that was assessed 3 weeks after surgery.Inhibition of histone deacetylases attenuated this impairment and POCD.Conclusion:Surgery induces a delayed POCD in rodents.Surgery results in systemic inflammation,which then activates MMP-9 to damage the brain-blood barrier to facilitate the systemic inflammation to be transmitted to the brain.Proinflammatory signals in the blood activate P2X7 receptors to induce neuroinflammation that inhibits growth factor expression through epigenetic regulation.Reduced growth factor expression results in decreased neurogenesis and dendritic arborization that then ultimately lead to the delayed POCD.Thus,surgery activates a series of cascade events to induce the delayed POCD.
文摘建立基于VGG16预训练模型的睑板腺缺失程度识别系统.收集福建医科大学附属第二医院2015年1月至2020年12月2 000例患者的睑板腺图像.通过图像预处理、标注、裁剪等构建4 364张睑板腺MGH小数据集.利用VGG16的迁移学习方法,在小样本情况下进行睑板腺缺失程度识别,并探讨不同优化方法、学习率、迭代次数、批量大小、数据集划分比例对识别准确率的影响.当优化器为Adam、学习率为10-5、批量大小为60、迭代次数为100、训练集测试集比例为7∶3时,模型识别效果最好,准确率为90%,模型评估每张图不超于3 s.
