BACKGROUND Type 2 diabetes mellitus(T2DM)is significantly increasing worldwide,and the incidence of its complications is also on the rise.One of the main complications of T2DM is diabetic kidney disease(DKD).The glome...BACKGROUND Type 2 diabetes mellitus(T2DM)is significantly increasing worldwide,and the incidence of its complications is also on the rise.One of the main complications of T2DM is diabetic kidney disease(DKD).The glomerular filtration rate(GFR)and urinary albumin creatinine ratio(UACR)increase in the early stage.As the disease progresses,UACR continue to rise and GFR begins to decline until endstage renal disease appears.At the same time,DKD will also increase the incidence and mortality of cardiovascular and cerebrovascular diseases.At present,the pathogenesis of DKD is not very clear.Therefore,exploration of the pathogenesis of DKD to find a treatment approach,so as to delay the development of DKD,is essential to improve the prognosis of DKD.AIM To detect the expression of tenascin-C(TNC)in the serum of T2DM patients,observe the content of TNC in the glomerulus of DKD rats,and detect the expression of TNC on inflammatory and fibrotic factors in rat mesangial cells(RMCs)cultured under high glucose condition,in order to explore the specific molecular mechanism of TNC in DKD and bring a new direction for the treatment of DKD.METHODS The expression level of TNC in the serum of diabetic patients was detected by enzyme-linked immunosorbent assay(ELISA),the protein expression level of TNC in the glomerular area of DKD rats was detected by immunohistochemistry,and the expression level of TNC in the rat serum was detected by ELISA.Rat glomerular mesangial cells were cultured.Following high glucose stimulation,the expression levels of related proteins and mRNA were detected by Western blot and polymerase chain reaction,respectively.RESULTS ELISA results revealed an increase in the serum TNC level in patients with T2DM.Increasing UACR and hypertension significantly increased the expression of TNC(P<0.05).TNC expression was positively correlated with glycosylated haemoglobin(HbA1c)level,body mass index,systolic blood pressure,and UACR(P<0.05).Immunohistochemical staining showed that TNC expression in the glomeruli of rats with streptozotocin-induced diabetes was significantly increased compared with normal controls(P<0.05).Compared with normal rats,serum level of TNC in diabetic rats was significantly increased(P<0.05),which was positively correlated with urea nitrogen and urinary creatinine(P<0.05).The levels of TNC,Toll-like receptor-4(TLR4),phosphorylated nuclear factor-κB p65 protein(Ser536)(p-NF-κB p65),and miR-155-5p were increased in RMCs treated with high glucose(P<0.05).The level of TNC protein peaked 24 h after high glucose stimulation(P<0.05).After TNC knockdown,the levels of TLR4,p-NF-κB p65,miR-155-5p,connective tissue growth factor(CTGF),and fibronectin(FN)were decreased,revealing that TNC regulated miR-155-5p expression through the TLR4/NF-κB p65 pathway,thereby regulating inflammation(NF-κB p65)and fibrosis(CTGF and FN)in individuals with DKD.In addition,metformin treatment may relive the processes of inflammation and fibrosis in individuals with DKD by reducing the levels of the TNC,p-NF-κB p65,CTGF,and FN proteins.CONCLUSION TNC can promote the occurrence and development of DKD.Interfering with the TNC/TLR4/NF-κB p65/miR-155-5p pathway may become a new target for DKD treatment.展开更多
Background Unsedated colonoscopy is an important method used for diagnosing colorectal cancer,but it can cause discomfort such as pain and bloating,as well as anxiety.At present,the relief is mainly achieved through m...Background Unsedated colonoscopy is an important method used for diagnosing colorectal cancer,but it can cause discomfort such as pain and bloating,as well as anxiety.At present,the relief is mainly achieved through methods such as changing positions and manual pressing,but the efficacy is limited.Hence alternative therapies for sedation and analgesia in unsedated colonoscopy warrant further study.Electroacupuncture(EA)can simplify the procedure of anesthesia and analgesia,while the efficacy of EA on unsedated colonoscopy remains unclear.Therefore,a well-designed randomized controlled trial is needed to demonstrate the potential efficacy of acupuncture in unsedated colonoscopy,particularly for pain relief.Methods In this prospective randomized sham-controlled trial,105 eligible participants will be recruited and randomly assigned to either EA group(n=35),sham EA group(n=35),or control group(n=35)in a 1:1:1 ratio.The EA group will receive acupuncture intervention on bilateral Hegu(LI4),Neiguan(PC6),Zusanli(ST36),and Shenmen(HT7),with LI4 and PC6 on both sides connected to the EA device.The sham EA group will received non transdermal needling on points of no meridian,and deliberately connect the needle to the incorrect output socket of EA device to block the stimulation.The needling will conducted from 30 min before the unsedated colonoscopy to the end of the colonoscopy,the whole retention time would be approximately 40 min.The participants in the control group will not receive any acupuncture intervention.All participants of the three groups will not receive any other treatment.Primary outcomes:Numerical Rating Scale(NRS)reported by participants and Face Pain Scale Revised(FPS-R)evaluated by observers of four areas of the participants during the unsedated colonoscopy.Secondary outcomes:tolerance reported by endoscopists,tolerance reported by participants,satisfaction reported by endoscopists,satisfaction reported by participants,adverse events during the unsedated colonoscopy,postoperative discomfort,unsedated colonoscopy smoothness(cecal insertion time,unwinding time,success rate of one-time intubation).Both intention-to-treat(ITT)and per-protocol(PP)analyses will be performed to assess the efficacy of EA.Discussion The trial will explore the efficacy of relieving pain,improving tolerability,and reducing undesirable adverse events of EA for unsedated colonoscopy.The results of this trial will provide sound evidence for promoting the clinical application of EA for unsedated colonoscopy.Trial registration ClinicalTrials.gov Identifier:ChiCTR2300069903,retrospectively registered on March 16,2023.展开更多
Irritable bowel syndrome(IBS)is common gastrointestinal problems.It is characterized by abdominal pain or discomfort,and is associated with changes in stool frequency and/or consistency.The etiopathogenesis of IBS may...Irritable bowel syndrome(IBS)is common gastrointestinal problems.It is characterized by abdominal pain or discomfort,and is associated with changes in stool frequency and/or consistency.The etiopathogenesis of IBS may be multifactorial,as is the pathophysiology,which is attributed to alterations in gastrointestinal motility,visceral hypersensitivity,intestinal microbiota,gut epithelium and immune function,dysfunction of the brain-gut axis or certain psychosocial factors.Current therapeutic strategies are often unsatisfactory.There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS.Probiotics are living organisms which,when ingested in certain numbers,exert health benefits beyond inherent basic nutrition.Probiotics have numerous positive effects in the gastrointestinal tract.Recently,many studies have suggested that probiotics are effective in the treatment of IBS.The mechanisms of probiotics in IBS are very complex.The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.展开更多
Two-dimensional(2 D) polymers are fascinating as they exhibit unique physical, chemical, mechanical, and electronic properties that are completely different from those of traditional linear or branched polymers. They ...Two-dimensional(2 D) polymers are fascinating as they exhibit unique physical, chemical, mechanical, and electronic properties that are completely different from those of traditional linear or branched polymers. They are very promising for applications in catalysis, separation, optoelectronics, energy storage, and nanomedicine. Recently, ultrathin 2 D conjugated polymers have emerged as advanced materials for converting solar energy into chemical energy. The inherent 2 D planar structure with in-plane periodicity offers many features that are highly desirable for photon-involved catalytic energy conversion processes, including high absorption coefficients,large surface areas, abundant surface active sites, and efficient charge separation. Moreover, the possibility of finely tuning the optoelectronic and structural properties through precise molecular engineering has opened up new opportunities for design and synthesis of novel 2 D polymer nanosheets with unprecedented applications. Herein, we highlight recent advances in developing ultrathin 2 D conjugated polymer nanosheets for solar-to-chemical energy conversion. Specifically, we discuss emerging applications of ultrathin 2 D conjugated polymer nanosheets for solar-driven water splitting and CO2 reduction. Meanwhile, future challenges and prospects for design and synthesis of ultrathin 2 D conjugated polymer nanosheets for solar fuel generation are also included.展开更多
BACKGROUND A nomogram is a diagram that aggregates various predictive factors through multivariate regression analysis,which can be used to predict patient outcomes intuitively.Lymph node(LN)metastasis and tumor depos...BACKGROUND A nomogram is a diagram that aggregates various predictive factors through multivariate regression analysis,which can be used to predict patient outcomes intuitively.Lymph node(LN)metastasis and tumor deposit(TD)conditions are two critical factors that affect the prognosis of patients with colorectal cancer(CRC)after surgery.At present,few effective tools have been established to predict the overall survival(OS)of CRC patients after surgery.AIM To screen out suitable risk factors and to develop a nomogram that predicts the postoperative OS of CRC patients.METHODS Data from a total of 3139 patients diagnosed with CRC who underwent surgical removal of tumors and LN resection from 2010 to 2015 were collected from the Surveillance,Epidemiology,and End Results program.The data were divided into a training set(n=2092)and a validation set(n=1047)at random.The Harrell concordance index(C-index),Akaike information criterion(AIC),and area under the curve(AUC)were used to assess the predictive performance of the N stage from the American Joint Committee Cancer tumor-node-metastasis classification,LN ratio(LNR),and log odds of positive lymph nodes(LODDS).Univariate and multivariate analyses were utilized to screen out the risk factors significantly correlating with OS.The construction of the nomogram was based on Cox regression analysis.The C-index,receiver operating characteristic(ROC)curve,and calibration curve were employed to evaluate the discrimination and prediction abilities of the model.The likelihood ratio test was used to compare the sensitivity and specificity of the final model to the model with the N stage alone to evaluate LN metastasis.RESULTS The predictive efficacy of the LODDS was better than that of the LNR based on the C-index,AIC values,and AUC values of the ROC curve.Seven independent predictive factors,namely,race,age at diagnosis,T stage,M stage,LODDS,TD condition,and serum carcinoembryonic antigen level,were included in the nomogram.The C-index of the nomogram for OS prediction was 0.8002(95%CI:0.7839-0.8165)in the training set and 0.7864(95%CI:0.7604-0.8124)in the validation set.The AUC values of the ROC curve predicting the 1-,3-,and 5-year OS were 0.846,0.841,and 0.825,respectively,in the training set and 0.823,0.817,and 0.835,respectively,in the validation test.Great consistency between the predicted and actual observed OS for the 1-,3-,and 5-year OS in the training set and validation set was shown in the calibration curves.The final nomogram showed a better sensitivity and specificity than the nomogram with N stage alone for evaluating LN metastasis in both the training set(-4668.0 vs-4688.3,P<0.001)and the validation set(-1919.5 vs-1919.8,P<0.001)through the likelihood ratio test.CONCLUSION The nomogram incorporating LODDS,TD,and other risk factors showed great predictive accuracy and better sensitivity and specificity and represents a potential tool for therapeutic decision-making.展开更多
Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldw...Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldwide health issue.Patients with sarcopenia experience decreases in muscle mass and function,becoming frail and eventually bedridden.Type 2 diabetes mellitus(T2DM)is also a major health issue;the incidence of T2DM increases with aging.T2DM is associated with reduced muscle strength and poor muscle quality and may contribute to acceleration of the aging process,augmenting age-related sarcopenia.Recent studies indicate that elderly patients with diabetes are at an increased risk for sarcopenia.Therefore,these older diabetic patients with sarcopenia need specific anti-diabetic therapies targeting not only glycemic control but also sarcopenia,with the goal of preventing sarcopenia in presarcopenic patients.Presently,various types of hypoglycemic drugs are available,but which hypoglycemic drugs are better suited for geriatric T2DM patients with sarcopenia remains undetermined.In this review,we discuss the association between diabetes and sarcopenia in geriatric patients,and how anti-diabetic drugs may influence sarcopenia outcomes.This review will guide clinical workers in the selection of drugs best suited for this patient population.展开更多
基金Supported by National Key Research and Development Program of China,No.2018YFC1313900 and No.2018YFC1313901The Higher School High-end Talent Team Construction of Liaoning Province,No.[2014]187.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is significantly increasing worldwide,and the incidence of its complications is also on the rise.One of the main complications of T2DM is diabetic kidney disease(DKD).The glomerular filtration rate(GFR)and urinary albumin creatinine ratio(UACR)increase in the early stage.As the disease progresses,UACR continue to rise and GFR begins to decline until endstage renal disease appears.At the same time,DKD will also increase the incidence and mortality of cardiovascular and cerebrovascular diseases.At present,the pathogenesis of DKD is not very clear.Therefore,exploration of the pathogenesis of DKD to find a treatment approach,so as to delay the development of DKD,is essential to improve the prognosis of DKD.AIM To detect the expression of tenascin-C(TNC)in the serum of T2DM patients,observe the content of TNC in the glomerulus of DKD rats,and detect the expression of TNC on inflammatory and fibrotic factors in rat mesangial cells(RMCs)cultured under high glucose condition,in order to explore the specific molecular mechanism of TNC in DKD and bring a new direction for the treatment of DKD.METHODS The expression level of TNC in the serum of diabetic patients was detected by enzyme-linked immunosorbent assay(ELISA),the protein expression level of TNC in the glomerular area of DKD rats was detected by immunohistochemistry,and the expression level of TNC in the rat serum was detected by ELISA.Rat glomerular mesangial cells were cultured.Following high glucose stimulation,the expression levels of related proteins and mRNA were detected by Western blot and polymerase chain reaction,respectively.RESULTS ELISA results revealed an increase in the serum TNC level in patients with T2DM.Increasing UACR and hypertension significantly increased the expression of TNC(P<0.05).TNC expression was positively correlated with glycosylated haemoglobin(HbA1c)level,body mass index,systolic blood pressure,and UACR(P<0.05).Immunohistochemical staining showed that TNC expression in the glomeruli of rats with streptozotocin-induced diabetes was significantly increased compared with normal controls(P<0.05).Compared with normal rats,serum level of TNC in diabetic rats was significantly increased(P<0.05),which was positively correlated with urea nitrogen and urinary creatinine(P<0.05).The levels of TNC,Toll-like receptor-4(TLR4),phosphorylated nuclear factor-κB p65 protein(Ser536)(p-NF-κB p65),and miR-155-5p were increased in RMCs treated with high glucose(P<0.05).The level of TNC protein peaked 24 h after high glucose stimulation(P<0.05).After TNC knockdown,the levels of TLR4,p-NF-κB p65,miR-155-5p,connective tissue growth factor(CTGF),and fibronectin(FN)were decreased,revealing that TNC regulated miR-155-5p expression through the TLR4/NF-κB p65 pathway,thereby regulating inflammation(NF-κB p65)and fibrosis(CTGF and FN)in individuals with DKD.In addition,metformin treatment may relive the processes of inflammation and fibrosis in individuals with DKD by reducing the levels of the TNC,p-NF-κB p65,CTGF,and FN proteins.CONCLUSION TNC can promote the occurrence and development of DKD.Interfering with the TNC/TLR4/NF-κB p65/miR-155-5p pathway may become a new target for DKD treatment.
基金Supported by National Basic Evidence-based Capacity Building Project of Traditional Chinese Medicine([2019]130)Natural Science Foundation of Liaoning Province:2024-MS-042+1 种基金Xingliao Talent Program Medical Master Project:YXMJ-QNMZY-10Liaoning University of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine Theory and Application of Ministry of Education open fund project:zyzx2302.
文摘Background Unsedated colonoscopy is an important method used for diagnosing colorectal cancer,but it can cause discomfort such as pain and bloating,as well as anxiety.At present,the relief is mainly achieved through methods such as changing positions and manual pressing,but the efficacy is limited.Hence alternative therapies for sedation and analgesia in unsedated colonoscopy warrant further study.Electroacupuncture(EA)can simplify the procedure of anesthesia and analgesia,while the efficacy of EA on unsedated colonoscopy remains unclear.Therefore,a well-designed randomized controlled trial is needed to demonstrate the potential efficacy of acupuncture in unsedated colonoscopy,particularly for pain relief.Methods In this prospective randomized sham-controlled trial,105 eligible participants will be recruited and randomly assigned to either EA group(n=35),sham EA group(n=35),or control group(n=35)in a 1:1:1 ratio.The EA group will receive acupuncture intervention on bilateral Hegu(LI4),Neiguan(PC6),Zusanli(ST36),and Shenmen(HT7),with LI4 and PC6 on both sides connected to the EA device.The sham EA group will received non transdermal needling on points of no meridian,and deliberately connect the needle to the incorrect output socket of EA device to block the stimulation.The needling will conducted from 30 min before the unsedated colonoscopy to the end of the colonoscopy,the whole retention time would be approximately 40 min.The participants in the control group will not receive any acupuncture intervention.All participants of the three groups will not receive any other treatment.Primary outcomes:Numerical Rating Scale(NRS)reported by participants and Face Pain Scale Revised(FPS-R)evaluated by observers of four areas of the participants during the unsedated colonoscopy.Secondary outcomes:tolerance reported by endoscopists,tolerance reported by participants,satisfaction reported by endoscopists,satisfaction reported by participants,adverse events during the unsedated colonoscopy,postoperative discomfort,unsedated colonoscopy smoothness(cecal insertion time,unwinding time,success rate of one-time intubation).Both intention-to-treat(ITT)and per-protocol(PP)analyses will be performed to assess the efficacy of EA.Discussion The trial will explore the efficacy of relieving pain,improving tolerability,and reducing undesirable adverse events of EA for unsedated colonoscopy.The results of this trial will provide sound evidence for promoting the clinical application of EA for unsedated colonoscopy.Trial registration ClinicalTrials.gov Identifier:ChiCTR2300069903,retrospectively registered on March 16,2023.
文摘Irritable bowel syndrome(IBS)is common gastrointestinal problems.It is characterized by abdominal pain or discomfort,and is associated with changes in stool frequency and/or consistency.The etiopathogenesis of IBS may be multifactorial,as is the pathophysiology,which is attributed to alterations in gastrointestinal motility,visceral hypersensitivity,intestinal microbiota,gut epithelium and immune function,dysfunction of the brain-gut axis or certain psychosocial factors.Current therapeutic strategies are often unsatisfactory.There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS.Probiotics are living organisms which,when ingested in certain numbers,exert health benefits beyond inherent basic nutrition.Probiotics have numerous positive effects in the gastrointestinal tract.Recently,many studies have suggested that probiotics are effective in the treatment of IBS.The mechanisms of probiotics in IBS are very complex.The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.
基金financially supported by National Key R&D Program of China(Nos.2017YFA0207301 and 2015CB351903)the National Natural Science Foundation of China(Nos.21474095and 21875235)the Fundamental Research Funds for the Central Universities
文摘Two-dimensional(2 D) polymers are fascinating as they exhibit unique physical, chemical, mechanical, and electronic properties that are completely different from those of traditional linear or branched polymers. They are very promising for applications in catalysis, separation, optoelectronics, energy storage, and nanomedicine. Recently, ultrathin 2 D conjugated polymers have emerged as advanced materials for converting solar energy into chemical energy. The inherent 2 D planar structure with in-plane periodicity offers many features that are highly desirable for photon-involved catalytic energy conversion processes, including high absorption coefficients,large surface areas, abundant surface active sites, and efficient charge separation. Moreover, the possibility of finely tuning the optoelectronic and structural properties through precise molecular engineering has opened up new opportunities for design and synthesis of novel 2 D polymer nanosheets with unprecedented applications. Herein, we highlight recent advances in developing ultrathin 2 D conjugated polymer nanosheets for solar-to-chemical energy conversion. Specifically, we discuss emerging applications of ultrathin 2 D conjugated polymer nanosheets for solar-driven water splitting and CO2 reduction. Meanwhile, future challenges and prospects for design and synthesis of ultrathin 2 D conjugated polymer nanosheets for solar fuel generation are also included.
基金Supported by Science and Technology Support Program of Shenyang,No.20-205-4-094.
文摘BACKGROUND A nomogram is a diagram that aggregates various predictive factors through multivariate regression analysis,which can be used to predict patient outcomes intuitively.Lymph node(LN)metastasis and tumor deposit(TD)conditions are two critical factors that affect the prognosis of patients with colorectal cancer(CRC)after surgery.At present,few effective tools have been established to predict the overall survival(OS)of CRC patients after surgery.AIM To screen out suitable risk factors and to develop a nomogram that predicts the postoperative OS of CRC patients.METHODS Data from a total of 3139 patients diagnosed with CRC who underwent surgical removal of tumors and LN resection from 2010 to 2015 were collected from the Surveillance,Epidemiology,and End Results program.The data were divided into a training set(n=2092)and a validation set(n=1047)at random.The Harrell concordance index(C-index),Akaike information criterion(AIC),and area under the curve(AUC)were used to assess the predictive performance of the N stage from the American Joint Committee Cancer tumor-node-metastasis classification,LN ratio(LNR),and log odds of positive lymph nodes(LODDS).Univariate and multivariate analyses were utilized to screen out the risk factors significantly correlating with OS.The construction of the nomogram was based on Cox regression analysis.The C-index,receiver operating characteristic(ROC)curve,and calibration curve were employed to evaluate the discrimination and prediction abilities of the model.The likelihood ratio test was used to compare the sensitivity and specificity of the final model to the model with the N stage alone to evaluate LN metastasis.RESULTS The predictive efficacy of the LODDS was better than that of the LNR based on the C-index,AIC values,and AUC values of the ROC curve.Seven independent predictive factors,namely,race,age at diagnosis,T stage,M stage,LODDS,TD condition,and serum carcinoembryonic antigen level,were included in the nomogram.The C-index of the nomogram for OS prediction was 0.8002(95%CI:0.7839-0.8165)in the training set and 0.7864(95%CI:0.7604-0.8124)in the validation set.The AUC values of the ROC curve predicting the 1-,3-,and 5-year OS were 0.846,0.841,and 0.825,respectively,in the training set and 0.823,0.817,and 0.835,respectively,in the validation test.Great consistency between the predicted and actual observed OS for the 1-,3-,and 5-year OS in the training set and validation set was shown in the calibration curves.The final nomogram showed a better sensitivity and specificity than the nomogram with N stage alone for evaluating LN metastasis in both the training set(-4668.0 vs-4688.3,P<0.001)and the validation set(-1919.5 vs-1919.8,P<0.001)through the likelihood ratio test.CONCLUSION The nomogram incorporating LODDS,TD,and other risk factors showed great predictive accuracy and better sensitivity and specificity and represents a potential tool for therapeutic decision-making.
基金Supported by National Natural Science Foundation of China,No.81600693.
文摘Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldwide health issue.Patients with sarcopenia experience decreases in muscle mass and function,becoming frail and eventually bedridden.Type 2 diabetes mellitus(T2DM)is also a major health issue;the incidence of T2DM increases with aging.T2DM is associated with reduced muscle strength and poor muscle quality and may contribute to acceleration of the aging process,augmenting age-related sarcopenia.Recent studies indicate that elderly patients with diabetes are at an increased risk for sarcopenia.Therefore,these older diabetic patients with sarcopenia need specific anti-diabetic therapies targeting not only glycemic control but also sarcopenia,with the goal of preventing sarcopenia in presarcopenic patients.Presently,various types of hypoglycemic drugs are available,but which hypoglycemic drugs are better suited for geriatric T2DM patients with sarcopenia remains undetermined.In this review,we discuss the association between diabetes and sarcopenia in geriatric patients,and how anti-diabetic drugs may influence sarcopenia outcomes.This review will guide clinical workers in the selection of drugs best suited for this patient population.
