BACKGROUND The duodenum plays a significant role in metabolic regulation,and thickened mucous membranes are associated with insulin resistance.Duodenal mucosal resurfacing(DMR),a new-style endoscopic procedure using h...BACKGROUND The duodenum plays a significant role in metabolic regulation,and thickened mucous membranes are associated with insulin resistance.Duodenal mucosal resurfacing(DMR),a new-style endoscopic procedure using hydrothermal energy to ablate this thickened layer,shows promise for enhancing glucose and lipid metabolism in type 2 diabetes(T2D)patients.However,the mechanisms driving these improvements remain largely unexplored.AIM To investigate the mechanisms by which DMR improves metabolic disorders using a rat model.METHODS Rats with T2D underwent a revised DMR procedure via a gastric incision using a specialized catheter to abrade the duodenal mucosa.The duodenum was evaluated using histology,immunofluorescence,and western blotting.Serum assays measured glucose,lipid profiles,lipopolysaccharide,and intestinal hormones,while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and ultra performance liquid chromatography-mass spectrum/mass spectrum,severally.RESULTS DMR significantly improved glucose and lipid metabolic disorders in T2D rats.It increased the serum levels of cholecystokinin,gastric inhibitory peptide,and glucagon-like peptide 1,and reduced the length and depth of duodenal villi and crypts.DMR also enhanced the intestinal barrier integrity and reduced lipopolysaccharide translocation.Additionally,DMR modified the gut microbiome and metabolome,particularly affecting the Blautia genus.Correlation analysis revealed significant links between the gut microbiota,metabolites,and T2D phenotypes.CONCLUSION This study illustrates that DMR addresses metabolic dysfunctions in T2D through multifaceted mechanisms,highlighting the potential role of the Blautia genus on T2D pathogenesis and DMR’s therapeutic impact.展开更多
Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-cal...Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction,in particular following a major traumatic event such as MI.Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI,coronary catheterization,or cardiothoracic surgeries.In this review,we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression.We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors(SSRIs)and cognitive behavior and exercise therapies.We further envisage a possible role played by certain chemokines,e.g.,Chemokine(C-X-C motif)ligand 12(CXCL12)and Chemokine(C-C motif)ligand 2(CCL22),in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period.Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.展开更多
We and others have published extensively on the benefits of physical activity(PA),exercise training,and cardiorespiratory fitness(CRF)to decrease the prevalence of cardiovascular diseases(CVDs)and CVD and all-cause mo...We and others have published extensively on the benefits of physical activity(PA),exercise training,and cardiorespiratory fitness(CRF)to decrease the prevalence of cardiovascular diseases(CVDs)and CVD and all-cause morbidity and mortality.^(1-5)Both PA and CRF are important;however,CRF,which is mostly obtained through PA,although there is a genetic component,seems to be even more important than PA for predicting prognosis.^(1,4-6)Certainly,the wealth of data from across the world has indicated that increasing PA to enhance CRF while mitigating sedentary behavior would go a long way to lessen the world-wide obesity epidemic and reduce CVD and all-cause mortality.展开更多
BACKGROUND Gout is a disease characterized by hyperuricemia,and resultant deposition of uric acid crystals in tissues.While typically manifested as intraarticular crystals or tophi,gout can also cause pathology at ent...BACKGROUND Gout is a disease characterized by hyperuricemia,and resultant deposition of uric acid crystals in tissues.While typically manifested as intraarticular crystals or tophi,gout can also cause pathology at entheses.Gouty deposition within tendinous structures put them at risk for traumatic and degenerative rupture.Furthermore,allografts can also be at risk of rupture in the setting of severe gout.We present the case of a 56-year-old female with severe gouty disease who sustained a re-rupture of a patellar tendon allograft reconstruction.CASE SUMMARY A 56-year-old female presented to clinic after feeling her left knee pop and collapse beneath her while descending stairs.She had a history of tophaceous gout and left patellar tendon rupture with reconstruction and multiple revisions over the course of 19 years.This patient presented with pain and extensor lag.A magnetic resonance image demonstrated a ruptured patellar tendon allograft reconstruction and avulsion fracture at the tibial tubercle.The patient was treated with a novel intervention of Achilles allograft with bone block in a unique configuration with a dermal allograft incorporated into the reconstruction.She was made non-weight bearing in the operative extremity in extension for the first four weeks postoperatively and was then progressed to active flexion over the course of eight weeks.At twelve weeks,she was able to fully extend her operative knee and at five months she was resuming her normal activities and exercises.CONCLUSION Failed patellar tendon reconstruction due to gouty infiltration is treated with dermal allograft augmented Achilles tendon reconstruction with bone block.展开更多
Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobeha...Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.展开更多
Background: Thyroid Eye Disease (TED) is known to alter tissues of the orbital cavity, including the optic nerve. However, its effect on measured global Retinal Nerve Fiber Layer (gRNFL) is not well elucidated. This c...Background: Thyroid Eye Disease (TED) is known to alter tissues of the orbital cavity, including the optic nerve. However, its effect on measured global Retinal Nerve Fiber Layer (gRNFL) is not well elucidated. This case evaluates the effect of teprotumumab on gRNFL in a patient with moderate TED. Observations: A 60-year-old female with controlled ocular hypertension and moderate TED received 8 standard IV teprotumumab infusions. Comprehensive ocular evaluations were performed pre-, during-, and post-treatment. Bilateral gRNFL thickness decreased (10 m OD;12 m OS) at 4 months post-treatment start, persisting at 8 months, but recovered at 20 months. Conclusions and Importance: Teprotumumab treatment in patients with TED led to a transient bilateral decrease in gRNFL thickness, which was restored to baseline levels with no adverse events reported. Monitoring gRNFL changes in teprotumumab-treated patients is crucial as gRNFL thinning indicates retinal ganglion cell damage. Teprotumumabs ability to dampen the IGF-IR inflammatory cascade may have reduced retinal inflammation, leading to recovery.展开更多
Large language models,such as ChatGPT,use vast textual data to mimic human-like responses and interact with users in a natural conversational way.This capability has introduced several opportunities and challenges in ...Large language models,such as ChatGPT,use vast textual data to mimic human-like responses and interact with users in a natural conversational way.This capability has introduced several opportunities and challenges in the field of language education and has sparked both excitement and concern among language educators.This study seeks to contribute to the ongoing debate surrounding the advantages and drawbacks of using ChatGPT in the language classroom by attempting to evaluate its effectiveness in Arabic language learning,with a particular focus on teaching case endings.To achieve this,this study analyzes and discusses data collected from ChatGPT learning sessions,quizzes,and surveys conducted with university students studying Arabic.The findings of this study revealed that while ChatGPT was efficient in providing detailed and personalized explanations,it was deficient in providing accurate and reliable information regarding Arabic case endings.展开更多
Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic c...Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2,interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.展开更多
Peritoneal carcinomatosis(PC),the dissemination of cancer cells throughout the lining of the abdominal cavity,is the second most common presentation of colon cancer distant metastasis.Despite remarkable advances in cy...Peritoneal carcinomatosis(PC),the dissemination of cancer cells throughout the lining of the abdominal cavity,is the second most common presentation of colon cancer distant metastasis.Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years,it has been repeatedly shown that these therapies remain ineffective for colon cancer PC.Recently,there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC) prolongs the life of colon cancer PC patients.Here,we will review the clinical presentation,the mechanisms of disease progression,and current treatment options for colon cancer PC,with a focus on the benefits and limitations of CRSHIPEC.展开更多
基金Supported by the National Natural Science Foundation of China,No.82474318the Jiangsu Administration of Traditional Chinese Medicine,No.zt202105+1 种基金Subject of Jiangsu Province Hospital of Chinese Medicine,No.Y2021rc22a Research Career Scientist。
文摘BACKGROUND The duodenum plays a significant role in metabolic regulation,and thickened mucous membranes are associated with insulin resistance.Duodenal mucosal resurfacing(DMR),a new-style endoscopic procedure using hydrothermal energy to ablate this thickened layer,shows promise for enhancing glucose and lipid metabolism in type 2 diabetes(T2D)patients.However,the mechanisms driving these improvements remain largely unexplored.AIM To investigate the mechanisms by which DMR improves metabolic disorders using a rat model.METHODS Rats with T2D underwent a revised DMR procedure via a gastric incision using a specialized catheter to abrade the duodenal mucosa.The duodenum was evaluated using histology,immunofluorescence,and western blotting.Serum assays measured glucose,lipid profiles,lipopolysaccharide,and intestinal hormones,while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and ultra performance liquid chromatography-mass spectrum/mass spectrum,severally.RESULTS DMR significantly improved glucose and lipid metabolic disorders in T2D rats.It increased the serum levels of cholecystokinin,gastric inhibitory peptide,and glucagon-like peptide 1,and reduced the length and depth of duodenal villi and crypts.DMR also enhanced the intestinal barrier integrity and reduced lipopolysaccharide translocation.Additionally,DMR modified the gut microbiome and metabolome,particularly affecting the Blautia genus.Correlation analysis revealed significant links between the gut microbiota,metabolites,and T2D phenotypes.CONCLUSION This study illustrates that DMR addresses metabolic dysfunctions in T2D through multifaceted mechanisms,highlighting the potential role of the Blautia genus on T2D pathogenesis and DMR’s therapeutic impact.
文摘Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction,in particular following a major traumatic event such as MI.Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI,coronary catheterization,or cardiothoracic surgeries.In this review,we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression.We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors(SSRIs)and cognitive behavior and exercise therapies.We further envisage a possible role played by certain chemokines,e.g.,Chemokine(C-X-C motif)ligand 12(CXCL12)and Chemokine(C-C motif)ligand 2(CCL22),in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period.Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.
文摘We and others have published extensively on the benefits of physical activity(PA),exercise training,and cardiorespiratory fitness(CRF)to decrease the prevalence of cardiovascular diseases(CVDs)and CVD and all-cause morbidity and mortality.^(1-5)Both PA and CRF are important;however,CRF,which is mostly obtained through PA,although there is a genetic component,seems to be even more important than PA for predicting prognosis.^(1,4-6)Certainly,the wealth of data from across the world has indicated that increasing PA to enhance CRF while mitigating sedentary behavior would go a long way to lessen the world-wide obesity epidemic and reduce CVD and all-cause mortality.
文摘BACKGROUND Gout is a disease characterized by hyperuricemia,and resultant deposition of uric acid crystals in tissues.While typically manifested as intraarticular crystals or tophi,gout can also cause pathology at entheses.Gouty deposition within tendinous structures put them at risk for traumatic and degenerative rupture.Furthermore,allografts can also be at risk of rupture in the setting of severe gout.We present the case of a 56-year-old female with severe gouty disease who sustained a re-rupture of a patellar tendon allograft reconstruction.CASE SUMMARY A 56-year-old female presented to clinic after feeling her left knee pop and collapse beneath her while descending stairs.She had a history of tophaceous gout and left patellar tendon rupture with reconstruction and multiple revisions over the course of 19 years.This patient presented with pain and extensor lag.A magnetic resonance image demonstrated a ruptured patellar tendon allograft reconstruction and avulsion fracture at the tibial tubercle.The patient was treated with a novel intervention of Achilles allograft with bone block in a unique configuration with a dermal allograft incorporated into the reconstruction.She was made non-weight bearing in the operative extremity in extension for the first four weeks postoperatively and was then progressed to active flexion over the course of eight weeks.At twelve weeks,she was able to fully extend her operative knee and at five months she was resuming her normal activities and exercises.CONCLUSION Failed patellar tendon reconstruction due to gouty infiltration is treated with dermal allograft augmented Achilles tendon reconstruction with bone block.
文摘Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.
文摘Background: Thyroid Eye Disease (TED) is known to alter tissues of the orbital cavity, including the optic nerve. However, its effect on measured global Retinal Nerve Fiber Layer (gRNFL) is not well elucidated. This case evaluates the effect of teprotumumab on gRNFL in a patient with moderate TED. Observations: A 60-year-old female with controlled ocular hypertension and moderate TED received 8 standard IV teprotumumab infusions. Comprehensive ocular evaluations were performed pre-, during-, and post-treatment. Bilateral gRNFL thickness decreased (10 m OD;12 m OS) at 4 months post-treatment start, persisting at 8 months, but recovered at 20 months. Conclusions and Importance: Teprotumumab treatment in patients with TED led to a transient bilateral decrease in gRNFL thickness, which was restored to baseline levels with no adverse events reported. Monitoring gRNFL changes in teprotumumab-treated patients is crucial as gRNFL thinning indicates retinal ganglion cell damage. Teprotumumabs ability to dampen the IGF-IR inflammatory cascade may have reduced retinal inflammation, leading to recovery.
基金This research received financial support from the College of Humanities and Sciences at Virginia Commonwealth University through the Seed Award program.
文摘Large language models,such as ChatGPT,use vast textual data to mimic human-like responses and interact with users in a natural conversational way.This capability has introduced several opportunities and challenges in the field of language education and has sparked both excitement and concern among language educators.This study seeks to contribute to the ongoing debate surrounding the advantages and drawbacks of using ChatGPT in the language classroom by attempting to evaluate its effectiveness in Arabic language learning,with a particular focus on teaching case endings.To achieve this,this study analyzes and discusses data collected from ChatGPT learning sessions,quizzes,and surveys conducted with university students studying Arabic.The findings of this study revealed that while ChatGPT was efficient in providing detailed and personalized explanations,it was deficient in providing accurate and reliable information regarding Arabic case endings.
基金National Institutes of Health Grants,R01 CA 83650 and R01 CA 39225 to A.E.S.
文摘Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2,interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.
基金Supported by NIH grants,No.R01CA160688(to Takabe K)and No.T32CA085159-10(to Terracina KP)
文摘Peritoneal carcinomatosis(PC),the dissemination of cancer cells throughout the lining of the abdominal cavity,is the second most common presentation of colon cancer distant metastasis.Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years,it has been repeatedly shown that these therapies remain ineffective for colon cancer PC.Recently,there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC) prolongs the life of colon cancer PC patients.Here,we will review the clinical presentation,the mechanisms of disease progression,and current treatment options for colon cancer PC,with a focus on the benefits and limitations of CRSHIPEC.
