BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achiev...BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achieve glucose control.CASE SUMMARY We describe a patient with MODY3 involving a novel splicing mutation,in whom low-dose gliclazide was sufficient to control clinically significant hyperglycemia.Sanger sequencing identified a splicing HNF1A mutation in 12q24 NM_000545.5 Intron5 c.1108-1G>A.Glycemic control has been maintained without insulin therapy for 28 mo after the diagnosis of diabetes.CONCLUSION This case report highlights a novel HNF1A gene mutation in MODY3 that is responsive to sulfonylurea therapy.展开更多
BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivati...BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivation leading to herpes zoster(HZ)is an adverse effect of this drug;however,recurrent HZ at the same site is a rare clinical condition.CASE SUMMARY A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment(10 mg daily).About 1 mo after initiation of oral tofacitinib,she developed blisters on the left flank and abdomen and was diagnosed with HZ;antiviral therapy with acyclovir was resolutory.However,5 d prior to presentation at our hospital,erythema and blisters with severe pain recurred at the same site.Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum,with a pain score of 8(visual analogue scale).Antiviral,nutritional supplement,analgesic and other treatments led to healing but over an atypically long period(approximately 26 d,vs approximately 1 wk).HZ is a common and serious adverse reaction of JAK inhibitors,but it rarely recurs.Our patient’s experience of HZ recurrence at the same site,with a wider affected area,more severe pain and longer healing period,is inconsistent with previous reports.CONCLUSION Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment,with more severe clinical manifestations than in the initial occurrence.展开更多
The presence of excess glucose in blood is regarded as a sweet hurt for patients with diabetes.Human serum albumin(HSA)is the most abundant protein in human plasma,which undergoes severe non-enzymatic glycation with g...The presence of excess glucose in blood is regarded as a sweet hurt for patients with diabetes.Human serum albumin(HSA)is the most abundant protein in human plasma,which undergoes severe non-enzymatic glycation with glucose in patients with diabetes;this modifies the structure and function of HSA.Furthermore,the advanced glycation end products produced by glycated HSA can cause pathological damage to the human body through various signaling pathways,eventually leading to complications of diabetes.Many potential glycation sites on HSA have different degrees of sensitivity to glucose concentration.This review provides a comprehensive assessment of the in vivo glycation sites of HSA;it also discusses the effects of glycation on the structure and function of HSA.Moreover,it addresses the relationship between HSA glycation and diabetes complications.Finally,it focuses on the value of non-enzymatic glycation of HSA in diabetes-related clinical applications.展开更多
The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
The aim of this study was to explore the neuroprotective effect and mechanism of DHA on cerebral ischemia injury and blood-brain barrier(BBB)disruption.the focal cerebral I/R model was established by middle cerebral a...The aim of this study was to explore the neuroprotective effect and mechanism of DHA on cerebral ischemia injury and blood-brain barrier(BBB)disruption.the focal cerebral I/R model was established by middle cerebral artery oclusion(MCAO).BBB permeability was assessed with the leaking amount of Evans Blue and the expression of occludin and ZO-1.The expression of pyrin domain containing(NLRP3)was checked to explore the inhibition of inflammation by DHA.The results showed that DHA could significantly reduce cortical and sub-cortical infarct volumes,neurologic de ficit scores,cerebral edema,BBB permeability after I/R injury.Leaking amount of Evans Blue was reduced by DHA,and occludin and ZO-1 were up-regulated by DHA.The expression of NLRP3 was inhibited after exposure of DHA.Our results indicated that DHA could effectively penetrate the brain of MCAO rats,aleviated the I/R injury by inhibiting NLRP3 inflammasomes and improve BBB disruption,showing a great clinical potential for stroke.展开更多
Dopamine replacement therapy is the most effective treatment to reduce motor symptoms in Parkinson's disease(PD).However,chronic L-Dopa treatment results in abnormal involuntary movements along with the prolongati...Dopamine replacement therapy is the most effective treatment to reduce motor symptoms in Parkinson's disease(PD).However,chronic L-Dopa treatment results in abnormal involuntary movements along with the prolongation of course of the disease and therapeutic time.Recent studies have shown that lithium has the potential for the treatment of neurodegenerative disorders.We tested whether lithium Chloride(LiCl)can reduce the progression of MPTP-induced damage by measuring weight and behavioral tests,further explored whether this is related to the PI3K/Akt signaling pathway using immunohistochemistry and WB.Our results showed that lithium chloride significantly improved motor function and increased body weight and the expression of PI3K,p-Akt Ser473,and p-caspase 3 were significantly increased,Bax/Bcl-2 ratio and the level of p-caspase 3 were decreased.展开更多
Stroke is one of the leading causes of global morbidity and mortality.However,the underlying mechanisms is yet to be fully understood,therefore this will be great challenges to finding appropriate protection.This revi...Stroke is one of the leading causes of global morbidity and mortality.However,the underlying mechanisms is yet to be fully understood,therefore this will be great challenges to finding appropriate protection.This review is to explore the neuroprotective effects and involved the molecular mechanisms of Chinese medicinal ingredients on the cerebral ischemia in rats.展开更多
AIM: To evaluate the computed tomography(CT) features of intraperitoneal tuberculous abscess(IPTA). METHODS: Eight patients with IPTA confirmed by pathology were analyzed retrospectively. The clinical symptoms, medica...AIM: To evaluate the computed tomography(CT) features of intraperitoneal tuberculous abscess(IPTA). METHODS: Eight patients with IPTA confirmed by pathology were analyzed retrospectively. The clinical symptoms, medical images, and surgical findings were evaluated. Involvement of the intestine, peritoneum, viscera, and lymph nodes was also assessed. RESULTS: All 8 patients had a history of abdominal discomfort for 1 to 6 mo. Physical examination revealed a palpable abdominal mass in 6 patients. Three patients had no evidence of pulmonary tuberculosis(TB). All IPTAs(11 abscesses) were seen as a multiseptated, peripherally enhanced, hypodense mass with enlarged, rim-enhanced lymph nodes. The largest abscess diameter ranged from 4.5 cm to 12.2 cm. CT showed 2 types of IPTA: Lymph node fusion and encapsulation. Of the 8 patients, one had liver tuberculosis and one had splenic and ovarian tuberculosis. Two cases showed involvement of the terminal ileum and ileocecal junction. Ascites were found in 4 cases. Three patients had peritonitis and mesenteritis. Three patients showed involvement of the omentum. Three patients had histological evidence of caseating granuloma, and 5 had histological evidence of acid-fast bacilli. CONCLUSION: CT is crucial in the detection and characterization of IPTA. Certain CT findings are necessary for correct diagnosis.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a chronic and serious microvascular complication of diabetes linked to redox imbalance.Sestrin2,a novel inducible stress protein,participates in glucose metabolic regul...BACKGROUND Diabetic peripheral neuropathy(DPN)is a chronic and serious microvascular complication of diabetes linked to redox imbalance.Sestrin2,a novel inducible stress protein,participates in glucose metabolic regulation and redox homeostasis.However,the association between serum Sestrin2 and DPN is unknown.AIM To explore the association between serum Sestrin2 and DPN in patients with type 2 diabetes mellitus(T2DM).METHODS A total of 96 T2DM patients and 39 healthy volunteers,matched by age and sex,participated in this cross-sectional study.Clinical features and metabolic indices were identified.Serum Sestrin2 was measured by ELISA.The association between Sestrin2 and DPN was studied.Correlation and logistic regression analyses were used to evaluate the associations of different metabolic indices with Sestrin2 and DPN.RESULTS The 96 patients with T2DM were divided into DPN(n=47)and patients without DPN(n=49).Serum Sestrin2 was significantly lower in healthy volunteers than in all T2DM patients combined[9.10(5.41-13.53)ng/mL vs 12.75(7.44-23.80)ng/mL,P<0.01].T2DM patients without DPN also had significantly higher levels of Sestrin2 than healthy volunteers[14.58(7.93-26.62)ng/mL vs 9.10(5.41-13.53)ng/mL,P<0.01].However,T2DM patients with DPN had lower circulating Sestrin2 levels compared to T2DM patients without DPN[9.86(6.72-21.71)ng/mL vs 14.58(7.93-26.62)ng/mL,respectively,P<0.01].Bivariate correlation analysis revealed that serum Sestrin2 was positively correlated with body mass index(r=0.672,P=0.000),hemoglobin A1c(HbA1c)(r=0.292,P=0.000),serum creatinine(r=0.206,P=0.016),triglycerides(r=0.731,P=0.000),and fasting glucose(r=0.202,P=0.040),and negatively associated with estimated glomerular filtration rate(r=-0.230,P=0.007).After adjustment for sex,age,HbA1c,and diabetes duration,multiple regression analysis revealed that Sestrin2 was independently correlated with body mass index and triglyceride levels(P=0.000).Logistic regression analyses indicated that Sestrin2,diabetes duration,and high-density lipoprotein were strongly associated with DPN(odds ratio=0.855,1.411,and 0.041,respectively).CONCLUSION Our results show Sestrin2 is decreased in T2DM patients with DNP.As lower Sestrin2 is independently associated with DPN,Sestrin2 may contribute to progression of DPN in T2DM patients.展开更多
Importance.The last decade has witnessed the advances of cognitive computing technologies that learn at scale and reason with purpose in medicine studies.From the diagnosis of diseases till the generation of treatment...Importance.The last decade has witnessed the advances of cognitive computing technologies that learn at scale and reason with purpose in medicine studies.From the diagnosis of diseases till the generation of treatment plans,cognitive computing encompasses both data-driven and knowledge-driven machine intelligence to assist health care roles in clinical decision-making.This review provides a comprehensive perspective from both research and industrial efforts on cognitive computing-based CDSS over the last decade.Highlights.(1)A holistic review of both research papers and industrial practice about cognitive computing-based CDSS is conducted to identify the necessity and the characteristics as well as the general framework of constructing the system.(2)Several of the typical applications of cognitive computing-based CDSS as well as the existing systems in real medical practice are introduced in detail under the general framework.(3)The limitations of the current cognitive computing-based CDSS is discussed that sheds light on the future work in this direction.Conclusion.Different from medical content providers,cognitive computing-based CDSS provides probabilistic clinical decision support by automatically learning and inferencing from medical big data.The characteristics of managing multimodal data and computerizing medical knowledge distinguish cognitive computing-based CDSS from other categories.Given the current status of primary health care like high diagnostic error rate and shortage of medical resources,it is time to introduce cognitive computing-based CDSS to the medical community which is supposed to be more open-minded and embrace the convenience and low cost but high efficiency brought by cognitive computing-based CDSS.展开更多
基金Supported by National Natural Science Foundation of China,No.81870593 and No.82170865Quality Improvement of Postgraduate Education in Shandong Province,No.SDYAL19156.
文摘BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achieve glucose control.CASE SUMMARY We describe a patient with MODY3 involving a novel splicing mutation,in whom low-dose gliclazide was sufficient to control clinically significant hyperglycemia.Sanger sequencing identified a splicing HNF1A mutation in 12q24 NM_000545.5 Intron5 c.1108-1G>A.Glycemic control has been maintained without insulin therapy for 28 mo after the diagnosis of diabetes.CONCLUSION This case report highlights a novel HNF1A gene mutation in MODY3 that is responsive to sulfonylurea therapy.
基金Supported by the Doctoral Startup Fund of Affiliated Hospital of Weifang Medical University,No.2021BKQ01.
文摘BACKGROUND Tofacitinib is an oral Janus kinase(JAK)inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis(RA).Varicella zoster virus reactivation leading to herpes zoster(HZ)is an adverse effect of this drug;however,recurrent HZ at the same site is a rare clinical condition.CASE SUMMARY A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment(10 mg daily).About 1 mo after initiation of oral tofacitinib,she developed blisters on the left flank and abdomen and was diagnosed with HZ;antiviral therapy with acyclovir was resolutory.However,5 d prior to presentation at our hospital,erythema and blisters with severe pain recurred at the same site.Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum,with a pain score of 8(visual analogue scale).Antiviral,nutritional supplement,analgesic and other treatments led to healing but over an atypically long period(approximately 26 d,vs approximately 1 wk).HZ is a common and serious adverse reaction of JAK inhibitors,but it rarely recurs.Our patient’s experience of HZ recurrence at the same site,with a wider affected area,more severe pain and longer healing period,is inconsistent with previous reports.CONCLUSION Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment,with more severe clinical manifestations than in the initial occurrence.
基金Supported by the National Natural Science Foundation of China,No.81870593Natural Science Foundation of Shandong Province of China,No.ZR2020MH106and Medical Health Science and Technology Project of Shandong Province,No.202003060400.
文摘The presence of excess glucose in blood is regarded as a sweet hurt for patients with diabetes.Human serum albumin(HSA)is the most abundant protein in human plasma,which undergoes severe non-enzymatic glycation with glucose in patients with diabetes;this modifies the structure and function of HSA.Furthermore,the advanced glycation end products produced by glycated HSA can cause pathological damage to the human body through various signaling pathways,eventually leading to complications of diabetes.Many potential glycation sites on HSA have different degrees of sensitivity to glucose concentration.This review provides a comprehensive assessment of the in vivo glycation sites of HSA;it also discusses the effects of glycation on the structure and function of HSA.Moreover,it addresses the relationship between HSA glycation and diabetes complications.Finally,it focuses on the value of non-enzymatic glycation of HSA in diabetes-related clinical applications.
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
文摘The aim of this study was to explore the neuroprotective effect and mechanism of DHA on cerebral ischemia injury and blood-brain barrier(BBB)disruption.the focal cerebral I/R model was established by middle cerebral artery oclusion(MCAO).BBB permeability was assessed with the leaking amount of Evans Blue and the expression of occludin and ZO-1.The expression of pyrin domain containing(NLRP3)was checked to explore the inhibition of inflammation by DHA.The results showed that DHA could significantly reduce cortical and sub-cortical infarct volumes,neurologic de ficit scores,cerebral edema,BBB permeability after I/R injury.Leaking amount of Evans Blue was reduced by DHA,and occludin and ZO-1 were up-regulated by DHA.The expression of NLRP3 was inhibited after exposure of DHA.Our results indicated that DHA could effectively penetrate the brain of MCAO rats,aleviated the I/R injury by inhibiting NLRP3 inflammasomes and improve BBB disruption,showing a great clinical potential for stroke.
文摘Dopamine replacement therapy is the most effective treatment to reduce motor symptoms in Parkinson's disease(PD).However,chronic L-Dopa treatment results in abnormal involuntary movements along with the prolongation of course of the disease and therapeutic time.Recent studies have shown that lithium has the potential for the treatment of neurodegenerative disorders.We tested whether lithium Chloride(LiCl)can reduce the progression of MPTP-induced damage by measuring weight and behavioral tests,further explored whether this is related to the PI3K/Akt signaling pathway using immunohistochemistry and WB.Our results showed that lithium chloride significantly improved motor function and increased body weight and the expression of PI3K,p-Akt Ser473,and p-caspase 3 were significantly increased,Bax/Bcl-2 ratio and the level of p-caspase 3 were decreased.
文摘Stroke is one of the leading causes of global morbidity and mortality.However,the underlying mechanisms is yet to be fully understood,therefore this will be great challenges to finding appropriate protection.This review is to explore the neuroprotective effects and involved the molecular mechanisms of Chinese medicinal ingredients on the cerebral ischemia in rats.
基金Supported by Project of Medicine and Health Development Plan of Shandong Province,No.2011HZ112,ChinaShan-dong Provincial Natural Science Foundation of China,No.ZR2014HL083
文摘AIM: To evaluate the computed tomography(CT) features of intraperitoneal tuberculous abscess(IPTA). METHODS: Eight patients with IPTA confirmed by pathology were analyzed retrospectively. The clinical symptoms, medical images, and surgical findings were evaluated. Involvement of the intestine, peritoneum, viscera, and lymph nodes was also assessed. RESULTS: All 8 patients had a history of abdominal discomfort for 1 to 6 mo. Physical examination revealed a palpable abdominal mass in 6 patients. Three patients had no evidence of pulmonary tuberculosis(TB). All IPTAs(11 abscesses) were seen as a multiseptated, peripherally enhanced, hypodense mass with enlarged, rim-enhanced lymph nodes. The largest abscess diameter ranged from 4.5 cm to 12.2 cm. CT showed 2 types of IPTA: Lymph node fusion and encapsulation. Of the 8 patients, one had liver tuberculosis and one had splenic and ovarian tuberculosis. Two cases showed involvement of the terminal ileum and ileocecal junction. Ascites were found in 4 cases. Three patients had peritonitis and mesenteritis. Three patients showed involvement of the omentum. Three patients had histological evidence of caseating granuloma, and 5 had histological evidence of acid-fast bacilli. CONCLUSION: CT is crucial in the detection and characterization of IPTA. Certain CT findings are necessary for correct diagnosis.
基金National Natural Science Foundation of China,No.81870593Natural Science Foundation of Shandong Province of China,No.ZR2020MH106+1 种基金Medical Health Science and Technology Project of Shandong Province,No.202003060396 and No.202003060400Quality Improvement of Postgraduate Education in Shandong Province,No.SDYAL19156.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a chronic and serious microvascular complication of diabetes linked to redox imbalance.Sestrin2,a novel inducible stress protein,participates in glucose metabolic regulation and redox homeostasis.However,the association between serum Sestrin2 and DPN is unknown.AIM To explore the association between serum Sestrin2 and DPN in patients with type 2 diabetes mellitus(T2DM).METHODS A total of 96 T2DM patients and 39 healthy volunteers,matched by age and sex,participated in this cross-sectional study.Clinical features and metabolic indices were identified.Serum Sestrin2 was measured by ELISA.The association between Sestrin2 and DPN was studied.Correlation and logistic regression analyses were used to evaluate the associations of different metabolic indices with Sestrin2 and DPN.RESULTS The 96 patients with T2DM were divided into DPN(n=47)and patients without DPN(n=49).Serum Sestrin2 was significantly lower in healthy volunteers than in all T2DM patients combined[9.10(5.41-13.53)ng/mL vs 12.75(7.44-23.80)ng/mL,P<0.01].T2DM patients without DPN also had significantly higher levels of Sestrin2 than healthy volunteers[14.58(7.93-26.62)ng/mL vs 9.10(5.41-13.53)ng/mL,P<0.01].However,T2DM patients with DPN had lower circulating Sestrin2 levels compared to T2DM patients without DPN[9.86(6.72-21.71)ng/mL vs 14.58(7.93-26.62)ng/mL,respectively,P<0.01].Bivariate correlation analysis revealed that serum Sestrin2 was positively correlated with body mass index(r=0.672,P=0.000),hemoglobin A1c(HbA1c)(r=0.292,P=0.000),serum creatinine(r=0.206,P=0.016),triglycerides(r=0.731,P=0.000),and fasting glucose(r=0.202,P=0.040),and negatively associated with estimated glomerular filtration rate(r=-0.230,P=0.007).After adjustment for sex,age,HbA1c,and diabetes duration,multiple regression analysis revealed that Sestrin2 was independently correlated with body mass index and triglyceride levels(P=0.000).Logistic regression analyses indicated that Sestrin2,diabetes duration,and high-density lipoprotein were strongly associated with DPN(odds ratio=0.855,1.411,and 0.041,respectively).CONCLUSION Our results show Sestrin2 is decreased in T2DM patients with DNP.As lower Sestrin2 is independently associated with DPN,Sestrin2 may contribute to progression of DPN in T2DM patients.
基金Our work is supported by the National Key Research and Development Program of China under No.2020AAA0109400.
文摘Importance.The last decade has witnessed the advances of cognitive computing technologies that learn at scale and reason with purpose in medicine studies.From the diagnosis of diseases till the generation of treatment plans,cognitive computing encompasses both data-driven and knowledge-driven machine intelligence to assist health care roles in clinical decision-making.This review provides a comprehensive perspective from both research and industrial efforts on cognitive computing-based CDSS over the last decade.Highlights.(1)A holistic review of both research papers and industrial practice about cognitive computing-based CDSS is conducted to identify the necessity and the characteristics as well as the general framework of constructing the system.(2)Several of the typical applications of cognitive computing-based CDSS as well as the existing systems in real medical practice are introduced in detail under the general framework.(3)The limitations of the current cognitive computing-based CDSS is discussed that sheds light on the future work in this direction.Conclusion.Different from medical content providers,cognitive computing-based CDSS provides probabilistic clinical decision support by automatically learning and inferencing from medical big data.The characteristics of managing multimodal data and computerizing medical knowledge distinguish cognitive computing-based CDSS from other categories.Given the current status of primary health care like high diagnostic error rate and shortage of medical resources,it is time to introduce cognitive computing-based CDSS to the medical community which is supposed to be more open-minded and embrace the convenience and low cost but high efficiency brought by cognitive computing-based CDSS.