Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we id...Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.展开更多
Introduction: The lack of follow-up and adequate management of chronic kidney disease-mineral and bone disorder (CKD-MBD) in chronic hemodialysis patients is associated with pathological fractures. Few studies are ava...Introduction: The lack of follow-up and adequate management of chronic kidney disease-mineral and bone disorder (CKD-MBD) in chronic hemodialysis patients is associated with pathological fractures. Few studies are available on the subject in sub-Saharan Africa. The objective of this work was to evaluate the prevalence of pathological fractures in our chronic hemodialysis patients, to analyze their clinical aspects and to determine the factors associated with their occurrence. Patients and Methods: We conducted a retrospective, descriptive and analytical study over 9 years (January 1, 2011, to December 31, 2020) based on the medical records of chronic hemodialysis patients at the CHU Aristide Le Dantec. The diagnosis of pathological fracture was retained in front of any fracture occurring spontaneously or following minimal trauma and confirmed by X-ray. Results: Nineteen cases of pathological fractures were collected with a hospital prevalence of 19.39%. The mean age was 53.32 ± 13.94 years with a sex ratio of 0.36. The average seniority in dialysis was 84.16 ± 29.88 months. Among these patients, one had had 3 episodes of fractures and another 6 episodes. The circumstances of occurrence of the fractures were the fall in 63% of the cases, spontaneously in 37% of the cases. The predominant site of fractures was the femoral neck (47.38% cases). Female gender (p 5 years (p = 0.049), gait disturbances prior to the fracture (p = 0.001), positive CRP (p = 0.028) and the presence of vascular calcifications (p = 0.002) were significantly associated with the occurrence of pathological fractures. Conclusion: This study has identified the factors associated with the occurrence of pathological invoices in hemodialysis patients in our context. These fractures are often associated with the lack of regular biological follow-up due to the low socioeconomic level of our patients.展开更多
The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancr...The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancreatitis were retrospectively studied. All patients were of Chinese nationality and hospitalized from January 2008 to December 2011. Their ages ranged from 14 to 76 years, with a mean of 43 years. Of 142 patients, there were 72 cases of obstructive chronic pancreatitis（50.70%）, 19 cases of alcoholic chronic pancreatitis（13.38%）, 14 cases of autoimmune pancreatitis（9.86%） and 37 cases of undetermined etiology（26.06%）. Pathologically, the average inflammatory mass diameter was 3.8±3.3 cm, biliary obstruction occurred in 36 cases, gall stones in 70 cases, calcification in 88 cases, ductal dilatation in 61 cases, side branch dilatation in 32 cases, ductal irregularity in 10 cases, lymphocytic inflammation in 23 cases, obliterative phlebitis in 14 cases, extra pancreatic lesion in 19 cases and fibrosis in 142 cases. Location of pancreatic lesion in the region of head（n=97）, neck（n=16）, body（n=12）, tail（n=15） and whole pancreas（n=2） influenced the choice of surgical procedures. Ninety-four patients（66.20%） received surgical treatment and 33.80% received other treatments. After operation, 80.85% of 94 patients experienced decreased pain, and 8.51% of 94 showed recovery of endocrine function but with a complication rate of 12.77%. All the operations were performed successfully. According to the pain scale of European Organization for Research and Treatment of Cancer（QLQ-C30） a decrease from 76±22 to 14±18 was observed. Etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population vary from others.展开更多
BACKGROUND Amyloidosis is a rare disorder that can be classified into various types,and the most common type is the systemic light chain type.The prognosis of this disease is extremely poor.In general,amyloidosis main...BACKGROUND Amyloidosis is a rare disorder that can be classified into various types,and the most common type is the systemic light chain type.The prognosis of this disease is extremely poor.In general,amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells.Cases in which the liver is the primary organ affected by amyloidosis,as in this report,are less common in clinical practice.CASE SUMMARY A 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes.His condition persisted,and he developed chronic liver failure,with severe cholestasis in the later stage that was gradually accompanied by renal injury.Ultimately,he was diagnosed with hepatic amyloidosis through liver biopsy and pathological examination.CONCLUSION Hepatic amyloidosis rarely occurs in the clinic,and liver biopsy and pathological examination can assist in the accurate and effective diagnosis of this condition.展开更多
BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the in...BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.展开更多
A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and...A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.展开更多
基金National Natural Science Foundation of China(81870850)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_0322)。
文摘Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.
文摘Introduction: The lack of follow-up and adequate management of chronic kidney disease-mineral and bone disorder (CKD-MBD) in chronic hemodialysis patients is associated with pathological fractures. Few studies are available on the subject in sub-Saharan Africa. The objective of this work was to evaluate the prevalence of pathological fractures in our chronic hemodialysis patients, to analyze their clinical aspects and to determine the factors associated with their occurrence. Patients and Methods: We conducted a retrospective, descriptive and analytical study over 9 years (January 1, 2011, to December 31, 2020) based on the medical records of chronic hemodialysis patients at the CHU Aristide Le Dantec. The diagnosis of pathological fracture was retained in front of any fracture occurring spontaneously or following minimal trauma and confirmed by X-ray. Results: Nineteen cases of pathological fractures were collected with a hospital prevalence of 19.39%. The mean age was 53.32 ± 13.94 years with a sex ratio of 0.36. The average seniority in dialysis was 84.16 ± 29.88 months. Among these patients, one had had 3 episodes of fractures and another 6 episodes. The circumstances of occurrence of the fractures were the fall in 63% of the cases, spontaneously in 37% of the cases. The predominant site of fractures was the femoral neck (47.38% cases). Female gender (p 5 years (p = 0.049), gait disturbances prior to the fracture (p = 0.001), positive CRP (p = 0.028) and the presence of vascular calcifications (p = 0.002) were significantly associated with the occurrence of pathological fractures. Conclusion: This study has identified the factors associated with the occurrence of pathological invoices in hemodialysis patients in our context. These fractures are often associated with the lack of regular biological follow-up due to the low socioeconomic level of our patients.
文摘The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancreatitis were retrospectively studied. All patients were of Chinese nationality and hospitalized from January 2008 to December 2011. Their ages ranged from 14 to 76 years, with a mean of 43 years. Of 142 patients, there were 72 cases of obstructive chronic pancreatitis（50.70%）, 19 cases of alcoholic chronic pancreatitis（13.38%）, 14 cases of autoimmune pancreatitis（9.86%） and 37 cases of undetermined etiology（26.06%）. Pathologically, the average inflammatory mass diameter was 3.8±3.3 cm, biliary obstruction occurred in 36 cases, gall stones in 70 cases, calcification in 88 cases, ductal dilatation in 61 cases, side branch dilatation in 32 cases, ductal irregularity in 10 cases, lymphocytic inflammation in 23 cases, obliterative phlebitis in 14 cases, extra pancreatic lesion in 19 cases and fibrosis in 142 cases. Location of pancreatic lesion in the region of head（n=97）, neck（n=16）, body（n=12）, tail（n=15） and whole pancreas（n=2） influenced the choice of surgical procedures. Ninety-four patients（66.20%） received surgical treatment and 33.80% received other treatments. After operation, 80.85% of 94 patients experienced decreased pain, and 8.51% of 94 showed recovery of endocrine function but with a complication rate of 12.77%. All the operations were performed successfully. According to the pain scale of European Organization for Research and Treatment of Cancer（QLQ-C30） a decrease from 76±22 to 14±18 was observed. Etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population vary from others.
基金Natural Science Foundation of Hubei Province,China,No.2022CFB120.
文摘BACKGROUND Amyloidosis is a rare disorder that can be classified into various types,and the most common type is the systemic light chain type.The prognosis of this disease is extremely poor.In general,amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells.Cases in which the liver is the primary organ affected by amyloidosis,as in this report,are less common in clinical practice.CASE SUMMARY A 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes.His condition persisted,and he developed chronic liver failure,with severe cholestasis in the later stage that was gradually accompanied by renal injury.Ultimately,he was diagnosed with hepatic amyloidosis through liver biopsy and pathological examination.CONCLUSION Hepatic amyloidosis rarely occurs in the clinic,and liver biopsy and pathological examination can assist in the accurate and effective diagnosis of this condition.
基金Supported by Construction of Key Medical Disciplines in Shenzhen,No.SZXK076.
文摘BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.
基金Supported by the Postgraduate Innovative Scientific Research Foundation Program of Helongjiang Province (YJSCX2012-026HLJ)
文摘A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.
