Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism

Alzheimer’s disease（AD）is a neurodegenerative disorder which is remarkably characterized by pathological hallmarks that include neurofibrillary tangles,neuronal loss extracellular senile plaques containing aggregated amyloid beta（Aβ）,and neurofibrillary tangles composed of the hyperphosphorylated form of the microtubule protein tau.It is the most common form of dementia which is characterized by severe neurodegenerative changes such as loss of neurons and synapses in brain（Kamat et al.,2014）.

Transition from minimal change disease to focal segmental glomerulosclerosis related to occupational exposure:A case report

BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a patient transitioning from MCD to FSGS,review the literature,and explore the relationship between the two diseases.CASE SUMMARY A 42-year-old male welder,presenting with lower extremity edema and elevated serum creatinine,was diagnosed with NS and end-stage kidney disease(ESKD)based on laboratory test results.The patient had undergone a kidney biopsy for NS 20 years previously,which indicated MCD,and a second recent kidney biopsy suggested FSGS.The patient was an electric welder with excessive levels of cadmium and lead in his blood.Consequently,we suspect that his aggravated pathology and occurrence of ESKD were related to metal nephrotoxicity.The patient eventually received kidney replacement therapy and quit his job which involved long-term exposure to metals.During the 1-year follow-up period,the patient was negative for metal elements in the blood and urine and recovered partial kidney function.CONCLUSION MCD and FSGS may be different stages of the same disease.The transition from MCD to FSGS in this case indicates disease progression,which may be related to excessive metal contaminants caused by the patient’s occupation.

Minimal change disease caused by polycythemia vera: A case report

BACKGROUND Polycythemia vera(PV),often attributed to the JAK2 V617F mutation,is characterized by enhanced red blood cell counts in the peripheral blood.PV-associated renal disease is clinically rare;to date,there have been reports of other chronic kidney diseases related to PV,but no reports on PV-associated minimal change disease.CASE SUMMARY A 37-year-old man presented with proteinuria and high red blood cell count on January 4,2021.The patient underwent bone marrow and renal biopsies,then was subsequently diagnosed with PV and minimal change in disease.Hydroxyurea was administered and proteinuria remission was achieved.The patient’s last visit was on April 14,2022.CONCLUSION We inferred that there may be a causal relationship between PV and minimal change disease.

Multifractal analysis of white matter structural changes on 3D magnetic resonance imaging between normal aging and early Alzheimer's disease

Applications of multifractal analysis to white matter structure changes on magnetic resonance imaging（MRI） have recently received increasing attentions. Although some progresses have been made, there is no evident study on applying multifractal analysis to evaluate the white matter structural changes on MRI for Alzheimer＇s disease（AD） research. In this paper, to explore multifractal analysis of white matter structural changes on 3D MRI volumes between normal aging and early AD, we not only extend the traditional box-counting multifractal analysis（BCMA） into the 3D case, but also propose a modified integer ratio based BCMA（IRBCMA） algorithm to compensate for the rigid division rule in BCMA. We verify multifractal characteristics in 3D white matter MRI volumes. In addition to the previously well studied multifractal feature,△α, we also demonstrated △ f as an alternative and effective multifractal feature to distinguish NC from AD subjects.Both △α and △ f are found to have strong positive correlation with the clinical MMSE scores with statistical significance.Moreover, the proposed IRBCMA can be an alternative and more accurate algorithm for 3D volume analysis. Our findings highlight the potential usefulness of multifractal analysis, which may contribute to clarify some aspects of the etiology of AD through detection of structural changes in white matter.

Abnormal skeletal metabolism and its changes after decopper therapy in patients with Wilson disease

BACKGROUND: Researches indicate that patients with Wilson disease (WD) have abnormal skeletal metabolism, which is induced by various factors. OBJECTIVE: To probe into the changing characteristics of abnormal skeletal metabolism in WD patients and observe the effect of decopper therapy. DESIGN: Case-contrast and self-control study. SETTING: Department of Neurology, Affiliated Hospital of Neurological Institute, Anhui College of Traditional Chinese Medicine. PARTICIPANTS: A total of 35 patients with WD including 21 males and 14 females aged from 10 to 42 years with the mean age of (20±8) years were selected from Department of Neurology, Affiliated Hospital of Neurological Institute, Anhui College of Traditional Chinese Medicine from September 2000 to February 2001. All the patients were in compliance with the diagnostic criteria: history of family heredity; cone symptoms in vitro, physical sign or liver symptoms; positive Kayser-Fleischer ring; serum copper protein < 200 mg/L or A copper oxidase < 0.2; urine copper > 1.6 μmol/24 hours; liver copper > 250 μg/g (dry weight). The control group was selected from 25 cases of health individuals including 13 males and 12 females aged from 16 to 35 years with the mean age of (22±6) years. All patients who participated in the study were informed first and consented. METHODS: Patients in treatment group were treated with venous injection of 1.0 g sodium dimercaptosulfonate, once a day for totally 6 successive days. And then, patients rested for 2 days. This procedure mentioned above was regarded as a course, and the treatment lasted for 4-8 courses. Before and after injection of sodium dimercaptosulfonate, serum calcitonin (CT), osteocalcin (BGP), parathyroid hormone (PTH) and 1,25-(OH)2VitD3 were measured with radio-immunity method; blood, urine calcium, phosphorum and urine creatinine were measured with biochemical analyzer; urine dihydropyrimidine dehydrogenase(DPD) was detected with enzyme-immunity method; bone mineral density (BMD) was checked at the one third from distal end of ulna and radius with single photon absorptiometry (SPA). MAIN OUTCOME MEASURES: Relative indexes of bone metabolism of blood and urine and results of BMD in both two groups before and after treatment. RESULTS: Among 35 patients with WD and 25 healthy subjects, 5 patients were excluded because of uncompleted decopper therapy; therefore, 30 patients with WD and 25 healthy subjects were involved in the final analysis. ① Comparisons between the two groups: Contents of serum calcium, PTH and 1,25-(OH)2VitD3 were lower in treatment group than those in control group [(2.49±0.34) mmol/L vs. (2.69±0.19) mmol/L; (218.7±50.5) ng/L vs. (262.5±88.9) ng/L; (23.53±14.21) ng/L vs. (42.78±14.44) ng/L; P < 0.05-0.01]; however, contents of serum BGP and CT were higher in treatment group than those in control group [(10.22±6.11) μg/L vs. (5.78±4.22) μg/L; (282.8±109.6) ng/L vs. (62.5±37.9) ng/L, P < 0.01]; moreover, there was no significant difference of contents of serum phosphorum, urine calcium, phosphorum and DPD/creatinine between treatment group and control group (P > 0.05). BMD of males and females was lower in treatment group than that in control group [(0.617±0.197) g/cm2 vs. (0.718±0.274) g/cm2; (0.594±0.124) g/cm2 vs. (0.677±0.157) g/cm2, P < 0.05]. ② Comparisons in treatment group before and after treatment: Contents of CT and urine calcium were lower after treatment than those before treatment [(95.3±55.4) ng/L vs. (283.3±96.7) ng/L; (2.38±1.68) mmol/L vs. (3.31±2.30) mmol/L; P < 0.01, 0.05]; however, contents of 1,25-(OH)2VitD3 and DPD/creatinine were higher after treatment than those before treatment [(33.61±19.30) ng/L vs. (24.21±14.47) ng/L; (42.95±19.92) nmol/mmol vs. (19.51±9.96) nmol/mmol, P < 0.05]; moreover, there were no significant differences among other indexes before and after treatment (P > 0.05). Furthermore, there was no significant difference of BMD before and after treatment (P > 0.05). CONCLUSION: WD patients have changes in the related indexes of abnormal skeletal metabolism. In addition, contents of CT and urine calcium are decreased remarkably after decopper therapy; however, value of BMD is not changed obviously.

Change and significance of fibrinolysis in coronary heart disease patients with angina pactoris

Objectives To study change and the clinical significance of fibrinolysis in coronary heart disease(CHD) patients with angina pactoris(AP).Methods Levels of plas-min plasminogen activator inhibitor-1(PAI-1),tissue-type plasminogen activator(t-PA),fibrinogen(FIB) in 110 CHD patients with AP and 20 normal cases as control group were analyzed in the same ways.Results Levels of PAI-1,FIB in CHD patients with AP were significantly higher than those in control cases,and those of t-PA were significantly lower than control cases;Levels of PAI-1,FIB in UA patients with UA heart events were significantly higher than those in patients with SA,and those of t-PA were significantly lower than patients with SA;Levels of PAI-1,FIB in patients with AP events were significantly higher than those in patients without AP events,and those of t-PA were significantly lower than patients without AP events.Conclusions There was abnormal of fibrinolysis function in CHD patients with AP, specially in patients with UA or with AP events,the abnormal of fibrinolysis might be play an important rule in coronary heart disease(CHD) patients with angina pactoris.

Changing Grains for the Prevention and Treatment of Kashin-Beck Disease in Children: a Meta-analysis

To evaluate the efficacy of changing grains on the prevention and treatment of Kashin-Beck Disease （KBD） in children, community-based trials were acquired from seven electronic databases （up to July 2014）. As a result, the methodological quality of the six trials that have been included into our analysis was low. The pooled ORs favoring the prevention and treatment effects of changing grains were 0.15 （95% CI： 0.03-0.70） and 2.13 （95% CI： 1.44-3.16） respectively by meta-analysis. Subgroup analysis demonstrated the pooled OR favoring treatment effect of exchanging grains rather than drying grains both compared with endemic grains. The results showed that changing grains had obvious effects on the prevention and treatment of KBD in children. However, the evidences were limited by the potential biases and confounders. Large and well-designed trials are still needed.

Reversible Chronic Interstitial Nephritis Induced by Tacrolimus —Tacrolimus Chronic Interstitial Nephritis

Calcineurin inhibitors (CNI) are potent immunosuppressive agents in prophylaxis against graft rejection and autoimmune diseases including primary glomerulopathies. Previous research showed reversible;acute afferent arteriolar vasculopathy and irreversible chronic interstitial fibrosis associated with CNI nephrotoxicity. In this case report we describe a patient, with minimal change disease, that had developed chronic and progressive renal disease while receiving therapeutic dose of Tacrolimus. His serum creatinine had reached 537 umol/L and his nephrotic state worsened. Kidney biopsy showed chronic interstitial nephritis. Tacrolimus was discontinued and he was treated with 1 mg/kg prednisone in addition to Mycophenolate mofetil (MMF) 1 g twice daily. By the 2nd month;serum creatinine returned to normal and by the 3rd month serum albumin too. After 1 month of therapy;the dose of Prednisone was tapered down gradually till 5 mg daily by the end of 3rd month. Moreover, the dose of MMF was reduced to 500 mg X2 by the end of 3rd month. After 2 years of follow up;he remained stable and without relapse of NS or renal failure. In conclusion, reversible renal disease, due to chronic interstitial nephritis can be induced by CNI which is amenable to treatment with Prednisone and MMF.

Children with Steroid-resistant Nephrotic Syndrome:Long-term Outcomes of Sequential Steroid Therapy

Objective This study aimed to investigate the long-term outcomes in children with steroid-resistant nephrotic syndrome （SRNS）, who received methylprednisolone pulse therapy （MPT）-based sequential steroid therapy. In particular, we aimed to observe whether these patients had a high risk of adverse events. Methods We conducted a retrospective study over a 5-year period. The long-term outcomes for children with SRNS receiving sequential therapy were observed. Results Sixty-three children were diagnosed with SRNS and underwent MPT-based sequential steroid therapy. Thirty-five （55.6%） achieved complete or partial remission, 19 （30.2%） of whom were in remission even after treatment cessation at last review. The mean time to initial remission after MPT was 24.3±13.1 days. Forty-nine children （77.8%） experienced relapses, of whom 31 （49.2%） demonstrated a frequent relapsing course. Adverse effects relevant to MPT were generally mild and infrequent. Five patients （7.9%） complained of vomiting or nausea during MPT infusion; 25 （39.7%） experienced excessive weight gain and developed an obvious Cushingoid appearance; and 26 （41.3%） had poor growth associated with long-term steroid use. Twenty-eight patients （44.4%） failed to respond to MPT, of whom 21 （33.3%） achieved complete or partial remission with immunosuppressive agents. Conclusion MPT-based sequential steroid therapy appears to be a safe and effective method for inducing rapid remission in childhood SRNS. Further clinical studies are needed to comprehensively evaluate this therapy.

Clinical features of acute kidney injury in patients with nephrotic syndrome and minimal change disease:a retrospective,cross-sectional study

Background:Minimal change nephropathy(MCD)is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury(AKI).This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome.Methods:Patients from Chinese People’s Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1,2013 to December 31,2017.Patients diagnosed with membranous nephropathy(MN)by renal biopsy from January 1,2013 to December 31,2017 are included as a control population.We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups.We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis.Results:A total of 367 patients with MCD were included in the analysis,with a sex ratio of 1.46:1(male:female)and an age range of 6 to 77 years.Among all the patients,109 developed AKI(29.7%),and of these patients,85 were male(78.0%).In the 586 patients with MN,27(4.6%)patients developed AKI.The percentage of AKI in MCD patients was significantly higher than that in MN patients(χ^(2)=41.063,P<0.001).The percentage of AKI increased with age in the MCD patients.The percentage of AKI in patients aged 50 years or older was 52.9%(46/87),which was significantly higher than that[22.5%(63/280)]in patients under 50 years(χ^(2)=6.347,P=0.013).We observed statistically significant differences in age(43[27,59]years vs.28[20,44]years,Z=5.487,P<0.001),male(78.0%vs.51.4%,χ^(2)=22.470,P<0.001),serum albumin(19.9±6.1 g/L vs.21.5±5.7 g/L,t=2.376,P=0.018),serum creatinine(129.5[105.7,171.1]μmol/L vs.69.7[57.7,81.9]μmol/L,Z=14.190,P<0.001),serum urea(10.1[6.2,15.8]mmol/L vs.4.7[3.6,6.4]mmol/L,Z=10.545,P<0.001),IgE(266.0[86.7,963.0]IU/ml vs.142.0[35.3,516.5]IU/ml,Z=2.742,P=0.007),history of diabetes(6.4%vs.1.2%,P=0.009),and history of hypertension(23.9%vs.5.1%,χ^(2)=28.238,P<0.001)between the AKI group and the non-AKI group.According to multivariate linear regression analysis,among the renal pathological features analyzed,renal tubular epithelial cell damage(β=178.010,95%CI:147.888-208.132,P<0.001)and renal interstitial edema(β=28.833,95%CI:11.966-45.700,P=0.001)correlated with serum creatinine values.Conclusions:The percentage of AKI in MCD patients is significantly higher than that in MN patients.Patients over 50 years old are more likely to develop AKI.Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.

Idiopathic Adult Nephrotic Syndrome: A Clinicopathological Study and Response to Steroid in a Sub-Saharan African Country

Introduction: Idiopathic nephrotic syndrome represents 25% to 30% of glomerulonephritis in adults. These glomerulonephritides are responsible of about the half of chronic kidney failure examined as well in United States as in Europe or Africa. The aim of this study was to determine the anatomoclinic, therapeutic and progression patterns of idiopathic nephritic syndrome in Dakar. Patients and Methods: It is a retrospective ten-year study in the nephrology department of Aristide Le Dantec Hospital. Patients with idiopathic nephrotic syndrome were included. We analyzed anatomoclinic, therapeutic and progression data of idiopathic nephrotic syndrome. Results: On 202 patients with nephrotic syndrome, 156 (77%) were primitive. The mean age was 29.7 ± 12 years with a sex ratio of 2.4. Edema was found in 98 patients (62.8%) and hypertension in 63 patients (40%). The mean proteinuria was 6.8 ± 4.8 g/24h. Histologic lesions found at renal biopsy were focal segmental glomerulosclerosis in 71 patients (45.5%), minimal change disease in 68 patients (43.5%) and membranous nephropathy in 8 patients (5%). 134 patients (85.8%) received steroids alone, 12 patients (7.6%) received cyclophosphamide and 4 patients (2.5%) azathioprine in association with steroids. 44 patients (28.2%) reached remission. The factors of poor prognosis were: age, above 40 years, proteinuria above 10 g/24h, existence of renal failure at admission, absence of use of steroids therapy. Conclusion: This study shows that idiopathic nephrotic syndrome is frequent in our country with a prevalence of 77%. The most common lesion found at the renal biopsy is the focal segmental glomerulosclerosis. Remission is found only in 28% which is very low. 33% of patients progress towards chronic kidney disease due to the lack of early diagnosis and the use of traditional medicine.

The Beneficial Effect of Combination of Mycophenolate with Low-Dose Corticosteroids and Calcineurin-Inhibitor as Well as Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Blocker in Induction and Maintenance of Remission in Corticosteroid- and Rituximab-Resistant Minimal Change Nephrotic Syndrome in Adults

Management of steroid-resistant minimal change disease remains elusive with international guidelines suggesting high-dose corticosteroids and/or Calcineurin inhibitors for months similar to those with refractory idiopathic FSGS. Unfortunately, with such approach, the overall remission rates were 47% - 66%. Moreover, complete remission rates were 32% - 47% and partial remission ones were 19% - 29%. Those limited options of treatment and their poor outcomes led us to conduct the present study to assess the efficacy and safety of a new combined drug-therapy at induction and subsequent maintenance of such disease. The regimen consisted of an initial induction phase of 3-month Prednisone, Calcineurin-inhibitor, Mycophenolate and ACEI/ARB. The latter was followed by a maintenance phase of minimal dose Prednisone and nearly 1/2 the induction dose of Calcineurin inhibitors to decrease their long-term side effects. The results were satisfactory with 14 of the 22 patients, had complete remission. Moreover, 5 patients manifested partial remission and only 3 did not respond. Creatinine clearance was maintained in patients with complete remission yet, was mildly reduced in the partial and non-responsive ones. The safety and efficacy of such new combined drug-therapy provide new tool and future prospective in management of such relentless disease.

Study on the changes in pulmonary artery pressure in elderly Chronic kindney disease patients without end-stage renal disease

Objective To prospectively investigate the characteristics and correlative influential factors for the changes in pulmonary artery hypertension(PAH)in chronic kidney disease(CKD)patients without end-stage renal disease.Methods Complete clinical and laboratory data of133 outpatients without ESRD(CKD stage 2,3 and 4)