Objective To investigate the elinicopathoiogical features of Castleman disease with kidney injury. Methods Clinicopathological data of 10 Castleman disease patients with kidney injury from Peking University First Hospital and China-Japan Friendship Hospital were analyzed retrospectively. All the cases received biopsies of lymph node and kidney. Their renal tissues were examined by light microscopy, immunofluorescence and electron microscopy. Results Ten patients were all male with mean age (493:14) years. They presented edema and proteinuria, with mean urinary protein at (2.79±3.56) g/24 h, including one nephrotie syndrome (NS). Hematuria occurred in 8 cases, acute renal insufficiency in 6 cases, hypertension in 4 cases. Most of the patients had fever, fatigue, anorexia, weight loss, increased ESR and CRP, hypergammaglobulinaemia and decreased complements. Other abnormalities included anemia, thrombocytopenia, pleural effusion, hepatomegaly, splenomegaly, hypothyroidism, etc. Two cases demonstrated POEMS syndrome, one presented Sjogren syndrome. The enlargement of multiple cervical, axillary and inguinal lymph nodes were identified in all the patients. The pathological patterns of lymph node were plasma cell type in 4 cases, hyaline-vascular type in 3 cases, and mixed type in 3 cases. Pathological examination of renal biopsy showed thrombotic microangiopathy in 5 cases, crescentic glomerulonephritis in 2 cases, renal amyloidosis, minimal change disease and chronic tubular interstitial nephropathy in 1 case respectively. After immunosupressive reagents or COP therapy, lymph nodes became smaller, systemic symptoms were alleviated, proteinuira was decreased or disappeared, and renal function was recovered in most of patients. Conclusions Castleman disease with kidney injury manifests various symptoms with high prevalence of renal insufficiency and multiple systemic damage. Renal lesions present many patterns of pathological change with a higher frequency of thrombotic microangiopathy. It is necessary to examine the lymph nodes by ultrasound, radiology or biopsy for the patients of renal diseases with multiple systemic symptoms.

Objective To elucidate the clinical and pathological characteristics of patients with mercury poisoning-associated glomerulonephropathy. Methods Seven patients with mercury poisoning-associated glomerulonephropathy were enrolled in this study. The pattern of mercury exposure, feature of mercury toxicity, and clinicopathological presentation of the kidneys were investigated. Results They were all female, averaged (28.9 ±8.1) years old. Skin-whitening cream was the only cause of mercury poisoning. Proteinuria occurred 5 to 8 months after exposure. Serum mercury were 27.0 to 98.0 μg/L, and spot urinary mercury were 34.4 to 204.0 μg/L. The presentation of all the patients was mild to moderate edema with proteinuria and decreased serum albumin level. Five patients (5/7) were diagnosed as nephrotic syndrome. Six patients underwent renal biopsy: 3 cases with minimal change disease, 2 cases with membranous nephropathy and 1 case with focal segmental glomerular sclerosis. All the patients were administrated chelation therapy with sodium dimercaptopropanal sulfonate or sodium dimercaptosuccinic acid for 3 to 7 courses. They got complete remission by 3 to 5 weeks treatment. Conclusions Patients in this study with glomerulonephropathy induced by mercury poisoning are all from skin-whitening cream exposure. Mild to moderate edema and proteinuria are the common clinical pattern. Minimal change disease, membranous nephropathy and focal segmental glomerular sclerosis are found pathologically. Chelation therapy is effective.

Objective To report the clinicopathological features of 2 cases of nephronophthisis-medullary cystic kidney disease (NPH-MCKD). Methods The clinical data and pathological changes of renal biopsy in two patients of NPH-MCKD from our hospital were analyzed, and associated literatures were reviewed simultanously. The clinicopathological featuresand diagnosis of NPH-MCKD were discussed. Results Two adolescent patients were admitted to our hospital for indolent renal insufficiency, polyuria accompanied by polydipsia as first signs.Urine analysis showed low specific density urine, mild proteinuria, and few formed elements in urinary sediments. The ability of urine concentration and acidification was decreased. Familial history of renal disease and extra-renal lesions were not found. Renal ultrasound presented an increased echogenicity with diminished cortico-meduUary differentiation, and multiple small cysts in renal corticomedullary border were identified in one case by computed tomography. Pathological examination of renal biopsy revealed diffuse tubular interstitial lesion which was characterized by the triad of tubular basement disintegration, tubular atrophy with cyst development, and interstitial fibrosis. Some of glomerular sclerosis occurred. Cyst development at the corticomedullary border of the kidneys was the specific feature of NPH-MCKD. Conclusions Young patients with impaired tubular function should be suspected of NPH-MCKD. Renal ultrasound or computed tomography can provide an important clue. Multiple renal cysts at the corticomedullary border identified by renal biopsy can be a diagnostic indication for NPH-MCKD.

Objective To investigate the clinical and pathological characteristics of light chain proximal tubulopathy (LCPT).Methods Nine patients with LCPT diagnosed by renal biopsy in Peking University First Hospital from January 1,2011 to September 30,2016 were enrolled,and their clinical findings and pathological features were reviewed.Immunofluorescence (IF) of light chains (κ,λ) on paraffin sections after protease digestion and immunogold labeling of light chains (κ,λ) on ultrathin sections were performed in some cases.Results The main clinical manifestation of the nine patients was proteinuria of small molecules,with acute or chronic renal insufficiency,and six of them led to partial or complete Fanconi syndrome (FS).The hematologic diseases included 3 cases of multiple myeloma and 6 cases of monoclonal gammopathy of renal significance (MGRS).Pathological examination of renal biopsy showed two types:crystalline and noncrystalline LCPT.Seven cases of crystalline LCPT were stained for κ light chain,the proximal tubular epithelial cytoplasm exhibited fine granular vacuolation,with needle-shaped crystals and clear clefts by light microscopy,the intracytoplasmic inclusions of various shapes including rhomboidal,rectangular and rod-shaped crystals were identified by electron microscopy.Two cases of noncrystalline LCPT were stained for λ light chain,the prominent argyrophilic granules in cytoplasm of proximal tubular epithelia were observed by light microscopy,and intracytoplasmic large and irregular shaped phagolysosomes were found by electron microscopy,cast nephropathy were coexisted in these 2 cases,the additional light chain deposition disease were confirmed in one of them by electron microscopy and IF.All cases had monotypic staining of light chains in cytoplasm of proximal tubules by IF on frozen tissue and paraffin sections after protease digestion,with the latter method being more sensitive than the routine IF.The immunogold labeling showed specific monotypic labeling of κ and λ light chain on intracytoplasmic crystals and phagolysosomes respectively by immunoelectron microscopy.Conclusions LCPT is a rarely reported entity that manifested as acquired Fanconi syndrome and dysfunction of proximal tubules clinically.Pathologically it is divided into two types:crystalline and noncrystalline LCPT,with more prevalent of κ light chain related crystalline type,noncrystalline LCPT is mostly λ type,and is easily coexisted with cast nephropathy.The IF and immunoelectron microscopy of light chains(κ,λ) and ultrastructural examination by electron microscopy are important methods for the diagnosis of LCPT.

Objective:To investigate the clinicopathological characteristics of renal light and heavy chain amyloidosis (AHL).Methods:Ten patients with renal AHL diagnosed by renal biopsy in Peking University First Hospital and Institute of Nephrology of Peking University from January 2015 to June 2020 were enrolled. Clinicopathological data of these patients was collected and reviewed.Results:AHL typically affected older patients, with a male/female ratio of 7:3. The clinical manifestations were mainly edema and heavy proteinuria. At the same time, 7/10 of patients presented with nephrotic syndrome, 7/10 presented with microscopic hematuria, and 3/10 presented with renal insufficiency. Laboratory examinations showed monoclonal immunoglobulin in blood and urine in all patients, and IgGλ was the most common one (5/10). Decreased serum complement could be seen in some patients. The ratio of serum free κ light chain and free λ light chain was abnormal in all patients who underwent serum free light chain test. None of the 10 patients met the diagnostic criteria of multiple myeloma. Except for one of the 10 patients who was diagnosed as Waldenstrom's macroglobulinemia, the rest were diagnosed as monoclonal gammopathy of renal significance (MGRS). Bone marrow of 2/6 of patients were positive for amyloid. Cardiac involvement was confirmed in only one patient. Renal biopsy demonstrated amorphous eosinophilic material, which was Congo red positive, was deposited in glomerular mesangial area (10/10), capillary vessels (8/10), renal interstitium (9/10), peritubular capillary walls (9/10) and arterioles (8/10). This material showed apple green birefringence under polarized light. Immunofluorescence showed that single heavy chain and single light chain were positive at the same time, which was consistent with the results of mass spectrometry analysis. Ultrastructural evaluation revealed randomly oriented, non-branching fibrils with a diameter of 8-12 nm.Conclusions:Main clinical manifestations of AHL amyloidosis are edema and massive proteinuria, along with a high incidence of hematuria, a low portion of heart involvement and high frequency of whole molecule of monoclonal immunoglobulin (IgGλ dominant) by serum immunofixation electrophoresis. Renal pathology shows the commonly involved kidney compartments of amyloid deposits are glomerular capillary walls and peritubular capillary walls in patients with AHL amyloidosis.

Objective To investigate the efficacy of treatment and prevention of VitE on vacuous chewing move-ments (VCMs) of haloperidol-induced tardive dyskinesia (TD) rats and serum levels of brain-derived neurotrophic fac-tor ( BDNF) and total antioxidant capacity ( TAC) , and to explore the possible mechanisms.Methods Thirty-two male Sprague-Dawley (SD) rats were randomly divided into TD, P-Vit E, T-Vit E and control group (n=8), receiving to-week treatment with Haloperidol (Hal)+NS, Hal+Vit E (medicated at the baseline), Hal+VitE (medicated at the fifth week) or normal saline (NS), respectively.VCM was evaluated at each week.ELISA and spectrophotometer were used to detect the serum levels of BDNF and TAC, respectively.Results The VCM score of both TD group and T-Vit E group increased at the 2nd weekend, reached the peak at the 5th weekend.VCM score of T-Vit E group declined gradually at the 6th weekend and was significantly lower than that in the TD group [(6.5 ±3.3) vs.(27.9 ±5.8), P<0.001] but was not significantly different from the control group (3.5 ±1.9) (P>0.05) at the 10th weekend.There was no significant difference in VCM score between P-Vit E group and control group for ten weeks(P>0.05).At the 10th weekend, serum BDNF [(6.9 ±1.0) pg/mL] and TAC [(11.9 ±3.2) U/mL] levels of TD group were significantly lower than those of the controls [BDNF (8.6 ±2.5) pg/mL, TAC (18.2 ±5.5) U/mL] and T-Vit E group [BDNF (8.7 ±2.0) pg/mL, (18.6 ±5.9) U/mL] (P<0.01).However, there was no significant difference in the BDNF and TAC levels between TD and P-Vit E groups (P>0.05).Conclusions Vit E may relieve and prevent VCM in TD model rats though alleviation of free radical damage.

Objective:To investigate the roles of S100B protein and anti-brain antibody (ABAb) in the pathophysiology of Alzheimer's disease (AD) by analyzing the changes of the serum levels of S100B and ABAb and the relationships of the measures with cognition deficits in patients with AD.Methods:In this study,32 patients with AD(AD group) and 40 age-matched volunteers without cognitive impairment(control group) were enrolled.The diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-Ⅳ).The mental and social functional conditions were assessed with the Mini-Mental State Examination (MMSE) and Activity of Daily Living Scale(ADL),the cognitive function of patients was evaluated with the Alzheimer's Disease Assessment Scale-cognitive subscale(ADAS-Cog).The serum S100B proteinand ABAb levels were examined by enzyme-linked immuno sorbent assay(ELISA).Results:The serum S100B protein[(0.66 ± 0.17) μg/L vs.(0.30 ± 0.04)μg/L] and ABAb [(1.93 ± 0.95) U/L vs.(1.31 ± 0.25) U/L] levels were higher in AD patients than in the controls (Ps ＜ 0.01).In AD patients,the serum S 100B protein markedly negatively correlated with the scores of the MMSE(r =-0.66),while positively correlated with ADL and ADAS-Cog(r =0.57,r =0.53)(Ps ＜ 0.005).ABAb levels negatively correlated with the scores of the MMSE(r =-0.57),while positively correlated with ADL and ADAS-Cog(r =0.52,r =0.34)(Ps ＜0.05).The serum S100B protein levels were positively related to ABAb levels in AD group(r =0.51.P ＜0.005),but not in control group(r =0.076,P =0.654).Conclusions:It suggests that the serum levels of S100B protein and ABAb are related with cognitive function in patients with Alzheimer's disease,and S100B protein and ABAb might play key roles in mechanism of Alzheimer's disease.

Objective:To investigate the possible pathological mechanisms of tardive dyskinesia (TD) by analyzing brain cortex morphological changes and it's correlation to abnormal involuntary movement in schizophrenic patients with TD.Methods:Thirty-two schizophrenia patients with TD (TD group),31 schizophrenia patients without TD (non-TD group) and 21 healthy volunteers (control group) were recruited.Combined TD and non TD group into schizophrenia group.The psychopathological symptoms and abnormal involuntary movement were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS).The brain magnetic resonance imaging (MRI) data and Freesurfer software were used to measure the gray matter volume,cortical thickness,cortical surface area and volume of sub-conical regions among the three groups.Results:Schizophrenia group had significantly smaller gray matter volume in right nucleus accumbens,bilateral hippocampus,left superior frontal gyrus,left precentral sulcus superior part,and cortical surface area in left precentral sulcus superior part than the controls.The TD group had significantly smaller gray matter volume in right nucleus accumbens,larger gyrus gray matter volume and conical surface area in left precentral sulcus superior part than non-TD group (Ps ＜ 0.05).To test the difference between TD and non-TD group further,the chlorpromazine equivalent dose and PANSS negative scores Was controlled,the TD group still had significantly larger gray matter volume and surface area in left precentral sulcus superior part than the non-TD group [(2.03 ±0.07) × 103mm3 vs.(1.68-± 0.07) × 103 mm3,(1.01 ± 0.03) × 103 mm2 vs.(0.84 ± 0.03) × 103 mm2;Ps ＜ 0.05].Correlation analyses showed in schizophrenia group the cortical thickness in right inferior frontal gyrus correlated negatively with PANSS positive and general scores,positively with total scores;cortical volume in left occipital temporal sulcus correlated negatively with PANSS general and total scores,right inferior frontal gyrus correlated positively with PANSS positive scores,right intraparietal sulcus correlated positively with PANSS positive scores.In TD group,the cortical volume in left precentral sulcus superior part correlated positively with AIMS scores (r =0.46,P ＜0.01).Conclusions:The schizophrenia patients with TD had significantly increased gray matter volume and cortical surface area in left precentral sulcus superior part,which suggested there were motion compensation in the left precentral sulcus superior part in the pathogenesis of TD.

Objective:To investigate the association between catechol-O-methyl transferase (COMT)Vall58Met polymorphism and prepulse inhibition of the auditory startle reflex (PPI) in patients with schizophrenia.Methods:Totally 178 patients with schizophrenia and 190 healthy volunteers were recruited.The auditory startle reflex was detected by using SR-HLAB monitoring system.The indexed of the auditory startle reflex included the amplitude,habituation％ and PPI30,PPI60,PPI120 (the lead interval was set 30 ms,60 ms,120 ms).COMT Vall58Met polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP).The differences of PPI among COMT genotypes were compared.Results:Compared to the healthy volunteers,patients with schizophrenia had a significant lower the amplitude of auditory startle reflex[(563± 460) mV vs (695 ± 447) mY,P ＜ 0.05] and habituation％ [(32 ± 46) vs (48 ± 33),P ＜ 0.01] as well as the ％PPI120[(27 ± 5) vs (35 ± 3),P ＜ 0.05].The significant differences in COMT allelic and genotypic distribions were observed between patients with schizophrenia and healthy volunteers (x2 =8.16,11.74,Ps ＜ 0.05).The significant main effect of COMT genotype on habituation％ was observed (P ＜0.05) but no interaction genotype by diagnosis on the amplitude of auditory startle reflex,habituation％ and ％ PPI120 was observed (Ps ＞ 0.05).Conclusions:There may be a correlation between COMT genotype and adaptability,but not between COMT genotype and PPI deficit present in patients with schizophrenia

Objective To investigate the clinicopathological characteristics of renal light chain deposition disease coexisted with cast nephropathy (LCDD&LCN).Methods Patients with LCDD&LCN (n=10),isolated LCDD (I-LCDD,n=21) and isolated LCN(I-LCN,n=17) diagnosed byrenal biopsy in Peking University First Hospital from January 1,2000 to March 31,2018 were enrolled,and all cases were examined by light microscopy,immunofluorescence (IF) (including light chain) and electron microscopy (EM).The semi-quantitative evaluation of the main features of renal pathology was performed.The clinical manifestations and pathological features were reviewed and compared.Results LCDD&LCN was more prevalent in middle-aged males.Nine patients showed acute renal insufficiency with small molecular proteinuria (97.1％) and microscopic hematuria.The hematologic diseases included 9 patients of multiple myeloma.The type of monoclonal light chain in serum and urine by immunofixation electrophoresis showed λ dominant (5/8).By light microscopy,glomerular lesions presented with mild mesangial proliferation in most patients,and only one of them displayed mesangial nodular sclerosis.At the same time,acute tubular injury with light chain casts was the prominent feature,and the clinical manifestations and histological features of LCDD&LCN were similar to that of I-LCN.IF revealed linear staining of monoclonal light chain along the glomerular basement membrane (GBM),tubular basement membrane (TBM) and Bowman's capsule,and also positive in tubular casts.By electron microscopy,diffuse powder-like or granular electron-dense deposits located in the inner side of the GBM,the outer layer of the TBM,renal interstitium and arteriolar walls were observed.Conclusions Patients with LCDD&LCN manifest as acute renal insufficiency,and the majority have multiple myeloma.The pathology of LCDD&LCN possesses the features of both I-LCDD and I-LCN.The IF stain of light chains(κ,λ) and ultrastructural examination by electron microscopy are the inevitable methods for the diagnosis of LCDD&LCN.