Improving structure-based virtual screening performance via learning from scoring function components.

Scoring functions (SFs) based on complex machine learning (ML) algorithms have gradually emerged as a promising alternative to overcome the weaknesses of classical SFs. However, extensive efforts have been devoted to the development of SFs based on new protein-ligand interaction representations and advanced alternative ML algorithms instead of the energy components obtained by the decomposition of existing SFs. Here, we propose a new method named energy auxiliary terms learning (EATL), in which the scoring components are extracted and used as the input for the development of three levels of ML SFs including EATL SFs, docking-EATL SFs and comprehensive SFs with ascending VS performance. The EATL approach not only outperforms classical SFs for the absolute performance (ROC) and initial enrichment (BEDROC) but also yields comparable performance compared with other advanced ML-based methods on the diverse subset of Directory of Useful Decoys: Enhanced (DUD-E). The test on the relatively unbiased actives as decoys (AD) dataset also proved the effectiveness of EATL. Furthermore, the idea of learning from SF components to yield improved screening power can also be extended to other docking programs and SFs available.

Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection.

BACKGROUND: Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. METHODS: This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. RESULTS: Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %. CONCLUSIONS: The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients' renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.

Nephrotic-range proteinuria and central nervous involvement in typical hemolytic uremic syndrome: a case report.

BACKGROUND: Hemolytic uremic syndrome (HUS), a common subtype of thrombotic microangiopathy (TMA), is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin-producing Escherichia coli infection is the most common cause of post-diarrheal HUS. Kidney and central nervous system are the primary target organs. CASE PRESENTATION: A 64-year-old male presented with HUS following bloody diarrhea. Nephrotic-range proteinuria and hypoalbuminemia were present at the acute stage and renal histology revealed common TMA features. Neurological involvement presented as confusion and impaired cognitive function. Cranial magnetic resonance imaging demonstrated bilateral T2 hyperintensities in the brainstem and insula. The patient received plasma exchange and supportive care. Both the renal and neurological impairments were completely recovered 3 months after the onset. CONCLUSION: We report an adult patient presenting with nephrotic-range proteinuria and central nervous system involvement at the acute phase of post-diarrheal HUS. The reversibility of the organ damages might predict a favorable outcome.

Improving Docking-Based Virtual Screening Ability by Integrating Multiple Energy Auxiliary Terms from Molecular Docking Scoring.

Virtual Screening (VS) based on molecular docking is an efficient method used for retrieving novel hit compounds in drug discovery. However, the accuracy of the current docking scoring function (SF) is usually insufficient. In this study, in order to improve the screening power of SF, a novel approach named EAT-Score was proposed by directly utilizing the energy auxiliary terms (EAT) provided by molecular docking scoring through eXtreme Gradient Boosting (XGBoost). Here, EAT specifically refers to the output of the Molecular Operating Environment (MOE) scoring, including the energy scores of five different classical SFs and the Protein-Ligand Interaction Fingerprint (PLIF) terms. The performance of EAT-Score to discriminate actives from decoys was strictly validated on the DUD-E diverse subset by using different performance metrics. The results showed that EAT-Score performed much better than classical SFs in VS, with its AUC values exhibiting an improvement of around 0.3. Meanwhile, EAT-Score could achieve comparable even better prediction performance compared with other state-of-the-art VS methods, such as some machine learning (ML)-based SFs and classical SFs implemented in docking programs, in terms of AUC, LogAUC, or BEDROC. Furthermore, the EAT-Score model can capture important binding pattern information from protein-ligand complexes by Shapley additive explanations (SHAP) analysis, which may be very helpful in interpreting the ligand binding mechanism for a certain target and thereby guiding drug design.

Three-Level Hepatotoxicity Prediction System Based on Adverse Hepatic Effects.

Hepatotoxicity is a major cause of drug withdrawal from the market. To reduce the drug attrition induced by hepatotoxicity, an accurate and efficient hepatotoxicity prediction system must be constructed. In the present study, we constructed a three-level hepatotoxicity prediction system based on different levels of adverse hepatic effects (AHEs) combined with machine learning, using (1) an end point, hepatotoxicity; (2) four hepatotoxicity severity degrees; and (3) specific AHEs. After collecting and curing 15 873 compound-AHE pairs associated with 2017 compounds and 403 AHEs, we constructed 27 models with three end point levels with the random forest algorithm, and obtained accuracies ranging from 67.0 to 78.2% and the area under receiver operating characteristic curves (AUCs) of 0.715-0.875. The 27 models were fully integrated into a tiered hepatotoxicity prediction system. The existence of hepatotoxicity existence, severity degree, and potential AHEs for a given compound could be inferred simultaneously and systematically. Thus, the tiered hepatotoxicity prediction system allows researchers to have significant confidence in confirming compound hepatotoxicity, analyzing hepatotoxicity from multiple perspectives, obtaining warnings for the potential hepatotoxicity severity, and even rapidly selecting the proper in vitro experiments for hepatotoxicity verification. We also applied three external sets (11 drugs or candidates that failed in clinical trials or were withdrawn from the market, the PharmGKB (offsides) database, and an herbal hepatotoxicity data set) to test and validate the prediction ability of our system. Furthermore, the hepatotoxicity prediction system was adapted into a flow framework based on the Konstanz Information Miner, which was made available for researchers.

Morphology and ultrastructure of the adrenal gland in Bactrian camels (Camelus bactrianus).

In the present study, we examined the morphological features of the adrenal gland in Bactrian camel by means of digital anatomy, light and electron microscopy. Our findings testified that the gland was divided into three parts, capsule, cortex and medulla from outside to inside as other mammals, and the cortex itself was further distinguished into four zones: zona glomerulosa, zona intermedia, zona fasciculate and zona reticularis. Notably, the zona intermedia could be seen clearly in the glands from females and castrated males, whereas it was not morphologically clear in male. There was a great deal of lipid droplets in the zona fasciculate, while it was fewer in the zona glomerulosa and zona reticularis. The cytoplasm of adrenocortical cell contained rich mitochondria and endoplasmic reticulum. The adrenal medulla was well-developed with two separations of external and internal zones. The most obvious histological property of adrenal medulla cells were that they contained a huge number of electron-dense granules enveloped by the membrane, and so medulla cells could be divided into norepinephrine cells and epinephrine cells. Moreover, the cortical cuffs were frequently present in adrenal gland. Results of this study provides a theoretical basis necessary for ongoing investigations on Bactrian camels and their good adaptability in arid and semi-arid circumstances.

Underlying renal insufficiency: the pivotal risk factor for Pneumocystis jirovecii pneumonia in immunosuppressed patients with non-transplant glomerular disease.

PURPOSES: Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease. METHODS: Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis. RESULTS: All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m2] was present in 87.23 % of patients. The overall mortality rate was 29.79 %. A pulmonary coinfection and the need for mechanical ventilation were independently associated with PCP mortality. A lower eGFR, lower serum albumin level and a higher percentage of global glomerulosclerosis were independent predictors of PCP in patients with IgA nephropathy receiving immunosuppressants. AKI occurred in 60.47 % of patients who received TMP-SMX. After treatment cessation, 93.75 % of surviving patients showed a recovery of renal function to baseline values. CONCLUSIONS: PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.

[Chronic Disease Control among Rural Residents in Beijing Pinggu District].

OBJECTIVE: To analyze the composition and control status of chronic diseases among rural residents in a Beijing suburb district. METHODS: Rural residents aged 35 years or older were investigated by stratified random sampling in Pinggu District, Beijing. Each participant received questionnaire-based survey,physical examination,and laboratory tests including routine blood test,urine albumin creatinine ratio (ACR), liver and renal function,serum lipid, fasting blood glucose, and glycosylated hemoglobin. RESULTS: A total of 10 385 residents completed all items. Cerebrovascular disease was leading cause of hospitalization (accounting for 14.4%) and its incidence in the population was 9.6%. The incidences of hypertension,hyperlipidemia,diabetes mellitus,and gout/hyperuricemia,which were the main compositions related with metabolic diseases,were up to 64.4%,42.5%,24.4%, and 9.0%, respectively. The disease onset was significantly related with the age. The incidence of hypertension was gradually elevated with the increasing of age,while the peak age was 55-64 years for diabetes and 35-44 years for gout/hyperuricemia. The awareness rate of hypertension,diabetes,and chronic kidney disease was 60.2%, 55.1%,and 6.0%,respectively. The control rate of chronic disease was 19.2% and 28.8% in hypertensive and diabetic patients, respectively. CONCLUSIONS: Cerebrovascular diseases and metabolic-associated diseases are the main chronic diseases affecting rural residents in Pinggu district, Beijing. The awareness rate and control rate of chronic diseases needs to be further enhanced by strengthening health education and improving the community medical service.

[Long-term effects of arteriovenous fistula on cardiac structure and function in non-diabetic hemodialysis patients].

OBJECTIVE: To evaluate the long-term effects of arteriovenous fistula (AVF) on heamodynamic changes and cardiac structure and function in non-diabetic hemodialysis patients. METHODS: Data were collected from 50 non-diabetic hemodialysis patients (aged 18 to 60 years) who had used AVF as the vascular access. AVF flow (Qa), stoke volume (SV), cardiac output (CO), cardiac index (CI), central blood volume (CBV) and peripheral vascular resistance (PR) were measured using the ultrasound dilution technique. Echocardiography was performed in the second day after hemodialysis sessions to evaluate the influence of AVF on the cardiac structure and function. RESULTS: The cubic polynomial regression model best fit the relationships of Qa with SV, CO, and CI. CO and CI significantly increased and PR reduced when the Qa of AVF was more than 2.0 L/min(all P<0.05), and no statistical difference of CO, CI and PR in groups of Qa between 0.6-2.0 L/min and less than 0.6 L/min(all P>0.05). In different Qa groups, the grades of cardiac function (based on New York Heart Association classification) showed significant difference, among which the cardiac failure was significantly common when Qa >2.0 L/min(both P<0.05). Echocardiography showed the left atrium dimension, thickness of posterior wall and interventricular seprum of left ventricle, left ventricular end-systolic dimension (LVESD) and end-diastolic dimension (LVEDD), venae cava inferior, and pulmonary artery systolic pressure gradually increased when Qa increased, while the ejection fraction and fractional shortening reduced(all P<0.05). Notably, the changes of LVESD, LVEDD, and venae cava inferior with different Qa were statistically significant(all P<0.05). CONCLUSIONS: Long-term AVF remarkably affects the cardiovascular dynamics of non-diabetic hemodialysis patients. A cubic polynomial regression model best fits the relationship of AVF Qa with SV, CO, and CI. The cardiac adaptic changes after long-term AVF include the enlargement of left ventricle and the thickening of ventricular wall. The risk of cardiac failure significantly increases when the Qa of AVF is more than 2.0 L/min with much higher CO and lower PR.

[Association between cardiac function and intradialytic hypotension].

OBJECTIVE: To prospectively determinate the association of left ventricular systolic and diastolic function with intradialytic hypotension (IDH) in patients on maintenance hemodialysis. METHODS: Totally 115 patients with sinus rhythm were included in this study and divided into IDH group (n=29) and control group (n=86). The cardiac function was assessed by New York Heart Association (NYHA) classification before hemodialysis. Echocardiograms were performed in the next day after hemodialysis and the software of GE EchoPAC was used to estimate parameters of cardiac systolic and diastolic functions including ejection fraction, fractional shortening of left ventricular diameter, stroke volume (SV), cardiac output (CO), left ventricular mass index, Tei index, isovolumetric relaxation time, E-deceleration time, mitral inflow peak early diastolic velocity (E) to late diastolic velocities (A) ratio, and E to peak mitral annulus velocity (E/Em) ratio. RESULTS: The mean age (p=0.045) and the ratio of heart failure evaluated by the NYHA classification (p<0.01) were significantly higher in IDH group than those in control group. No difference was noted for gender, body mass index, duration of dialysis, body weight elevated rate and blood pressure between these two groups (all p>0.05). Left ventricular diameters at the end of diastolic phase, SV, and CO in IDH group were significantly lower than those in control group (all P<0.05), whereas no significant difference was found for EF, FS, Tei index, IVRT, EDT, E/A and E/Em ratio (all p>0.05). Multivariate logistic regression analysis showed that NYHA cardiac function was an independent predictor of IDH, and the risk of IDH increased by 1.134 times with incremental one grade of NYHA classification. CONCLUSIONS: IDH is a common complication of hemodialysis. Neither systolic dysfunction nor diastolic dysfunction of left ventricle evaluated in second day after hemodialysis affects its frequency, whereas the clinical cardiac function is an independent predictor of IDH.

[Clinical analysis of anti glomerular basement membrane disease with normal renal function].

OBJECTIVE: To investigate the clinical and pathologic characteristics of anti-glomerular basement membrane(GBM) disease with normal renal function. METHODS: The clinical and pathologic data of 6 patients with anti-GBM disease and normal renal function in Peking Union Medical College Hospital were reviewed retrospectively. Furthermore, 29 patients with anti-GBM disease and impaired renal function in the same period in the same hospital were enrolled as the control group. Factors that may influence the prognosis were analyzed. RESULTS: Six (17.1%) of all 35 patients maintained normal renal function for 12-133 months during follow-up. Five patients had microhematuria and proteinuria, one had pulmonary hemorrhage only, and three manifested as Goodpasture syndrome. Renal biopsies from 4 patients revealed linear deposition of IgG 2+-3+ along the glomerular capillary walls by immunofluorescence. As shown by normal light microscopy, mild mesangial proliferation and crescentic glomerulonephritis with a large amount of fibrinoid necrosis of glomerular capillary walls were observed in different patients; however, most pathological changes were mild. Five of these six patients were treated with immunosuppressive drugs and/or plasma exchange. Compared with the control group, the 6 patients with normal renal function had significantly higher hemoglobin[(77.97±20.62 vs.(99.67±19.80 g/L P=0.024], lower titers of anti-GBM antibody[(224.34 ± 145.79 vs.(80.23 ± 85.73 EU/ml P=0.027], and lower ratio of glomeruli with crescents[(0.58±0.29 vs.(0.17±0.27 ,P=0.005]. These 6 patients with normal renal function were followed up for 12-133 months, among whom 4 patients achieved complete remission and 2 had mild proteinuria and microhematuria. CONCLUSION: Anti-GBM disease with normal renal function is not uncommon. Most patients have mild pathologic changes and good prognosis.

Phytoremediation of arsenic contaminated paddy soils with Pteris vittata markedly reduces arsenic uptake by rice.

Arsenic (As) accumulation in food crops such as rice is of major concern. To investigate whether phytoremediation can reduce As uptake by rice, the As hyperaccumulator Pteris vittata was grown in five contaminated paddy soils in a pot experiment. Over a 9-month period P. vittata removed 3.5-11.4% of the total soil As, and decreased phosphate-extractable As and soil pore water As by 11-38% and 18-77%, respectively. Rice grown following P. vittata had significantly lower As concentrations in straw and grain, being 17-82% and 22-58% of those in the control, respectively. Phytoremediation also resulted in significant changes in As speciation in rice grain by greatly decreasing the concentration of dimethylarsinic acid (DMA). In two soils the concentration of inorganic As in rice grain was decreased by 50-58%. The results demonstrate an effective stripping of bioavailable As from contaminated paddy soils thus reducing As uptake by rice.

Arsenic speciation in phloem and xylem exudates of castor bean.

How arsenic (As) is transported in phloem remains unknown. To help answer this question, we quantified the chemical species of As in phloem and xylem exudates of castor bean (Ricinus communis) exposed to arsenate [As(V)], arsenite [As(III)], monomethylarsonic acid [MMA(V)], or dimethylarsinic acid. In the As(V)- and As(III)-exposed plants, As(V) was the main species in xylem exudate (55%-83%) whereas As(III) predominated in phloem exudate (70%-94%). The ratio of As concentrations in phloem to xylem exudate varied from 0.7 to 3.9. Analyses of phloem exudate using high-resolution inductively coupled plasma-mass spectrometry and accurate mass electrospray mass spectrometry coupled to high-performance liquid chromatography identified high concentrations of reduced and oxidized glutathione and some oxidized phytochelatin, but no As(III)-thiol complexes. It is thought that As(III)-thiol complexes would not be stable in the alkaline conditions of phloem sap. Small concentrations of oxidized glutathione and oxidized phytochelatin were found in xylem exudate, where there was also no evidence of As(III)-thiol complexes. MMA(V) was partially reduced to MMA(III) in roots, but only MMA(V) was found in xylem and phloem exudate. Despite the smallest uptake among the four As species supplied to plants, dimethylarsinic acid was most efficiently transported in both xylem and phloem, and its phloem concentration was 3.2 times that in xylem. Our results show that free inorganic As, mainly As(III), was transported in the phloem of castor bean exposed to either As(V) or As(III), and that methylated As species were more mobile than inorganic As in the phloem.

Glomerular disease associated with Takayasu arteritis: 6 cases analysis and review of the literature.

OBJECTIVE: To evaluate the clinical features, renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis (TA). METHODS: Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively. None of them had renal artery stenosis or occlusive changes. RESULTS: Six patients with glomerulopathy, accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period, were analyzed. All of them were females with a mean age of 35.5 +/- 10.0 years. Four cases presented with lower extremity edema. Laboratory tests showed that one was nephrotic syndrome, three were nephrotic range proteinuria, and two of them had mild renal dysfunction. The other two patients were asymptomatic microscopic hematuria and proteinuria. Renal pathology revealed mild immunoglobulin A nephropathy in two cases, mild mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, minimal change disease, and fibrillary GN in one case respectively. Five cases received glucocorticoids and cyclophosphamide therapy. Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases. The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment. CONCLUSIONS: TA may induce glomerular disease as a part of its histological spectrum. Apart from ischemic glomerular disease, glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria, that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.

[A clinicopathological analysis of non-haematological malignancy in nephrotic syndrome].

OBJECTIVE: To analysis the clinical and pathological features, results of laboratory tests and prognosis of nephrotic syndrome (NS) in patients with non-haematological malignancy. METHODS: The data were collected from 25 patients who presented with NS around the diagnosis of non-haematological malignancy. RESULTS: Twenty-five cases were investigated (age: (56.6 +/- 17.7) years; male/female ratio: 20/5). Malignancy and NS occurred within one year in 92% patients. There was a wide distribution of malignancy with involvement of 36% in digestive system and 20% in respiratory system. Ten patients (40%) presented with NS as their initial manifestation. Haematuria appeared in 67% patients and acute renal insufficiency was complicated in 12% cases before treatments. Some other non-specific laboratory tests were found including elevated serum gamma-globulin in 50% and anemia not related with renal failure in 28% cases. Membranous nephropathy was the most common pathological changes in 67% cases. Although NS still continued for several weeks in 8 of 9 cases after surgery and/or chemical therapy, glucocorticoids was helpful to achieve the remission in these patients. However, no remission was achieved in patients without the treatment for malignancy. CONCLUSION: Malignancy may present with NS as its initial manifestation. It should be inspected routinely and regularly in elder patients with NS, especially in those with membranous nephropathy, as well as gamma-globulinemia and anemia.

[Risk factors of post-renal biopsy bleeding].

OBJECTIVE: To evaluate the risk factors of post-renal biopsy bleeding (PBB). METHODS: We retrospectively analyzed the clinical data of 1 262 patients who received ultrasound-guided biopsy of native kidney at our hospital from January 2005 to December 2006. RESULTS: The overall incidence of PBB was 30.3% (383/1,262), among which the incidence of hematoma was 29.4% (371/1,262) (the percentages of less and more than 5cm were 73.9% and 26.1%, respectively) while that of gross hematuria was only 1.3% (17/1,262). The incidences of minor, intermediate, and major bleeding complications were 21.4% (270/1,262), 8.4% (106/1,262), and 0.6% (7/1,262), respectively. In seven patients with major bleeding complications, six had renal disease secondary to rheumatic disease (lupus nephritis, n = 5; scleroderma crisis, n = 1), while the other one had IgA nephropathy (Lee's classification V). The risk of PBB was relatively higher in women and younger patients. CONCLUSIONS: Patients with chronic connective tissue diseases are vulnerable to severe PBB complications. A close monitoring of these patients is necessary.

[Effects of oxidized low-density lipoprotein on expression of type A scavenger receptor in human mesangial cells].

OBJECTIVE: To explore the regulational effect of oxidized low-density lipoprotein (Ox-LDL) on expression of type A scavenger receptor (SR-A) in human mesangial cells (HMC). METHODS: HMC line (HMCL) with high expression of SR-A (HMCL-SRA) was established after stable transfection of expressive vector with cDNA encoding SR-A. Uptake of Ox-LDL by HMCL was evaluated using Oil Red "O" staining. SR-A mRNA expression was examined using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: More uptake of Ox-LDL was observed in the HMCL-SRA than that in the untransfected HMCL. Ox-LDL could induce SR-A mRNA expression in HMC in a dose-dependent manner, and reached a peak level after 24 h of stimulation. After 24 h of stimulation with Ox-LDL at the dose of 10, 50 and 100 micrograms/ml, SR-A mRNA expression was up-regulated to 1.35, 1.83 and 2.30-fold of controls, respectively. However, LDL had no effect on the expression of SR-A. CONCLUSIONS: It suggests that SR-A be a major binding receptor to uptake Ox-LDL in HMC. Ox-LDL may promote the progression of chronic renal diseases through up-regulation of SR-A.

[Non-diabetic renal disease in type II diabetes mellitus].

OBJECTIVE: Several studies have suggested that non-diabetic renal disease (NDRD) was common among non-insulin dependent diabetes mellitus (NIDDM) patients with renal involvement. METHODS: The prevalence of NDRD among Chinese NIDDM population in PUMC hospital center was retrospectively studied. Renal biopsy specimens were evaluated with light-, immunofluorescence- and electron-microscopy. The cohort consisted of 33 NIDDM patients who received renal biopsy. RESULTS: Patients with both isolated diabetic nephropathy (DN, n = 7) and NDRD (n = 22) had comparable duration of DM, creatinine clearance, serum creatinine, albumin and 24 hours proteinuria, as well as incidences of retinopathy, neuropathy and hypertension. Significantly more patients with NDRD had haematuria (P = 0.030) or non-nephrotic proteinuria (P = 0.016). IgA nephropathy accounted for 40.9% of the NDRD identified. CONCLUSIONS: In this study, haematuria and non-nephrotic proteinuria predicted the presence of NDRD among NIDDM patients complicated with renal disease. IgA nephropathy is the most frequent type of NDRD in Chinese.