Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs / 国际口腔科学杂志·英文版

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.

Practice of a hemodialysis alliance in the context of closed-loop hospital management / 中华医院管理杂志

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Research advances in the use of digital surgical guides in implantology / 华西口腔医学杂志

Dental implants have become the main choice for patients to fill in their missing teeth. A precise placement is the basis for a functional and aesthetic restoration. A digital surgical guide is a carrier that transfers the preoperative plan of dental implants to the actual surgery. This paper provides some references that can help clinicians improve the accuracy of implant surgery by stating the development, classification, advantages and disadvantages, and factors that affect the accuracy of digital guides.

Quality evaluation of Artemisiae Argyi Folium based on fingerprint analysis and quantitative analysis of multicomponents / 中国中药杂志

Artemisiae Argyi Folium, the dried leaves of Artemisia argyi, has been widely used in traditional Chinese and folk medicines for treatment of hemorrhage, pain, and skin itch. Phytochemical studies indicated that volatile oil, organic acid and flavonoids were the main bioactive components in Artemisiae Argyi Folium. Compared to the volatile compounds, the research of nonvolatile compounds in Artemisiae Argyi Folium are limited. In the present study, an accurate and reliable fingerprint approach was developed using HPLC for quality control of Artemisiae Argyi Folium. A total of 10 common peaks were marked，and the similarity of all the Artemisiae Argyi Folium samples was above 0.940. The established fingerprint method could be used for quality control of Artemisiae Argyi Folium. Furthermore, an HPLC method was applied for simultaneous determination of seven bioactive compounds including five organic acids and two flavonoids in Artemisiae Argyi Folium and Artemisiae Lavandulaefoliae Folium samples. Moreover, chemometrics methods such as hierarchical clustering analysis and principal component analysis were performed to compare and discriminate the Artemisiae Argyi Folium and Artemisiae Lavandulaefoliae Folium based on the quantitative data of analytes. The results indicated that simultaneous quantification of multicomponents coupled with chemometrics analysis could be a well-acceptable strategy to identify and evaluate the quality of Artemisiae Argyi Folium.

Quality evaluation of Taraxaci Herba based on fingerprint analysis and quantitative analysis of multi-components / 中国中药杂志

Taraxaci Herba was derived from the dried Herba of Taraxacum mongolicum, T. borealisinense and several species from the Taraxacum genus. Taraxaci Herba has been widely used in traditional Chinese and folk medicines. According to the different growth and cultivation pattern, Taraxaci Herba could be divided into two species, wild Taraxaci Herba and cultivated Taraxaci Herba. In the present study, an accurate and reliable fingerprint approach was developed using high performance liquid chromatography(HPLC) for quality control of Taraxaci Herba. A total of 9 common peaks were marked, and the similarity of all the Taraxaci Herba samples was above 0.960. The established fingerprint method could be used for quality control of Taraxaci Herba. Furthermore, an HPLC method was established for simultaneous determination of six bioactive compounds, including monocaffeoyl tartaric acid, chlorogenic acid, caffeic acid, cichoric acid, 4,5-dicaffeoylquinic acid and luteolin in wild Taraxaci Herba and cultivated Taraxaci Herba. Moreover,chemometrics analysis such as principal component analysis and orthogonal partial least squares discriminant analysis were performed to compare and discriminate the wild samples and cultivated samples based on the quantitative data. The chemometrics results indicated that 4,5-dicaffeoylquinic acid and luteolin were significant to effectively discriminate the wild Taraxaci Herba and cultivated Taraxaci Herba samples, and these two compounds could be recognized as chemical markers for quality evaluation of wild Taraxaci Herba and cultivated Taraxaci Herba. The fingerprint analysis and quantitative analysis of multi-components could be a well-acceptable strategy for evaluation the quality of Taraxaci Herba.

Telehealth-based dialysis registration system for the improvement of renal anemia in maintenance hemodialysis:multicenter experiences / 中华肾脏病杂志

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

Research on topographic factors of ecology suitability regionalization of Bupleuri Radix in Hebei province / 中国中药杂志

To study the correlation between the content of saikosaponins ingredient of Bupleuri Radix and topographic factors, we researched the ecology suitability regionalization of topographic of Bupleuri Radix from Hebei province to provide a scientific basis for selecting artificial planting. Based on 43 samples of Bupleuri Radix from Hebei province, the variation of the content of saikosaponins in different conditions of topographic factors and the influence of slope, altitude and aspect were comprehensively analyzed by SPSS 21.0. Then we studied topographic factors of ecology suitability regionalization of Bupleuri Radix on the basis of the relationship between the saikosaponins and topographic factors by ArcGIS. The most suitable conditions of topographic for cultivation of saikosaponins are as follows：altitude 600 m above, slope 4.00-5.50 degrees, aspect to the sun. In Hebei province, it is suitable for growth of Bupleuri Radix in the Taihang Mountains and the Yanshan Mountains where the content of saikosaponins is higher.

Gene chip screen in mice kidney with acute paraquat poisoning and preliminary analysis of the differentially expressed genes / 中华急诊医学杂志

Objective To study the gene expression profile in mice kidney with acute paraquat (PQ) poisoning and identify key genes related to renal injury.Methods A total of 20 mice (C57BL/6) were randomly (random number) divided into four groups, namely control group (group A, n =5) and poisoned groups (groups B, C, D, n =5/group).In group A, mice were administrated with distilled water (0.01 mL/g weight) while in groups B, C, D were administered with equivalent volume of PQ solution (diluted from 20％ to 0.05％ with distilled water) dissolved in distilled water via a gastric tube.Mice of group A were sacrificed immediately and mice of groups B and C at 6 h and 24 h after administration of PQ.The gene expression profile changes of kidney tissue were measured by cDNA Arraychip technology.Mice of group D were observed for mortality rate 48 h later.Results The body weights of mice decreased significantly after administration of PQ.The mortality in group D at 48 h after PQ poisoning was 100％.Compared with the control group, totally 1 792 genes with differential expression variations were identified in 6 h group and 24 h group.There were 8 key genes selected through bioinformatics analysis and they were arranged in real-time PCR: Nlrc5 , Serpinb9 , Cd40 , Rnf135 , Dhx58 , Spl 10 , Fcgrl , and Arhgef12.And then, Nlrc5 , Serpinb9 and Rnf135 were under Western blot investigation.The results of PCR and Western blot showed no significant difference to those from bioinformatics genetic analysis.Conclusions The investigation based on genome wide chip in researching related genes of PQ kidney has offered a novel idea in studying pathogenesis of acute PQ intoxication.

Degenerated Retained Product of Conception Misdiagnosed as Invasive Trophoblastic Disease

Retained products of conception (POC) complicates nearly 1% of all pregnancies, occurring with greater frequency after termination of pregnancy than after vaginal or caesarean delivery. The presenting symptoms of retained products of conception are similar to those of gestational trophoblastic disease and hence accurate differentiation is difficult based on clinical history and physical examination alone. The distinction between these two entities is extremely important as the treatment differs dramatically. These patients often need to be further evaluated with either ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis. Hence, radiologists play a vital role in clinching the diagnosis although at times it may be challenging to differentiate between these two entities. Herein, we discuss a case of degenerated retained products of conception which was initially misdiagnosed as invasive trophoblastic disease in a 41-year-old woman whom last known pregnancy was 10 years ago.

The clinical significance of determining serum paraquat by spectrometry / 中华急诊医学杂志

ObjectiveTo evaluate the reliability and clinical value for detecting paraquat (PQ)concentration in serum by spectrometry. MethodsThe determinations of wave length for detecting serum PQ concentration by ordinary spectrometry and second-derivative spectrometry were carried out. When the second-derivative spectrometry was used for detecting PQ in serum, the linear range and precision for PQ concentration were well defined. The results of serum PQ concentration determined by second-derivative spectrometry and by HPLC (high performance liquid chromatography) were compared in 8 patient with PQ poisoning. A total of 21 patients with acute poisoning after PQ ingestion over 4 hours admitted from October 2008 through September 2010 were retrospectively studied. Patients were divided into two groups as per the serum concentrations more than 1.8 μg/mL or less than that by second-derivative spectrometry on the day of admission. The severity of clinical manifestations between two groups was analyzed with t-test or Fisher's exact probabilities analysis. Results ( 1 ) The absorption peak of 257 nm could not be found by using ordinary spectrometry to detect the PQ concentration in serum. (2) The calibration curve in the 0. 4 ～ 8.0μg/mL range for detecting PQ concentration by second-derivative spectrometry observed the Beer's law (r =0. 996) . The average retrieval rate of PQ was within the range of 95.0％～ 99. 5％ with relative standard deviation (RSD) within 1.35％～ 5.41％ ( n = 6), and the lowest detection limit was 0. 05μg/mL. (3) The results of PQ concentrations from 8 patients with PQ poisoning detected by second-derivative spectrometry were consistent with those of the quantitative determinations by HPLC ( r = 0. 995,P＜0. 01 ) . (4) The survival rate of patients with serum PQ concentration more than 1.8 μg/mL was 22. 2％ ,and the incidences of acidosis, oligouria and pneumomediastium in these patients were 55.6％,55. 6％ and 77.8％, respectively. These clinical manifestations were significantly different from those in patients with serum PQ concentration less than 1.8 μg/mL ( P ＜ 0. 05 ) . Conclusions ( 1 ) It was inappropriate to take 257 nm as the determination wave length for detecting serum PQ concentration by ordinary spectrometry. (2) The method of second-derivative spectrometry was reliable for detecting serum PQ concentration. (3) Serum PQ concentration detected by second derivative spectrometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning and was an important predictive factor for poor prognosis if the serum PQ concentration more than 1.8 μg/mL after PQ ingestion over 4 hours.

Serum paraquat concentration detected by spectrophotometry in patients with paraquat poisoning / 世界急诊医学杂志（英文）

BACKGROUND: Paraquat (PQ) is a world-wide used herbicide and also a type of common poison for suicide and accidental poisoning. Numerous studies have proved that the concentration of serum PQ plays an important role in prognosis. Spectrophotometry, including common spectrophotometry and second-derivative spectrophotometry, is commonly used for PQ detection in primary hospitals. So far, lack of systematic research on the reliability of the method and the correlation between clinical features of patients with PQ poisoning and the test results has restricted the clinical use of spectrophotometry. This study aimed to evaluate the reliability and value of spectrophotometry in detecting the concentration of serum PQ. METHODS: The wavelengths for detecting the concentration of serum PQ by common and second-derivative spectrophotometry were determined. Second-derivative spectrophotometry was applied to detect the concentration of serum PQ. The linear range and precision for detection of PQ concentration by this method were confirmed. The concentration of serum PQ shown by second-derivative spectrophotometry and HPLC were compared in 8 patients with PQ poisoning. Altogether 21 patients with acute poisoning 4 hours after PQ ingestion treated in the period of October 2008 to September 2010 were retrospectively reviewed. The patients were divided into higher and lower than 1.8 μg/mL groups based on their concentrations of serum PQ measured by second-derivative spectrophotometry on admission. The severity of clinical manifestations between the two groups were analyzed with Student's t test or Fisher's exact test. RESULTS: The absorption peak of 257 nm could not be found when common spectrophotometry was used to detect the PQ concentration in serum. The calibration curve in the 0.4–8.0 μg/mL range for PQ concentration shown by second-derivative spectrophotometry obeyed Beer's law with r=0.996. The average recovery rates of PQ were within a range of 95.0％ to 99.5％, relative standard deviation (RSD) was within 1.35％ to 5.41％ (n=6), and the lower detection limit was 0.05 μg/mL. The PQ concentrations in serum of 8 patients with PQ poisoning shown by second-derivative spectrophotometry were consistent with the quantitative determinations by HPLC (r=0.995, P<0.0001). The survival rate was 22.2％ in patients whose PQ concentration in serum was more than 1.8 μg/mL, and the incidences of acidosis, oliguria and pneumomediastinum in these patients were 55.6％, 55.6％and 77.8％, respectively. These clinical manifestations were different significantly from those of the patients whose PQ concentration in serum was less than 1.8 μg/mL (P<0.05). CONCLUSIONS: For common spectrophotometry, the wavelength at 257 nm was not suitable for detecting serum PQ as no absorbance was shown. Second-derivative spectrophotometry was reliable for detecting serum paraquat concentration. Serum PQ concentration detected by second-derivative spectrophotometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning, and PQ content higher than 1.8 μg/mL 4 hours after ingestion could be an important predictive factor for poor prognosis.

Observation in effect of perineal cleansing with sterile water on reduction of the false negative rate of mid-stream urine culture / 中国实用护理杂志

Objective To compare the effect of perineal cleansing with the potassium permanganate or sterile water on mid- stream urine culture. Methods Mid- stream specimens of urine were obtained from inpatients in our hospital between January 2002 and December 2006. All these patients may be diag-nosed as urinary tract infection. The urine specimens were divided into the potassium permanganate group (n=1572, the sterilization group) and the sterile water group (n=544). The change of positive and contami-nation rate of mid-stream urine culture from the specimens was observed. More than two kinds of germs in one urine specimen were defined as contamination. Results 830 patients with urinary tract infection had been enrolled. 2116 specimens were collected and 531 strains of causative organism were detected. The positive rate of the sterilization group and the sterile water group was 20.04% and 39.71%, respectively,and such difference was significant. The rate of identical causative organism from the same patient whose spec-imen was cultivated twice in the sterilization group was 0.012% and the rate was 0.105% in the sterile water group. The difference was significant. The rate of different or one kind of causative organism from the same patient whose specimen was cultivated twice in these two groups hadn't significant deviation. The contami-nation rate of the sterilization group (0.028%) was significantly higher than that of the sterile water group (0.007%). Conclusions Perineal cleansing with sterile water can reduce the false negative rate of mid-stream urine culture without increasing the contamination rate. Potassium permanganate sterilization is re-sponsible for the high false-negative in mid-stream urine culture.

All-tram retinoic acid markedly inhibits over-excitement of renin-angiotensin system in 5/6 renal ablation rats / 中华肾脏病杂志

ObjectiveTo investigate the effect of all-trans retinoic acid (atRA) on the renin-angiotensin system (RAS) in 5/6 renal ablation model. MethodsAtRA was administered to 5/6 renal ablation rats by three dosages: 5 mg·kg-1·d-1 (n=8), 10 mg·kg-1d-1 (n=8) and 20 mg·kg-1 d-1 (n=8) and vehicle (vehicle group, n=8) for 10 weeks. Healthy rats consisted of shamoperation group (n =8). The level of renin and angiotensin Ⅱ in renal tissues were measured by radioimmunoassary. The level of angiotensin type 1 receptor (AT1R) in remnant renal cortex was measured by Western blot. The mRNA expression levels of two subunits of activative protein 1(AP-1),c-jun and c-fos was quantitated by real-time PCR. ResultsAfter 10 weeks of atRA treatment by gavarge, artery blood pressure decreased (P＜0.05). AtRA reduced the levels of renin (P＜0.05) and angiotensin Ⅱ (P＜0.05) in kidney and down-regulated the expression of AT1R protein in renal cortex. Larger dose of atRA (20 mg·kg-1·d-1) performed higher activity in inhibiting renin and AT1R. Compared with vehicle group, atRA could significantly inhibit the expression of renal c-jun and c-fos mRNA (P＜0.05). Conclusion atRA can decrease the over-expression of main components of RAS.

Astragali radix extract ameliorates renal resistance to atrial natriuretic peptide in rats with experimental nephrotic syndrome / 中国病理生理杂志

AIM:To study the effects of astragali radix extract(ARE)on renal resistance to atrial natriuretic peptide(ANP)in rats with experimental nephrotic syndrome.METHODS:Male Sprague-Dawley rats were randomly divided into normal control,adriamycin nephropathy(ADR),ADR treated with ARE(2.5 g? kg-1? d-1)and ADR treated with benazepril(10 mg? kg-1? d-1).After 6 weeks,rats received intravenous infusion of 2% body weight isotonic saline.Urinary cGMP excretion(UcGMPV),plasma ANP level,renal PDE5 activity and protein expression were also detected.RESULTS:ARE increased UNaV while ACEI was not natriuretic.Nephrotic rats had a blunted natriuretic response and reduced rate of UcGMPV after volume expansion despite higher plasma ANP concentration.ARE increased UcGMPV and restored partly natriuretic response to volume expansion.The activity and protein abundance of renal PDE5 were high in nephrotic rats.ARE significantly reduced the PDE5 activity and protein expression.CONCLUSION:ARE may ameliorate the renal resistance to ANP in rats with adriamycin nephropathy by inhibiting the PDE5.

The renoprotective role of all-trans retinoic acid in retarding rat glomerulosclerosis with 5/6 nephrectomy / 中国病理生理杂志

AIM: To explore if all trans retinoic acid (atRA) retards glomerulosclerosis of rats with 5/6 nephrectomy. METHODS: Wistar male rats were operated by subtotal nephrectomy and were randomly divided into A1 (5 mg?kg~(-1)?d~(-1) atRA), A2 (10 mg?kg~(-1)?d~(-1) atRA), A3 (20 mg?kg~(-1)?d~(-1) atRA) and NX (vehicle) groups. Each group included 8 rats. 8 health rats were assigned as sham-operation group (sham group). Animals were sacrificed 10 weeks after treatment. The concentrations of plasma atRA were measured by reversed phase high performance liquid chromatography (RP-HPLC). Glomerulosclerosis was evaluated by glomerulosclerosis index system. The expression of transforming growth factor-beta 1 (TGF?1) was measured by renal immunohistochemical staining and Western blotting. RESULTS: The concentrations of atRA in atRA groups were much higher than that in NX and sham groups. Compared to NX, the remnant kidney sclerosis was ameliorated significantly in A1, A2 and A3 groups. The expressions of TGF?1 decreased parallelized to the levels of glomerulosclerosis. CONCLUSION: atRA has a beneficial effect on retarding the progression of renal fibrosis in the 5/6 nephrectomic rats, possibly through downregulating the glomerular TGF?1 expression.

Rhein retards the progression of type 2 diabetic nephropathy in rats / 中华肾脏病杂志

Objective To assess the effect of rhein on diabetic nephropathy in rats with type 2 diabetes mellitus. Methods Diabetes was induced by high-lipids and high-sucrose diets (20% sucrose, 10% lard, 2.5% cholesterol, 1% cholic acid and 66.5 % regular chow, w/w) for 1 month and then intraperitoneal injection with 25 mg/kg streptozoticin(STZ) in female inbred Wistar rats. Rhein was continuously given 100 mg?kg-1?day-1 for 6 months 1 week after STZ injection in rhein-prevented group, and 1 month after STZ injection in rhein-treated group. Blood and urinary biochemistry and renal morphology were evaluated at divers times. Results Rhein ameliorated hypertriglyceridemia and hypercholesterolemia, but had few effect on the level of plasma glucose in both rhein-prevented group and rhein-treated group. Excretion of urinary protein reduced markedly and stable-state plasma glucose (SSPG) level decreased in both groups as compared with diabetic group. Examination of kidney sections from both rhein-prevented group and rhein-treated group showed that the structural lesions of glomeruli including mesangial expansion, diffuse glomerulosclersis and thickening of glomerular basement membrane, as well as artery injury such as arteriolar hyalinosis, atherosclerosis were markedly improved as compared with diabetic group. Morphometry of glomeruli from both rhein-prevented group and rhein-treated group showed that glomerular grow and mesangial hypertrophy occurred in diabetic group were ameliorated. The accumulation of fibronectin examined by immunostaining in glomeruli was reduced in both groups. Conclusion Therapeutic intervention with rhein can halt the progression of diabetic nephropathy and prevent the development of glomerulosclerosis and vascular injuries in this animal model of type 2 diabetes mellitus.

Ameliorative effect of adrenalectomy on remnant nephropathy in the rat depends on aldosterone level / 中华肾脏病杂志

4-fold elevation in renal cortex in plasma aldosterone as compared to those of the SHAM rats. The above pathologies were markedly improved in bi-ectomised rats with significantly lower aldosterone level. Being constantly infused exogenous aldosterone, bi-ectomized rats manifested greater proteinuria, hypertension, glomerulosclerosis and increased level of TGF-?1 compared to bi-ectomised rats. Indeed, these features were similar in exogenous aldosterone rats and 5/6 nephrectomized rats. Furthermore, the expression of mineralocorticoid receptor (MR) mRNA was remarkablely enhanced in SNX group and was decreased in ADX group. However, the mRNA expression of 11 ?-hydroxysteroid dehydrogenase II (11?-HSD2) in each group was opposite to that of MRmRNA. Ccr and kidney/body weight showed no differences among four experimental groups. Conclusion Aldosterone contributes to the progression of ablative nephropathy in the rat through mechanisms other than systolic blood pressure.