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Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.
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OBJECTIVE: To study the protective efffects of Chailing Guiqi Decoction (CLGQD) combined with lumbrukinase on renal function in rats with adriamycin nephropathy. METHODS: Thirty-six SD rats were randomly divided into four groups: normal control group, untreated group, simvastatin-treated group and CLGQD -treated group. Adriamycin nephropathy was induced by intravenous injection with 5 mg/kg adriamycin. After seven-day treatment, quantitative measurement of 24-h urine protein was determined with trichloroacetic acid, and serum total protein (TP), albumin (Alb), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine (Cr) and blood urea nitrogen (BUN) were assessed using automatic biochemistry analyzer. The pathomorphological changes of renal tissues were observed with light and electron microscopes. RESULTS: In the untreated group, the 24-h urine protein excretion, serum TC, TG, LDL, Cr and BUN were significantly higher than those in the normal control group (P<0.05 or P<0.01), while the serum TP, Alb, HDL were significantly lower than those in the normal control group (P<0.01). In the CLGQD-treated group, the 24-h urine protein excretion, serum TC, TG, LDL, Cr and BUN were significantly lower as compared with those in the untreated group (P<0.05 or P<0.01), while the serum TP, Alb and HDL were significantly higher as compared with those in the untreated group (P<0.05 or P<0.01). The pathomorphological findings of the renal tissues under the light microscope in the untreated group showed focal segmental glomerulosclerosis in a few of glomerulus, degenerated and swelled proximal tubular epithelial cells, proteins in cast formation in some renal tubules and scattered fibrosis in interstitial tissues of the kidney, while the electron microscope images showed the fusion of foot processes in glomerular epithelial cells. The pathomorphological changes in the CLGQD-treated group were slighter than those in the untreated group. CONCLUSION: CLGQD combined with lumbrukinase can reduce proteinuria, regulate lipid metabolism, protect renal function, and delay progressive renal damage in rats.
