Cuproptosis-related lncRNAs potentially predict prognosis and therapy sensitivity of breast cancer.

Background: Cuproptosis-related lncRNAs regulate the biological functions of various cancers. However, the role of cuproptosis-related lncRNAs in breast cancer remains unclear. In this study, we investigated the biological functions and clinical applications of cuproptosis-related lncRNAs in breast cancer. Methods: The Cancer Genome Atlas (TCGA) database and the GSE20685 dataset were used for screening cuproptosis-related lncRNAs. Colony formation and CCK-8 kit assays were performed for detecting the proliferative function of cuproptosis-related lncRNAs, whereas wound healing, migration, and invasion assays were performed for detecting the metastatic regulation of cuproptosis-related lncRNAs in breast cancer. Finally, a prognostic cuproptosis-related lncRNA model was constructed using LASSO Cox regression analysis for detecting survival and sensitivity to conventional treatment (endocrine therapy, chemotherapy, and radiotherapy) and novel therapy (PARP and CDK4/6 inhibitors). Results: In this study, we screened six cuproptosis-related lncRNAs associated with the survival of patients with breast cancer. Biofunctional experiments indicated that cuproptosis-related lncRNAs play essential roles in regulating the proliferation and metastasis of breast cancer cells. Finally, we applied a model of six cuproptosis-related lncRNAs to classify the patients into high- and low-risk groups. High-risk group patients exhibited worse survival rates (p < 0.001) and lower sensitivity to chemotherapy, endocrine therapy, and radiation therapy. Compared with high-risk patients, low-risk patients exhibited a lower expression of CDK4/6 inhibitor-resistant biomarkers (CCNE1, E2F1, and E2F2) and PARP inhibitor-resistant biomarkers (BRCA1/BRCA2), indicating that patients in the low-risk group were more suitable for PARP inhibitor and CDK4/6 inhibitor application. Conclusion: Cuproptosis-related lncRNAs are essential for regulating the biological functions of breast cancer, and they have the potential to predict prognosis and sensitivity of breast cancer to various therapies.

Nomogram predicting the risk of three-year chronic kidney disease adverse outcomes among East Asian patients with CKD.

BACKGROUND: Chronic kidney disease (CKD) is a common health challenge. There are some risk models predicting CKD adverse outcomes, but seldom focus on the Mongoloid population in East Asian. So, we developed a simple but intuitive nomogram model to predict 3-year CKD adverse outcomes for East Asian patients with CKD. METHODS: The development and internal validation of prediction models used data from the CKD-ROUTE study in Japan, while the external validation set used data collected at the First People's Hospital of Foshan in southern China from January 2013 to December 2018. Models were developed using the cox proportional hazards model and nomogram with SPSS and R software. Finally, the model discrimination, calibration and clinical value were tested by R software. RESULTS: The development and internal validation data-sets included 797 patients (191 with progression [23.96%]) and 341 patients (89 with progression [26.10%]), respectively, while 297 patients (108 with progression [36.36%]) were included in the external validation data set. The nomogram model was developed with age, eGFR, haemoglobin, blood albumin and dipstick proteinuria to predict three-year adverse-outcome-free probability. The C-statistics of this nomogram were 0.90(95% CI, 0.89-0.92) for the development data set, 0.91(95% CI, 0.89-0.94) for the internal validation data set and 0.83(95% CI, 0.78-0.88) for the external validation data-set. The calibration and decision curve analyses were good in this model. CONCLUSION: This visualized predictive nomogram model could accurately predict CKD three-year adverse outcomes for East Asian patients with CKD, providing an easy-to-use and widely applicable tool for clinical practitioners.

Comparative efficacy of different renin angiotensin system blockade therapies in patients with IgA nephropathy: a Bayesian network meta-analysis of 17 RCTs.

BACKGROUND: IgA nephropathy (IgAN) is still one of the most prevalent forms of primary glomerulonephritis globally. However, no guidelines have clearly indicated which kinds of renin angiotensin system blockade therapies (ACEIs or ARBs or their combination) in patients with IgAN result in a greater reduction in proteinuria and a better preservation of kidney function. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of these three therapy regimens in patients with IgAN. METHODS: The protocol was registered in PROSPERO with ID CRD42017073726. We comprehensively searched the PubMed, the Cochrane Library, Embase, China Biology Medicine disc, WanFang and CNKI databases for studies published since 1993 as well as some grey literature according to PICOS strategies. Pairwise meta-analysis and Bayesian network analysis were conducted to evaluate the effect of different regimens. RESULTS: Seventeen randomized controlled trials (RCTs) involving 1,006 patients were analyzed. Co-administration of ACEIs and ARBs had the highest probability (92%) of being the most effective therapy for reducing proteinuria and blood pressure, but ACEIs would be the most appropriate choice for protecting kidney function in IgAN. CONCLUSION: The combination of ACEIs and ARBs seems to have a significantly better antiproteinuric effect and a greater reduction of blood pressure than ACEI or ARB monotherapy in IgAN. ACEIs appear to be a more renoprotective therapy regimen among three therapies.

Comparative proteinuria management of different angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for normotensive patients with CKD: a Bayesian network meta-analysis.

BACKGROUND: Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are blood pressure-lowering agents, but they are also being used to control proteinuria in early chronic kidney disease (CKD) patients. However, clinically, some patients present merely proteinuria without hypertension. No guidelines pointed out how to select treatments for proteinuria in normotensive patients. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of different kinds of ACEI or ARB or their combination on proteinuria and blood pressure reduction. METHODS: The protocol was registered in PROSPERO with ID CRD42017073721. A comprehensive literature database query was carried out systematically according to PICOS strategies. The primary outcome was reduction in proteinuria, and the secondary outcomes were eGFR reduction and blood pressure reduction. Random-effects pairwise and Bayesian network meta-analyses were used to estimate the effect of different regimens. RESULTS: A total of 14 RCTs with 1,098 patients were included in the analysis. All treatment strategies of ACEI, ARB or their combination had significantly greater efficacy in reducing proteinuria than placebo in normotensive CKD patients. The combination therapy of olmesartan+temocapril had the highest probability (22%) of being the most effective treatment to reduce proteinuria in normotensive CKD patients. Olmesartan and lisinopril ranked second (12%), and temocapril ranked third (15%) but reduced blood pressure less than placebo. For IgA nephropathy, the combination therapy of olmesartan+temocapril also had the highest probability (43%) of being the best antiproteinuric treatment, while enalapril had the highest probability (58%) of being the best antiproteinuric therapy for diabetic nephropathy. CONCLUSIONS: The combination therapy of olmesartan plus temocapril appeared to be the most efficacious for reducing proteinuria in normotensive CKD patients and IgA nephropathy, but the clinical application should be balanced against potential harms. Temocapril can be an option when practitioners are searching for more proteinuria reduction but less blood pressure variation. In normotensive diabetic nephropathy, monotherapy with the ACEI enalapril seems to be the most efficacious intervention for reducing albuminuria. Future studies are required to give a more definitive recommendation.

Integrative Proteomic and Phosphoproteomic Analyses of Granulosa Cells During Follicular Atresia in Porcine.

Ovarian follicular atresia is a natural physiological process; however, the mechanism is not fully understood. In this study, quantitative proteomic and phosphoproteomic analyses of granulosa cells (GCs) in healthy (H), slightly atretic (SA), and atretic follicles (A) of porcine were performed by TMT labeling, enrichment of phosphopeptides, and liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. In total, 6,201 proteins were quantified, and 4,723 phosphorylation sites of 1,760 proteins were quantified. In total, 24 (11 up, 13 down) and 50 (29 up, 21 down) proteins with a fold change (FC) > 5 were identified in H/SA and H/A, respectively. In addition, there were 20 (H/SA, up) and 39 (H/A, up) phosphosites with an FC > 7 that could serve as potential biomarkers for distinguishing different quality categories of follicles. Western blotting and immunofluorescence confirmed the reliability of the proteomic analysis. Some key proteins (e.g., MIF, beta catenin, integrin ß2), phosphosites (e.g., S76 of caspase6, S22 and S636 of lamin A/C), pathways (e.g., apoptosis, regulation of actin cytoskeleton pathway), transcription factors (e.g., STAT5A, FOXO1, and BCLAF1), and kinases (e.g., PBK, CDK5, CDK12, and AKT3) involved in the atresia process were revealed via further analysis of the differentially expressed proteins (DEPs) and phosphorylated proteins (DEPPs). Further study showed that mutant caspase6 Ser76 to Ala increased the ratios of cleaved caspase6/caspase6 and cleaved caspase3/caspase3 and dephosphorylation of caspase6 at Ser76 increased cell apoptotic rate, a new potential pathway of follicular atresia. Collectively, the proteomic and phosphoproteomic profiling and functional research in the current study comprehensively analyzed the dynamic changes in protein expression and phosphorylation during follicular atresia and provided some new explanations regarding the regulation of this process.

Suspension precipitation: A simple sediment-collecting method for microbiological culturing in diagnosis of peritonitis
.

BACKGROUND: Rapid and accurate microbiological detection is crucial for effective treatment of peritonitis patients with peritoneal dialysis (PD). Although centrifugation of dialysis effluents can increase the pathogen culture-positive rate, a lack of both centrifugation facilities and experienced staff has prevented its widespread implementation, particularly in basic-level hospitals in developing countries. Thus, we developed a simple peritoneal sediment-collecting method, suspension precipitation method, for microbiological diagnosis of peritonitis. MATERIALS AND METHODS: In the suspension precipitation method, drained effluent bags from individual patients were hung for 1 hour to allow the suspension to drip to the bottom layer of the bag for sediment collection. Sediments obtained by centrifugation from the same batch of dialysis effluent were used as positive controls. Both sediment sample types were then cultured in blood-culture bottles. Subsequent analysis of the pathogen-positive detection rate and species comparison between the two methods were undertaken. RESULTS: Among 90 PD patients, the pathogen positive-detection rate between methods was comparable, as demonstrated by 75 (83.33%) with the suspension precipitation method and 77 (85.56%) by the centrifugation method. Their positive pathogen species were also similar, and the concordance rate was 97.78%. CONCLUSION: The suspension precipitation method is a simple, convenient, and reliable peritoneal sediment-collecting method that is suitable for a wide array of uses, particularly in basic-level hospitals without centrifugation technology.

A Bayesian network analysis on comparative efficacy of treatment strategies for dialysis patients with secondary hyperparathyroidism.

For dialysis patients with end-stage kidney disease and secondary hyperparathyroidism (SHPT), there are three therapeutic treatment options: Cinacalcet, paricalcitol and cinacalcet plus low-dose vitamin D analogues. However, their comparative efficacy remains unclear at present. Thus, in the current study, a Bayesian network analysis was conducted to evaluate the relative efficacy and safety of these three therapeutic regimens. A comprehensive literature database query was performed. The primary outcome was the treatment effect on serum parathyroid hormone (PTH) levels. Secondary outcomes included the occurrence of nausea and hypocalcaemia. A total of 20 randomized clinical trials, including 5,390 dialysis patients, were entered into the analysis. Paricalcitol, cinacalcet plus vitamin D analogue and cinacalcet were significantly more efficacious in controlling PTH levels compared with conventional therapy (which comprises calcium-based phosphate binders, non-calcium-based phosphate binders and vitamin D analogues) [odds ratio (OR)=3.99, 2.91 and 2.47, respectively] and placebo (OR=20.32, 14.89 and 12.56, respectively). Paricalcitol was identified as the most efficacious of the three treatments. According to a ranking analysis, patients treated with cinacalcet had a higher possibility of frequently developing nausea and hypocalcaemia compared with patients treated with cinacalcet plus low-dose active vitamin D analogues. All three therapeutic treatment options were efficacious for the treatment of dialysis patients with SHPT in controlling PTH levels. Paricalcitol had the highest possibility of being the most optimal one. Thus, paricalcitol therapy may be the most optimal regimen in controlling PTH levels, but this should be confirmed by further study.

[Study on preparation of a wound healing agent: fibronectin].

In search of the optimal preparation method for large-scale purification of human plasma fibronectin, we adopted affinity chromatography with gelatin and the Sepharose 4B activated with cyanogen bromide to purify fibronectin from type "C" plasma of healthy males, and scanned the best method under the conditions of different amount of plasma loading and different residence time in column. In a given column volume of gelatin, the absorbent was related with the plasma residence time in column and the total amount of plasma loaded. As a result, the optimal loading amount of plasma is 150 ml, and the residence time is 20 minutes. The preparation method, herein, has been proved to require small amount of plasma and yield large amount of fibronectin.