Can proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors regress coronary atherosclerotic plaque? A systematic review and meta-analysis.

OBJECTIVE: Whether inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the regression of coronary atherosclerotic plaque in statin-treated individuals remains unclear. This study examined whether PCSK9 inhibitors combined with statin therapy could increase atherosclerotic plaque regression compared with statin therapy alone. METHODS: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), the database Clinical trials, and the Web of Science were searched to report the coronary atherosclerotic plaque of PCSK9 inhibitors using intravascular ultrasonography (IVUS) or optical coherence tomography (OCT) in statin patients. The weighted mean difference (WMD) of the random-effects/fixed-effects model was used to pool data that satisfied our inclusion criteria obtained from the included studies. RESULTS: When compared with statin therapy alone, pooled studies revealed that PCSK9 inhibitors combined with statin therapy significantly decreased percent atheroma volume (PAV) (WMD: -1.06%, 95% confidence interval [CI]: -1.39 to -0.73; P<0.001) and total atheroma volume (TAV) (WMD: -6.38 mm3, 95% CI: -10.12 to -2.64; P=0.001). Moreover, the fibrous cap thickness (FCT) of the coronary atherosclerotic plaque increases to 21.31 um (WMD: 21.31, 95% CI: 7.08 to 35.53, P<0.001), and the maximum lipid arc decreases 10.9° (WMD: -10.9, 95% CI: -15.24 to -5.34, P<0.001). CONCLUSION: In our systematic review and meta-analysis, PCSK9 inhibitors combined with statin therapy were found to be more effective than statin therapy alone for slowing coronary plaque progression by decreasing PAV, TAV, and increasing FCT, maximum lipid arc.

Pathogen-driven gene expression patterns lead to a novel approach to the identification of common therapeutic targets.

Developing a common medication strategy for disease control and management could be greatly beneficial. Investigating the differences between diseased and healthy states using differentially expressed genes aids in understanding disease pathophysiology and enables the exploration of protein-drug interactions. This study aimed to find the most common genes in diarrhea-causing bacteria such as Salmonella enterica serovar Typhimurium, Campylobacter jejuni, Escherichia coli, Shigella dysenteriae (CESS) to find new drugs. Thus, differential gene expression datasets of CESS were screened through computational algorithms and programming. Subsequently, hub and common genes were prioritized from the analysis of extensive protein-protein interactions. Binding predictions were performed to identify the common potential therapeutic targets of CESS. We identified a total of 827 dysregulated genes that are highly linked to CESS. Notably, no common gene interaction was found among all CESS bacteria, but we identified 3 common genes in both Salmonella-Escherichia and Escherichia-Campylobacter infections. Later, out of 73 protein complexes, molecular simulations confirmed 5 therapeutic candidates from the CESS. We have developed a new pipeline for identifying therapeutic targets for a common medication strategy against CESS. However, further wet-lab validation is needed to confirm their effectiveness.

Reduction in risk of contrast-induced nephropathy in patients with chronic kidney disease and diabetes mellitus by enhanced external counterpulsation.

Objective: To evaluate the efficacy of enhanced external counterpulsation (EECP) in the prevention of contrast-induced nephropathy (CIN) in patients with combined chronic kidney disease (CKD) and diabetes mellitus (DM) by comparing the changes in renal function-related indicators in patients before and after coronary angiography (CAG) or percutaneous coronary intervention (PCI). Methods: There were 230 subjects consecutively included in the study. Of these, 30 cases with DM underwent rehydration therapy, and 200 cases underwent EECP therapy in addition to rehydration therapy, comprising 53 patients with DM and 147 patients without. All the patients were tested to measure the renal function indicators before and after CAG/PCI. Results: The postoperative results of blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), B2 microglobulin, and high-sensitivity C-reactive protein in the three groups showed a statistically significant difference (P < 0.05). After EECP therapy, patients with DM showed a significant decrease in BUN (9.1 ± 4.2 vs. 7.2 ± 3.0, t = 3.899, P < 0.001) and a significant increase in eGFR (41.5 ± 12.7 vs. 44.0 ± 15.6, t = -2.031, P = 0.047), while the patients without DM showed a more significant difference (P < 0.001). Patients with DM showed a lower percentage of elevated Scr (66.7% vs. 43.4%, P = 0.042), a higher percentage of elevated eGFR (30.0% vs. 52.8%, P = 0.044), and a lower incidence of CIN (16.7% vs. 3.8%, P = 0.042) after EECP therapy. Conclusion: Treatment with EECP can reduce Scr in patients with combined CKD and DM post CAG/PCI, increase eGFR, and decrease the incidence of CIN.