Effects of PCSK9 inhibitors on coronary microcirculation, inflammation and cardiac function in patients with CHD after PCI: a protocol for systematic review and meta-analysis.

INTRODUCTION: Coronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous coronary intervention (PCI) is one of the most effective surgical treatments for CHD with narrowed or blocked blood vessels, which can quickly unblock the blocked vessels and restore coronary blood supply. However, most patients may experience coronary microcirculation disorders (CMDs) and decreased cardiac function after PCI treatment, which directly affects the efficacy of PCI and the prognosis of patients. Preprotein converting enzyme subtilisin/Kexin 9 (PCSK9) inhibitors are novel pleiotropy lipid-lowering drug with dual anti-inflammation and lipid-lowering effects, and represent a new clinical pathway for rapid correction of dyslipidaemia. Therefore, we designed this protocol to systematically evaluate the effects of PCSK9 inhibitors on coronary microcirculation and cardiac function in patients with CHD after PCI, and to provide high-quality evidence-based evidence for the clinical application of PCSK9 inhibitors. METHODS AND ANALYSIS: This protocol is reported strictly in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Guidelines. We will search PubMed, EMBASE, Web of Science and three Chinese databases (CNKI, Wanfang and VIP database) according to preset search strategies, without language and publication data restrictions. We will work with manual retrieval to screen references that have been included in the literature. Google Scholar will be used to search for grey literature. The final included literature must meet the established inclusion criteria. Titles, abstracts and full text will be extracted independently by two reviewers, and disagreements will be resolved through discussion or the involvement of a third reviewer. Extracted data will be analysed using Review Manager V.5.3. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias. Publication bias will be assessed by funnel plots. Heterogeneity will be assessed by I2 test and subgroup analyses will be used to further investigate potential sources of heterogeneity. The quality of the literature will be assessed by GRADE score. This protocol will start in January 2026 and end in December 2030. ETHICS AND DISSEMINATION: This study is a systematic review of published literature data and no special ethical approval was required. PROSPERO REGISTRATION NUMBER: CRD42022346189.

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review.

Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS.

Dietary sodium, potassium intake, sodium-to-potassium ratio and risk of hypertension: a protocol for systematic review and dose-response meta-analysis of cohort studies.

INTRODUCTION: Hypertension (HTN) is the leading cause of disease and death on a global scale. Diet's sodium and potassium levels may synergistically affect blood pressure. Currently, the sodium-to-potassium (Na/K) ratio is becoming a more reliable indicator. There has not been a systematic investigation of the dose-response relationship between dietary sodium, potassium, the Na/K ratio and the incidence of HTN based on the same study criteria. This study will conduct a thorough dose-response meta-analysis of cohort studies to estimate the effects of dietary sodium, potassium, and the Na/K ratio on the incidence of HTN to provide the most accurate reference for sodium and potassium intake. METHODS AND ANALYSIS: We will identify all relevant prospective and retrospective cohort studies by searching PubMed, Embase and Web of Science (from inception until December 2022). Exposures are 24 hours urinary excretions, and the outcome is the incidence of HTN. Two researchers will perform the literature selection and data extraction separately. The Newcastle-Ottawa Scale will be used to evaluate the quality of the included studies. We will use both linear and non-linear regression models to investigate the dose-response relationship among different levels (≥3) of sodium, potassium, Na/K ratio intake and the incidence of HTN (OR/RR/HR). Subgroup and sensitivity analyses will be applied to assess the potential heterogeneity sources and examine the stability of the results. We will also evaluate heterogeneity across studies and publication bias. Stata V.15.0 and RevMan V.5.0 will be used for statistical analyses. ETHICS AND DISSEMINATION: According to the Institutional Review Board/Independent Ethics Committee of the Guang'anmen Hospital of the China Academy of Chinese Medical Science, this systematic meta-analysis protocol does not require ethical approval or informed consent. This meta-analysis will be published in a scientific journal with peer reviews. PROSPERO REGISTRATION NUMBER: CRD42022331203.

Massive Proteinuria-Induced Injury of Tubular Epithelial Cells in Nephrotic Syndrome is Not Exacerbated by Furosemide.

BACKGROUND/AIMS: Massive proteinuria, a significant sign of nephrotic syndrome (NS), has the potential to injure tubular epithelial cells (TECs). Furosemide is widely used for the treatment of edema, a common manifestation of NS. However, whether furosemide treatment affects massive proteinuria-induced TEC injury in patients with NS is unknown. METHODS: The effect of furosemide on TEC damage was investigated in vitro. In addition, a clinical study was conducted to study whether the short-term treatment of nephrotic edema with furosemide could exacerbate TEC injury. RESULTS: The proliferation of in vitro human kidney-2 (HK-2) cells exposed to massive urinary protein (8 mg/mL) significantly decreased (P<0.05), while the levels of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated lipocalin (NGAL) in the supernatants significantly increased (P<0.05). Importantly, furosemide treatment did not further increase the expression of Kim-1 and NGAL in HK-2 cells upregulated by massive proteinuria. For the clinical study, 26 patients with NS, all prescribed the recommended dosage of prednisone (1 mg/kg/day), were randomly assigned to two groups. One group (n=13) received furosemide (60-120 mg/day, intravenously) for 1 week; the remaining participants (control group) did not receive furosemide or any other diuretics. The results showed that the 24-h urine volume in the furosemide-treated group was slightly, but not significantly, higher than that in the control group (P>0.05). In addition, serum levels of BUN, Scr, Cys C, and urinary Kim-1 and NGAL were not significantly different between the two groups (all P>0.05). Twenty-three patients underwent a renal biopsy. Of these, 22 patients exhibited vacuolar degeneration of the TECs; 8 patients showed brush border membrane shedding of the TECs; and 12 patients showed protein casts. However, there were no significant differences between the two groups (all P>0.05). CONCLUSION: In summary, massive proteinuria induced the injury of TECs in patients with NS, and furosemide treatment did not aggravate this injury.

[Real-time transrectal ultrasonography in seminal vesiculoscopy].

OBJECTIVE: To compare three different pathways for transurethral seminal vesiculoscopy (SVS) and investigate the reliability and efficiency of transrectal ultrasonography (TRUS)-guided SVS (TRUS-SVS). METHODS: We retrospectively analyzed 90 cases of seminal vesiculoscopy conducted directly through the ejaculatory duct or prostatic utricle or under the guide of TRUS. We compared the success rate and complications among the three approaches. RESULTS: Operations were successfully performed in 87 (96.67%) of the 90 cases, 30 through the ejaculatory duct, 37 via the prostatic utricle, and 20 under the guide of TRUS, the operation time ranging from 25 to 75 minutes. Sperm was detected from the seminal vesicle fluid in (92.06%) of the azoospermia patients (58/63) during the surgery and in 77.78% of them (49/63) in semen analysis at 1 week postoperatively. Fifteen hematospermia and 12 spermatocystitis patients were cured. Postoperative follow-up found 20 cases of water-like semen and 3 cases of orchiepididymitis, but no such complications as retrograde ejaculation, incontinence, or rectourethral fistula. CONCLUSIONS: Transejaculatory duct and transprostatic utricle pathways are two common approaches to SVS, while TRUS-SVS may achieve a higher success rate and avoid injury of both the prostate and the rectum.

[Narrow band imaging-assisted holmium laser resection reduces the residual tumor rate of primary non-muscle invasive bladder cancer: a comparison with the standard approach].

OBJECTIVE: To assess the feasibity and efficacy of narrow band imaging (NBI) cystoscopy assisted holmium laser resection of primary non-muscle invasive bladder cancer (HoLRBt). METHODS: During the period of May 2013 to December 2014, 150 cases of primary non-muscle invasive bladder cancer (NMIBC) admitted in our hospital were randomly divided into NBI-HoLRBt and WLI-TURBt group. In NBI-HoLRBt group, all suspicious lesion identified by either WLI or NBI were resected during the surgery with WLI and in NBI mode for lesion only visible with NBI. At the end of the procedure, NBI cystoscopic examination was performed again to identify whether there was residual lesions at the margins of the resection areas. In WLI-TURBt group, only WLI and TURBt were applied. All patients from the two groups underwent routine intravesical instillation after surgery. A total of 124 patients were diagnosed NMIBC by pathological findings (NBI-HoLRBt group: n=60, WLI-TURBt group: n=64), they were followed-up at 3 months, at which both WLI and NBI cystoscopy were performed to examine the residual tumor, and cytology was checked for all patients. The residual tumor rates at the first follow-up (RR-fFU) were recorded and compared. RESULTS: Baseline characteristics of the patient and the tumor were comparable between the two groups. The overall detection rate of NMIBC and carcinoma in situ (CIS) were significantly higher with NBI than WLI (94.5% (137/145) vs 75.8% (110/145), 16/17 vs 10/17, both P<0.05). The RR-fFU for NBI-HoLRBt and WLI-TURBt was 3.3% (2/60) and 17.2% (11/64), respectively (P<0.05). CONCLUSION: NBI-HoLRBt was feasible, and more effective for identification of NMIBC as well as for the reduction of residual tumor rate compared with WLI-TURBt.

[Narrow band imaging-assisted holmium laser resection reduced the recurrence rate of non-muscle invasive bladder cancer: a prospective, randomized controlled study].

OBJECTIVE: To compare the differential effects of narrow band imaging (NBI)-assisted holmium laser with transurethral resection on the 1-year recurrence rate of non-muscle invasive bladder cancer (NMIBC), and to evaluate the clinical values of NBI-assisted holmium laser resection for NMIBC (NBI-HoLRBt). METHODS: During the period of February 2013 to February 2014, 178 cases of NMIBC were randomly divided into NBI-HoLRBt group and white light imaging (WLI) assisted transurethral resection of bladder tumor (WLI-TURBt) group. In NBI-HoLRBt, all suspicious lesion identified by either WLI or NBI were resected with WLI and in NBI mode for lesion only visible with NBI. At the end of the procedure, a NBI cystoscopic examination was performed to assess the margins of the resection areas and to identify eventual residual lesions. In WLI-TURBt group, only WLI and TURBt were applied. All patients underwent routine follow-up with WLI and NBI cystoscopy supplemented with cytology every 3 month. The recurrence risk of patients with NMIBC subjected to either NBI-HoLRBt or WLI-TURBt was compared at 3 and 12 month. RESULTS: The 3-month and 1-year recurrence rate was 18.48% (17/92) and 38.04% (35/92) respectively in the WLI-TURBt group, it was 5.81% (5/86) and 18.60% (16/86) in the NBI-HoLRBt group (both P<0.05). In addition, the in situ recurrence rate was less in the NBI-HoLRBt than WLI-TURBt group (2.33% vs 14.13%, P<0.05). CONCLUSION: NBI-assisted holmium laser resection of bladder tumor can reduce the 3-month and 1-year recurrence risk of NMIBC and should be considered a valuable clinical therapeutic method for NMIBC.

High pressure synthesis, structure, and multiferroic properties of two perovskite compounds Y2FeMnO6 and Y2CrMnO6.

High purity crystals of Y2FeMnO6 (YFMO) and Y2CrMnO6 (YCMO) have been synthesized for the first time using a flux method under a high temperature of 1573 K and high pressure of 6 GPa. Both YFMO and YCMO have orthorhombic structures in space group Pnma. The temperature-dependent magnetization and the nonlinear M-H hysteresis loops of both materials indicate that an antiferromagnetic transition occurs at the Néel temperature of 328 K for YFMO, and a ferrimagnetic transition occurs at 74 K for YCMO. YFMO is a relaxor ferroelectric in which three dielectric relaxations were observed at 245, 328 and 358 K, respectively. The first relaxation process is due to Maxwell-Wagner polarization at the grain boundary whereas the second and the third relaxation behaviours arise from the beginning and the ending of antiferromagnetic ordering, respectively. The presence of the dielectric anomaly near TN indicates the magnetoelectric effect. Ferroelectric hysteresis loops and PUND (positive-up & negative-down) pulse data reveal weak ferroelectric behavior of YFMO at 77 K. Otherwise one dielectric constant anomaly has been found for YCMO at about 390 K. But no ferroelectric polarization was observed in YCMO.

[Study of lanthanide complexes-doped silica gels and the Co-fluorescence effect by photoacoustic spectroscopy in situ].

Silica matrices, due to their good optical, thermal and chemical properties, are suitable candidates for the hosts of luminescent lanthanide complexes. However, lanthanide complexes would be unstable in the most common sol-gel precursor solution. It is important to study the coordination environment of lanthanide ions and the formation of lanthanide complexes in silica gels. In the present work, lanthanide complexes Ln(Sal)3 x H2O(Ln3+:La3+, Nd3+ and Tb3+; Sal:salicylic acid) were incorporated into silica gels via a sol-gel process. PA technique was firstly used to monitor the formation of lanthanide complexes in silica gels. Upon heat treatment at 110 degrees C, PA intensity of the ligand increased for Tb3+, La3+ and Nd3+ complexes in silica gels, respectively, while this difference could not be observed for the wet gels (samples without heat treatment). By comparison with fluorescence spectra, experimental data indicate that lanthanide complexes decompose in wet gels. The formation of lanthanide complexes in silica gels is discussed from two aspects: radiative and nonradiative processes. Co-luminescence effect was found for lanthanide complexes with aromatic carboxylic acid doped silica gels for the first time. For Tb0.8 Ln0.2 (Sal)3 x H2O (Ln3+:Gd3+ or Nd3+)-doped silica gel, the addition of Gd3+ increased the luminescence efficiency of Tb3+, while the luminescence of Tb3+ was quenched remarkably with the addition of Nd3+. Possible mechanism behind the co-luminescence phenomena of lanthanide complexes-doped silica gels is discussed.

Listening to lanthanide complexes: determination of the intrinsic luminescence quantum yield by nonradiative relaxation.

The photophysical properties of lanthanide complexes have been studied extensively; however, fundamental parameters such as the intrinsic quantum yield as well as radiative and nonradiative decay rates are difficult or even impossible to measure experimentally. Herein, a photoacoustic (PA) method is proposed to determine the intrinsic quantum yield of lanthanide complexes with lifetimes in the order of milliseconds. This method is used to determine the intrinsic quantum yields for europium(III)-containing metallomesogens as well as terbium(III) complexes. The results show that the PA signal is sensitive to both the lifetime and the ratio of the fast-to-slow heat component of the samples. It is found that there is an efficient ligand sensitization and a moderate intrinsic quantum yield for the complexes. The intrinsic quantum yield of Eu(3+) in the metallomesogens exhibits an obvious increase upon the isotropic liquid to smectic A transition. The proposed PA method is quite simple, and can contribute to a clearer understanding of the photophysical processes in luminescent lanthanide complexes.