Identification of Circulating Plasma Proteins as a Mediator of Hypertension-Driven Cardiac Remodeling: A Mediation Mendelian Randomization Study.

BACKGROUND: This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure. METHODS: A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects. RESULTS: Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% (P=0.024) and 4.15% (P=0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% (P=0.042) and 23.24% (P=0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% (P=0.013) and 4.54% (P=0.032) of the total effect of SBP and DBP on heart failure susceptibility. CONCLUSIONS: This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure.

Association between estimated pulse wave velocity and in-hospital mortality of patients with acute kidney injury: a retrospective cohort analysis of the MIMIC-IV database.

BACKGROUND: Estimated pulse wave velocity (ePWV) has been found to be an independent predictor of cardiovascular mortality and kidney injury, which can be estimated noninvasively. This study aimed to investigate the association between ePWV and in-hospital mortality in critically ill patients with acute kidney injury (AKI). METHODS: This study included 5960 patients with AKI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan-Meier survival curve to evaluate the differences in survival status. Cox proportional hazards models were used to explore the association between ePWV and in-hospital mortality in critically ill patients with AKI. To further examine the dose-response relationship, we used a restricted cubic spline (RCS) model. Stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups. RESULTS: Survival analysis indicated that patients with high ePWV had a lower survival rate than those with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with an increased risk of in-hospital mortality among AKI patients (HR = 1.53, 95% CI = 1.36-1.71, p < 0.001). Analysis using the RCS model confirmed a linear increase in the risk of hospital mortality as the ePWV values increased (P for nonlinearity = 0.602). CONCLUSIONS: A high ePWV was significantly associated with an increased risk of in-hospital mortality among patients with AKI. Furthermore, ePWV was an independent predictor of in-hospital mortality in critically ill patients with AKI.

Advances in the study of vascular related protective effect of garlic (Allium sativum) extract and compounds.

Garlic (Allium sativum) is a functional food containing multiple bioactive compounds that find widespread applications in culinary and medicinal practices. It consists of multiple chemical components, including allicin and alliin. This article offers a comprehensive review of the protective effects of garlic extracts and their active constituents on the vascular system. In vitro and in vivo experiments have shown that garlic extracts and their active ingredients possess various bioactive properties. These substances demonstrate beneficial effects on blood vessels by demonstrating anti-inflammatory and antioxidant activities, inhibiting lipid accumulation and migration, preventing lipid peroxidation, promoting angiogenesis, reducing platelet aggregation, enhancing endothelial function, and inhibiting endothelial cell apoptosis. In clinical studies, garlic and its extracts have demonstrated their efficacy in managing vascular system diseases, including atherosclerosis, diabetes, and high cholesterol levels. In summary, these studies highlight the potential therapeutic roles and underlying mechanisms of garlic and its constituents in managing conditions like diabetes, atherosclerosis, ischemic diseases, and other vascular disorders.

Discovery of natural polyphenols from the wild vegetable Suaeda salsa L. with potential cardioprotective functions.

Suaeda salsa L. (Chenopodiaceae) is a wild vegetable distributed along the northern coast of China. Searching for potential agents with health benefits from S. salsa L. led to the identification of 14 flavonoids (1-14), eight phenolic acids (15-22), one coumarin (23), one benzoquinone (24), two sesquiterpenes (25, 26), and three lignins (27-29) from an aqueous ethanol (EtOH) extract of the above-ground whole plant using various column chromatographic methods. High-resolution electrospray ionization mass spectrometry (HRESIMS) analyses and nuclear magnetic resonance (1H and 13C NMR) spectroscopy were adopted to examine the structural properties of the compounds. To date, our study is the first to identify 20 compounds from this genus. Some compounds exhibited significant health benefits in zebrafish models. Compounds 2, 4, 23, and 28 significantly improved oxidative damage, while compounds 1-5, 7, 11, 13, 18, 19, and 23 significantly improved zebrafish lateral line neuromast inflammation. Additionally, compounds 1, 4, 8, 13, and 16 significantly promoted zebrafish angiogenesis, while compounds 3-5 and 18 significantly improved zebrafish arrhythmia. Furthermore, a flavonoid-targeted metabolomics study revealed that flavanone was the precursor of all of the flavonoids and had its highest accumulation in August, while the others showed their highest accumulation in September. Thus, the best time to harvest most of the bioactive polyphenols is during September. The present study revealed that the wild vegetable S. salsa L. might be developed as a potential cardioprotective functional food.

Potential activity of Traditional Chinese Medicine against Ulcerative colitis: A review.

ETHNIC PHARMACOLOGICAL RELEVANCE: Plant materials are used as complementary and alternative therapies all over the world for the treatment of various diseases. Ulcerative colitis (UC), a chronic nonspecific inflammatory bowel disease listed as one of the modern refractory diseases by the World Health Organization, has a long course, is challenging to cure, and is prone to cause cancer. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) to UC. AIM OF THIS REVIEW: This review presents an overview of the pathogenesis of UC and reports the therapeutic effect of TCM on UC (including TCM prescriptions, single TCM, and treatments using TCM ingredients) to provide a theoretical basis for the use of TCM in treating UC. METHODS: We performed a collection and collation of relevant scientific articles from different scientific databases regarding TCM and its usefulness in treating UC. In this paper, the therapeutic effect of TCM is summarized and analyzed according to the existing experimental and clinical research. RESULTS: There are positive signs that TCM primarily regulates inflammatory cytokines, intestinal flora, and the immune system, and also protects the intestinal mucosa. Hence, it can play a role in treating UC. CONCLUSION: TCM has a definite curative effect in the treatment of UC. It can alleviate and treat UC in a variety of ways. We should take syndrome differentiation and treatment differentiation as the basis. With the help of modern medicine, TCM's clinical curative effects can be enhanced for the treatment of UC.

Association of a GATA Binding Protein 4 Polymorphism with the Risk of Hypospadias in the Chinese Children.

PURPOSE: GATA binding protein 4 (GATA4) has been implicated in the etiology of congenital malformation of the urogenital system. The present study investigated the influence of GATA4 polymorphisms on susceptibility to hypospadias. METHODS: We genotyped 4 potentially functional polymorphisms (rs12458, rs12825, rs884662, and rs904018) in GATA4 in the hospital-based case-control study including 410 child patients and 520 nonmalformed individuals by the TaqMan MGB method. Risk associations were assessed using unconditional logistic regression, adjusted for potential confounding factors. RESULTS: A significant association was found between rs12458 (3'-UTR of GATA4) and susceptibility to hypospadias (p = 0.008). Compared with rs12458 AA genotype individuals, those harboring the variant allele (rs12458 AT/TT) were correlated with significantly higher risk of hypospadias (AT/TT vs. AA: OR = 1.42, 95% CI = 1.17-2.35, p = 0.036). Furthermore, the rs12458T allele showed significantly decreased activity in a luciferase reporter assay, indicating a possible role of rs12458 variant in regulating the combination of microRNAs with the GATA4 mRNA. CONCLUSIONS: The present results indicate that the functional GATA4 rs12458 variant confers individuals' susceptibility to hypospadias, possibly through regulating the GATA4 expression level.

Pediatric laparoscopic partial cystectomy for the treatment of benign bladder tumors and urachal cysts.

OBJECTIVE: To investigate the feasibility and efficacy of carrying out pediatric laparoscopic partial cystectomies (LPC) when treating benign bladder tumors and urachal cysts. METHODS: Retrospectivey analyzing 4 clinical cases involving children with bladder tumors, which were collected from October 2017 to December 2018. In these clinical cases, there were 3 male children and 1 female child, aged from 4.5 to 9.4 years old, with an average age of 6.5 years. An intraperitoneal laparoscopic partial cystectomy was performed in the treatment of 3 of these patients with benign bladder tumors and in 1 patient with an urachal cyst. The surgical procedures included a partial cystectomy and a complete intracavitary bladder suture. RESULTS: All 4 cases were successful and no operation was transferred to opensurgery. The operation time was 100-120 min, with an average time of 108 min. The intraoperative blood loss was 10-20 ml, with an average loss of 15 ml. 6 h after the operation, the patients still maintained a fluid diet and 1 case of hematuria had occurred, with the catheter removed 12 days after the operation. No postoperative urine leakage, intestinal adhesion or intestinal obstruction occurred, and the average postoperative hospitalization time was 14 days. CONCLUSION: Laparoscopic partial cystectomy is a safe and feasible method to be used for the treatment of benign bladder tumors and urachal cysts. It presents the advantages of being minimally invasive, and having a quick recovery and short hospitalization time. It is an alternative surgical method for the treatment of pediatric benign bladder tumors.

Experience Summary of Laparoscopic Treatment for Pediatric Ureteral Polyps.

Objective: To investigate surgical techniques and challenges of laparoscopic in treating pediatric ureteral polyps under laparoscopy. Methods: The clinical data of 7 of pediatric ureteral polyps patients who were admitted to the hospital from July 2015 to January 2020 were analyzed retrospectively. There were 6 males and 1 female from 7.7 to 13.9 years old at the mean age of 10.4. Before surgery, all children performed urinary B ultrasound, magnetic resonance urography (MRU), and renal radionuclide scanning. Six cases were observed on the left lateral and 1 on the right. The lesions of 5 cases were located at the ureteropelvic junction, 1 in the upper ureter and 1 in the middle ureter. The polyps were treated intraoperatively by the resecting of the lesion segment and simple polypectomy to retain the attached part of the original diseased segment of the ureter. All surgeries were performed under laparoscopy and B-ultrasound was performed during follow up after surgery. Results: All 7 surgeries were performed successfully under the laparoscope. The surgery time was 80-110 min, and the average surgery time was 97.5 min. The intraoperative bleeding was 10-25 ml and the average postoperative hospital stay was 6 d. Postoperative hematuria occurred in 1 case. Neither urinary leakage nor urinary tract infection was reported post surgery. Preoperative affected pyelectasis of all patients was 2.0-3.7 cm. Three months postoperatively, the affected pyelectasis was measured at 1.2-3.0 cm. No recurrence of polyps was reported after surgery. During the follow-up to April 2020, there was no significant change in the kidney size of all patients, and hydronephrosis was alleviated compared with that before surgery. Conclusions: Laparoscopy is a safe, effective and minimally invasive surgical technique for pediatric multiple ureteral polyps. The surgery plan was designed according to the location and size of polyps, including segmental ureterectomy of polyps + pyeloureterostomy, segmental ureterectomy of polyps + ureter - ureteral anastomosis.

Carboplatin-based Nanomedicine to Enhance the Anticancer Effect in SK-NEP-1 WilmsꞌTumor Cells.

Wilms tumor (WT) is the most common pediatric malignant primary renal tumor. Carboplatin (CRB), a platinum compound is widely used in the treatment of multiple cancers including ovarian, lung, head and neck, and wilm's tumor. However, lower uptake of CRB in cancer cells and toxicity concerns in healthy cells often limited its clinical outcome. The aim of this study was to investigate the antitumor effect of CRB on SK-NEP-1 wilm's cancer cells. Earlier, CRB was formulated in nanoparticulate formulations and characterized its biophysical parameters. SK-NEP-1 cell growth in vitro was assessed by MTT. Then, apoptosis potential was investigated by TUNEL, Hoechst, and colony formation assay. CRB treatment resulted in inhibition of cell proliferation of SK-NEP-1cells in a dose-dependent manner. TUNEL, Hoechst, and colony formation assay demonstrated that CRB was more effective in killing wilm's cancer cell when encapsulated in nanoparticle formulations. Overall, the present study demonstrates that CRB treatment resulted in marked inhibition of cell proliferation and cell apoptosis. These results may pave way for the effective treatment of wilm's tumor in clinical models.

Functional promoter -31G/C variant of Survivin gene predict prostate cancer susceptibility among Chinese: a case control study.

BACKGROUND: Abnormal expression of Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin), a novel member of the inhibitor of apoptosis protein (IAP) family, has implications in many types of cancer and is considered as a new therapeutic target. We suppose that genetic variant rs9904341 in the 5' UTR region of survivin gene may be associated with the development and progression of prostate cancer (PCa) in Chinese population. METHODS: TaqMan assay method was used to genotype the polymorphism in the hospital-based case-control analysis of 665 patients with PCa and 710 age-matched cancer-free controls. The genetic associations with the occurrence and progression of PCa were calculated by logistic regression. RESULTS: Our results indicated that compared with GG genotypes, there was a statistically significant increased risk of PCa associated with those with CC genotypes [odds ratios (ORs) = 1.57, 95%confidence intervals (CIs) = 1.17-2.13, P = 0.004]. Moreover, stratification analysis revealed that the association was more pronounced in subgroups of nondrinkers, nonsmokers and those without a family history of cancer (all P < 0.05). In addition, we observed that PSA ≥ 20 was more frequent in patients carrying GC/CC genotypes than in those with a wild type genotype. CONCLUSION: The functional survivin rs9904341 genetic variant may have a substantial influence on the PCa susceptibility and evolution.

Effect of green tea on reward learning in healthy individuals: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Both clinical and preclinical studies revealed that regular intake of green tea reduced the prevalence of depressive symptoms, as well as produced antidepressant-like effects in rodents. Evidence proposed that disturbed reward learning has been associated with the development of anhedonia, a core symptom of depression. However, the relationship between green tea and reward learning is poorly investigated. Our goal was to test whether chronic treatment with green tea in healthy subjects affects the process of reward learning and subsequently regulates the depressive symptoms. METHODS: Seventy-four healthy subjects participated in a double-blind, randomized placebo-controlled study with oral administration of green tea or placebo for 5weeks. We used the monetary incentive delay task to evaluate the reward learning by measurement of the response to reward trial or no-reward trial. We compared the reaction time of reward responsiveness between green tea and placebo treatment. Furthermore, we selected Montgomery-Asberg depression rating scale (MADRS) and 17-item Hamilton Rating Scale for Depression (HRSD-17) to estimate the depressive symptoms in these two groups. RESULTS: The results showed chronic treatment of green tea increased reward learning compared with placebo by decreasing the reaction time in monetary incentive delay task. Moreover, participants treated with green tea showed reduced scores measured in MADRS and HRSD-17 compared with participants treated with placebo. CONCLUSIONS: Our findings reveal that chronic green tea increased the reward learning and prevented the depressive symptoms. These results also raised the possibility that supplementary administration of green tea might reverse the development of depression through normalization of the reward function.

Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease.

To investigate the expression levels of neurexins and neuroligins in the enteric nervous system (ENS) in Hirschsprung Disease (HSCR). Longitudinal muscles with adherent mesenteric plexus were obtained by dissection of the fresh gut wall of mice, guinea pigs, and humans. Double labeling of neurexin I and Hu (a neuron marker), neuroligin 1 and Hu, neurexin I and synaptophysin (a presynaptic marker), and neuroligin 1 and PSD95 (a postsynaptic marker) was performed by immunofluorescence staining. Images were merged to determine the relative localizations of the proteins. Expression levels of neurexin and neuroligin in different segments of the ENS in HSCR were investigated by immunohistochemistry. Neurexin and neuroligin were detected in the mesenteric plexus of mice, guinea pigs, and humans with HSCR. Neurexin was located in the presynapse, whereas neuroligin was located in the postsynapse. Expression levels of neurexin and neuroligin were significant in the ganglionic colonic segment of HSCR, moderate in the transitional segment, and negative in the aganglionic colonic segment. The expressions of neurexin and neuroligin in the transitional segments were significantly down-regulated compared with the levels in the normal segments (P < 0.05). Expression levels of neurexin and neuroligin in ENS are significantly down-regulated in HSCR, which may be involved in the pathogenesis of HSCR.

A new modification of transanal Soave pull-through procedure for Hirschsprung's disease.

BACKGROUND: One stage transanal Soave pull-through procedure (TSPP) is a recent popular operation in the treatment of Hirschsprung's disease (HD). With no visible scar and a short hospital stay, it is well accepted by surgeons and mothers. In the conventional Soave procedure, a long rectal muscular cuff left for anocolic anastomosis might increase the incidence of postoperative enterocolitis and constipation. This study presents a modified transanal Soave pull-through procedure (MTSPP) which includes an oblique mucosectomy and an oblique anastomosis with a short split muscular cuff. METHODS: A review of two groups of HD patients was made: 112 underwent conventional transanal Soave procedure from 1999 to 2001 (group 1) and 140 underwent modified transanal Soave procedure from 2002 to 2004 (group 2). A comparison was made between the two groups on operative data and postoperative complications. The data included: age at the operation, operating time, blood loss, time to feeds and hospital stay, occurrence of postoperative enterocolitis or constipation, need for anal dilatation, postoperative bowel function and perianal skin problems. RESULTS: There was no significant difference between two groups with respect to age, gender, length of colon resected, operating time, blood loss and hospital stay. However occurrence of postoperative enterocolitis, constipation, anastomotic stricture and time needed for anal dilatation were evidently less in group 2 (MTSPP). The mean operating time in group 1 was (106 +/- 39) minutes with a range of 60 to 170 minutes; in group 2 was (101 +/- 36) minutes with a range of 66 to 190 minutes. The average length of the bowel resected in group 1 was (24 +/- 7) cm, range 15 to 58 cm; in group 2 was (26 +/- 8) cm, range 15 to 70 cm. Two patients, one in each group, required laparoscopic assistance because of long aganglionic colon. Another patient in group 2 required laparotomy because of total colonic aganglionosis. Postoperative complications in group 1 included: temporary perianal excoriation in 34 patients (26 were < 3 months of age), enterocolitis in 21, anastomotic stricture in 11, recurrent constipation in 12, cuff abscess in 1, anastomosis leak in 1, soiling in 3 and rectal prolapse in 1. In group 2 post operative complications included: transient perianal excoriation in 37 patients (30 were < 3 months of age), enterocolitis in 13, anastomotic stricture in 5, recurrent constipation in 6, anastomotic leak in 1, adhesive bowel obstruction in 1 and soiling in 4. Complete bowel continence was found in 97 children (86.6%) in group 1 and in 129 children (92.1%) in group 2 at one year followup after operation. CONCLUSIONS: Modified transanal Soave pull-through procedure for HD with oblique mucosectomy and anastomosis and a short split muscular cuff is a safe and feasible operation with low incidence of postoperative complication. It is an encouraging improvement of the conventional transanal Soave pull-through procedure. MTSPP is a preferable choice in the surgery of HD.