Effect of banana intake on serum potassium level in patients undergoing maintenance hemodialysis: A randomized controlled trial.

Objective: This study aimed to assess the effect of banana intake during hemodialysis on serum potassium levels in maintenance hemodialysis (MHD) patients. Methods: This study was a single-center, randomized controlled clinical trial conducted from September 15 to December 15, 2021, at a tertiary hospital in southern China. A total of 126 MHD patients were randomly assigned to either the intervention group (n = 64) or the control group (n = 62). Patients in the intervention group consumed approximately 250 g of bananas during hemodialysis, while those in the control group did not consume any food during hemodialysis. Demographic information and hemodialysis-related parameters were collected through case information collection before hemodialysis. Laboratory indicators (such as complete blood count, biochemical indicators, inflammation markers, liver function, kidney function, etc.) were evaluated by collecting pre-hemodialysis blood samples from patients. Serum potassium and blood glucose levels were measured at 2 h and 4 h of hemodialysis, as well as before the next hemodialysis session, and hemodialysis-related complications were recorded. The blood potassium and blood glucose indicators during hemodialysis were compared using repeated measures analysis. Results: A total of 122 MHD patients completed the study (61 in each group). The results showed that there was no significant interaction between group and time on serum potassium levels. However, serum potassium levels in the intervention group were higher than those in the control group at 2 h (3.9 ± 0.5 mmol/L vs. 3.6 ± 0.3 mmol/L, P < 0.01) and 4 h (3.5 ± 0.4 mmol/L vs. 3.3 ± 0.3 mmol/L, P < 0.01) of hemodialysis. There was no interaction between group and time on blood glucose levels. The incidence of arrhythmias (8.2% vs. 29.5%, P = 0.003) and hypokalemia (52.5% vs. 80.3%, P = 0.002) during hemodialysis was significantly lower in the intervention group compared to the control group. Conclusion: Consuming approximately 250 g of bananas at the start of hemodialysis does not lead to hyperkalemia. It can effectively reduce the incidence of hypokalemia and arrhythmias, and prevent a rapid decline in serum potassium levels during hemodialysis.

Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study.

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, et al. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; Epub ahead of print.

Mg-Defect Compensation to Realize High Performance at Room Temperature in Mg3Bi2-Based Thermoelectric Single Crystals.

Mg3Bi2-based materials are a very promising substitute for current commercial Bi2Te3 thermoelectric alloys. The successful growth of Mg3Bi2-based single crystals with high room-temperature performance is especially significant for practical applications. Previous studies indicated that the effective suppression of Mg defects in Mg3Bi2-based materials was crucial for high performance, which was usually realized by applying excessive Mg during syntheses. However, utilization of excessive Mg generates Mg-rich phases between the crystalline boundaries and is unfavorable for the long-term stability of the materials. Here, bulk single crystals with a low-content Mg component such as Mg3.1Bi1.49Sb0.5Te0.01 were successfully grown. For compensating Mg defects, Li was chosen as the additional electron dopant. The results indicate that Li is a very effective electron compensator when low-concentration doping is applied. For high-concentration doping, Mg atoms in the lattice are substituted by Li, leading to decreased electron concentration again. This strategy is very significant for improving the room-temperature performance of Mg3Bi2-based materials. As a result, a record-high figure of merit of 1.05 at 300 K is achieved for Mg3+xLi0.003Bi1.49Sb0.5Te0.01 single crystals.

Nutritional and Body Composition Changes in Paediatric ß-Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Study Using Bioelectrical Impedance Analysis.

Objective: This retrospective study evaluated nutritional status and body composition changes in paediatric ß-thalassemia (ß-TM) patients before and after hematopoietic stem cell transplantation (HSCT), using bioelectrical impedance analysis (BIA), and explored their relationship with HSCT outcomes. Methods: A cohort of 40 paediatric ß-TM patients undergoing allogeneic HSCT was assessed for their nutritional status, anthropometric parameters, including body mass index (BMI), weight, and height, and body composition parameters pre-and post-HSCT, focusing on BIA measurements, including intracellular water (ICW), extracellular water (ECW), fat mass (FAT), fat-free mass (FFM), Skeletal Muscle Mass (SMM), soft Lean Mass (SLM), percent body fat (PBF), Body Cell Mass (BCM), Phase angle (PA) and muscle balance pre- and post-HSCT. Post-HSCT clinical outcomes, including acute graft-vs-host disease (aGVHD), engraftment time, oral mucositis (OM), sinusoidal obstruction syndrome (SOS), and diarrhoea in relation to nutrition status after HSCT were analysed. Results: After HSCT, 28.21% experienced diminished nutritional status, with 71.43% of those who were wasting before HSCT showing diminished nutritional status, significantly higher than the normal group (18.75%, P = 0.012). Anthropometric changes included significant weight reduction (87.5%, 22.15 ± 7.46 vs 20.74 ± 6.57, P < 0.001) and BMI decrease (90%, 15.19 ± 1.70 vs 14.05 ± 1.48, P < 0.001). Body composition parameters, which are FFM, SMM, SLM, ICW, ECW, BCM, and PA (18.26 ± 5.71 vs 17.27 ± 5.19, 8.68 ± 3.30 vs 7.93 ± 3.02, 17.11 ± 5.28 vs 16.06 ± 4.84, 8.19 ± 2.54 vs 7.62 ± 2.31, 5.15 ± 1.58 vs 4.94 ± 1.47, 11.74 ± 3.63 vs 10.92 ± 3.32, 4.42 ± 0.50 vs 3.90 ± 0.57, respectively, P < 0.001) analysis revealed significant decreases. No significant differences in clinical outcomes were observed based on nutritional status. Conclusion: Paediatric ß-TM patients undergoing HSCT exhibit significant changes in nutrition status and body composition, emphasizing the need for focused attention on malnourished children who are more prone to diminished nutritional status. Comprehensive BIA aids in understanding the impact, urging consideration for extended follow-up and larger cohorts in future research.

Causal associations between dietary factors and colorectal cancer risk: a Mendelian randomization study.

Background: Previous epidemiological studies have found a link between colorectal cancer (CRC) and human dietary habits. However, the inherent limitations and inevitable confounding factors of the observational studies may lead to the inaccurate and doubtful results. The causality of dietary factors to CRC remains elusive. Methods: We conducted two-sample Mendelian randomization (MR) analyses utilizing the data sets from the IEU Open GWAS project. The exposure datasets included alcoholic drinks per week, processed meat intake, beef intake, poultry intake, oily fish intake, non-oily fish intake, lamb/mutton intake, pork intake, cheese intake, bread intake, tea intake, coffee intake, cooked vegetable intake, cereal intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake. In our MR analyses, the inverse variance weighted (IVW) method was employed as the primary analytical approach. The weighted median, MR-Egger, weighted mode, and simple mode were also applied to quality control. Heterogeneity and pleiotropic analyses were implemented to replenish the accuracy of the results. Results: MR consequences revealed that alcoholic drinks per week [odds ratio (OR): 1.565, 95% confidence interval (CI): 1.068-2.293, p = 0.022], non-oily fish intake (OR: 0.286; 95% CI: 0.095-0.860; p = 0.026), fresh fruit intake (OR: 0.513; 95% CI: 0.273-0.964; p = 0.038), cereal intake (OR: 0.435; 95% CI: 0.253-0.476; p = 0.003) and dried fruit intake (OR: 0.522; 95% CI: 0.311-0.875; p = 0.014) was causally correlated with the risk of CRC. No other significant relationships were obtained. The sensitivity analyses proposed the absence of heterogeneity or pleiotropy, demonstrating the reliability of the MR results. Conclusion: This study indicated that alcoholic drinks were associated with an increased risk of CRC, while non-oily fish intake, fresh fruit intake, cereal intake, and dried fruit were associated with a decreased risk of CRC. This study also indicated that other dietary factors included in this research were not associated with CRC. The current study is the first to establish the link between comprehensive diet-related factors and CRC at the genetic level, offering novel clues for interpreting the genetic etiology of CRC and replenishing new perspectives for the clinical practice of gastrointestinal disease prevention.

Structural and physicochemical effects on the starch quality of the high-quality wheat genotype caused by delayed sowing.

Background: Bread wheat is one of the most important food crops associated with ensuring food security and human nutritional health. The starch quality is an important index of high-quality wheat. It is affected by a complex series of factors; among which, suitable sowing time is a key factor. Aim and methods: To analyze the integrative effects of sowing time on the starch quality of high-quality wheat, in the present study, we selected a high-quality bread wheat cultivar Jinan 17 and investigated the effect of different sowing times on the starch properties and the related genes by analyzing X-ray diffraction patterns, apparent amylose content, thermal properties, pasting properties, in vitro starch digestibility, and qRT-PCR. Meanwhile, we also investigated the agronomic and yield performance that may be associated with the starch properties. Results: Delayed sowing had little effect on starch crystalline morphology, but there was a tendency to reduce the formation of crystals within wheat starch granules: (1) delayed sowing for 15 days altered the thermal properties of starch, including onset, peak and termination temperatures, and enthalpy changes; (2) delayed sowing for 30 days changed the thermal characteristics of starch relatively insignificant; (3) significant differences in pasting characteristics occurred: peak viscosity and hold-through viscosity increased, while final viscosity, breakdown viscosity, and setback viscosity tended to increase and then decrease, suggesting that delayed sowing caused changes in the surface of the starch granules resulting in a decrease in digestibility. Analysis of related genes showed that several key enzymes in starch biosynthesis were significantly affected by delayed sowing, leading to a reduction in apparent straight-chain starch content. In addition to starch properties, thousand-kernel weight also increased under delayed sowing conditions compared with normal sowing. Conclusion: The impact of delayed sowing on starch quality is multifaceted and complex, from the fine structure, and functional properties of the starch to the regulation of key gene expression. Our study holds significant practical value for optimizing wheat planting management and maximizing the potential in both quality and yield.

Efficacy, safety, and advantages of magnetic anchor-guided endoscopic submucosal dissection vs conventional endoscopic submucosal dissection: A retrospective paired cohort study.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been recommended as the first-line treatment for early gastric cancer (EGC). However, poor visualization of the operative field increases both the procedure time and the risk of complications, especially for large and difficult lesions. We introduced a novel technique, magnetic anchor-guided ESD (MAG-ESD) and compared it with conventional ESD (C-ESD) for the treatment of large EGCs in terms of efficacy, safety, and advantages. METHODS: Patients with large EGCs who underwent MAG-ESD or C-ESD at the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to March 2022 were retrospectively enrolled in this study. The patients in the MAG-ESD cohort were matched to those in the C-ESD cohort using propensity score-based matching. The operation time, submucosal dissection time, complete resection status, magnetic anchor, adverse event rate, and tumor recurrence rate were evaluated. RESULTS: Twenty-two patients who underwent MAG-ESD were ultimately matched to those who underwent C-ESD. The median operation time of MAG-ESD and C-ESD was 43 minutes (IQR, 35.2-49.5) and 50.5 minutes (IQR, 42.0-76.0), respectively, among which the submucosal dissection time was 7.6 minutes (IQR, 5.2-10.4) and 14.8 minutes (IQR, 10.8-19.6), respectively. The operation time of MAG-ESD was shorter than that of C-ESD, especially the submucosal dissection time (P < .05). There was a lower incidence of adverse events associated with MAG-ESD (P < .05) when magnetic anchors were successfully placed and retrieved. CONCLUSION: MAG-ESD is feasible, effective, safe, and simple for the treatment of large EGCs at different sites and has a high anchor success rate, which could shorten the operation time and reduce the adverse event rate.

Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study.

Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.

Bioinformatic Identification and Expression Analyses of the MAPK-MAP4K Gene Family Reveal a Putative Functional MAP4K10-MAP3K7/8-MAP2K1/11-MAPK3/6 Cascade in Wheat (Triticum aestivum L.).

The mitogen-activated protein kinase (MAPK) cascades act as crucial signaling modules that regulate plant growth and development, response to biotic/abiotic stresses, and plant immunity. MAP3Ks can be activated through MAP4K phosphorylation in non-plant systems, but this has not been reported in plants to date. Here, we identified a total of 234 putative TaMAPK family members in wheat (Triticum aestivum L.). They included 48 MAPKs, 17 MAP2Ks, 144 MAP3Ks, and 25 MAP4Ks. We conducted systematic analyses of the evolution, domain conservation, interaction networks, and expression profiles of these TaMAPK-TaMAP4K (representing TaMAPK, TaMAP2K, TaMAP3K, and TaMAP4K) kinase family members. The 234 TaMAPK-TaMAP4Ks are distributed on 21 chromosomes and one unknown linkage group (Un). Notably, 25 of these TaMAP4K family members possessed the conserved motifs of MAP4K genes, including glycine-rich motif, invariant lysine (K) motif, HRD motif, DFG motif, and signature motif. TaMAPK3 and 6, and TaMAP4K10/24 were shown to be strongly expressed not only throughout the growth and development stages but also in response to drought or heat stress. The bioinformatics analyses and qRT-PCR results suggested that wheat may activate the MAP4K10-MEKK7-MAP2K11-MAPK6 pathway to increase drought resistance in wheat, and the MAP4K10-MAP3K8-MAP2K1/11-MAPK3 pathway may be involved in plant growth. In general, our work identified members of the MAPK-MAP4K cascade in wheat and profiled their potential roles during their response to abiotic stresses and plant growth based on their expression pattern. The characterized cascades might be good candidates for future crop improvement and molecular breeding.

[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

A Comprehensive Analysis of the Peanut SQUAMOSA Promoter Binding Protein-like Gene Family and How AhSPL5 Enhances Salt Tolerance in Transgenic Arabidopsis.

SPL (SQUAMOSA promoter binding protein-like), as one family of plant transcription factors, plays an important function in plant growth and development and in response to environmental stresses. Despite SPL gene families having been identified in various plant species, the understanding of this gene family in peanuts remains insufficient. In this study, thirty-eight genes (AhSPL1-AhSPL38) were identified and classified into seven groups based on a phylogenetic analysis. In addition, a thorough analysis indicated that the AhSPL genes experienced segmental duplications. The analysis of the gene structure and protein motif patterns revealed similarities in the structure of exons and introns, as well as the organization of the motifs within the same group, thereby providing additional support to the conclusions drawn from the phylogenetic analysis. The analysis of the regulatory elements and RNA-seq data suggested that the AhSPL genes might be widely involved in peanut growth and development, as well as in response to environmental stresses. Furthermore, the expression of some AhSPL genes, including AhSPL5, AhSPL16, AhSPL25, and AhSPL36, were induced by drought and salt stresses. Notably, the expression of the AhSPL genes might potentially be regulated by regulatory factors with distinct functionalities, such as transcription factors ERF, WRKY, MYB, and Dof, and microRNAs, like ahy-miR156. Notably, the overexpression of AhSPL5 can enhance salt tolerance in transgenic Arabidopsis by enhancing its ROS-scavenging capability and positively regulating the expression of stress-responsive genes. These results provide insight into the evolutionary origin of plant SPL genes and how they enhance plant tolerance to salt stress.

Accuracy and efficacy of ultrasound-guided puncture (vs. computed tomography-guided) in cervical medial branch blocks for cervicogenic pain: A randomized controlled study.

Cervical medial branch block (CMBB) has been recognized as an effective treatment for cervicogenic pain. Previous studies mostly used ultrasound-guided out-of-plane puncture for CMBB, while this prospective study was designed to investigate the efficacy of ultrasound-guided in-plane puncture, specifically focusing on the new target of CMBB for cervical pain. This study includes two parts: the accuracy study (N = 15, CMBB was completed by ultrasound and confirmed by computed tomography [CT], in which a good distribution percentage of the analgesic solution was observed) and the efficacy study (N = 40, CMBB was completed by ultrasound or CT, while the proportion of pain relief (numerical rating scale) decrease by more than 50% postoperatively was analyzed). The results showed that the good distribution percentage of the analgesic solution was 97.8%. Furthermore, in the early period (30 min and 2 h postoperatively), the proportion of patients with pain relief was lower in the ultrasound group than that in the CT group, especially at 2 h postoperatively (52% vs. 94%). However, at 24 h postoperatively and later, the proportion of patients with pain relief gradually stabilized to about 60%-70%, and lasted for about 2 weeks to 1 month. Therefore, the new target for CMBB, guided by ultrasound in-plane, offers high visibility and accuracy. A single CMBB performed under ultrasound guidance resulted in pain relief comparable to that of a CT-guided procedure (1 day to 1 month postoperatively). This study indicated that CMBB guided by ultrasound in-plane could be regarded as a promising approach for treatment of cervicogenic pain.

Differentially expressed genes of esophageal tissue in male acute and chronic sleep deprivation mice.

Gastroesophageal reflux disease (GERD) is associated with sleep disturbances. However, mechanisms underlying these interactions remain unclear. Male acute and chronic sleep deprivation (SD) mice were used for this study. Mice in the chronic SD group exhibited anxiety- and depression-like behaviors. We further performed high-throughput genome sequencing and bioinformatics analysis to screen for featured differentially expressed genes (DEGs) in the esophageal tissue. The acute SD group, comprised 25 DEGs including 14 downregulated and 11 upregulated genes. Compared with the acute SD group, more DEGs were present in the chronic SD group, with a total of 169 DEGs, including 88 downregulated and 81 upregulated genes. Some DEGs that were closely related to GERD and associated esophageal diseases were significantly different in the chronic SD group. Quantitative real-time polymerase chain reaction verified the downregulation of Krt4, Krt13, Krt15 and Calml3 and upregulation of Baxl1 and Per3. Notably, these DEGs are involved in biological processes, which might be the pathways of the neuroregulatory mechanisms of DEGs expression.

Efficacy and safety of pembrolizumab as first-line treatment for advanced non-small cell lung cancer complicated with chronic obstructive pulmonary disease: protocol for a prospective, single-arm, single-center, phase II clinical trial.

Background: The first-line standard treatment option for patients with NSCLC complicated with Chronic obstructive pulmonary disease (COPD) is still unclear and relies on the treatment option of NSCLC alone. To date, a limited number of retrospective studies have explored the efficacy and safety of immunotherapy in patients with NSCLC complicated with COPD. We therefore designed this study to further explore the efficacy and safety of first-line immunotherapy in patients with NSCLC complicated with COPD. Methods: This study was designed as a single-armed, single-center, prospective, phase II clinical study. It will include 30 advanced (stage IV) NSCLC combined with COPD primary treatment subjects. Each subject's diagnosis will be confirmed by clinical, radiographic, pathologic, and pulmonary function evaluation. A fixed dose of 200 mg pembrolizumab will be administered by intravenous infusion on day1 every 3 weeks (Q3W). The management of stable and acute exacerbations of COPD include home oxygen therapy, and the use of conventional medications are also administered. Imaging evaluation will be performed every 6 weeks for 6 months from the first pembrolizumab dose and approximately every 12 weeks thereafter until disease progression or early withdrawal. COPD status will be evaluated every 3 months by pulmonary function, GOLD grading, mMRC score, CAT score, ABCD grouping, and AECOPD severity. The primary outcome is Progression-free survival. The secondary outcome measures include objective response rate, overall survival, rate of acute exacerbations of COPD (times/year), lung function, mMRC score, CAT score, impact of treatment on patient's health-related quality of life, antibiotic use (including duration and classes), and adverse events associated with immune checkpoint inhibitors. Exploratory endpoint is to explore the association between COPD grade and the degree of immune cell (CD4+ T lymphocytes and CD8+ T lymphocytes) infiltration, as well as the association between COPD grade and the efficacy of immune checkpoint inhibitors. Clinical trial registration: ClinicalTrials.gov, identifier NCT05578222.

Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting purine metabolism and polyamine synthesis-associated vascular remodeling.

Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.

HDAC6-selective inhibitor CAY10603 ameliorates cigarette smoke-induced small airway remodeling by regulating epithelial barrier dysfunction and reversing.

BACKGROUND: Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD. METHODS: Cigarette smoke (CS) exposure was used to establish a CS-induced COPD mouse model. CAY10603 at doses of 2.5 and 10 mg/kg was injected intraperitoneally on alternate days. The protective effects of CAY10603 against CS-induced emphysema, epithelial barrier function and small airway remodeling were evaluated using hematoxylin and eosin (H&E) staining, Masson's trichrome staining, immunohistochemical staining, and western blot. The human lung bronchial epithelial cell line (HBE) was used to elucidate the underlying molecular mechanism of action of CAY10603. RESULTS: HDAC6 levels in the lung homogenates of CS-exposed mice were higher than that those in control mice. Compared to the CS group, the mean linear intercept (MLI) of the CAY10603 treatment group decreased and the mean alveolar number (MAN)increased. Collagen deposition was reduced in groups treated with CAY10603. The expression of α-SMA was markedly upregulated in the CS group, which was reversed by CAY10603 treatment. Conversely, E-cadherin expression in the CS group was further downregulated, which was reversed by CAY10603 treatment. CAY10603 affects the tight junction protein expression of ZO-1 and occludin. ZO-1 and occludin expression were markedly downregulated in the CS group. After CAY10603treatment, the protein expression level of ZO-1 and occludin increased significantly. In HBE cells, Cigarette smoke extract (CSE) increased HDAC6 levels. CAY10603 significantly attenuated the release of TGF-ß1 induced by CSE. CAY10603 significantly increased the E-cadherin levels in TGF-ß1 treated HBE cells, while concurrently attenuated α-SMA expression. This effect was achieved through the suppression of Smad2 and Smad3 phosphorylation. CAY10603 also inhibited TGF-ß1 induced cell migration. CONCLUSIONS: These findings suggested that CAY10603 inhibited CS induced small airway remodelling by regulating epithelial barrier dysfunction and reversing EMT via the TGF-ß1/Smad2/3 signalling pathway.

Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development.

Congenital anomalies of the lower genitourinary (LGU) tract are frequently comorbid due to genetically linked developmental pathways, and are among the most common yet most socially stigmatized congenital phenotypes. Genes involved in sexual differentiation are prime candidates for developmental anomalies of multiple LGU organs, but insufficient prospective screening tools have prevented the rapid identification of causative genes. Androgen signaling is among the most influential modulators of LGU development. The present study uses SpDamID technology in vivo to generate a comprehensive map of the pathways actively regulated by the androgen receptor (AR) in the genitalia in the presence of the p300 coactivator, identifying wingless/integrated (WNT) signaling as a highly enriched AR-regulated pathway in the genitalia. Transcription factor (TF) hits were then assayed for sexually dimorphic expression at two critical time points and also cross-referenced to a database of clinically relevant copy number variations to identify 252 TFs exhibiting copy variation in patients with LGU phenotypes. A subset of 54 TFs was identified for which LGU phenotypes are statistically overrepresented as a proportion of total observed phenotypes. The 252 TF hitlist was then subjected to a functional screen to identify hits whose silencing affects genital mesenchymal growth rates. Overlap of these datasets results in a refined list of 133 TFs of both functional and clinical relevance to LGU development, 31 of which are top priority candidates, including the well-documented renal progenitor regulator, Sall1. Loss of Sall1 was examined in vivo and confirmed to be a powerful regulator of LGU development.

Interface-Engineered NiFe/Ni-S Nanoparticles for Reliable Alkaline Oxygen Production at Industrial Current: A Sulfur Source Confinement Strategy.

Using powder-based ink appears to be the most suitable candidate for commercializing the membrane electrode assembly (MEA), while research on the powder-based NPM catalyst for anion exchange membrane water electrolyzer (AEMWE) is currently insufficient, especially at high current density. Herein, a sulfur source (NiFe Layered double hydroxide adsorbed SO 4 2 - ${\mathrm{SO}}_4^{2 - }$ ) confinement strategy is developed to integrate Ni3 S2 onto the surface of amorphous/crystalline NiFe alloy nanoparticles (denoted NiFe/Ni-S), achieving advanced control over the sulfidation process for the formation of metal sulfides. The constructed interface under the sulfur source confinement strategy generates abundant active sites that increase electron transport at the electrode-electrolyte interface and improve ability over an extended period at a high current density. Consequently, the constructed NiFe/Ni-S delivers an ultra-low overpotential of 239 mV at 10 mA cm-2 and 0.66 mA cm ECSA - 2 ${\mathrm{cm}}_{{\mathrm{ECSA}}}^{ - 2}$ under an overpotential of 300 mV. The AEMWE with NiFe/Ni-S anode exhibits a cell voltage of 1.664 V @ 0.5 A cm-2 and a 400 h stability at 1.0 A cm-2 .

The potential predictors for treatment-resistance depression after selective serotonin reuptake inhibitors therapy in Han Chinese: A resting-state functional magnetic resonance imaging study.

AIM: Selective serotonin reuptake inhibitors (SSRIs) are among the most important antidepressants. However, there is limited research on predicting the occurrence of treatment-resistant depression (TRD) after 5 years. Examining the predictive effect of TRD occurrence using resting-state fMRI in patients initiating SSRIs treatment at the onset of major depressive disorder (MDD) could potentially enhance TRD management. METHODS: A total of 60 first-episode drug-naive MDD patients who met the criteria, along with 41 healthy controls of Han Chinese ethnicity, were recruited. All MDD patients received SSRIs as the initial treatment for relieving depressive symptoms. Resting-state fMRI scans were conducted for all subjects. Follow-up assessments were conducted over a period of five years, during which MDD patients were categorized into treatment-resistant depression (TRD) and non-treatment-resistant depression (NRD) groups based on disease progression. Amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and Regional Homogeneity (ReHo) values were calculated and compared among the three groups. Additionally, receiver operating characteristic (ROC) curves were employed to identify potential predictors. RESULTS: After 5 years of follow-up, it was found that 43 MDD patients were classified as NRD, while 17 were classified as TRD. In comparison to TRD, NRD exhibited decreased ALFF in the left middle cingulum gyrus (MCG.L) and in the right middle frontal gyrus (MFG.R), as well as decreased ReHo in MCG.L. Furthermore, NRD showed increased fALFF in the left precuneus (PCUN.L). The area under the curve (AUC) values were as follows: 0.724 (MCG.L by ALFF), 0.732 (MFG.R), 0.767 (PCUN.L), 0.774 (MCG.L by ReHo), 0.878 (combined), 0.547 (HAMD), and 0.408 (HAMA) respectively. CONCLUSION: The findings suggest that PCUN.L, MFG.R, MCG.L, and the combined measures may indicate the possibility of developing TRD after 5 years when SSRIs are used as the initial therapy for relieving depressive symptoms in MDD patients.

Clinical effect of different concentrations of ropivacaine in the labor analgesia of dural puncture epidural technique for obese puerperae.

BACKGROUND: This study was performed to analyze the clinical effect of different concentrations of ropivacaine in the labor analgesia of the dural puncture epidural (DPE) technique for obese puerperae. METHODS: One hundred and fifty first-term obese women who received vaginal delivery and required labor analgesia in our hospital were selected prospectively for this study, and divided into groups A, B, and C. The three groups of puerpera were given epidurals with different concentrations of ropivacaine (0.075%, 0.10%, and 0.125%) with sufentanil (0.5 µg/ml) for the labor analgesia regimen. The visual analog scale (VAS), Ramsay scale, and Bromage scale of puerperae before analgesia and at different time points after anesthesia, and analgesic onset time, analgesia time, first PCEA time, PCEA pressing time, ropivacaine consumption, labor time, maternal blood pressure and heart rate, maternal adverse reactions, blood gas analysis in the neonatal umbilical artery, and Apgar score were observed. RESULTS: The analgesia onset time, PCEA pressing time, and ropivacaine consumption in group C were lower and the analgesia time and the first PCEA time were longer than those in groups A and B. At T1-T3 and T5, VAS scores of group A were higher than those in groups B and C, Ramsay score of group A was lower than that of groups B and C at T2-T3, and Bromage score of group C at any time point was higher than other two groups. The time of the second stage of labor in groups B and C was longer than that in group A, which in group C was longer than that in group B. Compared with groups A and C, the blood pressure and heart rate of puerperae in group B were closer to normal values. Three different concentrations of ropivacaine had no significant effect on the umbilical artery blood gas analysis indices and Apgar scores at 1st minute and 5th minute in neonates. The incidence of maternal adverse reactions in group C was lower than those in groups A and B. CONCLUSION: 0.1% ropivacaine combined with 0.5 µg/ml sufentanil through DPE technique has good analgesic efficacy and few adverse effects in obese puerperae.