[Resveratrol attenuates neuroinflammation and alleviates emotional dysfunction in mice with sepsis-associated encephalopathy through promoting chaperone-mediated autophagy (CMA)].

Objective To elucidate the role of chaperone-mediated autophagy (CMA) in alleviating emotional dysfunction in mice with sepsis-associated encephalopathy (SAE). Methods The SAE mouse model was established by cecal ligation and perforation (CLP). The severity of sepsis was assessed using the sepsis severity score (MSS). Emotional function in SAE mice was assessed by the open-field test and elevated plus-maze. The expression levels of cognitive heat shock cognate protein 70 (HSC70), lysosomal-associated membrane protein 2A (LAMP2A) and high mobility group box 1 protein B1 (HMGB1) were detected using Western blotting. Co-localization of LAMP2A in the hippocampal neurons was observed by immunofluorescence. The release of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was measured using ELISA. Following 12 hours post-CLP, mice were orally administered resveratrol at a dose of 30 mg/kg once daily until day 14. Results The mortality rate of CLP mice was 45.83% 24 days post CLP, and all surviving mice exhibited emotional disturbances. 24 hours after CLP, a significant decrease in HSC70 and LAMP2A expression in hippocampal neurons was observed, indicating impaired CMA activity. Meanwhile, HMGB1 and inflammatory cytokines (IL-6 and TNF-α) levels increased. After resveratrol treatment, an increase of HSC70 and LAMP2A expression, and a decrease of HMGB1 expression and inflammatory cytokine release were observed, suggesting enhanced CMA activity and reduced neuroinflammation. Behavioral tests showed that emotional dysfunction was improved in SAE mice after resveratrol treatment. Conclusion CMA activity of hippocampal neurons in SAE mice is significantly reduced, leading to emotional dysfunction. Resveratrol can alleviate neuroinflammation and emotional dysfunction in SAE mice by promoting CMA and inhibiting the expression of HMGB1 and the release of inflammatory factors.

LINC-p21 Regulates Pancreatic ß-Cell Function in Type 2 Diabetes Mellitus.

This study aimed to investigate the underlying mechanism and assess the biological role of long intergenic non-coding RNA (LINCRNA)-p21 in type 2 diabetes mellitus (T2DM). LINC-p21 and miR-335-3p expression levels were evaluated in blood from T2DM patients, healthy individuals, and mouse islet ß-cell line MIN6 cells grown in a high glucose environment. Apoptosis-related proteins, iNOS, and IGF-1 were detected in vitro and in vivo. Bioinformatics was used to predict that miR-335-3p had complementary binding sites to IGF-1, and a dual-luciferase reporter confirmed the targeting link between LINC-p21 and miR-335-3p. LINC-p21 was highly expressed in the T2DM serum and cells, and LINC-p21 was significantly associated with T2DM prognosis. In vitro and in vivo dysfunction of ß-cells was reduced by LINC-p21 knockdown. MiR-335-3p and IGF-1 may be potential targets of LINC-p21 and miR-335-3p, respectively, after the prediction of the target of LINC-p21 was verified by dual-luciferase assay. Anti-miR-335-3p made LINC-p21 knockdown function again; however, interference of IGF-1 mRNA restored the function of LINC-p21. The miR-335-3p/IGF-1 axis may have a role in the functional protection of pancreatic ß-cells by LINC-p21 silencing, boosting insulin production, and slowing the course of diabetes.

Dezocine as preemptive analgesia alleviates ultrapulse CO2 fractional laser treatment induced pain in patients with acne scars.

BACKGROUND: Ultrapluse CO2 fractional laser technology has emerged as an effective treatment for scar management. However, one drawback of this modality is the pain caused during the procedure. This study aims to explore the efficacy and safety of dezocine (DZC) as preemptive analgesia for reduction of pain induced by ultrapulse CO2 fractional laser treatment for acne scars. METHODS: The study cohort included 78 outpatients with acne scars between February and April 2023. Patients were randomly assigned into three groups with intravenous injection (iv) of DZC prior to laser treatment: (1) control, iv of saline; (2) DZC group 1 (DZC_1), iv of DZC at 0.15 mg/kg; and (3) DZC_2, iv of DZC at 0.20 mg/kg. After 30 min, one session of ultrapulse CO2 fractional laser treatment on acne scars was performed. Hemodynamics, visual analogue scale (VAS), and anxiety visual analog test (AVAT) were monitored prior to, during, and after the procedure. RESULTS: Operative success rates for patients in the control, DZC_1, and DZC_2 groups were 34.6%, 84.6%, and 100%, respectively. DZC administered with either dosage significantly reduced the VAS and AVAT scores of patients in treatment groups as compared with the subjects in the control group during the course of ultrapulse CO2 fractional laser treatment. Patients in DZC_1 and DZC_2 groups did not show any significant difference in hemodynamic parameters, VAS, and AVAT scores. Temporary adverse effects such as nausea and dizziness were observed in some subjects after treatment; the symptoms were quickly dissolved after a rest in supine position. CONCLUSIONS: DZC as preemptive analgesia could effectively reduce pain and anxiety induced by ultrapulse CO2 fractional laser treatment in patients. This study provided an option of preemptive anesthesia to minimize the pain and discomforts associated with laser treatments in clinical practices.

An elastic net regression model for predicting the risk of ICU admission and death for hospitalized patients with COVID-19.

This study aimed to develop and validate prediction models to estimate the risk of death and intensive care unit admission in COVID-19 inpatients. All RT-PCR-confirmed adult COVID-19 inpatients admitted to Fujian Provincial Hospital from October 2022 to April 2023 were considered. Elastic Net Regression was used to derive the risk prediction models. Potential risk factors were considered, which included demographic characteristics, clinical symptoms, comorbidities, laboratory results, treatment process, prognosis. A total of 1906 inpatients were included finally by inclusion/exclusion criteria and were divided into derivation and test cohorts in a ratio of 8:2, where 1526 (80%) samples were used to develop prediction models under a repeated cross-validation framework and the remaining 380 (20%) samples were used for performance evaluation. Overall performance, discrimination and calibration were evaluated in the validation set and test cohort and quantified by accuracy, scaled Brier score (SbrS), the area under the ROC curve (AUROC), and Spiegelhalter-Z statistics. The models performed well, with high levels of discrimination (AUROCICU [95%CI]: 0.858 [0.803,0.899]; AUROCdeath [95%CI]: 0.906 [0.850,0.948]); and good calibrations (Spiegelhalter-ZICU: - 0.821 (p-value: 0.412); Spiegelhalter-Zdeath: 0.173) in the test set. We developed and validated prediction models to help clinicians identify high risk patients for death and ICU admission after COVID-19 infection.

From driver genes to gene families: A computational analysis of oncogenic mutations and ubiquitination anomalies in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a widespread primary liver cancer with a high fatality rate. Despite several genes with oncogenic effects in HCC have been identified, many remain undiscovered. In this study, we conducted a comprehensive computational analysis to explore the involvement of genes within the same families as known driver genes in HCC. Specifically, we expanded the concept beyond single-gene mutations to encompass gene families sharing homologous structures, integrating various omics data to comprehensively understand gene abnormalities in cancer. Our analysis identified 74 domains with an enriched mutation burden, 404 domain mutation hotspots, and 233 dysregulated driver genes. We observed that specific low-frequency somatic mutations may contribute to HCC occurrence, potentially overlooked by single-gene algorithms. Furthermore, we systematically analyzed how abnormalities in the ubiquitinated proteasome system (UPS) impact HCC, finding that abnormal genes in E3, E2, DUB families, and Degron genes often result in HCC by affecting the stability of oncogenic or tumor suppressor proteins. In conclusion, expanding the exploration of driver genes to include gene families with homologous structures emerges as a promising strategy for uncovering additional oncogenic alterations in HCC.

First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.

Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

Reduced graphene oxide-wrapped ZnS-SnS2 heterojunction bimetallic hollow cubic boxes as high-magnification and long lifespan supercapacitor anode materials.

Metal sulfides have attracted extensive attention due to their excellent electrochemical performance. However, issues such as poor conductivity and severe volume expansion during charge and discharge processes affect the applications of sulfides as electrode materials. Here, a combination of coprecipitation and high-temperature sulfidation methods are employed to synthesize a ZnS-SnS2 composite with a hollow cubic structure, which is further composited with reduced graphene oxide (RGO) to form ZnS-SnS2 hollow cubic boxes encapsulated in a conductive framework of reduced graphene oxide (RGO) (denoted as ZnS-SnS2@RGO) for electrode materials. The hollow structure effectively alleviates the pulverization of ZnS-SnS2@RGO caused by volume expansion during charge and discharge processes. The heterogeneous structure formed by ZnS and SnS2 effectively reduces the electron transfer resistance of the material. The use of RGO wrapping enhances the conductivity of the ZnS-SnS2 hollow cubic boxes, and RGO's dispersion effect on the ZnS-SnS2 cubes improves particle agglomeration, further mitigating volume expansion of the material. These results indicate the outstanding electrochemical performance of heterostructural ZnS-SnS2 hollow cubic electrodes encapsulated with reduced graphene oxide as a conductive framework. The fabrication process provides a novel approach for addressing volume expansion and poor conductivity issues in other pseudocapacitive materials.

Machine learning and multi-omics data reveal driver gene-based molecular subtypes in hepatocellular carcinoma for precision treatment.

The heterogeneity of Hepatocellular Carcinoma (HCC) poses a barrier to effective treatment. Stratifying highly heterogeneous HCC into molecular subtypes with similar features is crucial for personalized anti-tumor therapies. Although driver genes play pivotal roles in cancer progression, their potential in HCC subtyping has been largely overlooked. This study aims to utilize driver genes to construct HCC subtype models and unravel their molecular mechanisms. Utilizing a novel computational framework, we expanded the initially identified 96 driver genes to 1192 based on mutational aspects and an additional 233 considering driver dysregulation. These genes were subsequently employed as stratification markers for further analyses. A novel multi-omics subtype classification algorithm was developed, leveraging mutation and expression data of the identified stratification genes. This algorithm successfully categorized HCC into two distinct subtypes, CLASS A and CLASS B, demonstrating significant differences in survival outcomes. Integrating multi-omics and single-cell data unveiled substantial distinctions between these subtypes regarding transcriptomics, mutations, copy number variations, and epigenomics. Moreover, our prognostic model exhibited excellent predictive performance in training and external validation cohorts. Finally, a 10-gene classification model for these subtypes identified TTK as a promising therapeutic target with robust classification capabilities. This comprehensive study provides a novel perspective on HCC stratification, offering crucial insights for a deeper understanding of its pathogenesis and the development of promising treatment strategies.

Global Trends and Hotspots in Pediatric Anesthetic Neurotoxicity Research: A Bibliometric Analysis From 2000 to 2023.

The impact of general anesthetics on brain function development is one of the top frontier issues of public concern. However, little bibliometric analysis has investigated this territory systematically. Our study aimed to visualize the publications between 2000 and 2023 to inspire the trends and hotspots in anesthetic neurodevelopmental toxicity research. Publications from 2000 to 2023 were collected from the Web of Science Core Collection. CiteSpace was utilized to plot and analyze the network maps of countries, institutions, authors, journals, and keywords associated with these publications. A total of 864 publications, consisting of 786 original articles and 78 reviews, were extracted from 2000 to 2023. The annual publications have increased constantly over the past two decades. The USA and the People's Republic of China were the leading driving forces in this field. Harvard University was the most productive institution. Zhang Y published the most related articles, and Jevtovic-Todorovic V was mostly cited in this field. The most prolific journal was Pediatric Anesthesia, and the most frequently co-cited journal was Anesthesiology. Keywords were divided into nine clusters: "apoptosis", "propofol", "developing brain", "cognitive dysfunction", "neuronal cell degeneration", "brain", "neuroinflammation", "local anesthesia", and "oxygen therapy". The strongest citation bursts in earlier years were "learning disability", "cell death", and "cognitive function". The emerging trends in the coming years were "awake regional anesthesia", "behavioral outcome", and "infancy general anesthesia compared to spinal anesthesia". We conclude that anesthetic-induced neurotoxicity has received growing attention in the past two decades. Our findings evaluated the present status and research trends in this area, which may provide help for exploring further potential prospects on hot topics and frontiers.

Transcriptomic and metabolomic insights into the antimony stress response of tall fescue (Festuca arundinacea).

Antimony (Sb) is a toxic heavy metal that severely inhibits plant growth and development and threatens human health. Tall fescue, one of the most widely used grasses, has been reported to tolerate heavy metal stress. However, the adaptive mechanisms of Sb stress in tall fescue remain largely unknown. In this study, transcriptomic and metabolomic techniques were applied to elucidate the molecular mechanism of the Sb stress response in tall fescue. These results showed that the defense process in tall fescue was rapidly triggered during the early stages of Sb stress. Sb stress had toxic effects on tall fescue, and the cell wall and voltage-gated channels are crucial for regulating Sb permeation into the cells. In addition, the pathway of glycine, serine and threonine metabolism may play key roles in the Sb stress response of tall fescue. Genes such as ALDH7A1 and AGXT2 and metabolites such as aspartic acid, pyruvic acid, and biuret, which are related to biological processes and pathways, were key genes and compounds in the Sb stress response of tall fescue. Therefore, the regulatory mechanisms of specific genes and pathways should be investigated further to improve Sb stress tolerance.

High-fat diet induces sarcopenic obesity in natural aging rats through the gut-trimethylamine N-oxide-muscle axis.

INTRODUCTION: The lack of suitable animal models for sarcopenic obesity (SO) limits in-depth research into the disease. Emerging studies have demonstrated that gut dysbiosis is involved in the development of SO. As the importance of microbial metabolites is starting to unveil, it is necessary to comprehend the specific metabolites associated with gut microbiota and SO. OBJECTIVES: We aimed to investigate whether high-fat diet (HFD) causes SO in natural aging animal models and specific microbial metabolites that are involved in linking HFD and SO. METHODS: Young rats received HFD or control diet for 80 weeks, and obesity-related metabolic disorders and sarcopenia were measured. 16S rRNA sequencing and non-targeted and targeted metabolomics methods were used to detect fecal gut microbiota and serum metabolites. Gut barrier function was evaluated by intestinal barrier integrity and intestinal permeability. Trimethylamine N-oxide (TMAO) treatment was further conducted for verification. RESULTS: HFD resulted in body weight gain, dyslipidemia, impaired glucose tolerance, insulin resistance, and systemic inflammation in natural aging rats. HFD also caused decreases in muscle mass, strength, function, and fiber cross-sectional area and increase in muscle fatty infiltration in natural aging rats. 16S rRNA sequencing and nontargeted and targeted metabolomics analysis indicated that HFD contributed to gut dysbiosis, mainly characterized by increases in deleterious bacteria and TMAO. HFD destroyed intestinal barrier integrity and increased intestinal permeability, as evaluated by reducing levels of colonic mucin-2, tight junction proteins, goblet cells and elevating serum level of fluorescein isothiocyanate-dextran 4. Correlation analysis showed a positive association between TMAO and SO. In addition, TMAO treatment aggravated the development of SO in HFD-fed aged rats through regulating the ROS-AKT/mTOR signaling pathway. CONCLUSION: HFD leads to SO in natural aging rats, partially through the gut-microbiota-TMAO-muscle axis.

Restraining the shuttle effect of polyiodides and modulating the deposition of zinc ions to enhance the cycle lifespan of aqueous Zn-I2 batteries.

The boom of aqueous Zn-based energy storage devices, such as zinc-iodine (Zn-I2) batteries, is quite suitable for safe and sustainable energy storage technologies. However, in rechargeable aqueous Zn-I2 batteries, the shuttle phenomenon of polyiodide ions usually leads to irreversible capacity loss resulting from both the iodine cathode and the zinc anode, and thus impinges on the cycle lifespan of the battery. Herein, a nontoxic, biocompatible, and economical polymer of polyvinyl alcohol (PVA) is exploited as an electrolyte additive. Based on comprehensive analysis and computational results, it is evident that the PVA additive, owing to its specific interaction with polyiodide ions and lower binding energy, can effectively suppress the migration of polyiodide ions towards the zinc anode surface, thereby mitigating adverse reactions between polyiodide ions and zinc. Simultaneously, the hydrogen bond network of water molecules is disrupted due to the abundant hydroxyl groups within the PVA additive, leading to a decrease in water activity and mitigating zinc corrosion. Further, because of the preferential adsorption of PVA on the zinc anode surface, the deposition environment for zinc ions is adjusted and its nucleation overpotential increases, which is favorable for the dense and uniform deposition of zinc ions, thus ensuring the improvement of the performance of the Zn-I2 battery. This investigation has inspired the development of a user-friendly and high-performance Zn-I2 battery.

Unraveling intestinal microbiota's dominance in polycystic ovary syndrome pathogenesis over vaginal microbiota.

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women, intricately linked to hormonal imbalances. The microbiota composition plays a pivotal role in influencing hormonal levels within the body. In this study, we utilized a murine model to investigate how intestinal and vaginal microbiota interact with hormones in the development of PCOS. Methods: Twenty female mice were randomly assigned to the normal group (N) and the model group (P), where the latter received daily subcutaneous injections of 0.1 mL DHEA (6 mg/100 g). Throughout the experiment, we evaluated the PCOS mouse model by estrus cycle, serum total testosterone (T), prolactin (PRL) and luteinizing hormone (LH) levels, and ovarian pathological morphology. The microbial composition in both intestinal content and vaginal microbiota were studied by 16S rRNA gene high-throughput sequencing. Results: Compared with the N group, the P group showed significant increases in body weight, T, and PRL, with significant decrease in LH. Ovaries exhibited polycystic changes, and the estrous cycle was disrupted. The intestinal microbiota result shows that Chao1, ACE, Shannon and Simpson indexes were decreased, Desulfobacterota and Acidobacteriota were increased, and Muribaculaceae, Limosilactobacillus and Lactobacillus were decreased in the P group. T was significantly positively correlated with Enterorhabdus, and LH was significantly positively correlated with Lactobacillus. The analysis of vaginal microbiota revealed no significant changes in Chao1, ACE, Shannon, and Simpson indices. However, there were increased in Firmicutes, Bacteroidota, Actinobacteriota, Streptococcus, and Muribaculaceae. Particularly, Rodentibacter displayed a robust negative correlation with other components of the vaginal microbiota. Conclusion: Therefore, the response of the intestinal microbiota to PCOS is more significant than that of the vaginal microbiota. The intestinal microbiota is likely involved in the development of PCOS through its participation in hormonal regulation.

The Roles of Circular RNAs in Ischemic Stroke through Modulating Neuroinflammation.

Ischemic stroke (IS) remains a serious threat to human health. Neuroinflammatory response is an important pathophysiological process after IS. Circular RNAs (circRNAs), a member of the non-coding RNA family, are highly expressed in the central nervous system and widely involved in regulating physiological and pathophysiological processes. This study reviews the current evidence on neuroinflammatory responses, the role of circRNAs in IS and their potential mechanisms in regulating inflammatory cells, and inflammatory factors affecting IS damage. This review lays a foundation for future clinical application of circRNAs as novel biomarkers and therapeutic targets.

Comparison of different genetic testing modalities applied in paediatric patients with steroid-resistant nephrotic syndrome.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) are monogenic in some cases, however, there are still no clear guidelines on genetic testing in the clinical practice of SRNS in children. METHODS: Three hundred thirty-two children were diagnosed with SRNS, and all children underwent genetic testing, including gene panels and/or whole-exome/genome sequencing (WES/WGS), during treatment. We analysed the relationship between clinical manifestation and genotype, and compared different genetic testing methods' detection rates and prices. RESULTS: In this study, 30.12% (100/332) of children diagnosed with SRNS had monogenic causes of the disease. With 33.7% (122/332) of children achieving complete remission, 88.5% (108/122) received steroids combined with tacrolimus (TAC). In detectability, WES increased by 8.69% (4/46) on gene panel testing, while WGS increased by 4.27% (5/117) on WES, and WES was approximately 1/7 of the price of WGS for every further 1% increase in pathogenicity. CONCLUSIONS: We verified that steroids combined with TAC were the most effective option in paediatric SRNS. In detection efficiency, we found that WGS was the highest, followed by WES. The panel was the lowest, but the most cost-effective method when considering the economic-benefit ratio, and thus it should be recommended first in SRNS.

A papain-based colorimetric catalytic sensing system for immunoassay detection of carcinoembryonic antigen.

A colorimetric immunoassay was built for determination of carcinoembryonic antigen (CEA) based on papain-based colorimetric catalytic sensing system through the use of glucose oxidase (GOx). In the presence of GOx, glucose was catalytically oxidized to produce H2O2. Through the assistance of papain (as a peroxide mimetic enzyme), the signal came from the oxidative color development of 3,3',5,5'-tetramethylbenzidine (TMB, from colorless to blue) catalyzed by the generated H2O2. Herein, a sandwich-type immunoassay was built based on GOx as labels. As the concentration of CEA increased, more GOx-labeled antibodies specifically associate with target, which leaded to more H2O2 generation. Immediately following this, more TMB were oxidized with the addition of papain. Accordingly, the absorbance increased further. As a result, the concentration of CEA is positively correlated with the change in absorbance of the solution. Under optimal conditions, the CEA concentration was linear in the range of 0.05-20.0 ng/mL, and the limit of detection (LOD) reached 37 pg/mL. The papain-based colorimetric immunoassay also exhibited satisfactory repeatability, stability, and selectivity.

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort.

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97-9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.

[Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy]. / ç‰›å¥¶è›‹ç™½è¿‡æ•å©´å„¿è‚ é“èŒç¾¤ç‰¹å¼‚æ€§å˜åŒ–åŠçŸ­é“¾è„‚è‚ªé ¸æ°´å¹³åˆ†æž.

OBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA. METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites. RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05). CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.

The Substitution of Fishmeal with Yeast Culture in the Yellow Catfish (Pelteobagrus fulvidraco) Diet: Growth, Serum Biochemical Indices, and Intestinal and Hepatopancreatic Histology.

Yeast culture is a complex fermentation product consisting of fermentation substrate, yeast cells and their metabolites. This study investigated the potential of yeast culture in replacing fishmeal in the diet of yellow catfish (Pelteobagrus fulvidraco). First, a basal diet was formulated to contain 160 g/kg fishmeal (CON), and then the dietary fishmeal was decreased to 120, 80, 40 and 0 g/kg via yeast culture inclusion, respectively, to form another four isonitrogenous and isolipidic diets (YC-12, YC-8, YC-4 and YC-0). Yellow catfish (3.00 ± 0.10 g) were fed with the above five diets with triplicates per treatment and 40 fish per replicate. After 8 weeks of feeding, the weight gain (WG), protein efficiency rate and protein retention in the YC-12 group and the feed conversion ratio (FCR) in the YC-12 and YC-8 groups showed no significant differences to the CON group (p > 0.05), but the WG in the YC-8, YC-4 and YC-0 groups was significantly lower, and the FCR in the YC-4 and YC-0 groups was significantly higher than in the CON group (p < 0.05). In terms of the whole-body composition, only the crude lipid content in the YC-0 group decreased significantly (p < 0.05). Compared with the CON group, the aspartate aminotransferase and alanine aminotransferase activities and D-lactic acid content in the YC-0 group were significantly increased, and the total cholesterol content was significantly reduced (p < 0.05). The activities of catalase, superoxide dismutase, and alkaline phosphatase, as well as the content of complement C3 and immunoglobulin M, were significantly increased, while the MDA content was significantly reduced in the YC-12 and YC-8 groups (p < 0.05). There were no significant differences in the intestinal amylase and lipase activity among all the groups (p > 0.05), while the trypsin activity in the YC-12 and YC-8 groups, as well as the diamine oxidase in the YC-4 and YC-0 groups, were significantly higher than those in the CON group (p < 0.05). In the intestine histology, there was a significant decrease in the intestinal villus height in the YC-4 and YC-0 groups as well as in the villus width in the YC-0 group (p < 0.05). In the hepatopancreas histology, lipid droplets appeared in the YC-4 and YC-0 groups, and severe cell vacuolation was observed in the YC-0 group. As a summary, in a practical diet containing 160 g/kg fishmeal, yeast culture can effectively replace 40 g/kg fishmeal without negatively affecting the growth performance, nutrient utilization, serum immune and antioxidant, intestinal and hepatopancreas histology of yellow catfish.

Summary of the best evidence for the prevention of nasal injury in preterm infants with nasal noninvasive ventilation.

Background: Due to immaturity, the nose of preterm infants can easily be injured, by even a short application of a nasal device. However, 20% to 60% of preterm infants suffer nasal damage while using nasal continuous positive airway pressure (NCPAP) due to weak skin tissue, prolonged use of nasal device, and improper nursing practices, leading to increased risk of infection and decreased compliance and tolerance. In this study, we retrieved, obtained and integrated the related evidences of prevention of nasal injury in premature infants with nasal noninvasive ventilation to provide reference for clinical practice. Methods: We searched the relevant guidelines, expert consensus, evidence summaries and systematic reviews in the databases and guideline websites of the National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), the Agency for Health care Research and Quality (AHRQ), Guidelines International Network (GIN), the World Health Organization (WHO) guideline websites, Registered Nurses' Association of Ontario (RANO), Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN), European Pressure Ulcer Advisory Panel (EPUAP), Yi Maitong, British Medical Journal best-practice, Cochrane Library, UpToDate, Embase, PubMed, China National Knowledge Infrastructure (CNKI), Wanfang. The search was limited to the time of library establishment to February 2023. Results: In total, 16 articles were included, including six guidelines, three expert consensuses, two evidence summaries and five systematic reviews. Twenty-eight pieces of evidence were summarized from six aspects: risk assessment, ventilation and connection, skin protection, skin assessment, training and support, and continuous quality improvement. Conclusions: This study summarized the best evidence for the prevention of nasal injury in premature infants through nasal noninvasive ventilation. It is suggested that nurses should consider the actual clinical situation when applying the suggestions from the evidence, formulate corresponding nursing measures, and reduce the occurrence of nasal injury in premature infants.