Numerous studies have established a link between hypertension (HTN) and a high-salt diet (HSD). However, the precise mechanisms are still being investigated, with increasing evidence suggesting that HSD can alter the gut microbiome balance, influence the production of microbiome metabolites and potentially lead to high blood pressure, presenting a promising avenue for targeting specific microbiota in HTN treatment. Short-chain fatty acids (SCFAs) are produced by gut bacteria and are associated with blood pressure regulation. Thus, the relationships among HSD, SCFAs, and blood pressure could provide valuable information on the pathophysiology of HTN. This study aimed to assess the impact of HSD on HTN by investigating its influence on the gut microbiota composition and SCFA levels in a rat model of HTN.

The HTN rat model was constructed by placing the rats on HSD (8% NaCl) for 8 weeks. On the 8th week, fecal samples were collected from the rats for DNA extraction. The profile of the gut microbiota was subsequently evaluated through 16S rRNA sequencing. The fecal SCFAs were subsequently measured and analyzed.

Analysis of 16S rRNA sequencing data revealed that consumption of HSD was associated with an increase in pathogenic bacteria, including Turicibacter and Clostridia_UCG-014, and a decrease in beneficial bacteria, including Bifidobacterium and Lactobacillus. Metabolomic analysis of fecal samples suggested that HSD could increase the concentrations of most SCFAs, except caproic acid. Notably, a significant correlation was observed through Spearman correlation analysis between SCFAs and the changes in the gut microbiota caused by HSD, leading to a direct effect on SCFA levels.

The alterations in the gut microbiota resulting from HSD impact the levels of SCFAs, potentially disrupting gut equilibrium and initiating HTN, thereby increasing susceptibility to cardiovascular disease and associated health complications.

ZW10 interacting kinetochore protein (ZWINT) has been demonstrated to play a pivotal role in the growth, invasion, and migration of cancers. Nevertheless, whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive. This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.

We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis. The approach included the Breast Cancer Gene-Expression Miner v5.1 (bc-GenExMiner v5.1), TNMplot, MuTarget, PrognoScan database, and Database for Annotation, Visualization, and Integrated Discovery (DAVID).

Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer. ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1 (CDH1) and tumor protein p53 (TP53), suggesting potential functional crosstalk in tumor progression pathways. The overexpression of ZWINT correlated with adverse clinical outcomes, showing 48% increased mortality risk (overall survival: HR 1.48, 95% CI 1.23–1.79), 66% higher recurrence probability (relapse-free survival: 1.66, 95% CI 1.50–1.84), and 63% elevated metastasis risk (distant metastasis-free survival: HR 1.63, 95% CI 1.39–1.90). Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant (P < 0.001, Harrell’s C-index = 0.7827), which was validated through bootstrap resampling (1000 iterations).

ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.

The molecular mechanisms of early-onset multigenerational diabetes remain unknown. This study aimed to investigate the clinical and genetic characteristics of early-onset diabetes involving at least two consecutive generations.

From 1296 inpatients with diabetes, we selected individuals who were ≤ 30 years of age and who were clinically suspected of having familial monogenic diabetes. Clinical data were collected from the probands and their family members. Whole-exome sequencing (WES) was used to identify possible causal variants for diabetes. Candidate pathogenic variants were verified by Sanger sequencing, assessed for cosegregation in family members, and evaluated on the basis of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines. Moreover, missense and synonymous variants were subjected to in silico pathogenicity prediction via MutationTaster and PolyPhen-2. RNAfold was used to predict RNA structural alterations for synonymous variants.

Twenty-five early-onset diabetes patients with a history of familial diabetes were enrolled. Pathogenic/likely pathogenic variants (p.Gly292fs in HNF1A, p.Gly245Argfs*22 in PDX1, p.Asp329His in KCNJ11, p.Leu734Phe and p.Val606Gly in WFS1) were detected in four patients, who were diagnosed accurately and treated with reasonable hypoglycemic agents based on genetic testing results. The variants of uncertain significance (ABCC8 c.3039 G > A (p.Ser1013 = Ser), MAPK8IP1 p.Gln144_Gly145insSerGln, and TBC1D4 p.Arg1249Trp) were identified in three probands.

Patients with early-onset diabetes involving at least two consecutive generations may harbor genetic variants. Genetic testing in this population enables precision diagnosis, informs individualized treatment, and facilitates genetic counseling.

Immune infiltration and ferroptosis play pivotal roles in the progression of diabetic kidney disease (DKD). However, investigations of immune cell-related ferroptosis genes (ICRFGs) in the context of DKD are insufficient. This study aimed to identify ICRFGs relevant to DKD and screen related inhibitors.

In this study, two DKD datasets from the GEO database were utilized. We adopted the ESTIMATE algorithm to generate microenvironment scores. The CIBERSORT and WGCNA methods were employed to identify immune-related differentially expressed genes (DEGs). The common ICRFGs were derived through a Venn diagram. We employed random forest, LASSO, K-M survival, receiver operating characteristic (ROC) curve, clinical relevance, and Spearman correlation analyses to select hub ICRFGs further. Immunohistochemical experiments were also performed to validate the expression. Additionally, we utilized the Selleck database to obtain ferroptosis-related compounds and used USCF Chimera 1.14 to minimize energy, combined with molecular dynamics (MD) simulations to explore possible ferroptosis inhibitors.

Immunohistochemical analysis revealed that arachidonate 5-lipoxygenase (ALOX5) was significantly highly expressed in the db/db group. Clinical correlation and K-M survival analyses confirmed ALOX5 as the most crucial ICRFG in DKD. Furthermore, ALOX5 was significantly enriched in the terms ECM-receptor interaction, regulation of chemokine production, and regulation of the inflammatory response. A positive correlation was observed between ALOX5 and M1 macrophages, γδ T cells, and monocytes. Moreover, virtual screening and MD revealed NSC348884, salvianolic acid B, and deltarasin as potential ferroptosis inhibitors in combination with ALOX5.

We identified ALOX5 as a reliable and prospective diagnostic marker associated with immunity and ferroptosis in DKD patients.

The pathogenesis and progression of heart failure (HF) are governed by complex, interconnected biological pathways, with dysregulated immune responses and maladaptive cardiac remodeling playing central roles. Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.

Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy (HCM) transcriptomic datasets identified pathologically relevant candidate genes. A protein-protein interaction (PPI) network was constructed from these candidates using the STRING database, followed by module analysis. Serum S100 calcium-binding protein A9 (S100A9) protein expression in HF patients was quantified by Western blotting under reducing conditions. The functional relevance of prioritized genes was subsequently validated through: (i) in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes, and (ii) in vivo pressure overload modeling via transverse aortic constriction (TAC) in mice.

Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling. Using CytoNCA, we identified core genes, among which the top 25 included multiple inflammatory pathway-related factors, such as S100A9 and Toll-like receptor 2 (TLR2). Notably, S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes. This increase correlated with upregulated expression of hypertrophy-related markers, including atrial natriuretic peptide (ANP). Furthermore, mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes. Importantly, TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression, as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.

The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes. This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.

Myocardial infarction (MI) and postmyocardial remodeling are the most common causes of heart failure worldwide and seriously affect the quality of life and prognosis of patients. Dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, is a novel class of hypoglycemic drug that has been proven to have cardiovascular protective effects. However, the underlying mechanisms by which dapagliflozin affects MI have yet to be elucidated.

An MI mouse model was created by ligating the left anterior descending branch of the coronary artery. Hematoxylin‒eosin (HE) and Masson’s trichrome (Masson) staining were used to assess myocardial damage. The levels of fibrosis-related and cuproptosis-related markers were assessed via Western blot analysis. A hypoxia-induced cardiomyocyte fibrosis model was constructed in vitro. The DCFH-DA probe was used to measure the levels of reactive oxygen species (ROS), and flow cytometry was used to identify cell apoptosis.

Dapagliflozin improved heart function, ameliorated fibrosis in the myocardium, and alleviated myocardial injury. Moreover, dapagliflozin reduced the copper ion concentration and ROS accumulation and inhibited the expression of cuproptosis-related markers. Dapagliflozin suppressed the expression of HIF-1α/TGF-β signal and the overexpression of HIF-1α effectively reversed the dapagliflozin-mediated myocardial protective effects.

Dapagliflozin reduced myocardial fibrosis by suppressing HIF-1α/TGF-β-mediated cuproptosis.

Electronic cigarettes (ECs) differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling. Pulmonary hypertension (PH), characterized by pulmonary artery and right ventricle remodeling, poses a significant risk of mortality in infants, children, and adolescents. However, the impact of maternal EC exposure on PH development in offspring remains unclear. To address this, we established a PH rat model with maternal EC exposure.

Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems. Offspring were administered monocrotaline (MCT) at 6 weeks of age (6-wo) to induce PH. Mechanistic experiments were conducted at 10-week-old (10-wo). Protein expression of NADPH oxidases, DNA methyltransferases, and autophagy-related markers was analyzed by Western blot. Morphological changes and the severity of PH were evaluated via hematoxylin and eosin (HE) staining and echocardiography, respectively. Furthermore, the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA, Western blot, HE staining, and echocardiography. Additionally, ATG5 mRNA expression was measured by qRT-PCR.

Compared with control conditions, maternal EC exposure significantly worsened MCT-induced PH in male offspring. This was associated with increased oxidative stress, DNA hypomethylation, and anomalous autophagy in the offspring. In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC. Furthermore, N-acetylcysteine (NAC), an antioxidant, attenuated maternal EC exposure-induced oxidative stress, DNA hypomethylation, and excessive autophagy, thereby improving PH. DNA hypermethylation also reversed PH development, accompanied by reduced oxidative stress and suppressed autophagy. ATG5, a key regulator of autophagy, was identified as a potential therapeutic target, as its repression mitigated PH in maternal EC-exposed offspring.

Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring, leading to anomalous autophagy and exacerbation of PH development. Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.

Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery, with all offspring undergoing PH induction at 6-wo. Offspring exposed to maternal EC presented increased oxidative stress, which in turn affected DNA methylation patterns. The decreased DNA methylation in male offspring led to the activation of autophagy, exacerbating the development of PH. Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.

This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy (SIC) in sepsis patients.

We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital (Central Campus and East Campus), and Shenxian People’s Hospital from January 2019 to September 2024. We used Kaplan-Meier analysis to assess survival outcomes. LASSO regression identified predictive variables, and logistic regression was employed to analyze risk factors for pre-SIC. A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Among 309 patients, 236 were in the training set, and 73 were in the test set. The pre-SIC group had higher mortality (44.8% vs. 21.3%) and disseminated intravascular coagulation (DIC) incidence (56.3% vs. 29.1%) than the non-SIC group. LASSO regression identified lactate, coagulation index, creatinine, and SIC scores as predictors of pre-SIC. The nomogram model demonstrated good calibration, with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort. DCA confirmed the model’s clinical utility.

SIC is associated with increased mortality, with pre-SIC further increasing the risk of death. The nomogram-based prediction model provides a reliable tool for early SIC identification, potentially improving sepsis management and outcomes.

Sepsis-induced acute lung injury (ALI) poses a critical challenge in critical care, yet its immunoregulatory mechanisms remain poorly defined. This study aimed to delineate immune dysregulation networks and identify therapeutic targets through multiomics data integration.

Transcriptomic datasets (GSE40180 and GSE165226) were analyzed through a multiphase bioinformatics workflow, including gene set enrichment analysis (GSEA), immune cell deconvolution (CIBERSORT), differential gene expression profiling (|log2FC|> 1.5, P.adj < 0.05), and pathway annotation (GO/KEGG). Protein–protein interaction (PPI) networks were constructed to identify hub genes. Experimental validation was done using a murine cecal ligation and puncture (CLP) model with histopathological lung injury scoring and RT-qPCR-based hub gene verification.

Integrated analysis revealed 26 consensus biological processes (24 upregulated, 2 downregulated) dominated by innate immune activation. CIBERSORT revealed significant infiltration of M1 macrophages, neutrophils, activated dendritic cells (DCs), and activated natural killer (NK) cells in septic lungs, which was concurrent with Th17/naive CD8+ T-cell dysregulation. Among the 58 differentially expressed genes (DEG), 7 hub genes (Cxcl1, Cxcl2, Ccl3, Cd14, Saa3, Timp1, and Socs3) were significantly correlated with immune cell dynamics. CLP modeling confirmed severe alveolar damage (lung injury score: 8.11 ± 1.17 vs. 1.97 ± 0.29; P < 0.0001) and upregulated hub gene expression (all P < 0.01) in septic lungs, with hub gene expression levels strongly correlated with the lung injury score (Pearson’s r > 0.85, P < 0.001).

Innate adaptive immune crosstalk, particularly dysregulated immune cell infiltration, drives sepsis-induced ALI pathogenesis. The 7 hub genes mechanistically connect immune dyshomeostasis to tissue injury, suggesting novel targets for precision immunomodulation and biomarker development in critical care.

Current autosomal short tandem repeat (STR) assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles (CHM), with a maternal genotype serving as an essential reference for comparative analysis. However, their application in pathology represents a challenge because of deficiency or contamination of maternal-origin tissues. This study aimed to develop a novel STR genotyping method for identifying CHM genotypes without a maternal component.

Samples with the pathologic description of molar pregnancy were collected. Routine hematoxylin–eosin (HE) staining and p57 immunohistochemistry staining were conducted in accordance with standard guidelines. A novel 26-plex system was explored to classify CHM and diploid pregnancies. The system combined 22 STRs on chromosomes 21/18/13/X, 3 sex loci, and 1 quality control marker (TAF9L), enabling molecular diagnosis in the absence of maternal tissue. At last, traditional DNA typing based on villi and decidua (maternal component) of each case was used for result consistency analysis.

CHM and nonmolar abortus could not be distinguished by the basic HE staining with no fetal evidence or other prominent features. DNA typing was successfully processed for all cases according to the novel 26-plex and traditional system. CHM (46XX) diagnosis required single A-STR/X-STR peaks and absent Y-chromosome markers, excluding chromosomal abnormalities via TAF9L analysis. When the villous tissue analysis revealed single peaks at X-STR/SRY loci, a 1:1 amelogenin ratio, and a 2:1 TAF9L peak ratio, these results overlapped with those of 46XY hydropic abortus or CHM. Notably, p57 immunohistochemical staining resolved the ambiguity. Consistency with traditional DNA genotyping confirmed system accuracy. This multiplex assay enhanced reliability in mole diagnosis, supporting clinical differentiation and genetic counseling.

This study presents a rapid and cost-effective assay for the genotypic identification of CHM without the need for a maternal component. The method combined the characteristics of STR loci distributed across different chromosomes and developed the clinic application of forensic biomarkers.

Sleep is fundamental to the physical and mental health of both the general population and pregnant women. Most studies have focused on the impact of certain trimester sleep behaviors on gestational complications and birth outcomes. This study aimed to explore the association between maternal sleep duration and fetal growth development from as early as 23 gestational weeks to birth.

A total of 803 pregnant women were prospectively enrolled. The self-reported maternal nocturnal sleep duration during all 3 trimesters was recorded. The outcome measures were reference-population-based Z-scores of fetal biometric measurements obtained through routine ultrasonographic examination.

Using multiple linear regression, a marginally significant negative association was observed between second-trimester sleep duration and second-trimester fetal head circumference (HC) and third-trimester fetal biparietal diameter (BPD). Then the associations of long sleep duration in each trimester with fetal biometry extreme values were evaluated. A significant impact of second-trimester long sleep duration on the second-trimester BPD below the 10th percentile of the reference population was observed. Longitudinal analysis reported similar results for BPD and HC.

Overall, a negative association between sleep duration and fetal biometric measurements was observed. Long sleep durations in the second trimester might negatively impact fetal growth, particularly brain parameters, including BPD and HC.

This is a self-controlled multicenter retrospective study based on the clinical efficacy and complications of physiological reconstruction in the treatment of moderate and severe pelvic organ prolapse.

From December 2014 to August 2021, 517 women were included and registered for physiological reconstruction at four Chinese urogynecology institutions. We enrolled 364 women with POP-Q stage ≥ 3. The degree of POP was quantified via a POP-Q system. The surgical purpose of physiological reconstruction is to repair the vagina, levator ani muscle, perineum, and urogenital hiatus and adopt a repair method in accordance with the axial direction of physiology. All 330 evaluable participants were followed for 2 years. The evaluation indices included the PFDI-20, PGI-I, PFIQ-7, PISQ-12, PGI-I, and PGI-S. All complications were coded according to the category-time-site system proposed by the International Urogynecological Association (IUGA) and International Continence Society (ICS).

Compared with the preoperative POP-Q scores, statistically significant improvements were observed at the 6-month, 1-year and 2-year time points (P < 0.001). Statistically significant improvements in quality of life were observed across all time points.

Physiologic reconstructive surgical techniques combined with modified anterior pelvic floor mesh implantation could help restore the physiologic axis and vaginal shape, which may be the most important factors in maintaining the functional position of pelvic floor organs and is the most effective method for repairing the pelvic fascia tendon arch. This surgical method is safe, feasible, and effective in patients with severe prolapse.

Overactive bladder, a storage syndrome characterized by urinary urgency, frequency, and nocturia with or without urgency urinary incontinence, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of the C/EBP homologous protein in the overactive bladder.

An overactive bladder mouse model was established via the intraperitoneal injection of cyclophosphamide in wild-type and Chop-deficient mice. An in vitro model was established using interleukin (IL)-6-induced mouse bladder epithelial cells. Hematoxylin–eosin (HE) staining was used to assess bladder tissue damage, and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine p-PERK, ATF-6, p-eIF2α, BiP, ATF-4, Bax, Bcl-2, and cleaved caspase-3 protein expression levels. TUNEL staining and flow cytometry were conducted to measure the degree of apoptosis in bladder epithelial cells and macrophages.

C/EBP homologous protein levels were decreased in overactive bladder tissues; nevertheless, macrophage infiltration was found to be increased. Knockout of Chop exacerbated bladder dysfunction, tissue injury, macrophage infiltration, and bladder epithelial apoptosis and alleviated endoplasmic reticulum stress.

Chop deficiency exacerbates inflammation, injury, and bladder epithelial apoptosis in overactive bladder model mice by inhibiting endoplasmic reticulum stress.

Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive, affective, and behavioral abnormalities. Existing treatments have yielded limited effects on improving cognitive function. Recent studies have identified the abnormal differentiation of hippocampal neural stem cells (NSCs), neuronal loss, and dysregulated proliferation of astrocytes as significant pathological mechanisms contributing to the symptoms of schizophrenia. Impaired hippocampal neurogenesis may lead to emotional and cognitive deficits and biases in learning and memory, indicating that NSC differentiation is critical. NEP1-40, a Nogo-A receptor inhibitor, has shown promise for nerve protection and repair promotion. However, the effects of NEP1-40 on stem cell differentiation, the reduction in neuronal apoptosis, and the amelioration of schizophrenia-like behaviors have not been adequately investigated. This study examined the influence of NEP1-40 on NSC differentiation, hippocampal neuronal apoptosis, and proliferation in adolescent mice, along with its potential to enhance cognitive and behavioral outcomes in MK-801-induced schizophrenia mouse models.

In in vivo experiments, a schizophrenia mouse model was successfully established. Subsequently, behavioral tests were conducted, followed by Western blotting (WB) and immunofluorescence (IF) analyses. In in vitro settings, NSCs were cultured and transfected. Flow cytometry, along with WB and IF assays, was employed to evaluate the effects of NEP1-40.

Schizophrenia-like behaviors in mice were significantly improved with the overexpression of NEP1-40. Compared with the model group, the NEP1-40 treatment group presented increased expression of a neuronal marker (Tuj1), reduced expression of an astroglial marker (GFAP), and decreased hippocampal neuronal apoptosis. NSC differentiation was assessed by quantifying the number of BrdU-positive cells coexpressing Tuj1 and GFAP in the hippocampal dentate gyrus. NEP1-40 treatment led to an increase in BrdU/Tuj1-positive cells and a reduction in BrdU/GFAP-positive cells. In cellular studies, NEP1-40 overexpression similarly increased the number of Tuj1-positive cells, reduced the number of GFAP-positive cells, decreased the degree of neuronal apoptosis, and promoted neuronal proliferation.

These findings demonstrated the neurogenic effects of NEP1-40 on NSCs and their potential to mitigate schizophrenia-like behaviors in vivo.

This study aimed to investigate the therapeutic effects and underlying mechanisms of the combination of Yinchenhao decoction (YCHD) and praziquantel (PZQ) in a Schistosoma japonicum (S. japonicum)-induced mouse model of schistosomiasis.

Six-week-old male BALB/c mice were randomly divided into five groups: control group, infected group, infected-PZQ group (I-PZQ), infected-YCHD group (I-YCHD), and infected-PZQ + YCHD group (I-PZQ + YCHD). The mice were infected with S. japonicum cercariae in infected group, I-PZQ group, I-YCHD group, and I-PZQ + YCHD group (n = 6 per group) and maintained for 63 days. From day 43 to day 63 postinfection, the mice received PZQ (150 mg/kg, intragastric gavage), YCHD (10 mL/kg, intragastric gavage), or a combination of both. The control and infected groups received equal amounts of sterile double-distilled water for the same period. At the end of the experiment, the mice were anesthetized with pentobarbital sodium and sacrificed. Serum alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured. Network pharmacology analysis was used to predict the targets of YCHD in the treatment of schistosomiasis. Histopathological analysis, Western blotting, immunofluorescence, quantitative polymerase chain reaction and flow cytometry were employed to evaluate liver pathology and molecular changes.

Compared with the other groups, the I-PZQ + YCHD group presented significantly decreased serum ALT and AST levels (P < 0.001). The I-PZQ + YCHD group exhibited improved pathological changes in the liver, as evidenced by reduced area of single granuloma (P < 0.01), granuloma area (P < 0.01), and Ishak score of liver fibrosis (P < 0.01). Network pharmacology analysis suggested that YCHD may alleviate schistosomiasis-related liver injury through the modulation of the endoplasmic reticulum stress (ERS) pathway. Western blot analysis revealed that ERS-related markers, including glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1 alpha (IRE1α), X-box binding protein 1 (XBP-1), and C/EBP homologous protein (CHOP), were significantly downregulated in the I-PZQ + YCHD group (P < 0.05). Furthermore, the I-PZQ + YCHD group presented reduced hepatocyte apoptosis (P < 0.05), diminished hepatic macrophage infiltration (P < 0.05) and downregulated expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6) (P < 0.05).

YCHD combined with PZQ reduced schistosomiasis-associated hepatic granulomatous inflammation and fibrosis by inhibiting hepatic apoptosis and ERS.

Abnormal gastrointestinal motility plays a crucial role in the pathogenesis of functional dyspepsia (FD). Although electroacupuncture (EA) has demonstrated efficacy in FD treatment, its precise mechanism remains unclear. This study aimed to elucidate the specific mechanism through which EA improves gastrointestinal motility in FD.

Physiological indices, including body weight, food intake, gastrointestinal motility, and gastrointestinal morphology, were utilized to assess the FD model in rats. EA interventions were applied at meridian points, as well as non-meridian points and non-acupoints, in FD model rats. The effects of EA at zusanli (ST36) and taichong (LR3) on gastrointestinal motility in FD model rats were elucidated using gastrointestinal motility test indices. Techniques such as Western blotting, quantitative real-time PCR, and immunofluorescence were employed to determine the specific mechanisms by which EA improved gastrointestinal motility in FD model rats.

Multifactorial stress intervention could be used to effectively establish an FD rat model. EA at ST36 and LR3 significantly improved gastrointestinal motility. Furthermore, EA at ST36 and LR3 upregulated the protein expression of glial cell line-derived neurotrophic factor (GDNF), GDNF family receptor alpha 1 (GFRα1), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), along with their mRNA expression levels and the number of enteric glial cells (EGCs).

EA was capable of increasing the number of EGCs by activating the GDNF/GFRα1/PI3K/Akt signaling pathway, thereby improving gastrointestinal motility in FD.

The middle turbinate axilla (MTA) is a crucial anatomical landmark for localizing the lacrimal sac (LS) during endonasal dacryocystorhinostomy (En-DCR). Despite being a standard surgical procedure, En-DCR may lead to severe complications, such as cerebrospinal fluid (CSF) leakage, which is closely associated with anatomical variations between the LS and the anterior skull base (ASB). This study aimed to investigate the anatomical location of the LS relative to the MTA and ASB in Chinese patients with nasolacrimal duct obstruction (NLDO) and analyze the influencing factors.

This cross-sectional study enrolled 227 Chinese patients who were diagnosed with NLDO and underwent computed tomographic dacryocystography (CT-DCG). Anatomical distances between LS and MTA, as well as LS and ASB, were measured using CT-DCG images.

The mean distances from the superior and inferior edges of the LS to the MTA were 9.94 ± 4.70 mm and − 0.23 ± 4.15 mm, respectively. Male patients showed significantly more superior–anterior displacement of the LS compared to female patients (P < 0.001), while patients with chronic dacryocystitis (CD) had an inferior and posterior LS position relative to those with simple NLDO (P = 0.005, P = 0.001). The mean distance from the intersection (Point P) of the superior and posterior boundaries of the LS to the ASB (MP) was 18.35 ± 4.48 mm, which was shorter in females and those with frontal sinus aplasia (P = 0.001; P < 0.001). A subgroup (28/227, 12.3%) with a critical anatomical feature was identified, where the distance from Point Q (10 mm posterior to P) to the ASB (NQ distance) was ≤ 10 mm. This subgroup had a higher prevalence of complete supra-MTA LS positioning (71.4% vs. 41.2%, P = 0.003).

Preoperative CT-DCG provides essential anatomical insights into the spatial relationship between the LS and MTA in Chinese patients with NLDO. The LS position varies significantly by gender and disease type, with males showing more superior–anterior and CD patients more inferior–posterior positioning relative to the MTA. Special attention should be paid to patients with frontal sinus aplasia or LS entirely above the MTA to minimize the risk of CSF leakage during En-DCR.

Acquired aplastic anemia (aAA) is characterized by an autologous immunological attack against hematopoietic stem and progenitor cells, and immunotolerance disruption is frequent, with reduced T regulatory cells (Tregs) frequencies and increased effector cytotoxic cells. Tregs are reduced in aAA and increase in number after successful immunosuppressive therapies.

In this retrospective study, we investigated the frequency of circulating Tregs by multiparametric flow cytometry immunophenotyping in non-severe aAA patients before and after immunosuppressive therapy. The samples were stained with the following antibodies: ECD anti-CD3, PE or PC5 anti-CD4, FITC anti-CD8, and PE anti-CD25, and Tregs were identified by first gating on linear parameters for lymphocyte identification and then for CD3 expression. In CD3⁺CD4⁺ cells, Tregs were further identified on the basis of CD25 and FOXP3 expression.

Although the number of Tregs tended to increase after immunosuppressive treatments, their circulating frequency remained lower than that of healthy subjects, regardless of their responsiveness to therapies. Moreover, the relative frequency combined with absolute Treg counts might be more informative in the differential diagnosis of bone marrow failure syndromes.

The persistent decrease in circulating Tregs could be the result of immunosuppressive agents that could preferentially expand other T-cell subsets. At the same time, an imbalance in immunotolerance might persist, which is also favored by chronic antigen stimulation.