Initial gastrointestinal endocrine cells (GIECs) likely appear at the proximal and distal sites of abdominal intestines and may take a close topographical relation with neural elements in the gut. We examined immunohistochemically-stained sections from 10 fetuses at approximately 8–18 weeks of gestational age (36–155 mm of crown-rump length). Irrespective of whether physiological herniation was present (early 5 specimens) or absent (the other 5), the duodenum and jejunum had well-developed mucosa with villi containing abundant flask-like chromogranin-positive cells. In the earlier 5 specimens, the rectum, standing up to a level of the umbilicus, had a lumen and villi with a few positive cells, but the colon carried neither the lumen or chromogranin-positive cells. The initial GIECs seemed to appear in the basal payer of the epithelium at the distal and proximal foci depending on double pathways of neural crest cell migration. Less number of the colic chromograninpositive cells, more than 5-times difference in density relative to small intestine, was seen in the larger 5 specimens. The appearance of GIECs was delayed at the anal transitional zone (a border area between the columnar and squamous epithelia).The reactivity of neuronal nitric oxide synthase was restricted in the myenteric plexus, whereas clusters of slender calretininpositive cells existed in the lamina propria or core of villi in the duodenum and colon. Relatively small, round or oval positive cells were also seen in the basal layer of the columnar epithelium. Therefore, calretinin-positive cells might exist closely to GIECs in the developing villi.

Meconium is changed from defoliated intestinal villi with apoptosis. A meconium corpuscle is a limited architecture in the meconium at the light microscopic level. In histological and immunohistochemical sections of the abdomen from 40 fetuses at 20–31 weeks of gestation, we found 12 fetuses with meconium and examined the architecture.A solid or loose meconium was seen depending on sites. The solid meconium in the colon and rectum contained numerous spherical or rugby ball-like corpuscles comprising of a core with tightly-packed atrophied cells and a laminar fibrous sheath.The solid meconium surrounded and incorporated villi that maintained the original architecture. The loose meconium was seen not only in the stomach and duodenum but also, depending on specimens, in the colon and rectum. It was composed of a large mucosal fold, a single small villus and/or fragmented epithelia. Notably, these mucosal tissues still contained chromogranin-positive gastrointestinal cells and cytokeratin-positive epithelia. A large ring-like meconium was composed of the entirely circular mucosa or epithelia that seemed to be detached along the muscularis mucosae or the basal lamina.A sheath-like fibrous structure in meconium seemed to originate from the lamina propria and basal lamina of villi. A defoliation of villi with apoptosis seemed difficult to explain a detachment of the entirely circular mucosa or epithelia in large fetuses examined. The latter event might require a specific mechanism such as an in utero intussusception in which a proximal side of the colon was invaginated into the distal lumen.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

The epidemiological and spatiotemporal clustering characteristics of dengue fever in Fujian Province were ana-lyzed,to provide a scientific basis for dengue fever prevention and control.Descriptive epidemiology,spatial autocorrelation a-nalysis,and spatiotemporal scanning were used to analyze dengue fever cases in Fujian Province from 2011 to 2023.In this peri-od,a total of 3 586 cases of dengue fever were reported in Fujian Province,including 2 360 local cases,1 134 imported cases from abroad,and 92 imported cases from China.Cases were reported in ten prefectures and cities of the province,and 81 out of 88 counties reported cases.Imported cases were reported throughout the year in Fujian Province,but the occurrence of local ca-ses showed clear seasonality.Local cases and domestic imports were concentrated in August to October,whereas overseas im-ports occurred primarily from June to October.The imported cases were mainly from Southeast Asian countries,but a trend of spreading from Southeast Asian countries to South Asia,Africa,the Americas,and other regions,was observed.Spatio-tem-poral clustering of dengue fever was found in Fujian Province(Moran's I value 0.14-0.66,P＜0.05),and the high-high ag-gregation areas were distributed primarily in Fuzhou,Quanzhou,and Putian.Spatio-temporal scanning detected three aggrega-tion areas:one main and two secondary.The aggregation time was from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.The distribution of dengue fever in Fujian Province showed clear spatial and temporal clustering from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.For high concentration areas,national health campaigns,mosquito prevention and control,epidemic surveillance,medical personnel training,and other relevant measures could be carried out in advance before local cases appear every year.Reduce local transmission of dengue fever due to importation.

The treatment of non-small cell lung cancer (NSCLC) faces significant challenges due to tumor heterogeneity and the complexity of the immune microenvironment. The cyclic GMP-AMP synthase (cGAS) -stimulator of interferon gene (STING) signaling pathway plays a dual role in NSCLC, serving both as a crucial hub for anti-tumor immunity and as a potential driver of metastasis. The clinical translation of STING agonists confronts a series of challenges, including delivery barriers, double-edged sword effects, and patient heterogeneity. Consequently, exploring the combined application of STING agonists with radiotherapy/chemotherapy, immune checkpoint inhibitors, and novel immunotherapies, alongside leveraging artificial intelligence-driven multi-omics models for individualized prediction and treatment, holds significant importance. A deeper understanding of the molecular regulatory network of the cGAS-STING signaling pathway and its dynamic functions within the tumor microenvironment is essential for overcoming the current clinical challenges of targeted therapies and advancing the precision development of NSCLC immunotherapy strategies.

The clinical and genetic characteristics of a male child diagnosed with autosomal recessive cerebellar ataxia caused by compound heterozygous variants in VPS41, who was admitted to the Department of Neurology, Children′s Medical Center, Peking University First Hospital in July 2023, was retrospectively analyzed with a comprehensive literature review.The 10-year-old patient exhibited motor delay since infancy, achieving independent sitting at age 1 and independent walking at age 2, yet manifested unsteady gait with frequent falls.Motor skills progressed slowly, alongside academic underperformance.Physical examination revealed impaired ocular pursuit, nystagmus, and signs of ataxia.Brain magnetic resonance imaging (MRI) demonstrated mild cerebellar atrophy.Trio-based whole-exome sequencing identified compound heterozygous VPS41 variants (c.1247G>A, p.R416H and c. 1175dup, p.H392Qfs*2), segregating from each parent.This represents the first reported Chinese case of autosomal recessive cerebellar ataxia associated with VPS41 variants.Globally, only 13 patients with VPS41-related hereditary ataxia have been documented, involving 7 distinct variants.Both variants detected in this case are novel, expanding the disease′s mutational spectrum.

Objective:To study the preoperative predictors for lower extremity intermuscular venous thrombosis (IMVT) in patients with thoracolumbar fracture.Methods:A retrospective study was conducted to analyze the 421 spinal fracture patients who had been admitted to Department of Spinal Surgery, The Fourth Hospital of Wuhan from November 2023 to October 2024. The cohort included 110 males and 311 females, aged from 16 to 89 years. They were stratified into a thrombosis group (26 cases) and a control group (395 cases) based on the presence or absence of lower extremity IMVT. Univariate analysis was performed of the following variables: gender, age, body mass index, multisegmental spinal fractures, fracture location, Caprini thrombosis risk score, visual analogue scale (VAS) pain score, D-dimer level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen, coagulation factor activity assay, fibrinogen level, estimated fibrinolytic ratio, clotting time, 30-minute fibrinolytic ratio, coagulation comprehensive index, clot mechanical strength, platelet function, and fibrin generation rate. The variables with a significance level of P<0.05 in the univariate analysis were further analyzed using multivariate logistic regression to identify the independent risk factors for lower extremity IMVT. The predictive efficacy of these factors was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Comparisons between the 2 groups showed that age, multisegmental spinal fractures, Caprini thrombotic risk score, and D-dimer level were variables with P<0.05. Binary logistic regression analysis of the above variables showed that a high Caprini thrombotic risk score, a high D-dimer level, and multisegmental spinal fractures were independent risk factors for preoperative lower extremity IMVT ( P<0.05). The ROC plot suggested an optimal cutoff point: a Caprini thrombotic risk score of 5 and a D-dimer level of 2.57 mg/L. Combination of Caprini thrombotic risk score, D-dimer level, and multisegmental spinal fractures demonstrated a sensitivity of 88.5%, a specificity of 71.9%, and an area under the curve (AUC) of 0.881 for diagnosis of lower extremity IMVT. Conclusions:The Caprini thrombosis risk score and presence of multisegmental spinal fractures are critical indicators for the preoperative risk of lower extremity IMVT in patients with thoracolumbar fracture. For individuals with a low Caprini thrombosis risk score, a D-dimer test is necessary in combination to determine the necessity of color Doppler ultrasound examination.