[The efficacy and safety of ibrutinib in the treatment of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia].

Objective: To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) . Methods: Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety. Results: A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion: Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

[Electrophysiological properties of neurons in the visual sensory layers of the superior colliculus in early postnatal mice].

Objective: To investigate the action potential firing patterns of neurons in the visual sensory layers of the superior colliculus in early postnatal mice and the electrophysiological characteristics of neurons with different firing patterns. Methods: This experimental study utilized whole-cell patch-clamp recordings performed on neurons in the visual sensory layers of the superior colliculus using brain slices from 57 healthy male C57BL/6J mice aged 14 to 20 days (weighing 5.0 to 8.9 g) using brain slices. In current-clamp mode, action potential characteristics were analyzed based on the first action potential generated by depolarizing current, and the firing patterns of neurons were recorded using step depolarizing currents. Neuronal firing patterns were analyzed using hierarchical clustering, and the active electrical properties of neurons with different firing patterns were compared. Results: A total of 135 neurons from the visual sensory layers of the superior colliculus were successfully recorded. Cluster analysis of the neuronal firing patterns identified three types of firing patterns: tonic firing (97, 72%), phasic firing (26, 19%), and single firing (12, 9%). The number of action potentials for each firing pattern was 13.30±7.38, 3.73±3.61, and 0.83±0.39, respectively, with significant differences (P<0.001). There was no significant difference in the membrane potential response to step currents among the three firing pattern types (P>0.05). The action potential amplitudes were (60.45±12.22), (53.67±13.20), and (44.04± 12.92) mV, and the afterhyperpolarization amplitudes were (13.45±13.79), (12.02±13.11), and (20.75±2.85) mV, respectively. The maximum rising slopes were (171.29±77.46), (130.14±61.83), and (78.89±37.08) V/s, and the maximum falling slopes were (-76.33±33.61), (-68.17±31.65), and (-47.97±13.92) V/s, respectively, with all differences being statistically significant (all P<0.05). There were no significant differences in the resting membrane potential, action potential threshold, half-width, and afterhyperpolarization duration among the three firing pattern types (all P>0.05). Conclusions: In the early postnatal mice, neurons in the visual sensory layers of the superior colliculus exhibit three distinct firing patterns: tonic, phasic, and single firing. These firing pattern types show significant differences in action potential amplitude, afterhyperpolarization amplitude, maximum rising slopes, and maximum falling slopes.

Anti-Heat Shock Protein 70 Autoantibodies from Patients with Idiopathic Pulmonary Fibrosis Epigenetically Enhance Lung Fibroblast Apoptosis Resistance and Bcl-2 Expression.

IgG autoantibodies to heat shock protein 70 (HSP70) are found in many immune-mediated clinical syndromes, and their presence among patients with idiopathic pulmonary fibrosis (IPF) portends especially poor outcomes. However, pathological effects of IPF anti-HSP70 have not been studied extensively. IPF lung fibroblasts are apoptosis resistant, and this dysregulation contributes to the accumulation of fibroblasts that characterizes the disease. During stress, HSP70 protein is exported extracellularly, where it binds to cognate cell surface receptors that mediate a variety of functional effects, including apoptosis inhibition. We hypothesized anti-HSP70 could engage HSP70-receptor complexes on fibroblasts that alter their apoptosis susceptibility. We found HSP70 is ubiquitously expressed on primary human lung fibroblasts. Treatment with anti-HSP70 isolated from patients with IPF with acute exacerbations increased Bcl-2 expression in human lung fibroblasts and reduced their susceptibility to staurosporine-induced apoptosis. Chromatin immunoprecipitation assays showed Bcl-2 gene promoter regions are enriched with the active histone mark H4 lysine 16 acetylation, and this was increased in the autoantibody-treated fibroblasts. When H4 lysine 16 acetylation was decreased by knocking down its acetyltransferase, MOF (males absent on the first), the anti-HSP70 treatments failed to upregulate Bcl-2. This study describes a heretofore unknown, to our knowledge, pathogenic consequence of autoimmunity in which autoantibodies affect the epigenetic regulation of fibroblast apoptosis. In addition to IPF, this autoimmune process could also have relevance in other immunological syndromes characterized by anti-HSP70 autoimmunity. These findings lend credence to the importance of autoimmunity in IPF and illustrate pathways that could be targeted in innovative therapies for this morbid, medically refractory lung disease.

[The progress in classification and prognosis evaluation of BCR::ABL1 positive acute lymphoblastic leukemia].

The application of tyrosine kinase inhibitors and targeted immunotherapy has revolutionized the therapeutic strategies and clinical outcome for BCR::ABL1-positive B-cell acute lymphoblastic leukemia (BCR::ABL1(+) B-ALL). The classification was updated successively by the World Health Organization and the International Consensus Classification in 2022. The risk stratification of this entity, for the first time, was modified by the National Comprehensive Cancer Network in 2023, both minimal residual disease assessment and IKZF1(plus) genotyping recognized as critical prognostic factors. These important updates would have significant implications for clinical management. Therefore, this review focused on the latest advances in the classification and prognostic evaluation of BCR::ABL1(+) B-ALL.

Association between non-alcoholic fatty liver disease and metabolic abnormalities in children with different weight statuses.

OBJECTIVES: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. METHODS: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. RESULTS: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. CONCLUSIONS: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status.

[Surgical management strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma].

Objective: To explore the surgical intervention strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma. Methods: A total of 62 patients with advanced head and neck tumors and carotid wrap by disease treated in Department of Otorhinolaryngology and Head and Neck Surgery, the Affiliated BenQ Hospital of Nanjing Medical University between June 2019 and December 2023 were reviewed, of whom 9 patients presented with metastatic squamous cell carcinoma in cervical lymph nodes of unknown primary or with no recurrence of primary lesion and all the 9 patients were males, aged from 48 to 79 years old, with≤level 2 of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS). Radiographically common carotid artery (CCA) and/or internal carotid artery (ICA) were surrounded by≥270° with tumor. All the 9 patients received implantation of covered stent in carotid artery and radical resection of metastatic cervical lymph nodes. The success rate, complications, surgery-related complications, local recurrence rate, quality of life (QOL) and overall survival (OS) were analyzed. The QOL of patients was compared by paired rank sum test, and P<0.05 indicated statistically significant difference. The OS was analyzed by Kaplan-Meier. Results: The success rate of stent implantation was 100%, with no implantation-related complications. R0 resection was performed in 8 cases and R1 resection in 1 case. The QOL of patients after surgery was improved, and the improvements in "pain", "mood" and "anxiety" were statistically significant(Z values were -2.236, -2.460 and -2.200, respectively, and all P values were<0.05). Follow-up was 1-18 months, with a median of 7 months, and 1 case was lost to follow-up. Local recurrence occurred in 3 patients with an incidence of 37.5% (3/8). OS was 59.9% at 12 months after surgery. Conclusion: Implantation of covered stent in carotid artery combined with radical resection is an effective method for the treatment of cervical lymph node metastasis.

[Characteristics of electrocardiogram in fulminant myocarditis].

Objective: To investugate the unique electrocardiogram (ECG) characteristics of fulminant myocarditis (FM) patients and provide important clues for the diagnosis of FM. Methods: This was a retrospective study. Patients diagnosed with acute myocarditis at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 2017 to April 2022 were enrolled and divided into fulminant myocarditis group (FM) and non-fulminant myocarditis group (NFM) according to clinical diagnosis. A total of 246 healthy people who underwent physical examination in the Health examination Center of Tongji Hospital at the same period were selected as the control group. The clinical data and ECG characteristics of the above 3 groups were analyzed and compared. Logistic regression model was used to analyze the influence of ECG parameters on left ventricular ejection fraction in FM patients. Receiver operating curves were constructed to evaluate the predictive value of different ECG parameters for FM. Results: A total of 180 patients were included in this study (FM group: n=123; NFM group: n=57), with an age of (35.0±16.2) years and 106 males (58.89%). Compared with NFM group, ECG was significantly abnormal in FM group, with a higher incidence of sinus tachycardia, ventricular tachycardia or ventricular fibrillation, escape rhythm, right bundle branch block, third degree atrioventricular block, ST-segment elevation, low voltage, prolonged QTc interval, and widened QRS wave in the FM group (all P<0.05). The ECG parameters showed that the amplitude of the full lead QRS wave in FM group was lower than that in NFM group (P<0.01). The average heart rate and QTc interval of FM group were significantly higher than those of NFM and control groups (all P<0.05). Although ST-segment elevation had a higher incidence in the FM group, ECG parameters showed that except for leads Ⅲ and aVF, the ST segment levels in all leads in the FM group were lower than those in the control group (all P<0.05). There was a statistically significant difference in some ST segment changes between FM and NFM groups, while there was no statistical difference between the NFM and control groups. Multivariate regression analysis showed that widened QRS wave and increased heart rate were the influencing factors for left ventricular systolic dysfunction in FM patients (OR=16.914, 95%CI: 1.367-209.224, P=0.028; OR=1.026, 95%CI: 1.010-1.042, P=0.001). Receiver operating curve analysis showed that heart rate>86.90 beat/min, QTc>431.50 ms, and RV5+SV1<1.72 mV had certain predictive value for FM diagnosis. Conclusions: FM patients displayed marked and severe ECG abnormalities, and characteristic changes in ECG can provide important first clues for the diagnosis of FM.

Optimisation of monoenergetic images to reduce banding artifacts in the lower cervical spine using dual-layer spectral computed tomography: a retrospective study.

AIM: To investigate the application value of dual-layer detector computed tomography (CT) single-energy spectral images for reducing artefacts in the lower cervical spine. MATERIALS AND METHODS: Sixty-three patients who underwent neck examination using spectral CT between March 2022 and January 2023 were selected as the participants. Conventional mixed-energy images and spectral imaging data at 40-200 KeV were obtained from the spectral CT scans. The standard deviation (SD), signal-to-noise ratio (SNR), |CTdifference| (the difference in CT value between the C6-7 and C3-4 artefact regions), and contrast-to-noise ratio (CNR) of the C6-7 spinal canal were measured. The image quality of the artefact region in the conventional and single images were compared. RESULTS: The SDintervertebral disc value was highest in the single-level 40 KeV images and lowest in the 120 KeV images (P<0.05). The SNR was lowest in the 40 KeV images (2.07 ± 2.74) and highest in the 120 KeV images (6.20 ± 5.26) (P<0.05). The CTdifference was highest in the 40 KeV images and lowest in the 120 KeV images (108.38 vs. 10.63 ± 8.58). The subjective image quality scores were lowest in the 40 KeV images and highest in the 120 KeV images. CONCLUSION: Our findings suggest that single-energy 120 KeV images may offer benefits such as low SDintervertebral disc, elevated SNR, higher CNR, and improved image quality.

FGF receptors mediate cellular senescence in the cystic fibrosis airway epithelium.

The number of adults living with cystic fibrosis (CF) has already increased significantly because of drastic improvements in life expectancy attributable to advances in treatment, including the development of highly effective modulator therapy. Chronic airway inflammation in CF contributes to morbidity and mortality, and aging processes like inflammaging and cell senescence influence CF pathology. Our results show that single-cell RNA sequencing data, human primary bronchial epithelial cells from non-CF and CF donors, a CF bronchial epithelial cell line, and Cftr-knockout (Cftr-/-) rats all demonstrated increased cell senescence markers in the CF bronchial epithelium. This was associated with upregulation of fibroblast growth factor receptors (FGFRs) and mitogen-activated protein kinase (MAPK) p38. Inhibition of FGFRs, specifically FGFR4 and to some extent FGFR1, attenuated cell senescence and improved mucociliary clearance, which was associated with MAPK p38 signaling. Mucociliary dysfunction could also be improved using a combination of senolytics in a CF ex vivo model. In summary, FGFR/MAPK p38 signaling contributes to cell senescence in CF airways, which is associated with impaired mucociliary clearance. Therefore, attenuation of cell senescence in the CF airways might be a future therapeutic strategy improving mucociliary dysfunction and lung disease in an aging population with CF.

Changes in energy expenditure and physical activity over 15 years of environmental changes: The Maycoba project.

OBJECTIVE: This work aimed to parse out the role of changing environments on body composition, total energy expenditure, and physical activity in the Mexican Pima, a population experiencing rapid industrialization. METHODS: Using doubly labeled water, we compared energy expenditure and physical activity in a longitudinal cohort of Mexican Pima (n = 26; female: 12) in 1995 and 2010. Body mass and composition were assessed by bioimpedance analysis. To determine the effects of environmental factors on body weight independent of age, we compared the 1995 longitudinal cohort with an age- and sex-matched cross-sectional cohort (n = 26) in 2010. RESULTS: Body mass, fat mass, and fat-free mass all significantly increased between 1995 and 2010. Despite a 13% average increase in body weight, weight-adjusted total daily energy expenditure decreased significantly. Measured physical activity levels also decreased between 1995 and 2010, after we adjusted for weight. CONCLUSIONS: Our results suggest that the recent industrialization of the Maycoba region in Sonora, Mexico, has contributed to a decrease in physical activity, in turn contributing to weight gain and metabolic disease among the Mexican Pima.

Netrin-1 Promotes M2 Type Activation and Inhibits Pyroptosis of Microglial Cells by Depressing RAC1/Nf-?B Pathway to Alleviate Inflammatory Pain.

Netrin-1 (NTN-1) plays a vital role in the progress of nervous system development and inflammatory diseases. However, the role and underlying mechanism of NTN-1 in inflammatory pain (IP) are unclear. BV2 microglia were treated with LPS to mimic the cell status under IP. Adeno-associated virus carrying the NTN-1 gene (AAV-NTN-1) was used to overexpress NTN-1. Complete Freund's Adjuvant (CFA)-induced mouse was recruited as an in vivo model. MTT and commercial kits were utilized to evaluate cell viability and cell death of BV2 cells. The mRNA expressions and secretions of cytokines were measured using the ELISA method. Also, the pyroptosis and activation of BV2 cells were investigated based on western blotting. To verify the role of Rac1/NF-kappaB signaling, isochamaejasmin (ISO) and AAV-Rac1 were presented. The results showed that NTN-1 expression was decreased in LPS-treated BV2 microglia and spinal cord tissues of CFA-injected mice. Overexpressing NTN-1 dramatically reversed cell viability and decreased cell death rate of BV2 microglia under lipopolysaccharide (LPS) stimulation, while the level of pyroptosis was inhibited. Besides, AAV-NTN-1 rescued the activation of microglia and inflammatory injury induced by LPS, decreasing IBA-1 expression, as well as iNOS, IL-1beta and IL-6 secretions. Meanwhile AAV-NTN-1 promoted the anti-inflammation response, including increases in Arg-1, IL-4 and IL-10 levels. In addition, the LPS-induced activation of Rac1/NF-kappaB signaling was depressed by NTN-1 overexpression. The same results were verified in a CFA-induced mouse model. In conclusion, NTN-1 alleviated IP by suppressing pyroptosis and promoting M2 type activation of microglia via inhibiting Rac1/NF-?B signaling, suggesting the protective role of NTN-1 in IP. Keywords: Netrin-1, Inflammatory pain, Pyroptosis, Microglia M2 activation, Rac1/NF-kappaB.

Mechanism studies for relativistic attosecond electron bunches from laser-illuminated nanotargets.

To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.

The Effectiveness of Interventions for Reducing Loneliness Among Chinese Older Adults: A Systematic Review and Meta-Analysis.

This review assesses interventions to reduce loneliness in Chinese older adults, analyzing 36 studies involving 3965 participants. Focusing on individuals aged 50 and over, the meta-analysis reveals a significant overall effect size (Hedges' g = 0.937, 95% CI [0.71,1.16], p<0.001), highlighting the effectiveness of psychological and mixed-method approaches. Despite promising results, methodological concerns suggest cautious interpretation. Future research should aim to refine intervention quality and examine the impact of technology-supported methods on loneliness.

O-GlcNAc regulates anti-fibrotic genes in lung fibroblasts through EZH2.

Epigenetic modifications are involved in fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), and contribute to the silencing of anti-fibrotic genes. H3K27me3, a key repressive histone mark, is catalysed by the methyltransferase enhancer of Zeste homologue 2 (EZH2), which is regulated by the post-translational modification, O-linked N-Acetylglucosamine (O-GlcNAc). In this study, we explored the effects of O-GlcNAc and EZH2 on the expression of antifibrotic genes, cyclooxygenase-2 (Cox2) and Heme Oxygenase (Homx1). The expression of Cox2 and Hmox1 was examined in primary IPF or non-IPF lung fibroblasts with or without EZH2 inhibitor EZP6438, O-GlcNAc transferase (OGT) inhibitor (OSMI-1) or O-GlcNAcase (OGA) inhibitor (thiamet G). Non-IPF cells were also subjected to TGF-ß1 with or without OGT inhibition. The reduced expression of Cox2 and Hmox1 in IPF lung fibroblasts is restored by OGT inhibition. In non-IPF fibroblasts, TGF-ß1 treatment reduces Cox2 and Hmox1 expression, which was restored by OGT inhibition. ChIP assays demonstrated that the association of H3K27me3 is reduced at the Cox2 and Hmox1 promoter regions following OGT or EZH2 inhibition. EZH2 levels and stability were decreased by reducing O-GlcNAc. Our study provided a novel mechanism of O-GlcNAc modification in regulating anti-fibrotic genes in lung fibroblasts and in the pathogenesis of IPF.

Schizosthetus Athias-Henriot, 1982 (Mesostigmata: Parasitidae): the description of a new species from China.

A new species, Schizosthetus baixuelii sp. nov., is described based on females from Ningxia Hui Autonomous Region, China. A key to the known species of the genus is presented.

[Incidence and mortality of endometrial cancer in China, data from China Cancer Registry Annual Report, 2004-2017].

Objective: To analysis the incidence rate and mortality rate of endometrial cancer in China from 2004 to 2017 according to the data from China Cancer Registry Annual Report. Methods: The incidence and mortality data of endometrial cancer were extracted from the China Cancer Registry Annual Report 2004 to 2017, and the incidence, mortality, number of new cases, number of deaths were extracted according to the region (national, urban, rural and eastern, middle and western areas) and the age composition of population to estimate the incidence and mortality of endometrial cancer nationwide. The age-standardized incidence rate and mortality rate were calculated based on the Chinese standard population in 2000 (ASIRC, ASIRW) and Segi's world population (ASMRC, ASMRW). Join Point regression was used to calculate the annual percentage change of morbidity rate, and Cochran-Armitage trend test was used to analyze the changing trend of morbidity and mortality. Results: From 2004 to 2017, the number of women covered by the China Cancer Registry Annual Report has increased from 35 571 657 to 215 201 995, and the total population of the covered areas has increased from 5.53% to 31.39%. The crude incidence rate of endometrial cancer increased from 6.20/100 000 to 10.06/100 000, and showed an upward trend over time (P<0.001). After adjusting for age, ASIRC increased from 5.75/100 000 in 2004 to 6.79/100 000 in 2017, and ASIRW increased from 5.60/100 000 in 2004 to 6.56/100 000 in 2017, both showing an upward trend over time (all P<0.001). The crude incidence rates in urban area and rural area were respectively 10.89/100 000 and 9.25/100 000 in 2017, and the ASIRC was higher in urban than rural areas (7.14/100 000 vs 6.43/100 000) after adjusting for age. The ASIRW was higher in eastern areas than middle areas and western areas (7.16/100 000 vs 6.44/100 000 vs 5.60/100 000). The incidence rate in rural areas showed more significant growth than urban areas [annual percent change (APC): 3.2% vs 0.7%, P<0.001]. The age-specific incidence rate increased with age and reached a peak in the age group of 50-54 years (25.70/100 000). Incidence rate in the under-40 age group increased more in rural areas than in urban areas (69.84% vs-7.09%). From 2004 to 2017, the age-standardized mortality rate shows a decreasing trend, with the ASMRC from 1.83/100 000 to 1.47/100 000, and the ASMRW from 1.81/100, 000 to 1.46/100, 000. There was no significant difference between urban and rural areas in mortality of endometrial cancer. Age-specific mortality rates increased with age, reaching a peak in the age group 85 years and older (13.16/100 000). Conclusions: Recent years, there was an increasing incidence rate of endometrial cancer in China. Especially in rural areas, the incidence rate of endometrial cancer is increasing rapidly in young women under 40 years of age. There were differences between urban and rural areas and regions in the incidence rate of endometrial cancer. The incidence rates of endometrial cancer in some high-income cities have occupied the first place of female reproductive system malignant cancers. The age-standardized mortality rate of endometrial cancer shows a decreasing trend.

Claudin-2 upregulation enhances intestinal permeability, immune activation, dysbiosis, and mortality in sepsis.

Intestinal epithelial expression of the tight junction protein claudin-2, which forms paracellular cation and water channels, is precisely regulated during development and in disease. Here, we show that small intestinal epithelial claudin-2 expression is selectively upregulated in septic patients. Similar changes occurred in septic mice, where claudin-2 upregulation coincided with increased flux across the paracellular pore pathway. In order to define the significance of these changes, sepsis was induced in claudin-2 knockout (KO) and wild-type (WT) mice. Sepsis-induced increases in pore pathway permeability were prevented by claudin-2 KO. Moreover, claudin-2 deletion reduced interleukin-17 production and T cell activation and limited intestinal damage. These effects were associated with reduced numbers of neutrophils, macrophages, dendritic cells, and bacteria within the peritoneal fluid of septic claudin-2 KO mice. Most strikingly, claudin-2 deletion dramatically enhanced survival in sepsis. Finally, the microbial changes induced by sepsis were less pathogenic in claudin-2 KO mice as survival of healthy WT mice injected with cecal slurry collected from WT mice 24 h after sepsis was far worse than that of healthy WT mice injected with cecal slurry collected from claudin-2 KO mice 24 h after sepsis. Claudin-2 upregulation and increased pore pathway permeability are, therefore, key intermediates that contribute to development of dysbiosis, intestinal damage, inflammation, ineffective pathogen control, and increased mortality in sepsis. The striking impact of claudin-2 deletion on progression of the lethal cascade activated during sepsis suggests that claudin-2 may be an attractive therapeutic target in septic patients.

[Study on primary screening technique for children with autism spectrum disorder].

To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi'an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi 'an Children's Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.