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Abstract Immune system regulation is a key indicator of the gut microbiota (GM) influencing disease development. The causal role of the GM in Guillain-Barré syndrome (GBS) and whether it can be mediated by immune cells is unknown. Genome-wide association study (GWAS) summary statistics for the GM were obtained from the Dutch Microbiota Project (n = 7,738) and the FINRISK 2002 (FR02) cohort (n = 5,959). Inverse variance weighting method (IVW) were used as the main method to evaluate the causal relationship between GM and GBS. Subsequently, the mediating effects of 731 immune traits were evaluated. Additionally, we also executed the Bayesian Weighting algorithm for verification. Mendelian randomization (MR) analysis determined the protective effect of the pyrimidine deoxyribonucleoside degradation superpathway on GBS (IVW: P = 0.0019, OR = 0.4508). It is worth noting that in the causal effects of pyrimidine deoxyribonucleoside degradation superpathway on GBS, the mediated proportions of herpesvirus entry mediator (HVEM) ( HVEM on CM CD4 + , HVEM on naive CD4 + , HVEM on CD45RA − CD4 + , HVEM on CM CD8br) in the T cell maturation stage on GBS were -0.0398, -0.0452, -0.0414, -0.0425, accounting for 5.00%, 5.67%, 5.19% and 5.34% of the total effect. 11 types of intestinal bacteria might be involved in the pyrimidine deoxyriboside degradation superpathway, including Staphylococcus A fleurettii, AR31,CAG-274 sp000432155, Photobacterium, Acetobacteraceae, Dysgonomonadaceae, NK4A144,Leptospirae, CAG-81 sp000435795, Leptospirales and CAG-873 sp001701165. This study suggests that there is a causal relationship between pyrimidine deoxyribonucleoside degradation superpathway and GBS, which may be mediated by HVEM on CD4 + and CD8 + T cells. As a bidirectional molecular switch, HVEM plays an important role in T cell regulation. 11 intestinal flora were found to be involved in pyrimidine deoxyribonucleoside degradation superpathway, and their changes may be related to the occurrence of GBS. However, extensive research is still warranted before microbiome sequencing can be used for prevention and targeted treatment of GBS.

Abstract Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011–2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism.

Abstract In this paper, a novel compact bandpass filter (BPF) with a wide out-of-band rejection is proposed. It can achieve broadband characteristics by combining hollow bowtie-type spoof surface plasmon polaritons (SSPPs) with complementary H-type defected grounded structures (DGSs) through aperture coupling. Compared with the conventional SSPP unit cells, the hollow bowtie-type structure exhibits much better slow-wave characteristics. The introduced slant antenna type port-coupling can produce a very strong high-performance rejection outside the high frequency stopband. Simulation results show that the SSPPs-DGS-based BPF has an excellent band pass characteristics in a broadband range with − 3dB fractional bandwidth of 43.5% at center frequency f 0 of 2.04 GHz. The return loss in the passband is better than − 12 dB. Furthermore, because of the multiple transmission zeros generated in upper-stop-band, the designed BPF has an extremely strong out-of-band rejection of -40dB from 1.5 f 0 to 4 f 0 (f 0 is the center frequency). The designed SSPPs-DGS-based BPF is fabricated by conventional printed circuit board (PCB) technology with a compact size of only 0.68λg*0.34λg (λg is the wavelength at the center frequency). The measured results have a good agreement with the simulation ones, which verifies the rationality and feasibility of the design. The miniaturized wideband BPF with broad out-of-band rejection may make it has good application prospect in the new generation microwave communication field.

Abstract Purpose Early detection of lifestyle factors, skin and hair color, circulating parameters, and metabolic comorbidities is crucial for personalized prevention and treatment of early age-related macular degeneration (AMD). This study aimed to assess the relationships between genetically predicted comprehensive risk factors and early AMD. Methods and results Publicly available genome-wide association study (GWAS) data were utilized to identify genetic variants significantly associated with each trait. We applied a Bonferroni-corrected significance level of P

Background Improving the level of benefit finding can help alleviate the high prevalence of negative emotional problems and promote mental health in maintenance hemodialysis (MHD) patients, so the research group has constructed a benefit finding promotion program for MHD patients based on the PERMA flourish model in the earlier stage, which is urgently needed to be applied in clinical practice. Objective To explore the barriers and facilitators to the implementation of benefit finding promotion program for MHD patients, and provide reference for psychological intervention of them. Methods Using purposive sampling method, 12 healthcare workers and 9 MHD patients in the hemodialysis unit of the Second Affiliated Hospital of the Naval Medical University were selected as the study subjects from March to May 2023, and semi-structured interviews were conducted with them using the phenomenological research method, and the results of the interviews were analyzed in terms of the three dimensions of change, change recipients, and the organizational environment based on the i-PARIHS framework, and the responses to the obstacle factors were developed. Results Barriers to the application of the program at the change level include lack of detail, high professionalism, and cultural differences in the program content; at the recipient level include cognitive differences in the team, lack of psychosocial training for healthcare workers, low motivation of patients to participate, and inconsistent acceptance; at the organizational environment level, the lack of incentives in the ward, and the lack of a suitable place for the intervention. Factors facilitating the implementation of the program include, on the change side, interventions derived from high-quality research, richness and variety of program content, etc., on the receiver side, strong support from the ward leadership, positive cooperation from team members, etc., and on the organizational environment side, the ward has a certain base of psychological interventions, and changes are in line with national and health policies. Conclusion The application of benifit finding promotion program for MHD patients is affected by a variety of factors, the need to comprehensively analyze the barriers and facilitators, and to take specific action strategies to promote the program to the ground, so that it is orderly and efficient in the clinical implementation of the application.

We aimed to explore the role of T helper cell 1 (Th1)/Th2 imbalance mediated by T cell glycolytic rate-limiting enzymes hexokinase 2 (HK2), phosphofructokinase-1 (PEK1) and pyruvate kinase M2 (PKM2) in oral lichen planus (OLP).

Abstract Background Several tetraspanin (TSPAN) proteins have been implicated in tumorigenesis and disease progression. However, the precise function of tetraspanin 6 (TSPAN6) in glioma remains unclear. Methods Integrated raw data from the Tumor Genome Atlas (TCGA) and Gene Expression Profiling (GEO) databases were processed using R4.2.1. Bioinformatic methods were used to analyze the gene expression levels of TSPAN6 in both glioma and normal brain tissues, correlating them with clinical characteristics. Additionally, the predictive value of TSPAN6 in relation to the immune checkpoint blockade (ICB) therapy response was assessed. In vitro experiments were conducted to investigate the effects of TSPAN6 knockdown on glioma cell proliferation, migration, cell cycle regulation, and macrophage recruitment. Results TSPAN6 expression was significantly upregulated in glioma tissues compared to normal tissues. Elevated TSPAN6 expression is strongly correlated with unfavorable clinical characteristics in gliomas. Bioinformatic analyses revealed a significant correlation between elevated TSPAN6 expression and reduced overall survival. Additionally, TSPAN6 was co-expressed with several immune checkpoint genes and revealed a prognostic value in the context of ICB therapy. Functional enrichment analysis revealed the involvement of TSPAN6 in cell-cycle regulation. Furthermore, TSPAN6 expression positively correlated with macrophage and neutrophil infiltration. In vitro experiments confirmed that the downregulation of TSPAN6 inhibited U251 cell proliferation, disrupted the cell cycle, diminished migratory capabilities, and reduced the recruitment of macrophages. Conclusion Our findings emphasize its potential as both a diagnostic and therapeutic target as well as a predictor of immune therapy response in gliomas.

Objective To provide foundational data for exploring the association between KIR genes and diseases by analyzing the frequency and polymorphism of killer-cell immunoglobulin-like receptor (KIR) genes in Han, Manchu and Korean populations in Jilin Province. Methods KIR gene typing was performed on 129 Manchu, 198 Korean and 201 Han individuals from Jilin using the polymerase chain reaction-sequence specific primers (PCR-SSP) technique. Results KIR3DL2, KIR3DL3, KIR3DP1 and KIR2DL4 were detected in all subjects. KIR2DL1, KIR2DL3, KIR2DS4, KIR3DL1 and KIR2DP1 genes had high detection frequencies, ranging from 93% to 98% across the three ethnic groups. In contrast, the detection rates of KIR2DL2, KIR2DL5, KIR3DS1, KIR2DS1, KIR2DS2, KIR2DS3 and KIR2DS5 were lower, ranging from 13% to 45%. Notably, the detection frequencies of KIR2DL5 (17.83%) and KIR2DS1 (17.83%) in the Manchu population were significantly lower than those in the Korean (42.93%, 47.47%) and Han (33.83%, 33.33%) populations in Jilin. The detection frequencies of KIR2DL5 (42.93%) and KIR2DS1 (47.47%) were significantly higher in the Korean population compared to the Han (33.83%, 33.33%) and Manchu (17.83%, 17.83%) population. The frequency of the KIRAA haplotype in the Han population was the highest among the three ethnic groups in Jilin at 61.19%, significantly higher than that in the Korean population (42.93%). Differences between the three groups were statistically significant (P

Objective To study the quality comparability of human coagulation factor Ⅷ (FⅧ) produced before and after the change of factory site. Methods A comparative study was carried out on quality quantitative indexes, related impurities and stability data of FⅧ produced before and after the change of factory site. Results The FⅧ quantitative quality before and after the change of factory site all met the quality standard, and the related impurities including aluminum residue, tributyl phosphate residue, polysorbate 80 residue and PEG residue all met the quality standard. Other impurities including human fibrinogen, fibronectin, plasminogen, IgA, IgM and IgG were extremely low in content and equivalent in quality. The content of VWF (von Willebrand factor) had no obvious change before and after the change of factory site, but was significantly higher than that of other domestic manufacturers’ commercial products. The results of accelerated stability and long-term stability tests showed that the titer of FⅧ fluctuated within the methodological error range, and the results all met the quality standard. Conclusion The change of factory site of FⅧ has no effect on the quality.

Abstract Background Although gray matter (GM) volume alterations have been extensively documented in previous voxel-based morphometry studies on vestibular migraine (VM), little is known about the impact of this disease on the topological organization of GM morphological networks. This study investigated the altered network patterns of the GM connectome in patients with VM. Methods In this study, 55 patients with VM and 57 healthy controls (HCs) underwent structural T1-weighted MRI. GM morphological networks were constructed by estimating interregional similarity in the distributions of regional GM volume based on the Kullback–Leibler divergence measure. Graph-theoretical metrics and interregional morphological connectivity were computed and compared between the two groups. Partial correlation analyses were performed between significant GM connectome features and clinical parameters. Logistic regression (LR), support vector machine (SVM), and random forest (RF) classifiers were used to examine the performance of significant GM connectome features in distinguishing patients with VM from HCs. Results Compared with HCs, patients with VM exhibited increased clustering coefficient and local efficiency, as well as reduced nodal degree and nodal efficiency in the left superior temporal gyrus (STG). Furthermore, we identified one connected component with decreased morphological connectivity strength, and the involved regions were mainly located in the STG, temporal pole, prefrontal cortex, supplementary motor area, cingulum, fusiform gyrus, and cerebellum. In the VM group, several connections in the identified connected component were correlated with clinical measures (i.e., symptoms and emotional scales); however, these correlations did not survive multiple comparison corrections. A combination of significant graph- and connectivity-based features allowed single-subject classification of VM versus HC with significant accuracy of 77.68%, 77.68%, and 72.32% for the LR, SVM, and RF models, respectively. Conclusion Patients with VM had aberrant GM connectomes in terms of topological properties and network connections, reflecting potential dizziness, pain, and emotional dysfunctions. The identified features could serve as individualized neuroimaging markers of VM.

Abstract Background Factor XII (FXII or F12) deficiency is a rare inherited disorder, typically lacking haemorrhagic symptoms. There is limited literature exists on FXII deficiency and mutations within the Chinese population. This study aimed to characterize the spectrum of F12 gene mutations in a Chinese cohort and to investigate the relationship between FXII mutations and clinical phenotypes. Methods Genetic and clinical data from 51 unrelated probands with FXII deficiency, along with their families, were meticulously collected and analysed. Results Genetic analysis revealed that 94.1% of probands carried genetic defects, with 29 mutations pinpointed in the F12 gene. Of these, 18 mutations were previously reported for the first time by our research group, including c.303_304delCA, c.1078G > A, c.1285 C > T, among others. Of the mutations, 17 are missense, constituting 58.6% of the total. Additionally, 11 are deletions or insertions, of which 8 result in frameshifts, while the remaining one is a nonsense mutation. These mutations were predominantly concentrated in two crucial regions: the catalytic domain and the kringle domain. The most frequently observed mutations were c.1681G > A, closely followed by c.1561G > A and c.1078G > A, indicating a dominance among these mutations. Additionally, a prevalent polymorphism at position 46 was observed in the majority of probands, with 47.1% having the 46T/T genotype and 13.7% having the 46 C/T genotype, which may potentially impact FXII activity. The broad spectrum of asymptomatic FXII deficiency observed within the Han population of East China. Conclusions We speculate on the potential impact of recurrent mutations on the efficacy of new drugs being developed to target FXII for thrombosis prevention and treatment. Furthermore, it is important to explore their influence on FXII-related pathways beyond the activation of the contact pathway in the coagulation cascade.

Abstract Asthma and lung cancer are both significant public health concerns worldwide. Previous observational studies have indicated a potential link between asthma and an increased risk of lung cancer, whereas the causal relationship remains uncertain. We aimed to investigate the potential causal relationship between asthma and lung cancer risk utilizing Mendelian randomization (MR) design.The present study employed a two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) with European descent of asthma and lung cancer. The MR analysis was performed using inverse variance weighting (IVW), supplemented with MR-Egger regression and weighted median method to investigate the potential causality between asthma and lung cancer. Furthermore, Sensitivity analyses were also conducted to ensure the reliability of the findings. The MR analysis showed that genetically predicted asthma had suggestive causal association with the elevated risk of lung cancer [odds ratio (OR), 1.05 (95%Cl,1.01–1.09), P = 0.01]. The consistent direction of effects observed in the three methods further supported this finding. In addition, sensitivity analyses demonstrated the reliability of the results. This study provided potential evidence supporting a causal association between asthma and lung cancer. These findings highlighted the importance of early detection and prevention strategies for lung cancer in individuals with asthma. Further research was needed to elucidate the underlying mechanisms linking asthma and lung cancer.

Objective·To investigate the effects of multiple sevoflurane exposures on the proliferation and differentiation of primary oligodendrocytes.Methods·Oligodendrocyte precursor cells (OPCs) were extracted from the cortex of rats on the day of birth and cultured in vitro. The cells were divided into control and sevoflurane groups. To simulate the clinical situation of sevoflurane exposure, cells in the sevoflurane group were exposed to 3% sevoflurane for 3 consecutive days, 2 h for each time. After the OPCs were differentiated and matured, immunofluorescence staining and Western blotting were used to detect the expression of myelin basic protein (MBP) and the myelin-associated glycoprotein (MAG). Cell proliferation assays (BrdU and Ki67) and a cell viability assay (CCK8) were used to detect the effects of sevoflurane on the proliferation ability of OPCs and the survival rate of oligodendrocytes. Western blotting was used to detect the protein content of caspase-3. Lentiviral transfection technology was used to overexpress YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) in OPCs, and then CCK8 was used to detect cell proliferation and survival.Results·Immunofluorescence results showed that multiple sevoflurane exposures led to a decrease in the number of primary oligodendrocytes expressing mature myelin surface markers (MBP, MAG); Western blotting results showed that these exposures led to upregulation of caspase-3 expression in primary OPCs; CCK8 results showed that the survival rate of primary OPCs decreased with the increase in the number of sevoflurane treatments; however, BrdU and Ki67 staining results showed that the proliferation ability of primary OPCs was enhanced after sevoflurane exposure. In addition, overexpression of YTHDF1 could partially improve the decreased survival rate of primary OPCs caused by multiple sevoflurane exposures (all P

Abstract Background The general education course, Oral Science, has been offered by Guanghua School of Stomatology, Sun Yat-sen University for many years in order to improve students' knowledge of oral health. Information about the oral health knowledge, status, and behaviors among undergraduates who had taken Oral Science was collected to evaluate the impact of this course, and to provide a basis for further improvement of the course teaching quality. Methods Undergraduates taking Oral Science as an elective course were selected as the research subjects. The research time is the second semester of the 2022 academic year, from February 2023 to June 2023. Undergraduates who had not taken the course served as the control group. To investigate the oral health knowledge, status, and behaviors among undergraduate students who have taken the general education course of Oral Science, course students and non-course students were asked to fill out the same questionnaire at both the beginning and end of semester. The answer scores and accuracy of these two groups were compared and analyzed. Before and after the first lesson, and at the end of the semester, course students were asked to fill out the same oral knowledge questionnaire. Another questionnaire was released in week 10 to collect the data of the course students' oral health status and behaviors. The control group completed the same oral knowledge questionnaire at the beginning and end of the semester, respectively. SPSS 20.0 statistical software was used to analyze the data. Statistical significance level was set at 0.05 for all tests. Results At the beginning of the semester, there was no significant difference in the accuracy of the 16 questions nor the scores between two groups (P > 0.05). After one semester of learning, the accuracy of the 16 questions answered by the course students at the end of the semester was significantly higher (P

Abstract Objectives To propose a magnetic resonance imaging (MRI) classification of brucellosis spondylitis (BS) to determine a standard treatment method and a standard of post-treatment MRI follow-up. Methods This is a multicenter retrospective cohort study. All patients diagnosed with BS at six hospitals for 12 years, were included in the study. Data were collected retrospectively from the medical records of the patients. The classification of the cases was based on MRI. We analyzed MRI features of BS was categorized them into three types. Results Six hundred fifteen patients were included in the study, 78.9% of whom were males. The mean age was 53.05 ± 11.06 years. Involvement of single vertebrae occurred in 6.2% of patients, while 72.7% involved two vertebrae and 21.1% involvement of more than two vertebrae. The most common of the lumbar spine was 64.6%. The main findings of MRI were affected vertebral endplate 2/3 above (60.7%), intervertebral space narrow (77.9%), intervertebral disc involvement (83.6%), paravertebral abscess (50.9%), disc abscess (49.6%), epidural abscess (43.3%), vertebra height change (22.1%), psoas abscess (22.0%), and abnormal vertebral accessory (10.2%). MR imaging of BS was categorized into three types. Type I: 57 (9.3%) patients; Type II: 526 (85.5%) patients, including IIa (26.5%), IIb (36.9%), and IIc (22.1%); Type IV: vertebral appendage type, 63 (10.2%) cases; Type III: 32 (5.2%) patients. Conclusions MRI features of multicenter data can provide theoretical support for diagnosing BS. MRI classification of BS can afford better help for clinical treatment and follow-up after clinical treatment.

Abstract Cardiovascular disease remains the leading cause of death worldwide, with air pollution’s impact on cardiovascular health being closely monitored. However, the specific effects of air pollution on the risk of hospital readmission for heart failure (HF) in patients with unstable angina (UA) have not been fully explored. We conducted a retrospective study involving 12,857 consecutive patients diagnosed with acute coronary syndrome (ACS) between January 2015 and March 2023. After rigorous screening, we included 8,737 patients with UA in the analysis. Furthermore, we used a Cox proportional hazards regression model to examine the relationship between air quality indicators and hospital readmission for HF in patients with UA. Additionally, a decision tree model identified air quality indicators levels that had the most significant impact on readmission for HF risk. After adjusting for confounding factors, we found that elevated levels of PM10 [hazard ratio (HR) = 1.003, 95% confidence interval (CI): 1.000-1.005, p = 0.04453] and CO (HR = 1.013, 95% CI: 1.005–1.021, p = 0.00216) were associated with an increased risk of hospital readmission for HF in UA patients. Specifically, patients exposed to PM10 levels above 112.5 µ g/m3 had a 1.61-fold higher risk of readmission for HF in UA patients. (HR = 1.609, 95% CI: 1.190–2.176, p = 0.00201), and those exposed to CO levels above 37.5 mg/m3 had a 2.70-fold higher risk of readmission for HF in UA patients. (HR = 2.681, 95% CI: 1.731–4.152, p

Abstract Selecting appropriate global climate models (GCMs) is crucial for minimizing uncertainty in regional climate projections under future scenarios. Previous studies have predominantly assessed the modeling capability of GCMs for regional precipitation climatology and its long-term patterns based on annual and seasonal precipitation data. Building upon these, we primally evaluated the performance of five GCMs from phase 3b of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3b) in simulating precipitation concentration and its variations in the Southwest River Basin (SWRB) of China using the precipitation concentration index (PCI). The results indicate that: (1) The 5 GCMs generally capture the spatial distribution of annual average precipitation in the SWRB but significantly overestimate its magnitude, with a maximum regional average deviation of 207.80 mm. Furthermore, all models tend to overestimate the overall drying trend in the SWRB and show limited capability in simulating interdecadal variations of annual precipitation. (2) While the 5 GCMs reasonably simulate the spatial distribution of annual average PCI in the SWRB, they tend to overestimate its values, with a maximum regional average deviation of 1.54. Additionally, their simulation performance in capturing PCI trends and interdecadal variations is also limited. (3) The 5 GCMs tend to overestimate seasonal precipitation in the SWRB, with the best simulation performance for the distribution of autumn precipitation, followed by spring and summer, and the poorest for winter. Significant differences exist in the simulation performance of the models for seasonal precipitation proportions, which result in discrepancies in the models’ representation of PCI. Moreover, the models’ poor simulation performance of PCI trends is partly due to their inadequate modeling of trends in seasonal precipitation proportions. The findings will contribute to laying the foundation for meteorological hydrological research and water resource management in the SWRB.

Abstract Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged

Abstract Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood–brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Abstract Many studies have shown that drinking coffee and tea may be associated with the risk of hypertension and dementia. Limited research exists on their impact on dementia risk in hypertensive patients. This study aimed to determine the association between coffee and tea consumption and the risk of dementia development in hypertensive population by utilizing Cox proportional risk modeling with 453,913 participants from a UK biobank. Our findings reveal a J-shaped and U-shaped association between the risk of all-cause dementia and the consumption of coffee and tea respectively in hypertensive people. The hypertensive patients who drink 0.5–1 cup of coffee or 4–5 cups of tea per day have the lowest risk of dementia. A U-shaped relationship was observed between daily caffeine consumption and the risk of developing all-cause dementia and vascular dementia in the hypertensive population. Furthermore, the significant association between the amount of coffee and tea consumed and the risk of all-cause and vascular dementia were more likely to be found in hypertensive patients than in the non-hypertensive population.

Background With the continuous development of society and technological innovations, the average life expectancy of human beings has gradually increased, leading to the gradual increase in the number of perimenopausal women. This trend poses a serious challenge to the management of perimenopausal health in the community. Objective To understand the health characteristics and health needs of perimenopausal women in the community, explore the relationship between the two, and provide evidence to support the development and improvement of perimenopausal health management in community health service organisations. Methods Perimenopausal women (n=260) who attended or were accompanied to the Huamu Community Health Service Centre and its subordinate stations in Pudong New Area, Shanghai, from February to March 2023 were selected as study subjects. Questionnaires were used to collect information on the health characteristics of the study subjects (related to physiological stage, social characteristics, disease status, lifestyle, and quality of life), their knowledge of menopause and attitudes toward treatment, as well as their needs for knowledge related to menopause and preventive health care for menopausal diseases. Results Fifty percent (130/260) of perimenopausal women had a current history of chronic disease, 51.9% (135/260) of perimenopausal women had a past history of chronic disease, 73.8% (192/260) of perimenopausal women had fair/poor quality of sleep, 33.5% (87/260) of perimenopausal women did little exercise. 58.5% (152/260) of perimenopausal women were completely unaware or had only heard of menopause, 41.9% (109/260) of perimenopausal women had a negative attitude towards menopause treatment, 45.0% (117/126) of perimenopausal women needed menopause-related knowledge, and 66.6% (173/260) of perimenopausal women needed preventive health care for menopausal diseases. The results of ordered multicategorical Logistic regression analyses showed that literacy, the number of menopausal symptoms in the last 3 monthss, and attitudes toward menopause treatment were the factors influencing perimenopausal women's need for menopause-related knowledge (P

ObjectiveTo assess the implementation of insurance-based compensation for adverse reactions following immunization in Wuxi City,Jiangsu Province.MethodsData on basic insurance and supplementary insurance for adverse reactions following immunization from 2020 to 2022 in Wuxi City was collected, and a descriptive epidemiological method was used to analyze the data.ResultsA total of 2 272 cases were compensated for adverse reactions following immunization,with a total compensation amount of 5.255 9 million yuan, and an average of 2.3 thousand yuan per case. Basic insurance accounted for 0.62% of the total cases and 10.72% of the total compensation amount, while supplementary insurance accounted for 99.43% of the total cases and 89.28% of the total compensation amount. Compensation amounts for disability and third-degree damage in basic insurance accounted for 63.18% and 88.71%, respectively, while fourth-degree and lower damage in supplementary insurance accounted for 96.52%. The compensation rate for supplementary insurance was higher than that for basic insurance. The highest number of compensated cases was in the 0‒ year age group, and vaccines included in the Expanded Program on Immunization (EPI) accounted for the majority of the cases and compensation amounts, with a percentage of 70.11% and 73.84%, respectively. For basic insurance, the largest number of compensated cases involved the Bacillus Calmette-Guérin (BCG) vaccine. For supplementary insurance, the top three compensated cases for EPI vaccines were the measles-mumps-rubella (MMR) vaccine, the hepatitis B (HepB) vaccine, and the acellular diphtheria-tetanus-pertussis (DTaP) vaccine. For non-EPI vaccines, the top three compensated cases were the 13 valent pneumococcal polysaccharide conjugate (PPCV13) vaccine, the acellular DPT-inactivated poliovirus-haemophilus influenzae type b combined vaccine (DPT-IPV/Hib), and enterovirus 71 (EV71) inactivated vaccine. In basic insurance, thrombocytopenic purpura and BCG local abscess both accounted for 21.43% of the cases, while in supplementary insurance, respiratory system diseases accounted for 77.47% of the cases. The time intervals from reporting to submission of compensation materials (

The prevalence of sarcopenia in type 1 diabetes is higher than that in type 2 diabetes and non-diabetes patients. Screening, diagnosis and intervention of sarcopenia in type 1 diabetes patients as early as possible is of great significance for improving the life quality of these patients. The occurrence of sarcopenia in type 1 diabetes mellitus may be closely related to the decline of skeletal muscle function caused by the decrease of insulin-like growth factor-1, activation of inflammatory factors, mitochondrial dysfunction, and accumulation of advanced glycation end-products. At present, the mechanism of the occurrence and development of sarcopenia induced by type 1 diabetes is not completely clear, and the relevant new drug treatment lacks data support. Further in-depth research may bring a new direction for the prevention and treatment of sarcopenia in type 1 diabetes patients.

Abstract Background Automated test assembly (ATA) represents a modern methodology that employs data science optimization on computer platforms to automatically create test form, thereby significantly improving the efficiency and accuracy of test assembly procedures. In the realm of medical education, large-scale high-stakes assessments often necessitate lengthy tests, leading to elevated costs in various dimensions (such as examinee fatigue and expenses associated with item development). This study aims to augment the design of the medical education assessments by leveraging modern ATA approaches. Methods To achieve the objective, a four-step process employing psychometric methodologies was used to calibrate and analyze the item pool of the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU), a nationwide summative test comprising 300 multiple-choice questions (MCQ) in China. Subsequently, two modern ATA approaches were employed to determine the optimal item combination, accounting for both statistical and content requirements specified in the test blueprint. The qualities of the assembled test form, generated using modern ATA approaches, underwent meticulous evaluation. Results Through an exploration of the psychometric properties of the SCTCMU as a foundational step, the evaluation revealed commendable quality in the item properties. Furthermore, the evaluation of the quality of assembled test form using modern ATA approaches indicated the ability to ascertain the optimal test length within the predefined measurement precision. Specifically, this investigation demonstrates that the application of modern ATA approaches can substantially reduce the test length of assembled test form, while simultaneously maintaining the required statistical and content standards specified in the test blueprint. Conclusions This study harnessed modern ATA approaches to facilitate the automatic construction of test form, thereby significantly enhancing the efficiency and precision of test assembly procedures. The utilization of modern ATA approaches offers medical educators a valuable tool to enhance the efficiency and cost-effectiveness of medical education assessment.

Abstract Respiratory diseases are a growing concern in public health because of their potential to endanger the global community. Cell death contributes critically to the pathophysiology of respiratory diseases. Recent evidence indicates that necroptosis, a unique form of programmed cell death (PCD), plays a vital role in the molecular mechanisms underlying respiratory diseases, distinguishing it from apoptosis and conventional necrosis. Necroptosis is a type of inflammatory cell death governed by receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein (MLKL), resulting in the release of intracellular contents and inflammatory factors capable of initiating an inflammatory response in adjacent tissues. These necroinflammatory conditions can result in significant organ dysfunction and long-lasting tissue damage within the lungs. Despite evidence linking necroptosis to various respiratory diseases, there are currently no specific alternative treatments that target this mechanism. This review provides a comprehensive overview of the most recent advancements in understanding the significance and mechanisms of necroptosis. Specifically, this review emphasizes the intricate association between necroptosis and respiratory diseases, highlighting the potential use of necroptosis as an innovative therapeutic approach for treating these conditions.

Abstract To investigate the safety of Indocalamu Iatifolius McClur leaves sold in the market, a study was conducted using Indocalamu Iatifolius McClur leaves randomly collected from an online store and a large supermarket. Acute toxicity experiments were performed on mice, and their body weight was monitored for 14 days after administration. After the observation period, blood samples were collected for biochemical analysis, and organ pathology was examined. Then, the content of copper (Cu), lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and the residues of nine organochlorine pesticides in Indocalamu Iatifolius McClur leaves were measured according to the National Food Safety Standard (GB/T5009-2003) and the pesticide residue determination methods in the 2020 edition of the Chinese Pharmacopoeia. The results showed that the mice in the Indocalamu Iatifolius McClur leaves (online store) group experienced mortality and severe liver and lung damage. The levels of lead, cadmium, mercury, arsenic, and the nine organochlorine pesticides met the relevant standards and regulations. However, the copper content in the Indocalamu Iatifolius McClur leaves (online store) group was nearly 80 times higher than that in the supermarket group. Mice in the Indocalamu Iatifolius McClur leaves (supermarket) group remained healthy without any abnormalities, and the levels of harmful metals and organochlorine pesticides complied with the standards and regulations. The study suggests the need for regulatory policies and safety standards for the sale of Indocalamu Iatifolius McClur leaves.

Objective To identify the relationship between physical activity,insulin resistance and cardiovascular risk in individuals with different glucose tolerance status and to provide evidence for exercise intervention in people with different glucose tolerance status. Methods A total of 691 patients with different glucose metabolism status were recruited as subjects of the research. Spearman correlation analysis was used to study the relationship between exercise frequency and insulin resistance, insulin sensitivity, neck circumference (NC) and neck circumference height ratio (NHtR) in the subjects with different glucose metabolism status, the relationship between NC and insulin resistance and insulin sensitivity in different glucose metabolism groups. Results 171(62.9%) Subjects with diabetes were intervened by exercised every day. Spearman correlation analysis showed the correlation between exercise frequency and tri-glyceride triglyceride-glucose index (TyG index) (r=-0.120, P＜0.05) and NC (r=-0.168, P＜0.05) were negatively correlated. In subjects with diabetes, NC was positively correlated with triglycerides(TG) (r=-0.100, P＜0.05), homeostasis model assessment of insulin resistance(HOMA-R) (r=-0.163, P＜0.05), total cholesterol/high-density lipoprotein(TC/HDL-C)(r=-0.214, P＜0.05) and TyG index (r=-0.156, P＜0.05). Conclusions Increased frequency of exercise is associated with reduced NC, improved insulin resistance, and cardiovascular risk factors in subjects of our team with newly diagnosed diabetes. Exercise has no significant effect on insulin resistance of subjects with normal glucose tolerance and pre-diabetes.

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE) intervention timing and liver injury periodization in patients with exertional heat stroke(EHS). Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected, then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT, AST, TBIL and DBIL. According to propensity score matching analysis, 11 patients in the survival group and 12 patients in the death group were included in the statistical analysis, and 20 of them were treated with TPE. The changes in indicators and clinical outcomes before and after TPE were observed, in order to evaluate the impact of intervention timing on prognosis. Results Among the 23 patients, 14 had no liver injury or could progress to the repair phase, resulting in 3 deaths(with the mortality rate of 21.43%), while 9 patients failed to progress to the repair phase, resulting in 9 deaths(with the mortality rate of 100%), with significant differences(P

Objective To review the occurrence of allergic reactions during therapeutic plasma exchange (TPE) and to explore the risk factors of TPE allergic reactions. Methods The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected. The influencing factors of allergic reactions were analyzed by univariate analysis, and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis. Results A total of 4 071 TPEs were performed in 929 patients.Among them, 198 patients (21.31%) experienced 349 times (8.57%) of allergic reactions, with the incidence of grade Ⅰ, Ⅱ and Ⅲ allergic reactions of 16.33%, 81.38% and 2.29%, respectively, and no deaths. The univariate analysis showed that the patient′s age, allergy history, diagnosis of immune-related diseases, ICU admission, plasma consumption, total blood volume, maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions (P

Abstract Nematodes serve as key indicators of soil health in ecological studies. Therefore, the current study examined the community structure and metabolic footprint of soil nematodes in alfalfa fields across varying levels of N supply in the semi-arid Loess Plateau. The findings offer theoretical guidance for the sustainable management of artificial alfalfa grasslands in this region. The research was based on alfalfa fields with different N application rates (0, 50, 100, 150 kg/ha2) as the research object, The shallow plate method was used to separate and extract soil nematodes, identify soil nematode groups, calculate ecological function index and metabolic footprint, and identify indicator species. A total of 6346 nematodes were isolated in this study, belonging to 27 genera and 19 families. Notably, the plant parasitic nematode Helicotylenchus was predominant. As N addition increased, the plant parasitic index (PPI) increased significantly. A N50 application significantly enhanced the soil nematode diversity index ( $$\text{H}$$ H ) and the free-living index (MI). The findings showcased a noticeable decrease in disturbance within the N50 soil nematode community. This resulted in a mature and stable community structure primarily attributed to the heightened abundance of omnivorous/predatory nematodes. Across various N levels, soil nematode communities underwent significant alterations in the soil food web structure through shifts in their metabolic footprint. Future strategies should focus on refining N management practices and integrating sustainable approaches like crop rotation and pest management. These efforts will contribute to guidelines ensuring artificial alfalfa grasslands lasting health and productivity.

Abstract Background High-altitude cerebral edema (HACE) is considered an end-stage acute mountain sickness (AMS) that typically occurs in people after rapid ascent to 2500 m or more. While hypoxia is a fundamental feature of the pathophysiological mechanism of HACE, emerging evidence suggests that inflammation serves as a key risk factor in the occurrence and development of this disease. However, little is known about the molecular mechanism underlying their crosstalk. Methods A mouse HACE model was established by combination treatment with hypobaric hypoxia exposure and lipopolysaccharides (LPS) stimulation. Lactylated-proteomic analysis of microglia was performed to reveal the global profile of protein lactylation. Molecular modeling was applied to evaluate the 3-D modeling structures. A combination of experimental approaches, including western blotting, quantitative real-time reverse transcriptionpolymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and RNA interference, were used to explore the underlying molecular mechanisms. Results We found that hypoxia exposure increased the lactate concentration and lactylation in mouse HACE model. Moreover, hypoxia aggravated the microglial neuroinflammatory response in a lactate-dependent manner. Global profiling of protein lactylation has shown that a large quantity of lysine-lactylated proteins are induced by hypoxia and preferentially occur in protein complexes, such as the NuRD complex, ribosome biogenesis complex, spliceosome complex, and DNA replication complex. The molecular modeling data indicated that lactylation could affect the 3-D theoretical structure and increase the solvent accessible surface area of HDAC1, MTA1 and Gatad2b, the core members of the NuRD complex. Further analysis by knockdown or selectively inhibition indicated that the NuRD complex is involved in hypoxia-mediated aggravation of inflammation. Conclusions These results revealed a comprehensive profile of protein lactylation in microglia and suggested that protein lysine lactylation plays an important role in the regulation of protein function and subsequently contributes to the neuroinflammatory response under hypoxic conditions.

Abstract Background To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. Methods We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20–54 and > 55 years from 1990–2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. Results From 1990–2019, the global prevalence rates of IHD, IS, and PAD in the 20–54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20–54 years group than in the > 55 years group. For PAD, DALYs among those aged 20–54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. Conclusions The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

Abstract Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 μm) and broad modulus adjusting capability (15.8–345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.

Abstract Polyploidization plays an important role in plant evolution and biodiversity. However, intraspecific polyploidy compared to interspecific polyploidy received less attention. Clintonia udensis (Liliaceae) possess diploid (2n = 2x = 14) and autotetraploid (2n = 4x = 28) cytotypes. In the Hualongshan Mountains, the autotetraploids grew on the northern slope, while the diploids grew on the southern slopes. The clonal growth characteristics and clonal architecture were measured and analyzed by field observations and morphological methods. The diversity level and differentiation patterns for two different cytotypes were investigated using SSR markers. The results showed that the clonal growth parameters, such as the bud numbers of each rhizome node and the ratio of rhizome branches in the autotetraploids were higher than those in the diploids. Both the diploids and autotetraploids appeared phalanx clonal architectures with short internodes between ramets. However, the ramets or genets of the diploids had a relatively scattered distribution, while those of the autotetraploids were relatively clumping. The diploids and autotetraploids all allocated more biomass to their vegetative growth. The diploids had a higher allocation to reproductive organs than that of autotetraploids, which indicated that the tetraploids invested more resources in clonal reproduction than diploids. The clone diversity and genetic diversity of the autotetraploids were higher than that of the diploids. Significant genetic differentiation between two different cytotypes was observed (P

Disturbances of gut microbiota may affect the balance of the host immune system. The metabolism of gut microbiota produces many bioactive molecules interacting with host, typically secondary bile acids (SBAs). SBAs are involved in regulating the energy metabolism and the expression of inflammatory response-related genes by binding to membrane receptors and nuclear receptors, such as takeda G protein-coupled receptor (TGR5) and farnesol X receptor (FXR), which are essential for maintaining host immune homeostasis.

Objective Aimed to evaluate patients with essential hypertension (EH) using four-dimensional automatic left atrial quantification (4DLAQ) To assess the occurrence of EH. Methods This study selected 80 patients with EH for the EH group and 36 healthy individuals for the control group. Various cardiac parameters, including left atrial diameter (LAD), interventricular septal thickness (IVST), left ventricular end-diastolic diameter (LVDD), left ventricular posterior wall thickness (LVPWT), early E-wave velocity of mitral valve diastole/mitral valve ring myocardial displacement velocity (E/e'), biplanar left ventricular ejection fraction (biplanLVEF), left atrial minimum volume (LAVmin), lateral left atrial maximum volume (LAVmax), left atrial presystolic volume (LAVpreA), left atrial ejection fraction obtained by two-dimensional echocardiography (LAEF), left atrial passive ejection fraction (LAPEF), left atrial active ejection fraction (LAAEF), left atrial reservoir longitudinal strain (LASr), left atrial catheter longitudinal strain (LAScd), left atrial systolic longitudinal strain (LASct), left atrial reservoir circular strain (LASr_c), left atrial catheter circular strain (LAScd_c), and left atrial systolic circular strain (LASct_c) were measured using 4DLAQ. Binary logistic regression was employed to analyze the effect of 4DLAQ strain parameters on EH. Receiver operating characteristic (ROC) curves were used to assess the predictive value of 4DLAQ strain parameters for EH. Results Systolic blood pressure and diastolic blood pressure in the EH group were higher than those in the control group (P = 0.000 and 0.000, respectively). In the EH group, LAD, IVST, LVDD, LVPWT, E/e', LAVmin, LAVmax, and LAVpreA were significantly increased (P = 0.000, 0.000, 0.072, 0.000, 0.000, 0.001, 0.052, and 0.004, respectively), whereas biplanLVEF, LAEF, LAPEF, LAAEF, LASr, LAScd, LASct, LASr_c, LAScd_c, and LASct_c significantly decreased (P = 0.090, 0.000, 0.009, 0.064, 0.000, 0.000, 0.000, 0.000, 0.000, and 0.689, respectively). Bland-Altman plots were used to illustrate the relationship between variables and audience consensus. LASr and LAScd were identified as independent risk factors for EH. The area under the ROC curve (AUC) for LASr was 0.925, (95% confidence interval [CI] = 0.879-0.971) with a sensitivity of 80.00%, specificity of 94.44%, using a cut-off value of 20%. For LAScd, the AUC-ROC was 0.878 (95% CI = 0.818-0.939 with a sensitivity of 76.25%, specificity 86.11%, and using a critical value of -11%. Conclusion LASr and LAScd exhibited superior predictive capabilities for EH, with LASr performing the best. This study fills a critical gap in left atrial research and holds significant clinical implications.

Abstract Plant‐derived extracellular vesicles (EVs) are promising therapeutic agents owing to their natural abundance, accessibility, and unique biological properties. This review provides a comprehensive exploration of the therapeutic potential of plant‐derived EVs and emphasizes their anti‐inflammatory, antimicrobial, and tumor‐inhibitory effects. Here, we discussed the advancements in isolation and purification techniques, such as ultracentrifugation and size‐exclusion chromatography, which are critical for maintaining the functional integrity of these nanovesicles. Next, we investigated the diverse administration routes of EVs and carefully weighed their respective advantages and challenges related to bioavailability and patient compliance. Moreover, we elucidated the multifaceted mechanisms of action of plant‐derived EVs, including their roles in anti‐inflammation, antioxidation, antitumor activity, and modulation of gut microbiota. We also discussed the impact of EVs on specific diseases such as cancer and inflammatory bowel disease, highlighting the importance of addressing current challenges related to production scalability, regulatory compliance, and immunogenicity. Finally, we proposed future research directions for optimizing EV extraction and developing targeted delivery systems. Through these efforts, we envision the seamless integration of plant‐derived EVs into mainstream medicine, offering safe and potent therapeutic alternatives across various medical disciplines.

Plant diversity is the basis for human survival and development, directly affecting the function and stability of urban ecosystems. Its distribution pattern and causes have been a central issue in ecological and landscape gardening research. Rapid urbanization in Zhengzhou City has led to the fragmentation of urban green spaces and damage to ecosystems, seriously affecting urban biodiversity conservation. Understanding the distribution pattern of plant diversity in the region and its relationship with environmental factors is crucial for maintaining and enhancing urban plant diversity. Plant data from 178 sample plots in the built-up area of Zhengzhou City were collected and combined with environmental factors, and the characteristics of plant diversity, richness patterns, and their main environmental explanations in Zhengzhou City were explored. Results showed that there were 596 plant species belonging to 357 genera and 110 families in the study area. There were five dominant families and four dominant genera. Four distinct spatial patterns of plant diversity were identified along the urban–rural gradient. Urbanization factors such as GDP per capita, house prices, and imperviousness within 500 m from the patch significantly influenced plant diversity. There was an imbalance between the spatial pattern of plant diversity and application of urban landscape greening in Zhengzhou City. Future studies should focus on the application of native plants, curb plant homogenization, and reduce anthropogenic interference, which are conducive to protecting and enhancing urban plant diversity. These results can provide a basis for understanding the distribution pattern and influence mechanism of urbanization factors on plant diversity and serve as a reference for policymakers and planners of plant diversity conservation in Zhengzhou City.

In the process of colorectal cancer metastasis, the tumor microenvironment interacts with primary tumors, secondary tumors, circulating tumor cells, and disseminated tumor cells. This article introduces its dynamic evolution process. The tumor microenvironment can not only exert its host defense mechanism to kill cancer cells, but also help cancer cells metastasize and spread through changes in the composition and structure of the microenvironment. Cancer cells complete their invasion, infiltration, circulation, extravasation, and seeding processes through phenotype transformation, secretion of cytokines, and cell dormancy.

Abstract Background Oral squamous cell carcinoma (OSCC) is a malignant tumor with a poor prognosis. Traditional treatments have limited effectiveness. Regulation of the immune response represents a promising new approach for OSCC treatment. B cells are among the most abundant immune cells in OSCC. However, the role of B cells in OSCC treatment has not been fully elucidated. Methods Single-cell RNA sequencing analysis of 13 tissues and 8 adjacent normal tissues from OSCC patients was performed to explore differences in B-cell gene expression between OSCC tissues and normal tissues. We further investigated the relationship between differentially expressed genes and the immune response to OSCC. We utilized tissue microarray data for 146 OSCC clinical samples and RNA sequencing data of 359 OSCC samples from The Cancer Genome Atlas (TCGA) to investigate the role of T-cell leukemia 1 A (TCL1A) in OSCC prognosis. Multiplex immunohistochemistry (mIHC) was employed to investigate the spatial distribution of TCL1A in OSCC tissues. We then investigated the effect of TCL1A on B-cell proliferation and trogocytosis. Finally, lentiviral transduction was performed to induce TCL1A overexpression in B lymphoblastoid cell lines (BLCLs) to verify the function of TCL1A. Results Our findings revealed that TCL1A was predominantly expressed in B cells and was associated with a better prognosis in OSCC patients. Additionally, we found that TCL1A-expressing B cells are located at the periphery of lymphatic follicles and are associated with tertiary lymphoid structures (TLS) formation in OSCC. Mechanistically, upregulation of TCL1A promoted the trogocytosis of B cells on dendritic cells by mediating the upregulation of CR2, thereby improving antigen-presenting ability. Moreover, the upregulation of TCL1A expression promoted the proliferation of B cells. Conclusion This study revealed the role of B-cell TCL1A expression in TLS formation and its effect on OSCC prognosis. These findings highlight TCL1A as a novel target for OSCC immunotherapy.

Objective To discuss the possible etiology, pathogenesis, clinical features, diagnosis and treatment of epidermoid cysts of the jaw and to provide a reference for clinical diagnosis and treatment. Methods A case of an epidermoid cyst in the right mandible with retained deciduous teeth and succedaneous impacted teeth was reviewed and analyzed in combination with the relevant literature. Results A patient presented with a mass in the right mandible that had persisted for 1 month after being found at imaging examination. Tooth 83 was retained, and tooth 43 was unerupted. Swelling was characterized by no obvious tenderness, fluctuation, or table tennis sensation and was observed in the lingual alveoli of teeth 83, 44, and 45. Imaging revealed a low-density shadow in the apex of teeth 83, 44, 45, and 46, approximately 1.9 cm × 2.6 cm × 1.6 cm in size, which wrapped around the dental crown of tooth 43. Preliminary diagnoses were as follows: right mandibular mass thought to be a dentigerous cyst; impacted tooth 43; and retained primary tooth 83. The mass in the right mandible was removed, and teeth 43 and 83 were extracted under intravenous and inhalation anesthesia. During the operation, the mass was observed to have a thin cyst wall and contained bean-like residue. Histopathological examination indicated an epidermoid cyst in the right mandible. At the 1-week follow-up examination, the patient reported no discomfort, and the surgical area showed good recovery. According to the literature, epidermoid cysts are benign cysts originating from ectopic ectodermal tissue that can occur throughout the body but rarely in the oral cavity and are even extremely rarer in the jaw. Epidermoid cysts of the jaw, which have no specific clinical manifestations, can be confused with odontogenic cysts such as dentigerous cysts and odontogenic tumors. Dental pulp tests and other techniques can serve as a reference for clinicians. The diagnosis is confirmed via histopathology. Surgical removal is a common treatment, with a good prognosis and a low recurrence rate. Conclusion The principle of treatment for an epidermoid cyst of the jaw is similar to that for a jaw cyst. The prognosis is good when the cyst is removed completely.

Background: Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others. Aims: To investigate the role of TSLP in the pathogenesis of psoriasis. Study Design: In vitro and in vivo study. Methods: To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4+ T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4+ T cells. Conclusion: These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.

Abstract Bovine viral diarrhea virus (BVDV) is considered to be the most common agent of severe diarrhea in cattle worldwide, causing fever, diarrhea, ulcers, and abortion. Bovine herpesvirus 1 (BoHV-1) is also a major bovine respiratory disease agent that spreads worldwide and causes extensive damage to the livestock industry. Recombinase polymerase amplification (RPA) is a novel nucleic acid amplification method with the advantages of high efficiency, rapidity and sensitivity, which has been widely used in the diagnosis of infectious diseases. A dual RPA assay was developed for the simultaneous detection of BVDV and BoHV-1. The assay was completed at a constant temperature of 37 °C for 30 min. It was highly sensitive and had no cross-reactivity with other common bovine viruses. The detection rate of BVDV RPA in clinical samples (36.67%) was higher than that of PCR (33.33%), the detection rate of BoHV-1 RPA and PCR were equal. Therefore, the established dual RPA assay for BVDV and BoHV-1 could be a potential candidate for use as an immediate diagnostic.

Abstract. Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

Abstract Rammed earth is a kind of cleaning material, widely used in all kinds of buildings in the world. The Great Wall of ancient China is a typical world cultural site built from rammed earth. The rammed earth Great Wall of Shanhaiguan is close to Bohai Bay, which has suffered from long-term erosion by rain, causing a series of problems such as soil loss, collapse and gully flushing. The protection materials of the rammed earth site have always puzzled scholars. However, during the rainy season, it was found that some of the walls at Xiaowan Gouge and Nantuzhuang Gouge in the Shanhaiguan Great Wall had unwashed traces, the soil surface of the walls was intact, and the anti-erosion ability of the walls was significantly higher than that of other places. In order to explore the reasons for its strong anti-erosion ability in the natural state of rammed earth wall, guide the protection of rammed earth Great Wall, and carry out different experimental tests to explore its anti-erosion reasons and internal mechanisms. Firstly, the characteristics of rammed soil were understood through the composition test of rammed soil, and the indoor and outdoor erosion test was carried out to determine that the anti-erosion reason was the protection of gray-green soil crust. The property and composition of soil crust were determined through the immersion test and genome sequencing. Finally, the protection mechanism of soil crust was analyzed by scanning electron microscopy.

Abstract Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague–Dawley rats aged 2–3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1β for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague–Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1β-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh.

Abstract Deep vein thrombosis (DVT) is a common complication in patients with lower extremity fractures. Once it occurs, it will seriously affect the quality of life and postoperative recovery of patients. Therefore, early prediction and prevention of DVT can effectively improve the prognosis of patients. This study constructed different machine learning models to explore their effectiveness in predicting DVT. Five prediction models were applied to the study, including Extreme Gradient Boosting (XGBoost) model, Logistic Regression (LR) model, RandomForest (RF) model, Multilayer Perceptron (MLP) model, and Support Vector Machine (SVM) model. Afterwards, the performance of the obtained prediction models was evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, F1 score, and Kappa. The prediction performances of the models based on machine learning are as follows: XGBoost model (AUC = 0.979, accuracy = 0.931), LR model (AUC = 0.821, accuracy = 0.758), RF model (AUC = 0.970, accuracy = 0.921), MLP model (AUC = 0.830, accuracy = 0.756), SVM model (AUC = 0.713, accuracy = 0.661). On our data set, the XGBoost model has the best performance. However, the model still needs external verification research before clinical application.

Abstract The integrated development of agricultural land and finance not only promotes rural financial innovation and breaks the bottleneck of agricultural financing but also facilitates agricultural land transfer and scaled operations. This leads to the advancement of the effective growth of contemporary agriculture. The reform of the 'separation of three rights' in agricultural land promotes land circulation, which, in turn, offers an institutional guarantee for the tandem development of rural finance and agricultural land management. This paper measures the comprehensive development index of agricultural land management and rural finance in 30 provinces of China from 2005 to 2020. In light of this, it calculates the degree of coupling and coordination between China's agricultural land management and rural financial development. The Dagum Gini coefficient, kernel density, and the Moran index were used to analyze regional differences and patterns of agglomeration. The study found that the degree of coupling coordination between China's agricultural land management and rural finance is increasing annually. However, there remains a significant gap in achieving high-quality coupling. Notably, the growth rate of rural financial development exceeds that of agricultural land management, and hypervariable density is a major source of regional variation. There is polarization in the coupled development of farmland management and rural finance. Provinces in the eastern and central regions tend to be located in the high–high agglomeration (H–H) in terms of the level of development of agricultural land and financial integration, while the western region tends to fall in low–low aggregation (L–L).

Abstract Background Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. Methods HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. Results ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = − 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p