Objective:To explore the effect of hyperbaric oxygen (HBO) combined with Saccharomyces boulardii in ulcerative colitis (UC) and effect of serum asymmetric dimethylarginine (ADMA). Methods:A total of 100 patients with UC admitted to the First Hospital of Yulin from August 2021 to August 2023 were prospectively selected as the study objects and divided into control group and observation group according to random number table method, with 50 cases in each group. The control group was treated with mesalazine + Saccharomyces boulardii sachets, and the observation group was treated with mesalazine + Saccharomyces boulardii sachets + HBO, and both groups were treated for 60 d. The clinical efficacy and the levels of intestinal flora, ADMA, intestinal mucosal barrier function indexes, inflammatory factors and immune function indexes before and after treatment were compared between the two groups, and the occurrence of adverse reactions were compared between the two groups. Results:After treatment, the total effective rate in the observation group was higher than that in the control group: 74.00%(37/52) vs. 50.00%(26/52), there was statistical difference ( χ2 = 5.19, P<0.05). After treatment, the number of Enterococcus and Escherichia coli in the observation group were lower than those in the control group: (4.37 ± 0.91) lgcfu/g vs. (7.95 ± 1.32) lgcfu/g, (6.17 ± 0.92) lgcfu/g vs. (9.36 ± 1.35) lgcfu/g; and the number of Lactobacillus and Bifidobacterium were higher than those in the control group: (10.24 ± 2.57) lgcfu/g vs. (8.38 ± 1.48) lgcfu/g, (10.72 ± 3.15) lgcfu/g vs. (8.69 ± 2.64) lgcfu/g, there were statistical differences ( P<0.05). After treatment, the level of ADMA in the observation group was lower than that in control group: (0.51 ± 0.08) μmol/L vs. (0.85 ± 0.12) μmol/L; and the intestinal mucosal barrier function indexes of diamine oxidase, D-lactic acid and endotoxin were lower than those in the control group: (5.82 ± 1.13) U/L vs. (7.13 ± 1.89) U/L, (3.96 ± 0.42) mmol/L vs. (4.38 ± 0.85)mmol/L, (0.18 ± 0.02) kEU/L vs. (0.23 ± 0.04) kEU/L, there were statistical differences ( P<0.05). After treatment, the inflammatory factor C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in the observation group were lower than those in the control group: (4.84 ± 0.68) mg/L vs. (7.16 ± 0.82) mg/L, (13.24 ± 1.98) ng/L vs. (17.61 ± 2.25) ng/L, (22.13 ± 4.16) μg/L vs. (29.36 ± 5.37) μg/L; and IL-10 was higher than that in the control group:(15.35 ± 2.98) ng/L vs. (11.27 ± 3.26) ng/L, there were statistical differences ( P<0.05). After treatment, the immune function indexes CD 3+, CD 4+, CD 4+/CD 8+ in the observation group were higher than those in the control group: 0.563 ± 0.063 vs. 0.459 ± 0.052, 0.420 ± 0.049 vs. 0.383 ± 0.053, 1.35 ± 0.32 vs. 1.16 ± 0.26, there werestatistical differences ( P<0.05). The incidence of adverse reactions between the two groups had no statistical difference ( P>0.05). Conclusions:HBO combined with Saccharomyces boulardii can significantly improve clinical symptoms, reduce intestinal mucosal damage and improve intestinal microenvironment in UC patients.

Background Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder in children, often diagnosed during school age. The etiology of ADHD remains unclear; however, existing studies suggest that environmental factors, such as exposure to triclosan (TCS), may be associated with the occurrence of ADHD-like symptoms in offspring. Nevertheless, relevant research in China remains limited. Objective To investigate the impact of early pregnancy TCS exposure on ADHD-like symptoms in 7-year-old children. Methods This study was based on the Shanghai Birth Cohort (SBC) and included 662 mother-child pairs. TCS concentrations in early pregnancy urine samples were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Demographic information was collected via questionnaires and medical record abstraction. ADHD-like symptoms in 7-year-old children were first assessed using the Strengths and Difficulties Questionnaire (SDQ). Further differentiation of ADHD-like symptom subtypes (inattentive and hyperactive/impulsive) was conducted using the SNAP-IV, a clinically validated ADHD screening tool. Negative binomial regression models were applied to evaluate the associations between prenatal TCS exposure and hyperactive behavior (SDQ assessment) as well as ADHD-like symptom subtypes (SNAP-IV assessment) in 7-year-old children. Results The positive rate of TCS in early pregnancy urine samples was 91.39%, with median concentrations of 0.69 μg·L⁻¹ and 0.63 μg·g⁻¹ before and after the creatinine adjustment, respectively. The modeling results indicated that prenatal TCS exposure was associated with an increased risk of hyperactive symptoms (SDQ assessment) in 7-year-old children (RR=1.04, 95%CI: 1.02, 1.06); the stratified analyses by children sex revealed similar effects for both boys (RR=1.04, 95%CI: 1.02, 1.07) and girls (RR=1.04, 95%CI: 1.01, 1.07). Further analysis of ADHD-like symptom subtypes showed that prenatal TCS exposure increased the risk of inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.05); the sex-stratified analyses indicated associations between TCS exposure and inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.07) as well as hyperactive/impulsive symptoms (RR=1.04, 95%CI: 1.01, 1.08) in girls. Conclusion Prenatal TCS exposure is associated with an increased risk of ADHD-like symptoms in 7-year-old children, primarily contributing to the risk of the inattention subtype. The impact is more pronounced in girls.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

We analyzed the epidemiological features and spatial distribution characteristics of human brucellosis in Jining city from 2014 to 2023,to provide a reference for further development of targeted prevention and control strategies and measures.Descrip-tive epidemiological methods were used to analyze the epidemiological characteristics of brucellosis cases in Jining from 2014 to 2023.The spatial regional correlation of brucellosis incidence in Jining and the clustering patterns of local areas were studied through spatial autocorrelation analysis with townships as the basic unit.A total of 3 520 cases of brucellosis were reported in Jining from 2014 to 2023,and the average annual incidence rate was 4.23/100 000,thus indicating a fluctuating trend overall.Reported cases peaked from March to August,and a sex ratio of 2.71 males to 1 female was observed.The 40-59 year age group had the most reported cases(50.39％).The incidence of brucellosis in Jining showed an imbalanced spatial distribution.Brucellosis incidence showed a spatially clustered distribution(Moran's I>0,P<0.05).Hotspots were distributed primarily in Sishui,Qufu,and Zoucheng.A total of one class Ⅰ clustering area and one class Ⅱ clustering area were detected in the spatial and temporal scans,and were located in Sishui,Qufu,and Liangshan county.After pathogenic AMOS-PCR typing analysis,64 Brucella isolates collected from Jinan City from 2022 to 2024 were all of the sheep strain,and sheep biovar 3 was predominant(70.31％).In 2014-2023,although Jining City experienced a high incidence of brucellosis,a downward trend was observed.Brucellosis showed a spatial clustering pattern concentrated in the northeastern region.Therefore,awareness and education must be strengthened among brucellosis practitioners in cluster areas,to en-hance case surveillance,improve the level of protection,and achieve early detection and treatment.

ObjectiveThis nested case-control study, based on the Shanghai Birth Cohort (SBC), aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants (OPFRs) on attention deficit hyperactive disorder (ADHD)-like symptoms in 4-year-old children, so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children. MethodsStrengths and Difficulties Questionnaire (SDQ) was used to assess ADHD like symptoms in 4-year-old children. Children with an SDQ hyperactivity subscale score ≥6 points were defined as cases, while those with a score <5 points were considered as controls. The case and control groups were matched at 1∶1 based on the child’s age (±6 months), sex, and parental or primary caregiver’s education level. A total of 105 cases and 112 controls were included eventually. Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including di-phenyl phosphate (DPHP), di-m-cresylphosphate (DmCP), di-o-cresylphosphate (DoCP), di-p-cresylphosphate (DpCP), di-n-butyl phosphate (DnBP), di-iso-butyl phosphate (DiBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(2-ethylhexyl) phosphate (BEHP). Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction. Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms, while a quantile g-computation (Qgcomp) regression model was employed to assess the effects of mixed OPFRs exposure (with detection rates >75%) on ADHD-like symptoms in 4-year-old children. ResultsIn this study, the detection rates of DPHP, DoCP, and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%, with DPHP having the highest detection rate (86.18%). The median concentrations of DPHP were highest in both the case and control groups (0.396 μg·L^-1 and 0.305 μg·L^-1, respectively). Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children (OR=1.262, 95%CI: 1.017‒1.565). The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms (OR=1.508, 95%CI: 1.012‒2.258), with DPHP being the primary contributor to the association. ConclusionEarly pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children. Additionally, DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms. However, these findings require further validation through other large-scale prospective cohort studies.

We analyzed the epidemiological features and spatial distribution characteristics of human brucellosis in Jining city from 2014 to 2023,to provide a reference for further development of targeted prevention and control strategies and measures.Descrip-tive epidemiological methods were used to analyze the epidemiological characteristics of brucellosis cases in Jining from 2014 to 2023.The spatial regional correlation of brucellosis incidence in Jining and the clustering patterns of local areas were studied through spatial autocorrelation analysis with townships as the basic unit.A total of 3 520 cases of brucellosis were reported in Jining from 2014 to 2023,and the average annual incidence rate was 4.23/100 000,thus indicating a fluctuating trend overall.Reported cases peaked from March to August,and a sex ratio of 2.71 males to 1 female was observed.The 40-59 year age group had the most reported cases(50.39％).The incidence of brucellosis in Jining showed an imbalanced spatial distribution.Brucellosis incidence showed a spatially clustered distribution(Moran's I>0,P<0.05).Hotspots were distributed primarily in Sishui,Qufu,and Zoucheng.A total of one class Ⅰ clustering area and one class Ⅱ clustering area were detected in the spatial and temporal scans,and were located in Sishui,Qufu,and Liangshan county.After pathogenic AMOS-PCR typing analysis,64 Brucella isolates collected from Jinan City from 2022 to 2024 were all of the sheep strain,and sheep biovar 3 was predominant(70.31％).In 2014-2023,although Jining City experienced a high incidence of brucellosis,a downward trend was observed.Brucellosis showed a spatial clustering pattern concentrated in the northeastern region.Therefore,awareness and education must be strengthened among brucellosis practitioners in cluster areas,to en-hance case surveillance,improve the level of protection,and achieve early detection and treatment.

Constipation is a common functional gastrointestinal disorder with a global prevalence of approximately 10％to 20％.Its causes include functional disorders,organic diseases,and drug factors,with the majority being functional constipation.In recent years,driven by advancements in biomedicine,artificial intelligence(AI),and microbiome research,significant progress has been made in the diagnosis and treatment of constipation.This review systematically explores the latest developments in constipation treatment,including the role of the gut microbiota in constipation,the metabolic regulatory effects of short-chain fatty acids(SCFAs),the impact of mental factors on intestinal motility.Additionally,it discusses future development directions such as AI-assisted diagnosis,AI-based consultation systems,personalized microbiota transplantation,and minimally invasive neuromodulation,providing new insights for precision medicine in constipation.

Constipation is a common functional gastrointestinal disorder with a global prevalence of approximately 10％to 20％.Its causes include functional disorders,organic diseases,and drug factors,with the majority being functional constipation.In recent years,driven by advancements in biomedicine,artificial intelligence(AI),and microbiome research,significant progress has been made in the diagnosis and treatment of constipation.This review systematically explores the latest developments in constipation treatment,including the role of the gut microbiota in constipation,the metabolic regulatory effects of short-chain fatty acids(SCFAs),the impact of mental factors on intestinal motility.Additionally,it discusses future development directions such as AI-assisted diagnosis,AI-based consultation systems,personalized microbiota transplantation,and minimally invasive neuromodulation,providing new insights for precision medicine in constipation.

Objective:To explore the effect of hyperbaric oxygen (HBO) combined with Saccharomyces boulardii in ulcerative colitis (UC) and effect of serum asymmetric dimethylarginine (ADMA). Methods:A total of 100 patients with UC admitted to the First Hospital of Yulin from August 2021 to August 2023 were prospectively selected as the study objects and divided into control group and observation group according to random number table method, with 50 cases in each group. The control group was treated with mesalazine + Saccharomyces boulardii sachets, and the observation group was treated with mesalazine + Saccharomyces boulardii sachets + HBO, and both groups were treated for 60 d. The clinical efficacy and the levels of intestinal flora, ADMA, intestinal mucosal barrier function indexes, inflammatory factors and immune function indexes before and after treatment were compared between the two groups, and the occurrence of adverse reactions were compared between the two groups. Results:After treatment, the total effective rate in the observation group was higher than that in the control group: 74.00%(37/52) vs. 50.00%(26/52), there was statistical difference ( χ2 = 5.19, P<0.05). After treatment, the number of Enterococcus and Escherichia coli in the observation group were lower than those in the control group: (4.37 ± 0.91) lgcfu/g vs. (7.95 ± 1.32) lgcfu/g, (6.17 ± 0.92) lgcfu/g vs. (9.36 ± 1.35) lgcfu/g; and the number of Lactobacillus and Bifidobacterium were higher than those in the control group: (10.24 ± 2.57) lgcfu/g vs. (8.38 ± 1.48) lgcfu/g, (10.72 ± 3.15) lgcfu/g vs. (8.69 ± 2.64) lgcfu/g, there were statistical differences ( P<0.05). After treatment, the level of ADMA in the observation group was lower than that in control group: (0.51 ± 0.08) μmol/L vs. (0.85 ± 0.12) μmol/L; and the intestinal mucosal barrier function indexes of diamine oxidase, D-lactic acid and endotoxin were lower than those in the control group: (5.82 ± 1.13) U/L vs. (7.13 ± 1.89) U/L, (3.96 ± 0.42) mmol/L vs. (4.38 ± 0.85)mmol/L, (0.18 ± 0.02) kEU/L vs. (0.23 ± 0.04) kEU/L, there were statistical differences ( P<0.05). After treatment, the inflammatory factor C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in the observation group were lower than those in the control group: (4.84 ± 0.68) mg/L vs. (7.16 ± 0.82) mg/L, (13.24 ± 1.98) ng/L vs. (17.61 ± 2.25) ng/L, (22.13 ± 4.16) μg/L vs. (29.36 ± 5.37) μg/L; and IL-10 was higher than that in the control group:(15.35 ± 2.98) ng/L vs. (11.27 ± 3.26) ng/L, there were statistical differences ( P<0.05). After treatment, the immune function indexes CD 3+, CD 4+, CD 4+/CD 8+ in the observation group were higher than those in the control group: 0.563 ± 0.063 vs. 0.459 ± 0.052, 0.420 ± 0.049 vs. 0.383 ± 0.053, 1.35 ± 0.32 vs. 1.16 ± 0.26, there werestatistical differences ( P<0.05). The incidence of adverse reactions between the two groups had no statistical difference ( P>0.05). Conclusions:HBO combined with Saccharomyces boulardii can significantly improve clinical symptoms, reduce intestinal mucosal damage and improve intestinal microenvironment in UC patients.

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.