BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Objective: To investigate if high glucose (HG) exacerbates Porphyromonas gingivalis (P.g) lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs) and to explore the underlying mechanisms. To provide a basis for the mechanism of diabetes aggravating periodontitis. Methods: HGFs were divided into four groups: the control group (basal medium), the LPS group (treated with 5 μg/mL P.g-LPS for 24 h), the HG group (treated with 25 mmol/L glucose for 24 h), and the HG+LPS group (treated with 25 mmol/L glucose + 5 μg/mL P.g-LPS for 24 h). After culturing for 24 h in the respective media, the cells were harvested for experiments. Intracellular reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) were detected using 2 ', 7' - dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX Red staining, respectively. Fluorescence intensity was analyzed by confocal fluorescence microscopy and directly measured in cell suspension. Immunofluorescence was used to detect changes in mitochondrial DNA (mtDNA) content of HGFs. Real-time fluorescence quantitative PCR was used to detect the content of mtDNA in cytoplasm and cell supernatant. Protein expression of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway was assessed by western blot, while mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were detected by PCR. Results: Compared to the control group, both the LPS group and the HG group exhibited a significant increase in ROS and mtROS, with a more pronounced elevation in the HG+LPS group, demonstrating a synergistic effect (ROS: F = 396.5, P < 0.001; mtROS: F = 29.38, P < 0.001, CI < 1). The cytoplasmic mtDNA content was significantly elevated in the LPS group, with a more marked increase in the HG+LPS group (F = 27.85, P < 0.001). The supernatant mtDNA levels were significantly higher in both the LPS and HG groups, with a more pronounced elevation in the HG+LPS group (F = 15.26, P < 0.001). The phosphorylated proteins p-STING, p-TBK1, and p-P65 in the cGAS-STING pathway showed varying degrees of activation in the LPS and HG groups, reaching the highest levels in the HG+LPS group (p-STING: F = 52.67, P < 0.001; p-TBK1: F = 15.67, P = 0.001; p-P65: F = 9.83, P = 0.005), while p-IRF3 showed no significant differences among the groups (P = 0.072). Pro-inflammatory cytokine TNF-α was significantly higher in the HG+LPS group compared to the control group (F = 15.05, P < 0.001), and IL-1β increased in both the LPS and HG groups, with a more pronounced rise in the HG+LPS group (F = 30.98, P < 0.001). IL-6 showed no significant differences among the groups (P = 0.847). Conclusion High glucose and LPS act synergistically to enhance oxidative stress, accompanied by increased mtDNA release, which activates the cGAS-STING pathway, thereby amplifying the inflammatory response in HGFs.

Hypertension is a major risk factor for cardiovascular diseases. Controlling blood pressure can reduce the incidence of cardiovascular events and mortality. The patients with hypertension are mainly treated with antihypertensive drugs. For the patients who can't achieve the target blood pressure with a single drug, comprehensive treatment strategies become particularly important. Chinese patent medicines are prepared by modern extraction and processing technology based on the basic theory of traditional Chinese medicine(TCM). Due to the stable antihypertensive effect, target organ protection, and synergistic effect with western medicine, Chinese patent medicines are becoming one of the effective options for the treatment of hypertension. At present, there are many systematic reviews on the treatment of hypertension with Chinese patent medicines, which makes it difficult for health policy makers and health service providers to choose the best evidence for the treatment. Umbrella review can integrate multiple systematic reviews to comprehensively assess the quality of evidence and potential bias, thereby providing high-quality evidence-based medicine basis for formulating clinical guidelines and optimizing treatment strategies. In this study, the systematic reviews/Meta-analysis of Chinese patent medicines in the treatment of essential hypertension were systematically searched. Sixty-nine articles were included for the umbrella review. Literature information was extracted, and the corrected covered area(CCA) was calculated to quantitatively evaluate the overlap degree of original studies in systematic reviews/Meta-analysis. The risk of bias in systematic reviews(ROBIS) tool and Cochrane RoB tool 2.0 were used to assess the risk of bias of the included studies. A Measure Tool to Assess Systematic Reviews 2(AMSTAR 2) was used to evaluate the methodological quality of systematic reviews/Meta-analysis. The quality of evidence was evaluated based on the Grade of Recommendations Assessment, Development and Evaluation(GRADE). The results showed that the Chinese patent medicines in the categories of treating wind, resolving stasis, and reinforcing healthy Qi were effective in lowering blood pressure. The Chinese patent medicines for resolving stasis combined with conventional treatment can lower blood pressure and the levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and total cholesterol in the treatment of hypertension complicated with coronary heart disease and hypertension complicated with left ventricular hypertrophy. Moreover, the combined therapy can recover the interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index, left ventricular end diastolic diameter, and left ventricular ejection fraction in the case of left ventricular hypertrophy. The Chinese patent medicines for resolving stasis and for replenishing Qi and restoring pulse can be used in combination with conventional treatment for hypertension complicated with arrhythmia, which can lower blood pressure while improving the outcome indicators such as the P-wave dispersion of arrhythmia, left atrial diameter, ejection fraction, heart rate, and recurrence time. Due to the heterogeneity, the efficacy evidence obtained by the umbrella review needs to be further verified through precise clinical studies and long-term follow-up.
Hypertension/physiopathology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; Nonprescription Drugs/therapeutic use* ; Blood Pressure/drug effects*

Objective To investigate the expression of circular RNA(Circ RNAS)Actinin α 4(ACTN4)and platelet thrombin protein 1(THBS1)in intrahepatic cholangiocarcinoma(ICC)and their relationship with clinicopathological characteristics and prognosis,and provide reference for clinical diagnosis and treatment.Method A retrospective analysis was conducted on 84 ICC patients diagnosed and treated in the Second Affiliated Hospital of Xian Jiaotong University from May 2017 to June 2020.The expressions of CircACTN4 mRNA,THBS1 mRNA and protein were detected by real-time fluorescent quantitative PCR and immunohistochemistry.Pearson correlation analysis was used to analyze the correlation between CircACTN4 mRNA and THBS1 mRNA in ICC cancer tissue.The prognostic differences of ICC patients with different CircACTN4 mRNA and THBS1 mRNA expressions were compared by the Kaplan-Meier method(log rank test).COX regression analysis was performed to identify prognostic factors in ICC patients.The prognostic value of CircACTN4 mRNA and THBS1 mRNA in evaluating the risk of death in ICC patients was assessed by receiver operating characteristic(ROC)curve analysis.Results The expression of CircACTN4 mRNA in ICC tissues(3.14±0.42)was higher than that in adjacent tissues(0.76±0.25),with significant difference(t=44.094,P＜0.001).The positive rates of THBS1 mRNA(2.82±0.36)and protein positive rate(92.86％)in ICC tissues were higher than those in adjacent tissues(0.81±0.24,7.14％),and the differences were statistically significant(t/x2=42.068,123.429,all P＜0.001).CircACTN4 mRNA was positively correlated with THBS1 mRNA in ICC cancer tissue(r=0.669,P＜0.001).The expressions of CircACTN4 mRNA,THBS1 mRNA in ICC cancer tissues with TNM stage Ⅲ,low differentiation,and lymph node metastasis were higher than those in TNM stage Ⅰ～Ⅱ,high differentiation,and non-lymph node metastasis cancer tissues,and the differences were statistically significant(x2=7.949,9.164,12.207;23.270,18.625,19.828,all P＜0.001).The 3-year cumulative survival rates of the high expression group of CircACTN4 mRNA and THBS1 mRNA were lower than those of the low expression group of CircACTN4 mRNA(25.00％vs 56.82％)and THBS1 mRNA(19.51％vs 62.79％),and the differences were statistically significant(Log rank x2=13.601,24.310,all P＜0.001).CircACTN4 mRNA(OR=1.839,95％CI:1.228～2.753),THBS1 mRNA(OR=1.744,95％CI:1.245～2.443),lymph node metastasis(OR=1.925,95％CI:1.316～2.816),TNM staging(OR=1.613,95％CI:1.223～2.126),and tumor differentiation(OR=1.510,95％CI:1.205～1.892)were independent factors affecting the prognosis of ICC.The area under the curve of the combination detection of circACTN4 and THBS1 mRNA on the prognosis of death in patients with ICC was 0.868,which was greater than that of the single index(0.812 and 0.784),with significant differences(Z=3.348,3.847,all P＜0.001).Conclusion The expressions of CircACTN4 mRNA and THBS1 mRNA were increased in ICC,and they were associated with TNM stage,differentiation,and lymph node metastasis.These markers may serve as novel indicators to evaluate the poor prognosis of ICC patients.

Objective:To investigate the safety and effectiveness of balloon occlusion and intra-sac thrombin injection in the endovascular repair of ruptured abdominal aortic aneurysm.Methods:From October 2019 to October 2022,the clinical data of 16 patients with rAAA treated with balloon occlusion technique and intra-sac thrombin injection combined with EVAR were retrospectively analyzed,including 13 males and 3 females,aged 42-85 years,with a median age of 70.5 years.The time of preoperative first aid(from hospital arrival to operation start),average operation time,stay in intensive care unit(ICU),average hospitalization time,success rate of surgical treatment,perioperative(30 d)mortality rate,incidence of complications,the maximum diameter and volume change of the aneurysm were observed and recorded.Results:Among the 16 patients with ruptured abdominal aortic aneurysm,the technical success rate was 100.0％(16/16).One patient died of multiple organ dysfunction 6 hours af-ter operation.The success rate of surgical treatment was 93.8％(15/16).The preoperative first aid time was(53.3±6.2)min,the average operation time was(89.9±17.1)min,the stay in the intensive care unit(ICU)was(1.7±0.8)d,and the average hospitalization time was(7.8±1.3)d.The intrao-perative balloon occlusion time was(32.4±4.1)min.The postoperative renal function of all the pa-tients had no significant deterioration compared with that preoperative.Abdominal compartment syndrome(ACS)occurred in 1 patient after operation,which improved after CT puncture and drainage.The medi-an follow-up time was 36 months.During the follow-up period,1 patient died of acute myocardial infarc-tion 2 years after operation,and the remaining 14 patients survived.Among the 14 follow-up patients,1 type Ⅱ endoleak occurred,and no other types of endoleak occurred.By the end of the follow-up,the maximum diameter of the aneurysm sac in 14 patients was significantly lower than that before operation[(44.6±8.0)mm vs.(66.0±15.5)mm,P＜0.001],and in 12 patients with CTA,the volume of the aneurysm sac was significantly shrunk than that before operation[(311.7±170.3)mm3 vs.(168.6±68.1)mm3,P＜0.05].Conclusion:Balloon occlusion during endovascular repair is safe and effective in the treatment of ruptured abdominal aortic aneurysm;intraoperative thrombin injection of the aneurysm sac can significantly reduce the incidence of intraoperative and postoperative abdominal compartment syndrome and endoleak and,to a certain extent,improve the success rate of treatment.

Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most prevalent types of degenerative neurological diseases.The biological activities of marine glycoconjugates, such as antioxidant, anticoagulant, antitumor, hypolipidemic, and antibacterial properties, have gained significant attention.There is a growing body of research exploring the role of marine glycoconjugates in AD and PD.This review aims to summarize the recent progress in the use of marine glycoconjugates for the prevention and treatment of AD and PD, providing new insights for future approaches in managing these diseases.

Objective To investigate the impact of metabolic labeling on Porphyromonas gingivalis(Pg)and com-pare the imaging effects of two fluorescent probes.Methods This study was reviewed by the unit Ethics Committee and was approved by the Experimental Animal Welfare Ethics Branch of the Unit Experimental Biomedical Ethics Com-mittee.Pg integrated N-azidoacetylgalactosamine(Ac4GalNAz)via a bioorthogonal reaction and was labeled with Cy5-DBCO or Cy7-DBCO via a click chemistry reaction.The bacteria were divided into Pg group(control,not fluorescently labeled),Cy5-Pg group(tagged by Cy5-DBCO),and Cy7-Pg group(tagged by Cy7-DBCO).A live/dead staining kit was applied to test the viability of Pg,Cy5-Pg,and Cy7-Pg.The mRNA levels of interleukin-6(IL-6)and IL-8 and cell pro-liferation were examined in human gingival fibroblasts(HGFs)after the challenge of Cy5-Pg,Cy7-Pg,or Pg.To investi-gate the stability of metabolic labeling,Cy5-Pg or Cy7-Pg was cocultured with Escherichia coli(E.coli).Cy5-Pg and Cy7-Pg signal intensity with serial dilutions were examined using an in vivo imaging system(IVIS).Finally,C57BL/6J mice were orally administered Cy5-Pg or Cy7-Pg for IVIS detection,and the signal-to-background ratios were calculated.Results Metabolic labeling could be applied to label live Pg in vitro.The optimal labeling concentrations for Cy5 and Cy7 were 20 μmol/L and 30 μmol/L,respectively.The area ratios of live to dead bacteria were approximately 2.0 in the three groups(F=0.318,P＞0.05).After a 6-h challenge with Cy5-Pg,Cy7-Pg,or Pg,the mRNA levels of HGFs in-creased by 7.86-,7.46-,and 6.56-fold for IL-6,respectively(F=40.886,P＜0.001)and 12.43-,13.03-,and 13.71-fold for IL-8(F=18.781,P＜0.01),were spectively,compared to that of the Ctrl group,which was not challenged by bacte-ria,where no significant differences were observed among the three groups(P＞0.05).HGFs were further challenged by Cy5-Pg,Cy7-Pg,or Pg at different MOIs,and cell proliferation was significantly inhibited(MOI=104∶1,F=153.52,P＜0.001;MOI=105∶1,F=331.21,P＜0.001;MOI=106∶1,F=533.65,P＜0.001),with no significant differences among the three groups(P＞0.05).Within 24 h of co-culturing Cy5-Pg or Cy7-Pg with E.coli,minimal E.coli was de-tected.The intensities of Cy5 and Cy7 remained stable for 3 h.Additionally,the fluorescence signal intensities of Cy5 and Cy7 were linearly correlated with the concentration(R2=0.97).After oral gavage of Cy5-Pg or Cy7-Pg in mice for the abdominal region at 1 h and 3 h,the signal-to-background ratios of Cy7-Pg were approximately 4.24-fold(t=6.893,P＜0.01)and 3.77-fold(t=4.407,P＜0.05)higher,respectively,than those of Cy5-Pg.For the isolated gastrointestinal tracts at 3 h,the signal-to-background ratio of Cy7-Pg was 5.19-fold higher than that of Cy5-Pg(t=4.418,P＜0.05).Conclusions Metabolic labeling did not significantly affect viability,immunomodulatory ability,and toxicity.The im-aging effect of Cy7 on IVIS was better than that of Cy5.Our study provided experimental evidence for the correlation be-tween periodontitis and overall health.

Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P＜0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P＜0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.

Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most prevalent types of degenerative neurological diseases.The biological activities of marine glycoconjugates, such as antioxidant, anticoagulant, antitumor, hypolipidemic, and antibacterial properties, have gained significant attention.There is a growing body of research exploring the role of marine glycoconjugates in AD and PD.This review aims to summarize the recent progress in the use of marine glycoconjugates for the prevention and treatment of AD and PD, providing new insights for future approaches in managing these diseases.