BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

With the rapid development of implant dentistry, increasing attention has been paid to the long-term stability and aesthetic outcomes of dental implants, among which sufficient volume and quality of soft and hard tissues are considered crucial contributing factors for successful treatment outcomes. Among the various available tissue regeneration strategies, plasmatrix, an autologous biomaterial derived from the patient ' s own peripheral blood, has demonstrated unique and significant clinical value in the regeneration and augmentation of both soft and hard tissues associated with dental implant therapy in recent years. This notable potential is primarily attributed to its rich content of multiple growth factors, viable cells, and a supportive fibrin scaffold, along with its excellent biocompatibility, tunable biodegradation profile, and a relatively simple and rapid preparation process that does not require complex laboratory equipment. As a result, its clinical applications have been continuously expanding across a wide range of indications. Based on a comprehensive review of the existing literature and current research evidence, this article provides an in-depth summary of the advancements in both basic science and clinical applications of plasmatrix in the context of implant dentistry. Particular attention is given to its classification from a materials science perspective, underlying molecular mechanisms, biological effects in promoting tissue regeneration, and its implementation under different clinical scenarios. Furthermore, the article discusses unresolved technical challenges and existing controversies, and outlines potential future directions for research and technological innovation, aiming to provide robust evidence-based guidance for clinical practice as well as a theoretical and methodological reference for future scientific investigations.
Humans ; Biocompatible Materials/therapeutic use* ; Dental Implants ; Tissue Scaffolds ; Fibrin/therapeutic use* ; Tissue Engineering/methods* ; Dental Implantation/methods* ; Dental Implantation, Endosseous/methods*

OBJECTIVES: To study the effect of CDC20 knockdown on proliferation, migration and invasion of cervical cancer cells and its underlying mechanism. METHODS: CDC20 expression in cervical cancer tissues was analyzed using the TCGA database, and the protein expressions of CDC20 and β-Catenin in clinical specimens of cervical cancer and adjacent tissues were detected using immunohistochemistry. A dual target sgRNA2&7 sequence for CDC20 gene was designed for CDC20 gene knockdown in cervical cancer C33A cells using CRISPR/Cas9 technology, and CDC20 mRNA and protein expression levels in the transfected cells were detected using qRT-PCR and Western blotting. The changes in proliferation, cell cycle, apoptosis, migration and invasiveness of the transfected cells were evaluated using colony-forming assay, fluorescence activated cell sorting (FACS) and Transwell assay. In the animal experiment, naïve C33A cells and the cells with CDC20 knockdown were injected subcutaneously into the left and right axillae of nude mice (n=5) to observe tumor growth. The expressions of CDC20 and β-Catenin proteins in transfected cells and the xenograft were analyzed using Western blotting, and their interaction was confirmed by co-immunoprecipitation (CoIP) and immunofluorescence co-localization assays. RESULTS: Cervical cancer tissues expressed significantly higher CDC20 and β‑Catenin levels than the adjacent tissues. C33A cells with CDC20 knockdown showed reduced proliferation, increased apoptosis, and lowered migration and invasion abilities. CDC20 knockdown significantly suppressed the growth of C33A cell xenograft in nude mice, and the tumor-bearing mice did not exhibit obvious body mass changes. CDC20 and β-Catenin levels were both significantly lowered in C33A cells with CDC20 knockdown. Co-immunoprecipitation and co-localization assays confirmed the interaction between CDC20 and β‑Catenin. CONCLUSIONS CDC20 is highly expressed in cervical cancer tissues, and CDC20 knockdown can suppress proliferation, invasion, and metastasis while enhancing apoptosis of C33A cells, which is closely related with the regulation of the Wnt/β-Catenin signaling pathway.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; Cdc20 Proteins/genetics* ; Cell Proliferation ; Animals ; Cell Movement ; Neoplasm Invasiveness ; Apoptosis ; Mice, Nude ; beta Catenin/metabolism* ; CRISPR-Cas Systems ; Mice ; Cell Line, Tumor ; Gene Knockout Techniques ; Neoplasm Metastasis

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective To investigate the effect of TRPC5 on intermittent hypoxia-induced myocardial pyroptosis.Methods TRPC5 knock out(TRPC5-/-)and SD rats were each randomly divided into chronic intermit-tent hypoxia group(CIH group)and normoxia group(Control group)(n=6 for each group).The myocardial fibrosis in rats was visualized by Masson staining,the levels of serum inflammatory factors were measured by ELISA and the relative expression levels of TRPC 5 and pyroptosis-related proteins were determined by Western blotting.Results Masson staining showed that the collagen volume fraction in the TRPC5-/--CIH group was higher than that in the TRPC5-/--Control group and lower than that in the WT-CIH group.The ELISA results showed that the serum levels of IL-1,IL-6,and TGF-β in the TRPC5-/--CIH group were higher than those in the TRPC5-/--Control group and lower in the WT-CIH group.Western blotting results showed that the relative expression levels of pyroptosis related proteins caspase-1,NLRP3,GSDMD,and GSDMD-N in the TRPC5-/--CIH group were higher than those in the TRPC5-/--Control group and lower than those in the WT-CIH group.Conclusion TRPC5 deficiency alleviates myocardial pyroptosis and myocardial fibrosis induced by hypoxia.

Objective:To treat the Crohn's disease(CD)patients with ustekinumab(UST),to eva-luate their clinical and endoscopic remission,and to evaluate their transmural response(TR)and trans-mural healing(TH)condition using intestinal ultrasonography(IUS).Methods:Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to Au-gust 2022,who were treated with UST for remission induction and maintenance therapy.All the patients were evaluated on both week 8 and week 16/20 after treatment,including clinical,biochemical indica-tors,colonoscopy and IUS examination.Results:A total of 13 patients were enrolled in this study,inclu-ding 11 males and 2 females.The minimum age was 23 years,the maximum age was 73 years and the mean age was 36.92 years.All the patients were in the active stage of disease before treatment,and the average Best Crohn's disease activity index(Best CDAI)score was 270.12±105.55.In week 8,the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66(t=4.977,P＜0.001).Eight patients achieved clinical remission while 5 patients remained in the active stage.Nine patients underwent colonoscopy evaluation.The average simple endoscopic score for Crohn's disease(SES-CD)score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483,P=0.048)in week 16/20.Four patients achieved endoscopic remission while 5 patients did not.In week 8,5 pa-tients achieved TR,2 patients achieved TH,the other 6 patients did not get TR or TH.In week 16/20,6 patients achieved TR,3 patients achieved TH while the other 4 patients did not get TR or TH.There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions(Fisher test,P＞0.999).The rate of UST transmural response in the patients who had had previous bio-logical agent therapy was lower than those with no previous biological agent therapy,but there was no sig-nificant statistical difference(Fisher test,P=0.491).Conclusion:After treatment of UST,the clinical and endoscopic conditions of the CD patients had been improved,and some patients could achieve clini-cal remission and endoscopic remission.UST had good TR and TH effects on CD.TR might appear in week 8,and the TR effect increased in week 16/20.There was no significant statistical difference in the TR effect between small intestine and colon lesions.TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents,but the result had no significant statistical difference.

Objective: To examine the association of 24 hour movement behaviors with emotional and behavioral problems among left behind children, so as to provide a theoretical reference for the practice of 24 hour activity interventions to promote emotional and behavioral problems in this population. Methods: From February to May 2023, 1 117 left behind children in grades 4-6 from 10 primary schools in five cities in Zhejiang Province were selected using a convenient cluster sampling method to conduct a questionnaire survey examining 24 hour movement behaviors, as well as emotional and behavioral problems. The general linear model was adopted to analyze the association between satisfying the 24 hour movement behavior guidelines, and emotional and behavioral problems among left behind children. Results: The sleep duration compliance rate was the highest (52.19%), while the moderate-to-vigorous PA (MVPA) compliance rate was the lowest (17.73%). The compliance rate of the three activities accounted for 7.43 %. There was a dose response between the number of guidelines satisfied, and the emotional and behavior of left behind children; that was, satisfaction of a higher number of guidelines was associated with a lower risk of emotional and behavioral problems among left behind children (difficulty factor: β=-0.56, 95%CI =-1.23--0.19; strength factor: β=0.50, 95%CI =-0.48-1.22, P < 0.01). Compared to satisfying none of the guidelines, satisfying the guidelines for screen time ( β=-0.23, 95%CI =-2.18- -0.14 ) and sleep duration ( β=-0.13, 95%CI =-1.66--0.11) was negatively correlated with the difficulty factor, while satisfying the guideline for MVPA ( β=0.13, 95%CI =0.09-1.08) and sleep duration ( β=0.18, 95%CI =0.09-1.40) was positively associated with the strength factor. In addition, satisfying two or all three of the guidelines was more strongly associated with these outcomes than satisfying one of the recommendations ( P <0.01). Conclusions Meeting the 24 hour movement behavior guidelines can improve emotional and behavioral problems among left behind children. It is necessary to raise their awareness of the effect of satisfying the 24 hour movement behavior guidelines and formulate comprehensive intervention measures.

Objective:To investigate the influence of varied oxygen (O 2) concentration environments on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMC) and the mechanism of pulmonary hypertension. Methods:Primary rat PASMC were isolated and cultured through the process of enzymatic digestion. Following identification, the stable passaged PASMC were subjected to a 6-hour incubation in sealed containers with normal O 2 content (group C) and relative O 2 content comprising 55% (group H55), 75% (group H75), and 95% (group H95). mRNA and protein expression of α-Actin (α-SMA), smooth muscle 22α (SM22α), osteopontin (OPN), and matrix metalloproteinase-2 (MMP-2) were measured using real-time quantitative PCR and western blot analysis. Results:The H55 group displayed no significant difference from the C group in terms of mRNA and relative protein expression levels for α-SMA, SM22α, OPN, and MMP-2 (all P>0.05). On the other hand, groups H75 and H95 exhibited a reduction in mRNA and relative protein expression of α-SMA and SM22α, along with an increase in mRNA and relative protein expression of OPN and MMP-2 when compared with both the C and H55 groups (all P<0.05). The H95 group showed a higher relative mRNA expression of MMP-2 as compared to the H75 group ( P<0.05). Conclusions:Oxygen concentration environments of 75% or higher can serve as the foundation for the pathogenesis of pulmonary hypertension, essentially by inducing a phenotypic transformation in PASMC towards adopting a robust secretory function. This induction is contingent upon the concentration of oxygen present.