Objective:To discuss the clinical efficacy of low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess for the treatment of congenital pyriform sinus fistula （CPSF） in the acute inflammatory period of children. Methods:Clinical data of 30 patients with CPSF in the acute inflammatory period who received low-temperature radiofrequency ablation assisted by endoscopy under laryngoscope, combined with resection and drainage of cervical abscess, from January 2018 to December 2023 were reviewed. After the operation, patients were followed up closely at different stages. All patients underwent color Doppler ultrasound and electronic laryngoscopy, and the results were analyzed. Results:All 30 children successfully completed the surgery without pharyngeal fistula, dysphagia, perifistula, or distal fistula infection, and the incision in the neck healed well. The follow-up survey ranged from 6 months to 2 years, and no recurrences were observed. Conclusion:Low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess is a promising method for treating CPSF in the acute inflammatory period. It is less traumatic, simple, safe, has a significant curative effect, and a low recurrence rate. This approach can be used as a supplementary operation for CPSF in children and provides a new way for clinical treatment.
Humans ; Pyriform Sinus/abnormalities* ; Abscess/surgery* ; Drainage ; Fistula/congenital* ; Female ; Male ; Child ; Radiofrequency Ablation ; Treatment Outcome ; Postoperative Period ; Endoscopy ; Laryngoscopy ; Inflammation ; Child, Preschool

Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ ^-/- colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Objective:This study aims to summarize the surgical efficacy of macroglossia reduction combined with radiofrequency ablation of Beckwith-Wiedemann Syndrome (BWS).Methods:A retrospective analysis was conducted on the clinical data of patients with macroglossia who received treatment at the Department of Otolaryngology-Head and Neck Surgery, Xiamen Children’s Hospital between May 2019 and July 2022. All patients with macroglossia underwent either one-stage or staged anterior tongue V-shaped incision massive resection, followed by needle tip low-temperature plasma radiofrequency ablation on the lateral and base of the tongue. The postoperative complications in pediatric patients were monitored, including the incision shape of the tongue body, restoration of tongue body structure and function. MRI scans of the tongue were performed at 3 and 12 months post-operation to evaluate tissue healing, changes in tongue volume, and whether there was successful retraction of the enlarged tongue into the oral cavity for evaluating treatment efficacy (cured or not cured).Results:The study included 70 cases, comprising 31 male and 39 female patients, with an average age of 15.4 months (ranging from 5 months to 4 years old). Among them, 68 cases underwent macroglossia reduction combined with radiofrequency ablation at the same time, and 2 cases underwent macroglossia reduction surgery first in other hospitals, and tongue body radiofrequency ablation was performed one year after the surgery. All children were followed up foran average follow-up time of 18 months (6 to 36 months). There were no serious complications such as massive hemorrhage and tongue hematoma. After the operation, 14 cases of superficial rupture of tongue tip wound were gradually improved after 5-7 days of no oral eating, and recovered after 4-12 weeks of liquid diet. Thirteen cases had suture reactions in the tongue back, which were self-resolving within 2 to 3 weeks with no special treatment. All patients showed significant reduction in tongue size after the surgery, which could be completely inserted into the oral cavity, and the treatment effect was satisfactory.Conclusion:Macroglossia reduction combined with radiofrequency ablation is a feasible and effective method for the treatment of BWS with macroglossia and is recommended for application.

Objective:This study aims to summarize the surgical efficacy of macroglossia reduction combined with radiofrequency ablation of Beckwith-Wiedemann Syndrome (BWS).Methods:A retrospective analysis was conducted on the clinical data of patients with macroglossia who received treatment at the Department of Otolaryngology-Head and Neck Surgery, Xiamen Children’s Hospital between May 2019 and July 2022. All patients with macroglossia underwent either one-stage or staged anterior tongue V-shaped incision massive resection, followed by needle tip low-temperature plasma radiofrequency ablation on the lateral and base of the tongue. The postoperative complications in pediatric patients were monitored, including the incision shape of the tongue body, restoration of tongue body structure and function. MRI scans of the tongue were performed at 3 and 12 months post-operation to evaluate tissue healing, changes in tongue volume, and whether there was successful retraction of the enlarged tongue into the oral cavity for evaluating treatment efficacy (cured or not cured).Results:The study included 70 cases, comprising 31 male and 39 female patients, with an average age of 15.4 months (ranging from 5 months to 4 years old). Among them, 68 cases underwent macroglossia reduction combined with radiofrequency ablation at the same time, and 2 cases underwent macroglossia reduction surgery first in other hospitals, and tongue body radiofrequency ablation was performed one year after the surgery. All children were followed up foran average follow-up time of 18 months (6 to 36 months). There were no serious complications such as massive hemorrhage and tongue hematoma. After the operation, 14 cases of superficial rupture of tongue tip wound were gradually improved after 5-7 days of no oral eating, and recovered after 4-12 weeks of liquid diet. Thirteen cases had suture reactions in the tongue back, which were self-resolving within 2 to 3 weeks with no special treatment. All patients showed significant reduction in tongue size after the surgery, which could be completely inserted into the oral cavity, and the treatment effect was satisfactory.Conclusion:Macroglossia reduction combined with radiofrequency ablation is a feasible and effective method for the treatment of BWS with macroglossia and is recommended for application.

AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.

Objective To investigate the relationship between the expression levels of long non-coding RNA(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)and leptin levels in the patients with multiple myeloma,as well as the role in the diagnosis and prognosis of multiple myeloma.Meth-ods A total of 60 patients with newly diagnosed multiple myeloma in this hospital from January 2018 to Oc-tober 2020 were selected as the patient group.Additionally,60 healthy individuals during the same period were recruited as the control group.The levels of serum lncRNA MALAT1 and leptin in the test population were detected.The correlation between the two and thier ratio as well as their role in disease prognosis were invest-gated.Results The expression levels of serum lncRNA MALAT1 and leptin in the patients group were signif-icantly higher than those in the control group,and the difference was statistically significant(P＜0.05).A-mong the various stages of Durie-Salmon(DS)staging,the expression levels of lncRNA MALAT1 and leptin from stage I,stage Ⅱ and stage Ⅲ were in turn from high to low,and the differences were statistically signifi-cant(P＜0.05).Among different immune types,the expression level of lncRNA MALAT1 in the patients with light chain type was highest,which in those with non-secretory type was lowest.The leptin levels in the patients with light chain type,IgG type,IgA type and non-secretory type were in turn from high to low,and the differences were statistically significant(P＜0.05).Furthermore,the expression level of lncRNA MAL-AT1 was positively correlated with leptin(r=0.41,P＜0.05).There were statistically significant differences in the expression levels of lncRNA MALAT1,leptin levels,and lncRNA MALAT1/leptin ratio between before and after treatment in the patients with treatment effect(P＜0.05).However,there was no statistically sig-nificant difference in these two indices between before and after treatment in the patients with no treatment effect(P＞0.05).After treatment,the median survival time for the patients with serum lncRNA MALAT1/leptin ratio＜3 was 27 months(95％CI:21.949-27.120),while which for the patients with serum lncRNA MALAT1/leptin ratio 3 was 14 months(95％CI:12.076-22.199),and the difference was statistically sig-nificant(P=0.014).Conclusion lncRNA MALAT1 and leptin exhibit a certain extent of synergistic effect in the de-velopment and progression of multiple myeloma.The ratio of these two could be used to evaluate the prognosis of the patients.