ObjectiveTo investigate the mechanism underlying the weight loss effect of electrothermal acupuncture （ETA） in diet-induced obese （DIO） model mice based on the hypoxia-inducible factor-1α （HIF-1α）/sphingosine-1-phosphate （S1P）sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway-mediated macrophage polarization. MethodsAn obesity mouse model was established by continuously feeding at a high-fat diet （HFD） for 8 weeks. Twenty successfully modeled obese mice were randomly divided into a model group and an electrothermal acupuncture （ETA） group with 10 mice per group， both of which continued to receive the HFD till week 12. Another 10 mice were assigned to the normal group and fed a standard chow diet continuously for 12 weeks. Starting from week 9 of the experiment， mice in the ETA group received electrothermal acupuncture stimulation at Zhongwan （CV12）， bilateral Tianshu （ST25）， and bilateral Zusanli （ST36） for 30 minutes per session， with the instrument current set at （40±0.5）mA and a constant temperature of （40±0.5）℃. Mice in the normal group and the model group were restrained in the same manner for 30 minutes without acupuncture. All interventions were performed once every other day for a total of 4 weeks. Ten hours after the final intervention， the body weight， waist circumference， and body length of mice in each group were measured， and Lee's index was calculated. Serum biochemical analysis was performed to assess fasting blood glucose （FBG）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （Cr）. Serum leptin （LEP） and adiponectin （ADPN） levels， as well as sphingosine-1-phosphate （S1P） levels in epididymal white adipose tissue （eWAT）， were detected by ELISA. Histomorphological changes in eWAT were monitored via HE staining. Flow cytometry was used to analyze macrophage subtype-related indexes in eWAT， including the total proportion of macrophages， the proportion of M1 macrophages， the proportion of M2 macrophages， and the M1/M2 ratio. Antibody array technology was used to determine the levels of differentially expressed inflammatory factors in eWAT between the model and blank groups， as well as between the ETA and model groups. Western blot and qPCR were used to detect the protein and mRNA expression levels of HIF-1α and S1PR3 in the eWAT， respectively. ResultsCompared to the normal group， the model group showed significantly increased body weight， Lee's index， waist circumference， and FBG， TC， TG， HDL-C， LDL-C， AST， and ALT levels， upgraded LEP and S1P levels， decreased ADPN level and ADPN/LEP ratio， elevated proportion of M1 macrophages and the M1/M2 ratio， reduced proportion of M2 macrophages， and upregulated protein and mRNA expression levels of HIF-1α and S1PR3 （P＜0.05 or P＜0.01）. With the exception of HDL-C， all the abovementioned indicators in the ETA group were significantly improved compared to the model group （P＜0.05 or P＜0.01）. Analysis of differentially expressed inflammatory cytokines revealed that， compared to the normal group， the levels of interleukin-1β （IL-1β）， interferon-γ （IFN-γ）， interleukin-6 （IL-6）， and interleukin-12p70 （IL-12p70） in the eWAT of the model group were elevated； conversely， the levels of interleukin-17 （IL-17）， interleukin-5 （IL-5）， IL-6， and interleukin-23 （IL-23） in the eWAT of the ETA group decreased compared to the model group （P＜0.05 or P＜0.01）. ConclusionETA exerts a weight-reducing effect in obese model mice， and the mechanism may involve inhibition of the HIF-1α/S1P/S1PR3 signaling pathway activation， which shifts macrophage polarization from the M1 to M2 phenotype， thereby alleviating chronic inflammation.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective To study the hearing intervention effects of the Shokz condyle-stimulated headband bone-conduction hearing aid on patients with conductive,mixed,and sensorineural hearing loss and to explore its clinical application prospects.Methods A total of 55 patients with hearing loss(age 18～82)participated in the study.Among them,9 had conductive hearing loss,15 had sensorineural hearing loss,and 31 had mixed hearing loss.Their bilat-eral bone conduction pure tone thresholds at 0.5,1,2,and 4 kHz were all ≤60 dB HL.The patients were fitted with the condyle-stimulated headband bone-conduction hearing aid.Hearing thresholds in sound field,single-syllable speech recogni-tion scores in quiet,and sentence recognition thresholds in quiet were assessed before fitting and on the day of 14±2 after fitting to compare differences in results.The effectiveness of the hearing aids on the day of 14±2 after fitting was also eval-uated using the IOI-HA questionnaire.Results After wearing the bone-conduction hearing aid,the average hearing thresh-old and sentence recognition threshold of the patients decreased significantly compared with before fitting(the average hear-ing threshold:56.5±8.2 dB HL before fitting,39.3±4.9 dB HL on the day of 14±2 after fitting;sentence recognition threshold:48.6±9.7 dB HL before fitting,34.3±5.6 dB HL on the day of 14±2 after fitting),and the difference was statistically significant(P＜0.001).The single-syllable speech recognition score before fitting was 29.8％±11.4％,and on the day of 14±2 after fitting,it was 72.4％±14.4％,the difference was statistically significant(P＜0.001).The av-erage total score of the IOI-HA questionnaire was 29.0±3.8 points.Conclusion Condyle-stimulated headband bone-con-duction hearing aids can significantly improve the hearing and speech recognition ability of patients with conductive,mixed and sensorineural hearing loss whose bone conduction pure tone thresholds at 0.5～4 kHz were ≤60 dB HL.It may poten-tially improve the quality of life for patients with hearing loss and holds substantial clinical application value.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective To explore the effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.