Chronic insomnia affects 10%–15% of the population, with one-third of Western adults struggling with sleep initiation or maintenance. Binaural beats, which involve two audio frequencies, have shown the potential for enhancing sleep and mood. This study examined the efficacy of customized binaural audio tracks generated using facial analysis software to treat chronic insomnia. Methods: A 45-minute personalized binaural beat audio session was delivered using the Spatial app and headband (SoundHealth) to 20 participants with moderate-to-severe insomnia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and Insomnia Severity Index (ISI) criteria, over four weeks in California. Statistical analysis (paired t-test and linear mixed modeling) was used to compare baseline ISI scores to posttreatment scores, with p<0.05 indicating significance. The study assumed 80% power and aimed to achieve a 7-point ISI reduction. Results: All participants completed the study with no adverse events or full protocol adherence. The cohort was 60% White, with a 3:1 female-to-male ratio and an average age of 51.9 years. The baseline ISI was 19.8, dropping to 8.5 after four weeks, showing an 11.3-point reduction (95% confidence interval [CI]: -15 to -7.6, p<0.001). Mixed modeling indicated a similar ISI decrease of 11.28 points (95% CI: -14.98 to -7.57, p<0.001). The treatment response rate was 70%. Conclusions: Customized binaural beats show promise for insomnia treatment, with no adverse effects and high adherence. Most participants improved to no insomnia or subthreshold insomnia. Further research is needed to validate these results using larger samples and to assess long-term effects.

Chronic insomnia affects 10%–15% of the population, with one-third of Western adults struggling with sleep initiation or maintenance. Binaural beats, which involve two audio frequencies, have shown the potential for enhancing sleep and mood. This study examined the efficacy of customized binaural audio tracks generated using facial analysis software to treat chronic insomnia. Methods: A 45-minute personalized binaural beat audio session was delivered using the Spatial app and headband (SoundHealth) to 20 participants with moderate-to-severe insomnia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and Insomnia Severity Index (ISI) criteria, over four weeks in California. Statistical analysis (paired t-test and linear mixed modeling) was used to compare baseline ISI scores to posttreatment scores, with p<0.05 indicating significance. The study assumed 80% power and aimed to achieve a 7-point ISI reduction. Results: All participants completed the study with no adverse events or full protocol adherence. The cohort was 60% White, with a 3:1 female-to-male ratio and an average age of 51.9 years. The baseline ISI was 19.8, dropping to 8.5 after four weeks, showing an 11.3-point reduction (95% confidence interval [CI]: -15 to -7.6, p<0.001). Mixed modeling indicated a similar ISI decrease of 11.28 points (95% CI: -14.98 to -7.57, p<0.001). The treatment response rate was 70%. Conclusions: Customized binaural beats show promise for insomnia treatment, with no adverse effects and high adherence. Most participants improved to no insomnia or subthreshold insomnia. Further research is needed to validate these results using larger samples and to assess long-term effects.

Chronic insomnia affects 10%–15% of the population, with one-third of Western adults struggling with sleep initiation or maintenance. Binaural beats, which involve two audio frequencies, have shown the potential for enhancing sleep and mood. This study examined the efficacy of customized binaural audio tracks generated using facial analysis software to treat chronic insomnia. Methods: A 45-minute personalized binaural beat audio session was delivered using the Spatial app and headband (SoundHealth) to 20 participants with moderate-to-severe insomnia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and Insomnia Severity Index (ISI) criteria, over four weeks in California. Statistical analysis (paired t-test and linear mixed modeling) was used to compare baseline ISI scores to posttreatment scores, with p<0.05 indicating significance. The study assumed 80% power and aimed to achieve a 7-point ISI reduction. Results: All participants completed the study with no adverse events or full protocol adherence. The cohort was 60% White, with a 3:1 female-to-male ratio and an average age of 51.9 years. The baseline ISI was 19.8, dropping to 8.5 after four weeks, showing an 11.3-point reduction (95% confidence interval [CI]: -15 to -7.6, p<0.001). Mixed modeling indicated a similar ISI decrease of 11.28 points (95% CI: -14.98 to -7.57, p<0.001). The treatment response rate was 70%. Conclusions: Customized binaural beats show promise for insomnia treatment, with no adverse effects and high adherence. Most participants improved to no insomnia or subthreshold insomnia. Further research is needed to validate these results using larger samples and to assess long-term effects.

Objective To investigate the anti-inflammatory properties of bergaptenand its inhibition of bone resorption in the treatment of periodontitis,as well as its potential underlying mechanisms.Methods A total of 35 male Wistar rats were randomly di-vided into five groups(control group,model group,and low-,medium-,and high-dose bergapten groups,with 7 rats in each group).Except for the control group,periodontitis was induced in all other groups by orthodontic ligation of the bilateral maxillary first molars(M1)and feeding a high-sugar diet.After successful modeling,the control and model groups received gavage of isotonic saline,while the bergapten groups received gavage of 50,100,and 200 mg/kg bergapten,respectively,once daily for 4 consecutive weeks.Perio-dontal symptoms were observed,and GI,SBI grades,and PLI scores were recorded.Rats were sacrificed within 24 hours after the last administration,and their maxillae were immediately subjected to Micro-CT scanning to assess alveolar bone resorption.Histopathological changes in the periodontal tissues were observed using HE staining,and serum levels of pro-inflammatory cytokines(IL-6 and IL-1β)were measured by ELISA.Results Compared with the control group,the model group exhibited significantly higher levels of IL-6,IL-1β,GI,SBI grades,PLI scores,and CEJ-ABC distance,while bone volume to total volume ratio(BV/TV),trabec-ular number(Tb.N),and trabecular thickness(Tb.Th)were significantly reduced(P＜0.001).In comparison to the model group,the bergapten groups(with the exception of the low-dose group for IL-6)demonstrated reductions in IL-6,IL-1β levels,GI,SBI grades,PLI scores,and CEJ-ABC distance,with the medium-dose group showing the most pronounced effect(except for IL-6).Conclusion Bergapten can effectively prevent and treat periodontitis by inhibiting the secretion of IL-6 and IL-1β cytokines,achieving anti-inflam-matory effects and inhibiting bone resorption.

Objective To investigate the efficacy and mechanism of the combination of cryoablation and Yangfei establish the Lewis lung cancer mouse model,and randomly divided into model group,cryoablation group,cryoablation+cisplatin group,cryoablation+Yangfei Prescription low-,medium-and high-dosage groups,with 5 mice in each group.Sham-operation was performed in the model group,cryoablation+cisplatin group were given intraperitoneal injection of cisplatin 3 mg/kg after cryoablation,cryoablation+Yangfei Prescription low-,medium-and high-dosage groups were given 1.64,3.28,6.56 g/kg Yangfei Prescription by gavage after cryoablation respectively,and the model group was given equal volume of normal saline by gavage for 14 consecutive days.Tumor volume and tumor mass were measured,the morphology of tumor tissue was observed by HE staining,the expression of Ki-67 protein in tumor tissue was detected by immunohistochemistry.The differentially expressed genes in tumor tissues after cryoablation combined with Yangfei Prescription intervention were analyzed by whole transcriptome sequencing,GO and KEGG pathway enrichment analysis was performed on differentially expressed genes,and the lncRNA/circNA-mediated ceRNA network was constructed.Differentially expressed genes were verified using RT-qPCR.Results The main active components of Yangfei Prescription were terpenoids,flavonoids and aldehydes.Compared with the model group,tumor volume and tumor mass decreased(P<0.05)in cryoablation+Yangfei Prescription low-,medium-and high-dosage groups and cryoablation+cisplatin group;cryoablation combined with Yangfei Prescription could destroy the structure of tumor tissue and inhibit cell proliferation(P<0.05).A total of 1 585 differentially expressed genes(1 160 mRNA,225 lncRNA,155 miRNA and 45 circRNA)of the model group and cryoablation+Yangfei Prescription high-doseage group were obtained.GO enrichment analysis mainly involved biological processes such as immune system response and cell proliferation,cellular components such as protein complex and cell junction,molecular functions such as transcription regulator activity and molecular function regulator;KEGG pathway enrichment mainly occurred in cancer-related pathways such as PI3K-Akt signaling pathway,Th17 cell differentiation,mTOR signaling pathway,FOXO signaling pathway,etc.The lncRNA-mediated ceRNA network was composed of 97 lncRNA,73 miRNA and 417 mRNA,and the circRNA-mediated ceRNA network was composed of 26 circRNA,68 miRNA and 157 mRNA.RT-qPCR validated the expressions of 15 differentially expressed genes,which was consistent with the sequencing results.Conclusion Cryoablation combined with Yangfei Prescription can inhibit the tumor growth of Lewis lung cancer bearing mice,destroy the structure of tumor tissue,inhibit cell proliferation,the mechanism may be related to the regulation of Gm38393/miRNA-136-5p/Zfp704 axis.

Objective To investigate the efficacy and mechanism of the combination of cryoablation and Yangfei establish the Lewis lung cancer mouse model,and randomly divided into model group,cryoablation group,cryoablation+cisplatin group,cryoablation+Yangfei Prescription low-,medium-and high-dosage groups,with 5 mice in each group.Sham-operation was performed in the model group,cryoablation+cisplatin group were given intraperitoneal injection of cisplatin 3 mg/kg after cryoablation,cryoablation+Yangfei Prescription low-,medium-and high-dosage groups were given 1.64,3.28,6.56 g/kg Yangfei Prescription by gavage after cryoablation respectively,and the model group was given equal volume of normal saline by gavage for 14 consecutive days.Tumor volume and tumor mass were measured,the morphology of tumor tissue was observed by HE staining,the expression of Ki-67 protein in tumor tissue was detected by immunohistochemistry.The differentially expressed genes in tumor tissues after cryoablation combined with Yangfei Prescription intervention were analyzed by whole transcriptome sequencing,GO and KEGG pathway enrichment analysis was performed on differentially expressed genes,and the lncRNA/circNA-mediated ceRNA network was constructed.Differentially expressed genes were verified using RT-qPCR.Results The main active components of Yangfei Prescription were terpenoids,flavonoids and aldehydes.Compared with the model group,tumor volume and tumor mass decreased(P<0.05)in cryoablation+Yangfei Prescription low-,medium-and high-dosage groups and cryoablation+cisplatin group;cryoablation combined with Yangfei Prescription could destroy the structure of tumor tissue and inhibit cell proliferation(P<0.05).A total of 1 585 differentially expressed genes(1 160 mRNA,225 lncRNA,155 miRNA and 45 circRNA)of the model group and cryoablation+Yangfei Prescription high-doseage group were obtained.GO enrichment analysis mainly involved biological processes such as immune system response and cell proliferation,cellular components such as protein complex and cell junction,molecular functions such as transcription regulator activity and molecular function regulator;KEGG pathway enrichment mainly occurred in cancer-related pathways such as PI3K-Akt signaling pathway,Th17 cell differentiation,mTOR signaling pathway,FOXO signaling pathway,etc.The lncRNA-mediated ceRNA network was composed of 97 lncRNA,73 miRNA and 417 mRNA,and the circRNA-mediated ceRNA network was composed of 26 circRNA,68 miRNA and 157 mRNA.RT-qPCR validated the expressions of 15 differentially expressed genes,which was consistent with the sequencing results.Conclusion Cryoablation combined with Yangfei Prescription can inhibit the tumor growth of Lewis lung cancer bearing mice,destroy the structure of tumor tissue,inhibit cell proliferation,the mechanism may be related to the regulation of Gm38393/miRNA-136-5p/Zfp704 axis.

Objective To investigate the anti-inflammatory properties of bergaptenand its inhibition of bone resorption in the treatment of periodontitis,as well as its potential underlying mechanisms.Methods A total of 35 male Wistar rats were randomly di-vided into five groups(control group,model group,and low-,medium-,and high-dose bergapten groups,with 7 rats in each group).Except for the control group,periodontitis was induced in all other groups by orthodontic ligation of the bilateral maxillary first molars(M1)and feeding a high-sugar diet.After successful modeling,the control and model groups received gavage of isotonic saline,while the bergapten groups received gavage of 50,100,and 200 mg/kg bergapten,respectively,once daily for 4 consecutive weeks.Perio-dontal symptoms were observed,and GI,SBI grades,and PLI scores were recorded.Rats were sacrificed within 24 hours after the last administration,and their maxillae were immediately subjected to Micro-CT scanning to assess alveolar bone resorption.Histopathological changes in the periodontal tissues were observed using HE staining,and serum levels of pro-inflammatory cytokines(IL-6 and IL-1β)were measured by ELISA.Results Compared with the control group,the model group exhibited significantly higher levels of IL-6,IL-1β,GI,SBI grades,PLI scores,and CEJ-ABC distance,while bone volume to total volume ratio(BV/TV),trabec-ular number(Tb.N),and trabecular thickness(Tb.Th)were significantly reduced(P＜0.001).In comparison to the model group,the bergapten groups(with the exception of the low-dose group for IL-6)demonstrated reductions in IL-6,IL-1β levels,GI,SBI grades,PLI scores,and CEJ-ABC distance,with the medium-dose group showing the most pronounced effect(except for IL-6).Conclusion Bergapten can effectively prevent and treat periodontitis by inhibiting the secretion of IL-6 and IL-1β cytokines,achieving anti-inflam-matory effects and inhibiting bone resorption.

Objective To investigate the effect of miR-217 on gefitinib resistance in non-small cell lung cancer(NSCLC),and to explore the downstream target genes and related pathways.Methods qRT-PCR was used to detect the expression of miR-217 in human lung normal epithelial cell lines BEAS-2B,NSCLC cell lines A549,HCC827,PC9,NCI-H1975 and gefitinib resistant strain PC9/GR.PC9/GR cells were selected and the cells of control group,NC-mimic group,miR-217 mimic group,miR-217 mimic+si-NC group,and miR-217 mimic+si-FOXO3 group were constructed using liposome transfection technique.CCK8 and clonal formation assay were used to detect changes in cell proliferation capacity,flow cytometry was used to detect changes in cell apoptosis capacity,and western blot was used to detect protein expression related to PI3K/AKT signaling pathway.The Targetscan bioinformatics website predicted the downstream target genes of miR-217,and the correlation between miR-217 and the target gene FOXO3 was detected by dual luciferase assay.Results Compared with BEAS-2B cells,the expression of miR-217 in A549,HCC827,PC9 and NCI-H1975 cells was significantly decreased(P＜0.05).With the increase of gefitinib concentration,the expression of miR-217 gene in PC9 cells was gradually decreased(P＜0.05),and the expression of miR-217 in PC9/GR cells was lower than that in PC9(P＜0.05).Compared with the control group and NC-mimic group,the cell proliferation capacity of miR-217 mimic group was significantly decreased(P＜0.05),the number of apoptosis was increased(P＜0.05),and the expression levels of p-PI3K and p-AKT were decreased(P＜0.05).Dual luciferase reporter gene assay proved that FOXO3 is the target of miR-217.Compared with miR-217 mimic group and miR-217 mimic+si-NC group,the cell drug resistance of miR-217 mimic+si-FOXO3 group was increased(P＜0.05),the proliferation ability was significantly increased(P＜0.05),and the number of apoptosis was decreased(P＜0.05).The expression levels of P-PI3K and P-AKT were increased(P＜0.05).Conclusion Overexpression of miR-217 reversed the resistance of PC9/GR to gefitinib in NSCLC cells and inhibited the proliferation and accelerated apoptosis of PC9/GR cells,which may be related to the regulation of PI3K/AKT signaling pathway by targeting FOXO3.

Objective:To investigate whether endoplasmic reticulum transmembrane protein IRE1(encoded by Ern1)can modulate the immunogenicity and tumorigenicity of cancer cells and explore the underlying mechanism.Methods:Correlation between ERN1 expression and the overall survival of cancer patients was explored with public cancer databases.CRISPR-Cas9 technology was used to delete Ern1 in mouse tumor cell lines MCA205 and TC-1.By CCK-8,flow cytometry,ELISA,luciferase reporter systems,subcutaneous tumor models,prime-boost regimens,we analyzed impact of Ern1 on tumor cell proliferation in vitro and tumor growth in vivo,intratumoral immune cell composition,tunicamycin-induced immunogenic cell death and activation of anti-tumor effector T cells.The growth kinetics of Ern1-/-tumors was also monitored in Ifnar-/-mice.Results:ERN1 expression was found to be negatively correlated with the overall survival of cancer patients across multiple cancer types.Although Ern1 deficiency didn't affect tumor cell proliferation in vitro,it largely delayed tumor growth or caused spontaneous tumor regression in immune-competent mice.As compared to wild type counterparts,Ern1-/-tumors harbored much more neutrophils but significantly less CD4+T cells.Upon tunicamycin-induced endoplasmic reticulum stress,Ern1-/-cells were more vulnerable to cell death.Although Ern1-deficiency reduced HMGB1 release and calreticulin exposure,IFN-α/β secretion was increased,and strongly elevated type Ⅰ IFN response in tumor cells and augmented IFN-γ production by anti-tumor effector T cells.Ern1-/-tumor cells restored the tumorigenic capacity in Ifnar-/-mice.Conclusion:Ern1 defi-ciency can enhance the immunogenicity of tumor cells and inhibit tumor outgrowth by boosting endoplasmic reticulum stress-induced type Ⅰ IFN response.

INTRODUCTION: Medical school fees are rising globally. Student debt and financial background may affect residency choices, but few studies have been conducted in Asia. This study aimed to explore the relationship between financial background, student debt and postgraduate residency choices among medical students in Singapore. METHODS: An anonymised survey of all medical students in Singapore was conducted and had a response rate of 67.9%. RESULTS: 40.5% of our study population would graduate with debt. Medical students with monthly per capita household income < SGD 1,000 were more likely to graduate with debt (unadjusted odds ratio [OR] 2.0, 95% confidence interval [CI] 1.6-2.7; p < 0.001) and feel burdened by the cost of medical education (unadjusted OR 2.8, 95% CI 2.0-3.9; p < 0.001). Students with monthly per capita household income < SGD 1,000 (unadjusted OR 1.818, 95% CI 1.338-2.470, p < 0.001; adjusted OR 1.692, 95% CI 1.202-2.381, p = 0.003) and those with debt (unadjusted OR 1.623, 95% CI 1.261-2.090, p < 0.001; adjusted OR 1.393, 95% CI 1.048-1.851, p = 0.022) were more likely to rank at least one economic factor as 'very significant' in influencing their postgraduate training choices. CONCLUSION It is concerning that despite financial aid schemes, the cost of medical education remains a burden to students from lower-income households in Singapore. Student debt and financial background may distort postgraduate career choices, creating an undue push towards high-paying specialties.
Career Choice ; Choice Behavior ; Education, Medical ; economics ; Humans ; Internship and Residency ; economics ; Odds Ratio ; Schools, Medical ; economics ; Singapore ; Social Class ; Students, Medical ; statistics & numerical data ; Surveys and Questionnaires ; Training Support