General anesthesia, pivotal for surgical procedures, requires precise depth monitoring to mitigate risks ranging from intraoperative awareness to postoperative cognitive impairments. Traditional assessment methods, relying on physiological indicators or behavioral responses, fall short of accurately capturing the nuanced states of unconsciousness. This study introduces a machine learning-based approach to decode anesthesia depth, leveraging EEG data across different anesthesia states induced by propofol and esketamine in rats. Our findings demonstrate the model's robust predictive accuracy, underscored by a novel intra-subject dataset partitioning and a 5-fold cross-validation method. The research diverges from conventional monitoring by utilizing anesthetic infusion rates as objective indicators of anesthesia states, highlighting distinct EEG patterns and enhancing prediction accuracy. Moreover, the model's ability to generalize across individuals suggests its potential for broad clinical application, distinguishing between anesthetic agents and their depths. Despite relying on rat EEG data, which poses questions about real-world applicability, our approach marks a significant advance in anesthesia monitoring.
Animals ; Machine Learning ; Electroencephalography/methods* ; Ketamine/administration & dosage* ; Rats ; Male ; Propofol/administration & dosage* ; Rats, Sprague-Dawley ; Anesthesia, General/methods* ; Brain/physiology* ; Intraoperative Neurophysiological Monitoring/methods*

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

Objective:To explore the causal relationships between human inflammatory proteins and keloids.Methods:This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.Results:Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids ( P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP. Conclusions:Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.

Objective:This study aimed to propose an innovative modular surgical technique and explore its safety and application value in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy for advanced proximal gastric cancer invading the greater curvature.Methods:A retrospective collection was conducted on 34 patients with proximal gastric cancer invading the greater curvature who underwent laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy in the same center from October 2020 to December 2022. The technical key points, precautions and crucial steps of the modular surgical technique were summarized, and the Clinical indicators were analyzed.Results:All 34 patients successfully completed the operation under laparoscopy without conversion to open surgery. The average operation duration was 151.9±4.1 minutes, and the duration of splenic hilar lymphadenectomy was 12.9±1.5 minutes. The median intraoperative blood loss was 50(20, 50) ml, and the blood loss during splenic hilar lymphadenectomy was 5 (2, 5) ml. The median number of harvested lymph nodes was 32.0 (23.5,39.5), and the number of submitted No.10 lymph nodes was 3 (2, 4). The metastasis rate of No.10 lymph nodes was 20.6% (7/34). No patient had intraoperative complications. During the postoperative hospital stay, one patient had incision infection (Clavien-Dindo I), and one patient had pulmonary infection (Clavien-Dindo II). The time for the first postoperative feeding was 3 (2, 5) days, the time for the first postoperative flatus was 2 (2,3) days, the time for the first postoperative defecation was 3 (3, 4) days, the total postoperative drainage volume was 1047.5 (607.5,1397.5) mL, the time for postoperative drainage tube removal was 7 (6, 9) days, and the length of postoperative hospital stay was 7.0 (6.0, 9.5) days.Conclusions:The application of the innovative modular surgical technique in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy can simplify surgical process and enable safe, precise and comprehensive dissection of splenic hilar lymph nodes.

Objective:To explore the causal relationships between human inflammatory proteins and keloids.Methods:This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.Results:Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids ( P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP. Conclusions:Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.

Objective:This study aimed to propose an innovative modular surgical technique and explore its safety and application value in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy for advanced proximal gastric cancer invading the greater curvature.Methods:A retrospective collection was conducted on 34 patients with proximal gastric cancer invading the greater curvature who underwent laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy in the same center from October 2020 to December 2022. The technical key points, precautions and crucial steps of the modular surgical technique were summarized, and the Clinical indicators were analyzed.Results:All 34 patients successfully completed the operation under laparoscopy without conversion to open surgery. The average operation duration was 151.9±4.1 minutes, and the duration of splenic hilar lymphadenectomy was 12.9±1.5 minutes. The median intraoperative blood loss was 50(20, 50) ml, and the blood loss during splenic hilar lymphadenectomy was 5 (2, 5) ml. The median number of harvested lymph nodes was 32.0 (23.5,39.5), and the number of submitted No.10 lymph nodes was 3 (2, 4). The metastasis rate of No.10 lymph nodes was 20.6% (7/34). No patient had intraoperative complications. During the postoperative hospital stay, one patient had incision infection (Clavien-Dindo I), and one patient had pulmonary infection (Clavien-Dindo II). The time for the first postoperative feeding was 3 (2, 5) days, the time for the first postoperative flatus was 2 (2,3) days, the time for the first postoperative defecation was 3 (3, 4) days, the total postoperative drainage volume was 1047.5 (607.5,1397.5) mL, the time for postoperative drainage tube removal was 7 (6, 9) days, and the length of postoperative hospital stay was 7.0 (6.0, 9.5) days.Conclusions:The application of the innovative modular surgical technique in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy can simplify surgical process and enable safe, precise and comprehensive dissection of splenic hilar lymph nodes.

Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

Objective:To construct a diabetes foot prediction model for adult patients with type 2 diabetes based on retrospective cohort study using data from a regional health data platform.Methods:Using Yinzhou Health Information Platform of Ningbo, adult patients with newly diagnosed type 2 diabetes from January 1, 2015 to December 31, 2022 were included in this study and divided randomly the train and test sets according to the ratio of 7∶3. LASSO regression model and bidirectional stepwise regression model were used to identify risk factors, and model comparisons were conducted with net reclassification index, integrated discrimination improvement and concordance index. Univariate and multivariate Cox proportional hazard regression models were constructed, and a nomogram plot was drawn. Area under the curve (AUC) was calculated as a discriminant evaluation indicator for model validation test its calibration ability, and calibration curves were drawn to test its calibration ability.Results:No significant difference existed between LASSO regression model and bidirectional stepwise regression model, but the better bidirectional stepwise regression model was selected as the final model. The risk factors included age of onset, gender, hemoglobin A1c, estimated glomerular filtration rate, taking angiotensin receptor blocker and smoking history. AUC values (95% CI) of risk outcome prediction at year 5 and 7 were 0.700 (0.650-0.749) and 0.715(0.668-0.762) for the train set and 0.738 (0.667-0.801) and 0.723 (0.663-0.783) for the test set, respectively. The calibration curves were close to the ideal curve, and the model discrimination and calibration powers were both good. Conclusions:This study established a convenient prediction model for diabetic foot and classified the risk levels. The model has strong interpretability, good discrimination power, and satisfactory calibration and can be used to predict the incidence of diabetes foot in adult patients with type 2 diabetes to provide a basis for self-assessment and clinical prediction of diabetic foot disease risk.

Objective:To develop a prediction model for the risk of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods:Patients with new diagnosis of T2DM recorded in Yinzhou Regional Health Information Platform between January 1, 2015 and December 31, 2022 were included in the study. The predictor variables were selected by using Lasso-Cox proportional hazards regression model. Cox proportional hazards regression models were used to establish the prediction model for the risk of DR. Bootstrap method (500 resamples) was used for internal validation, and the performance of the model was assessed by C-index, the receiver operating characteristic curve and area under the curve (AUC), and calibration curve.Results:The predictor variables included in the final model were age of T2DM onset, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, estimated glomerular filtration rate, and history of lipid-lowering agent and angiotensin converting enzyme inhibitor uses. The C-index of the final model was 0.622, and the mean corrected C-index was 0.623 (95% CI: 0.607-0.634). The AUC values for predicting the risk of DR after 3, 5, and 7 years were 0.631, 0.620, and 0.624, respectively, with a high degree of overlap of the calibration curves with the ideal curves. Conclusion:In this study, a simple and practical risk prediction model for DR risk prediction was developed, which could be used as a reference for individualized DR screening and intervention in newly diagnosed T2DM patients.