Objective·To explore the value of combined diaphragm and intercostal muscle ultrasound assessment compared with conventional diaphragm ultrasound in predicting the weaning outcome in mechanically ventilated patients with sepsis.Methods·Mechanically ventilated patients with sepsis,consecutively admitted to the Department of Critical Care Medicine of Affiliated Hospital of Nantong University from October 2022 to December 2023,were selected.During the peri-weaning period,after the patient's sepsis condition improved and the patient passed the spontaneous breathing trial(SBT),ultrasound evaluation of respiratory muscles was performed by ultrasound qualified personnel with ultrasound qualification and experience in bedside ultrasound examination.Diaphragm excursion(DE),thickening fraction of diaphragm(TFD),and thickening fraction of intercostal muscle(TFic)were measured,respectively.The patients were divided into a successful weaning group(n=114)and a failed weaning group(n=24)according to the weaning results.Receiver operating characteristic(ROC)curves were used to analyze the value of diaphragm ultrasound and intercostal muscle ultrasound,alone and in combination,in predicting ventilator weaning outcome.Results·TFic and TFic/TFD were significantly higher in the failed weaning group during SBT than in the successful weaning group(all P<0.05).The areas under the ROC curve(AUROC)of DE,TFD,and TFic to predict weaning failure in mechanically ventilated patients with sepsis during the period of SBT were 0.689(0.591?0.776),0.657(0.557?0.747),and 0.769(0.676?0.846),respectively,whereas the combined indexes TFic/TFD and TFic&TFD_mix had AUROCs of 0.867(0.786?0.925)and 0.860(0.778?0.920),respectively.TFic/TFD with a cutoff value of>0.95 had a sensitivity of 86.7%and a specificity of 75.3%in predicting weaning failure,and TFic&TFD_mix with a cutoff value of>0.13 had a sensitivity of 86.6%and a specificity of 80.9%in predicting weaning failure.Moreover,the intercostal muscle ultrasonography method had an intra-observer intraclass correlation coefficient(ICC)of 0.890 and an extra-observer ICC of 0.876 for measurement reliability,which were both rated as good(P<0.001).Conclusion·Combined diaphragm and intercostal muscle ultrasonography provides a more comprehensive picture of the patient's overall respiratory muscles,and has a higher guiding value in predicting the weaning outcomes in mechanically ventilated patients with sepsis than diaphragm ultrasound alone.

Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.

Objective To develop and validate a machine learning-based predictive model to assess the in-hospital mortality risk of patients with myocardial infarction(MI)complicated by heart failure(HF)undergoing percutaneous coronary intervention(PCI).Methods This retrospective study analyzed MI patients with HF who underwent PCI at The First Affiliated Hospital of Xinjiang Medical University from January 2019 to January 2023.Patient data,including demographic characteristics,vital signs,laboratory test results,imaging parameters and medication use,were collected and randomly divided into a training set(70％)and a validation set(30％).The extreme gradient boosting(XGBoost)model was used to identify variables significantly associated with in-hospital mortality,and the Shapley additive explanations(SHAP)model was applied to assess feature importance.A predictive model was then constructed using univariate and multivariate Logistic regression analyses.Model performance was evaluated using receiver operating characteristic(ROC)curves,area under the curve(AUC)values,calibration curves,and decision curve analysis.Finally,a nomogram was developed for intuitive risk assessment.Results A total of 1 214 MI patients with HF were included in the study,with a median age of 64 years.The in-hospital mortality rate was 7.41％(90 deaths).XGBoost feature selection identified ten key predictive variables:age,myoglobin,albumin,fasting blood glucose,N-terminal pro-B-type natriuretic peptide(NT-proBNP),diabetes mellitus,creatinine,cystatin C,procalcitonin,and left ventricular ejection fraction.Based on these variables,a Logistic regression model was developed,with seven final predictors:age,diabetes mellitus,creatinine,fasting blood glucose,cystatin C,NT-proBNP,and albumin.The model demonstrated high predictive accuracy,with AUC value of 0.869(95％CI:0.84-0.89)in the training set and 0.827(95％CI:0.79-0.85)in the validation set.The calibration curve indicated that the predicted probabilities were consistent with the actual observed outcomes,and decision curve analysis showed that the model had a high net benefit across various decision thresholds.Conclusion This study developed a machine learning-based predictive model incorporating Logistic regression to assess the in-hospital mortality risk of MI patients with HF undergoing PCI.The model demonstrated high predictive performance and clinical utility.The nomogram derived from this model provides an intuitive tool for individualized risk assessment,aiding clinicians in the early identification of high-risk patients,optimizing intervention strategies,and improving patient outcomes.

Objective To analyze the long-term trend in the disease burden of congenital birth defects(CBDs)among neonates in China from 1990 to 2021,compare the trend with global patterns,and identify key subtypes along with their association with socioeconomic status to provide evidence for public health interventions.Methods Utilizing data from the Global Burden of Disease Study 2021(GBD 2021),we extracted indicators including disability-adjusted life years(DALYs),mortality,and prevalence for the neonatal period(＜28 days)in China,encompassing ten major CBD subtypes.Joinpoint regression analysis was employed to calculate annual percent changes and estimate annual percent changes(EAPC),with comparisons of subtype composition between 1990 and 2021.Nonlinear regression was used to assess the relationship between DALYs rates and the Socio-demographic Index(SDI).Results From 1990 to 2021,DALYs rates for neonatal CBDs declined significantly both globally and in China,with China's EAPC at-4.67％[95％CI:(—5.06,—4.28)],substantially exceeding the global average of-1.70％[95％CI:(—1.75,—1.64)].Congenital heart anomalies remained the primary burden,while neural tube defects and orofacial clefts in China showed notable reductions(EAPCs of-7.25％and-11.22％,respectively).However,DALYs rates for congenital musculoskeletal and limb anomalies exceeded global expected levels.A resurgence in the prevalence was observed post-2015,with higher burdens in males.DALYs rates exhibited a negative correlation with SDI.Conclusion China has achieved significant reductions in the neonatal CBDs burden,surpassing global trends;yet challenges persist in managing congenital heart anomalies and musculoskeletal defects.Future efforts should focus on enhancing early screening,surgical interventions,and regional equity to align with global health objectives.

Objective To develop and validate a machine learning-based predictive model to assess the in-hospital mortality risk of patients with myocardial infarction(MI)complicated by heart failure(HF)undergoing percutaneous coronary intervention(PCI).Methods This retrospective study analyzed MI patients with HF who underwent PCI at The First Affiliated Hospital of Xinjiang Medical University from January 2019 to January 2023.Patient data,including demographic characteristics,vital signs,laboratory test results,imaging parameters and medication use,were collected and randomly divided into a training set(70％)and a validation set(30％).The extreme gradient boosting(XGBoost)model was used to identify variables significantly associated with in-hospital mortality,and the Shapley additive explanations(SHAP)model was applied to assess feature importance.A predictive model was then constructed using univariate and multivariate Logistic regression analyses.Model performance was evaluated using receiver operating characteristic(ROC)curves,area under the curve(AUC)values,calibration curves,and decision curve analysis.Finally,a nomogram was developed for intuitive risk assessment.Results A total of 1 214 MI patients with HF were included in the study,with a median age of 64 years.The in-hospital mortality rate was 7.41％(90 deaths).XGBoost feature selection identified ten key predictive variables:age,myoglobin,albumin,fasting blood glucose,N-terminal pro-B-type natriuretic peptide(NT-proBNP),diabetes mellitus,creatinine,cystatin C,procalcitonin,and left ventricular ejection fraction.Based on these variables,a Logistic regression model was developed,with seven final predictors:age,diabetes mellitus,creatinine,fasting blood glucose,cystatin C,NT-proBNP,and albumin.The model demonstrated high predictive accuracy,with AUC value of 0.869(95％CI:0.84-0.89)in the training set and 0.827(95％CI:0.79-0.85)in the validation set.The calibration curve indicated that the predicted probabilities were consistent with the actual observed outcomes,and decision curve analysis showed that the model had a high net benefit across various decision thresholds.Conclusion This study developed a machine learning-based predictive model incorporating Logistic regression to assess the in-hospital mortality risk of MI patients with HF undergoing PCI.The model demonstrated high predictive performance and clinical utility.The nomogram derived from this model provides an intuitive tool for individualized risk assessment,aiding clinicians in the early identification of high-risk patients,optimizing intervention strategies,and improving patient outcomes.

Objective To analyze the long-term trend in the disease burden of congenital birth defects(CBDs)among neonates in China from 1990 to 2021,compare the trend with global patterns,and identify key subtypes along with their association with socioeconomic status to provide evidence for public health interventions.Methods Utilizing data from the Global Burden of Disease Study 2021(GBD 2021),we extracted indicators including disability-adjusted life years(DALYs),mortality,and prevalence for the neonatal period(＜28 days)in China,encompassing ten major CBD subtypes.Joinpoint regression analysis was employed to calculate annual percent changes and estimate annual percent changes(EAPC),with comparisons of subtype composition between 1990 and 2021.Nonlinear regression was used to assess the relationship between DALYs rates and the Socio-demographic Index(SDI).Results From 1990 to 2021,DALYs rates for neonatal CBDs declined significantly both globally and in China,with China's EAPC at-4.67％[95％CI:(—5.06,—4.28)],substantially exceeding the global average of-1.70％[95％CI:(—1.75,—1.64)].Congenital heart anomalies remained the primary burden,while neural tube defects and orofacial clefts in China showed notable reductions(EAPCs of-7.25％and-11.22％,respectively).However,DALYs rates for congenital musculoskeletal and limb anomalies exceeded global expected levels.A resurgence in the prevalence was observed post-2015,with higher burdens in males.DALYs rates exhibited a negative correlation with SDI.Conclusion China has achieved significant reductions in the neonatal CBDs burden,surpassing global trends;yet challenges persist in managing congenital heart anomalies and musculoskeletal defects.Future efforts should focus on enhancing early screening,surgical interventions,and regional equity to align with global health objectives.

Objective·To explore the value of combined diaphragm and intercostal muscle ultrasound assessment compared with conventional diaphragm ultrasound in predicting the weaning outcome in mechanically ventilated patients with sepsis.Methods·Mechanically ventilated patients with sepsis,consecutively admitted to the Department of Critical Care Medicine of Affiliated Hospital of Nantong University from October 2022 to December 2023,were selected.During the peri-weaning period,after the patient's sepsis condition improved and the patient passed the spontaneous breathing trial(SBT),ultrasound evaluation of respiratory muscles was performed by ultrasound qualified personnel with ultrasound qualification and experience in bedside ultrasound examination.Diaphragm excursion(DE),thickening fraction of diaphragm(TFD),and thickening fraction of intercostal muscle(TFic)were measured,respectively.The patients were divided into a successful weaning group(n=114)and a failed weaning group(n=24)according to the weaning results.Receiver operating characteristic(ROC)curves were used to analyze the value of diaphragm ultrasound and intercostal muscle ultrasound,alone and in combination,in predicting ventilator weaning outcome.Results·TFic and TFic/TFD were significantly higher in the failed weaning group during SBT than in the successful weaning group(all P<0.05).The areas under the ROC curve(AUROC)of DE,TFD,and TFic to predict weaning failure in mechanically ventilated patients with sepsis during the period of SBT were 0.689(0.591?0.776),0.657(0.557?0.747),and 0.769(0.676?0.846),respectively,whereas the combined indexes TFic/TFD and TFic&TFD_mix had AUROCs of 0.867(0.786?0.925)and 0.860(0.778?0.920),respectively.TFic/TFD with a cutoff value of>0.95 had a sensitivity of 86.7%and a specificity of 75.3%in predicting weaning failure,and TFic&TFD_mix with a cutoff value of>0.13 had a sensitivity of 86.6%and a specificity of 80.9%in predicting weaning failure.Moreover,the intercostal muscle ultrasonography method had an intra-observer intraclass correlation coefficient(ICC)of 0.890 and an extra-observer ICC of 0.876 for measurement reliability,which were both rated as good(P<0.001).Conclusion·Combined diaphragm and intercostal muscle ultrasonography provides a more comprehensive picture of the patient's overall respiratory muscles,and has a higher guiding value in predicting the weaning outcomes in mechanically ventilated patients with sepsis than diaphragm ultrasound alone.

Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.

Objective:To explore the molecular mechanism of circDDX17 regulating the proliferation and apoptosis of non-small cell lung cancer cells by targeting the miR-223-3p/RIP3 molecular axis.Methods:The expression levels of circDDX17, miR-223-3p, and RIP3 in human normal lung epithelial cell lines BEAS-2B and non-small cell lung cancer cells H1299, A549, and H446 were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The plasmids of pcDNA, pcDNA-circDDX17, anti-miR-con, anti-miR-223-3p, pcDNA-circDDX17 and miR-con, pcDNA-circDDX17 and miR-223-3p mimics were transfected into H1299 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was used to detect the cell proliferation. Flow cytometry was used to detect the cell cycle and cell apoptosis. Plate cloning experiment was used to detect cell proliferation ability. The dual luciferase report experiment was applied to verify the targeting relationship between miR-223-3p with circDDX17 and RIP3. Western blot was used to detect the protein expression of cyclinD1, CDK2, cleaved caspase-3 and Bax.Results:The expression levels of circDDX17 and RIP3 mRNA in H1299, A549, and H446 cells were significantly reduced ( P<0.05), the expression level of miR-223-3p mRNA was significantly increased ( P<0.05) compared with BEAS-2B. The cell viability [(69.46±4.68)%], the number of cell clones (83.49±7.86), the proportion of cells in S phase [(22.52±1.41) %], the protein expression levels of cyclinD1 and CDK2 in PCDNa-CircDDX17 group were lower than those in pcDNA group [(97.54±7.72)%, 205.03±13.37, (28.69±1.49)%, respectively, P<0.05], while the percentage of G 0/G 1 phase cells [(64.45±3.56)%], apoptosis rate [(18.36±1.63)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17 group were higher than those of pcDNA group [(51.33±2.76) % and (5.21±0.54) %, respectively, P<0.05]. The viability [(72.64±5.44)%], the number of cell clones (78.16±8.23), the proportion of S-stage cells [(21.34±1.59) %], the protein expression levels of CyclinD1 and CDK2 in anti-miR-223-3p group were lower than those in anti-miR-con group [(103.47±6.25)%, 169.32±14.53, (28.43±1.26)%, respectively, P<0.05]. Percentage of G 0/G 1 phase cells [(62.86±3.28)%], apoptosis rate [(14.64±1.67)%], the protein expression levels of cleaved caspase-3 and Bax in the anti-miR-223-3p group were higher than those of anti-miR-con group [(51.33±2.71)% and (4.83±0.39)%, respectively, P<0.05]. MiR-223-3p has complementary sites with circDDX17 or RIP3. The viability [(135.45±9.28)%], the number of cell clones (174.64±10.68), the proportion of S-phase cells [(26.39±2.25)%], the protein expression levels of cyclinD1 and CDK2 in pcDNA-circDDX17+miR-223-3p group were higher than those in pcDNA-circDDX17+miR-con group [(101.56±6.68)%, 107.65±7.62, (21.64±1.72)%, P<0.05]. Percentage of G 0/G 1 phase cells [(56.64±2.76)%], apoptosis rate [(8.34±0.76)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17+miR-223-3p group were lower than those of pcDNA-circDDX17+miR-con group [(64.03±3.48)% and (15.21±1.18)%, respectively, P<0.05]. Conclusion:circDDX17 could inhibit the proliferation and induce apoptosis of non-small cell lung cancer cells via targeting the miR-223-3p / RIP3 molecular axis.

Objective:To explore the molecular mechanism of circDDX17 regulating the proliferation and apoptosis of non-small cell lung cancer cells by targeting the miR-223-3p/RIP3 molecular axis.Methods:The expression levels of circDDX17, miR-223-3p, and RIP3 in human normal lung epithelial cell lines BEAS-2B and non-small cell lung cancer cells H1299, A549, and H446 were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The plasmids of pcDNA, pcDNA-circDDX17, anti-miR-con, anti-miR-223-3p, pcDNA-circDDX17 and miR-con, pcDNA-circDDX17 and miR-223-3p mimics were transfected into H1299 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was used to detect the cell proliferation. Flow cytometry was used to detect the cell cycle and cell apoptosis. Plate cloning experiment was used to detect cell proliferation ability. The dual luciferase report experiment was applied to verify the targeting relationship between miR-223-3p with circDDX17 and RIP3. Western blot was used to detect the protein expression of cyclinD1, CDK2, cleaved caspase-3 and Bax.Results:The expression levels of circDDX17 and RIP3 mRNA in H1299, A549, and H446 cells were significantly reduced ( P<0.05), the expression level of miR-223-3p mRNA was significantly increased ( P<0.05) compared with BEAS-2B. The cell viability [(69.46±4.68)%], the number of cell clones (83.49±7.86), the proportion of cells in S phase [(22.52±1.41) %], the protein expression levels of cyclinD1 and CDK2 in PCDNa-CircDDX17 group were lower than those in pcDNA group [(97.54±7.72)%, 205.03±13.37, (28.69±1.49)%, respectively, P<0.05], while the percentage of G 0/G 1 phase cells [(64.45±3.56)%], apoptosis rate [(18.36±1.63)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17 group were higher than those of pcDNA group [(51.33±2.76) % and (5.21±0.54) %, respectively, P<0.05]. The viability [(72.64±5.44)%], the number of cell clones (78.16±8.23), the proportion of S-stage cells [(21.34±1.59) %], the protein expression levels of CyclinD1 and CDK2 in anti-miR-223-3p group were lower than those in anti-miR-con group [(103.47±6.25)%, 169.32±14.53, (28.43±1.26)%, respectively, P<0.05]. Percentage of G 0/G 1 phase cells [(62.86±3.28)%], apoptosis rate [(14.64±1.67)%], the protein expression levels of cleaved caspase-3 and Bax in the anti-miR-223-3p group were higher than those of anti-miR-con group [(51.33±2.71)% and (4.83±0.39)%, respectively, P<0.05]. MiR-223-3p has complementary sites with circDDX17 or RIP3. The viability [(135.45±9.28)%], the number of cell clones (174.64±10.68), the proportion of S-phase cells [(26.39±2.25)%], the protein expression levels of cyclinD1 and CDK2 in pcDNA-circDDX17+miR-223-3p group were higher than those in pcDNA-circDDX17+miR-con group [(101.56±6.68)%, 107.65±7.62, (21.64±1.72)%, P<0.05]. Percentage of G 0/G 1 phase cells [(56.64±2.76)%], apoptosis rate [(8.34±0.76)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17+miR-223-3p group were lower than those of pcDNA-circDDX17+miR-con group [(64.03±3.48)% and (15.21±1.18)%, respectively, P<0.05]. Conclusion:circDDX17 could inhibit the proliferation and induce apoptosis of non-small cell lung cancer cells via targeting the miR-223-3p / RIP3 molecular axis.