Objective To investigate the clinical factors affecting the risk of distant metastasis in patients with gallbladder carcinoma(GBC)and to construct a predictive model for metastasis risk.Methods Retrospective analysis was conducted on 4979 GBC patients from the surveillance,epidemiology,and end results(SEER)database from January 2000 to December 2021,which were divided into a training set(n=3485)and an internal validation set(n=1494)in a 7∶3 ratio.Additionally,47 GBC patients from Hefei First People's Hospital from January 2009 to December 2024 were collected as an external validation set.In the training set,univariate and multivariate analyses were performed to identify independent predictors of distant metastasis in GBC and to construct a predictive model.The predictive ability of the model was assessed by using area under the receiver operating characteristic curve.The model's calibration and clinical utility were evaluated through calibration curves and decision curve analysis.Results The results of univariate and multivariate analyses revealed that Caucasian,tumor size,T stage,and N stage were independent risk factors for distant metastasis in patients with GBC(P＜0.05).The predictive model constructed based on these factors had an AUC of 0.727,indicating good predictive performance.In the training set,internal validation set,and external validation set,the predictive results of this model showed good consistency with the actual situation.Conclusion The nomogram established by using SEER database can accurately predict the distant metastasis status in patients with GBC and demonstrates good clinical applicability.It assists clinicians in intuitively assessing the distant metastasis rate in GBC patients,thereby facilitating the formulation of personalized treatment plans.

Objective To construct a diagnostic model for phlegm-dampness syndrome in hypertension based on multimodal feature fusion.Methods Clinical text information(physiological/lifestyle data,symptoms,pulse characteristics)and tongue image data were collected from 261 hypertension patients.For clinical text data,statistical analyses,including ANOVA,Mann-Whitney U test,and Chi-square test,were performed to identify significant features(P<0.05),which were incorporated into a clinical text-based diagnosis model(CTDM)using a multilayer perceptron algorithm.For tongue images,a tongue image-based diagnosis model(TIDM)was constructed based on channel attention mechanisms and residual networks.A multimodal diagnostic model(MDM)was built by fusing clinical text and tongue image features using a feature concatenation method.The diagnostic performance of each model was evaluated using five-fold cross-validation with the area under the receiver operating characteristic curve(AUC),accuracy,specificity,and sensitivity.Results Seven clinical text features,including physiological/lifestyle factors(disease duration,body mass index),symptoms(chest tightness,loss of appetite,excessive phlegm),and pulse characteristics(slippery pulse,damp pulse),were identified as risk factors for phlegm-dampness syndrome in hypertension.The AUC of the CTDM was 0.831±0.021,the AUC of the TIDM was 0.878±0.035,and the MDM achieved an AUC of 0.972±0.015.Conclusion The multimodal diagnostic model that integrates clinical text and tongue image features demonstrates high diagnostic accuracy and provides valuable guidance for AI-assisted diagnosis of phlegm-dampness syndrome in hypertension.

Objective To establish and validate a method for simultaneous analysis of fluconazole,linezolid,voriconazole and cont-ezolid by liquid chromatography-tandem mass spectrometry,and conduct preliminary assessment its value of application value in clinical therapeutic drug monitoring.Methods Using an isotopic internal standard method,the serum samples were pretreated with protein precipitation.The supernatant was diluted after centrifugation,and detected by liquid chromatography-tandem mass spectrometer.Refer-ring to the Recommendations for Clinical Application of Liquid Chromatography-Mass Spectrometry(LC-MS)and Clinical and Labora-tory Standards Instituhe(CLSI)C62A,the performance of the LC-MS method was verified,including quantitation limits,linearity,trueness,precision,matrix effect,carry-over,interference,dilution consistency and stability.The blood samples from patients who were treated with fluconazole,linezolid,voriconazole,and contezolid were collected and measured for trough or peak concentrations.Results The quantitation limits of fluconazole,linezolid,voriconazole and contezolid by this method were 1 μg/mL,0.25 μg/mL,0.25 μg/mL and 0.1 μg/mL,respectively.The linear ranges were 1-100 μg/mL,0.25-25 μg/mL,0.25-25 μg/mL,and 0.1-10μg/mL,respectively.The recovery rates were 103.0％-105.7％,103.1％-108％,102.4％-106.2％and 101.0％-109.9％,respectively.The precisions,expressed as coefficient of variation(CV),were 1.7％-3.4％,2.1％-4.8％,1.9％-3.1％,and 3.1％-6.8％,respective-ly.No obvious matrix effect,carry-over contamination and interference were found.The dilution consistency and stability were satisfac-tory.The concentrations of fluconazole,linezolid and voriconazole within the reference interval accounted for 49.1％,52.5％and 80.7％of the total samples,respectively.The peak concentration of contezolamide was(14.02±4.94)μg/mL(n=4),and the trough concen-tration was(0.34±0.20)μg/mL(n=5).Conclusion In this study,a method for simultaneous analysis of the concentrations of flu-conazole,linezolid,voriconazole and contezolid was successfully established and verified by liquid chromatography-tandem mass spec-trometry.This method is simple,rapid,and suitable for therapeutic drug monitoring,and providing a basis for the optimization of drug regimens.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Objective To investigate the clinical factors affecting the risk of distant metastasis in patients with gallbladder carcinoma(GBC)and to construct a predictive model for metastasis risk.Methods Retrospective analysis was conducted on 4979 GBC patients from the surveillance,epidemiology,and end results(SEER)database from January 2000 to December 2021,which were divided into a training set(n=3485)and an internal validation set(n=1494)in a 7∶3 ratio.Additionally,47 GBC patients from Hefei First People's Hospital from January 2009 to December 2024 were collected as an external validation set.In the training set,univariate and multivariate analyses were performed to identify independent predictors of distant metastasis in GBC and to construct a predictive model.The predictive ability of the model was assessed by using area under the receiver operating characteristic curve.The model's calibration and clinical utility were evaluated through calibration curves and decision curve analysis.Results The results of univariate and multivariate analyses revealed that Caucasian,tumor size,T stage,and N stage were independent risk factors for distant metastasis in patients with GBC(P＜0.05).The predictive model constructed based on these factors had an AUC of 0.727,indicating good predictive performance.In the training set,internal validation set,and external validation set,the predictive results of this model showed good consistency with the actual situation.Conclusion The nomogram established by using SEER database can accurately predict the distant metastasis status in patients with GBC and demonstrates good clinical applicability.It assists clinicians in intuitively assessing the distant metastasis rate in GBC patients,thereby facilitating the formulation of personalized treatment plans.

Objective To construct a diagnostic model for phlegm-dampness syndrome in hypertension based on multimodal feature fusion.Methods Clinical text information(physiological/lifestyle data,symptoms,pulse characteristics)and tongue image data were collected from 261 hypertension patients.For clinical text data,statistical analyses,including ANOVA,Mann-Whitney U test,and Chi-square test,were performed to identify significant features(P<0.05),which were incorporated into a clinical text-based diagnosis model(CTDM)using a multilayer perceptron algorithm.For tongue images,a tongue image-based diagnosis model(TIDM)was constructed based on channel attention mechanisms and residual networks.A multimodal diagnostic model(MDM)was built by fusing clinical text and tongue image features using a feature concatenation method.The diagnostic performance of each model was evaluated using five-fold cross-validation with the area under the receiver operating characteristic curve(AUC),accuracy,specificity,and sensitivity.Results Seven clinical text features,including physiological/lifestyle factors(disease duration,body mass index),symptoms(chest tightness,loss of appetite,excessive phlegm),and pulse characteristics(slippery pulse,damp pulse),were identified as risk factors for phlegm-dampness syndrome in hypertension.The AUC of the CTDM was 0.831±0.021,the AUC of the TIDM was 0.878±0.035,and the MDM achieved an AUC of 0.972±0.015.Conclusion The multimodal diagnostic model that integrates clinical text and tongue image features demonstrates high diagnostic accuracy and provides valuable guidance for AI-assisted diagnosis of phlegm-dampness syndrome in hypertension.

Objective To establish and validate a method for simultaneous analysis of fluconazole,linezolid,voriconazole and cont-ezolid by liquid chromatography-tandem mass spectrometry,and conduct preliminary assessment its value of application value in clinical therapeutic drug monitoring.Methods Using an isotopic internal standard method,the serum samples were pretreated with protein precipitation.The supernatant was diluted after centrifugation,and detected by liquid chromatography-tandem mass spectrometer.Refer-ring to the Recommendations for Clinical Application of Liquid Chromatography-Mass Spectrometry(LC-MS)and Clinical and Labora-tory Standards Instituhe(CLSI)C62A,the performance of the LC-MS method was verified,including quantitation limits,linearity,trueness,precision,matrix effect,carry-over,interference,dilution consistency and stability.The blood samples from patients who were treated with fluconazole,linezolid,voriconazole,and contezolid were collected and measured for trough or peak concentrations.Results The quantitation limits of fluconazole,linezolid,voriconazole and contezolid by this method were 1 μg/mL,0.25 μg/mL,0.25 μg/mL and 0.1 μg/mL,respectively.The linear ranges were 1-100 μg/mL,0.25-25 μg/mL,0.25-25 μg/mL,and 0.1-10μg/mL,respectively.The recovery rates were 103.0％-105.7％,103.1％-108％,102.4％-106.2％and 101.0％-109.9％,respectively.The precisions,expressed as coefficient of variation(CV),were 1.7％-3.4％,2.1％-4.8％,1.9％-3.1％,and 3.1％-6.8％,respective-ly.No obvious matrix effect,carry-over contamination and interference were found.The dilution consistency and stability were satisfac-tory.The concentrations of fluconazole,linezolid and voriconazole within the reference interval accounted for 49.1％,52.5％and 80.7％of the total samples,respectively.The peak concentration of contezolamide was(14.02±4.94)μg/mL(n=4),and the trough concen-tration was(0.34±0.20)μg/mL(n=5).Conclusion In this study,a method for simultaneous analysis of the concentrations of flu-conazole,linezolid,voriconazole and contezolid was successfully established and verified by liquid chromatography-tandem mass spec-trometry.This method is simple,rapid,and suitable for therapeutic drug monitoring,and providing a basis for the optimization of drug regimens.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Objective:The aim of this study was to develop and validate a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of melatonin in human serum.Methods:We describe the performance and validation of melatonin by LC-MS/MS. 182 serum samples from the patients diagnosed with Sleep disturbance who visited the Department of Psychiatry at Zhongshan Hospital affiliated to Fudan University from February 2022 to March 2023(56 males,162 females,mean age [45.51±16.31]years), as well as 182 healthy individuals were included(87 males,95 females,mean age [48.55±11.93]years). The two groups were used to assess the application of serum melatonin levels as a diagnostic indicator for sleep disorders (SDs). The liquid chromatography mass spectrometry (LC-MS) system with an chromatography column (2.1×100 mm, 1.8 μm) was used for separation. The column temperature was set at 35 ℃, as well as the mobile phase consisting of a 0.1% formic acid aqueous solution and pure acetonitrile. The flowing rate was set at 0.4 ml/min for gradient elution. The LC-MS/MS method was validated according to guidance documents, including the following parameters: specificity, selectivity, matrix effect, carryover contamination and reproducibility, lower limit of measuring interval, linearity, precision, recovery rate, dilution consistency, and serum sample stability. Then, it was subsequently employed to profile melatonin changes in Sleep disturbance.Results:The lower limit of quantification for melatonin was 1 pg/ml, and the linear range of detection was 1 pg/ml to 500 pg/ml ( r=0.999). The intra-day and intra-batch precision, expressed as the coefficient of variation ( CV), was within the range from 3.07% to 6.86%, which met the requirement of less than 15%. The recovery rate of the spiked samples ranged from 105.91% to 116.30%. The level of serum melatonin in the sleep disturbance group was significantly lower than that in the healthy control group ([2.00(1.00,3.28)] vs [8.35(4.28,14.80)] pg/ml, P<0.001). Conclusions:The LC-MS/MS method we developed for the quantification of melatonin is clinical practicable.

Objective To compare the efficacy and safety of everolimus combined with endocrine therapy and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine thera-py. Methods Ninety-three breast cancer patients were selected from January 2014 to February 2017. The primary end points were progression-free survival and clinical benefit rate and the secondary end points was tolerability. Re-sults The progression-free survival in fulvestrant group was slightly higher than that in the everolimus group(13.4 months vs 12.2 months,P = 0.297). The clinical benefit rates were 46.15% and 31.71% in fulvestrant group and everolimus group,respectively. Patients treated with fewer than 2 lines and endocrine resistant patients benefited more from fulvestrant but without statistical difference. The main adverse events related to everolimus were stomati-tis,with a prevalence rate of about 26% and a localized pneumonia with a prevalence rate of about 10%. The main adverse reaction of fulvestrant was the injection site reaction. Conclusions The efficacy of everolimus in combina-tion with endocrine therapy is not superior to that of fulvestrant for the treatment of advanced breast cancer pro-gressed after endocrine therapy. After weighing the clinical benefits and quality of life,fulvestrant may be better for patients treated with fewer than 2 lines and endocrine resistance.