Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Objective To explore the effect of the horticultural therapy in the elderly with mild cognitive impairment in elderly care institutions.Methods A convenient cluster sampling method was used.The study was conducted among the elderly with mild cognitive impairment in 2 nursing homes with 5A-level in Guangzhou,from March to September 2024.Using a lottery method,subjects from 2 nursing areas across 2 elderly care institutions were allocated to an experimental group,with the other 2 nursing areas serving as a control group,each group comprising 55 cases.The experimental group participated in horticultural therapy on the basis of control group interventions,while the control group was given routine care and daily leisure activities.The cognitive function,basic psychological needs and quality of life were compared between the 2 groups after the intervention.Results Eventually,37 cases in the experimental group and 38 cases in the control group completed the study.After the intervention,the cognitive function,basic psychological needs and quality of life in the experimental group were all better than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion The horticultural therapy program can delay the progression of cognitive decline in the elderly with mild cognitive impairment in nursing homes,meet their basic psychological needs and improve their quality of life.

Objective To explore the effect of the horticultural therapy in the elderly with mild cognitive impairment in elderly care institutions.Methods A convenient cluster sampling method was used.The study was conducted among the elderly with mild cognitive impairment in 2 nursing homes with 5A-level in Guangzhou,from March to September 2024.Using a lottery method,subjects from 2 nursing areas across 2 elderly care institutions were allocated to an experimental group,with the other 2 nursing areas serving as a control group,each group comprising 55 cases.The experimental group participated in horticultural therapy on the basis of control group interventions,while the control group was given routine care and daily leisure activities.The cognitive function,basic psychological needs and quality of life were compared between the 2 groups after the intervention.Results Eventually,37 cases in the experimental group and 38 cases in the control group completed the study.After the intervention,the cognitive function,basic psychological needs and quality of life in the experimental group were all better than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion The horticultural therapy program can delay the progression of cognitive decline in the elderly with mild cognitive impairment in nursing homes,meet their basic psychological needs and improve their quality of life.

Objective To explore the effects of image registration using various regions of interest(ROI)on the setup error for nasopharyngeal carcinoma(NPC)patients who were immobilized individually.Methods Forty-three NPC patients who required radiotherapy were enrolled.The patients were immobilized with customized plastic foam and thermoplastic mask,and CBCT verification was performed once a week.In CBCT images,ROI was divided into the whole ROI(ROIPTV)and 7 local ROI containing different cervical structures(ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,ROIneck4,ROIneck5,ROIneck6,and ROIneck7),which were then used for registrations with localized CT image.The setup errors in superior-inferior(SI),left-right(LR),anterior-posterior(AP),Pitch,Roll,and Yaw directions were recorded.Results In SI direction,the setup errors within 0.3 cm accounted for 89.74%for ROIneck7,and more than 90%for the other ROI.The proportion of setup errors within 0.3 cm gradually increased with the neck upward in LR direction,and they were 76.78%,81.70%,85.26%,and above 90%for ROIneck7,ROIneck6,ROIneck5,and the other ROI,respectively.In AP direction,the proportions of setup errors within 0.3 cm were less than 90%,except for ROIatlantoaxial and ROIneck3.The setup errors of ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,and ROIneck4 were significantly positively correlated with ROIPTV in SI direction,and the correlation coefficients(R)were 0.94,0.95,0.90,and 0.83,respectively.In LR direction,there were positive correlations between the setup errors of ROIatlantoaxial and ROIsphenoid sinus(R=0.95),ROIneck3 and ROIsphenoid sinus(R=0.91),ROIPTV and ROIneck3(R=0.91).The setup errors of ROIPTV in AP direction were positively correlated with ROIatlantoaxial vertebrae and ROIneck3(R=0.88,0.90).The margins of all ROIs ranged from 0.38 cm to 1.01 cm.The extension of ROIneck6 and ROIneck7 in AP direction exceeded 0.9 cm,and the extension of ROIneck7 reached 0.95 cm in SI direction.Conclusion ROIPTV and ROIsphenoid sinus,ROIatlantoaxial,ROIneck3 are significantly correlated in SI,LR,and AP directions.The setup error of nasopharyngeal carcinoma patients gradually increases with the neck down.The nasopharyngeal and cervical regions need to be expanded in segments when patients are immobilized individually.

Objective To establish a high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method for determining the plasma concentration of methylprednisolone in patients with hematological diseases,and apply it to guide the clinical application.Methods Plasma samples were subjected to methanol-precipitated protein containing internal standard methylprednisolone-d3.The HPLC system was equipped with an Ultimate XB-C18(4.6mm×50mm,5 μm particle size),maintained at 60℃,and 5 μl of the supernatant was injected.Mobile phases consisting of 0.1%(v/v)formic acid(1∶1 000)and 2 mmol/L ammonium acetate in water(B)and 0.1%(v/v)formic acid(1∶1 000)in methanol at a flow rate of 0.8 ml/min was used.The electrospray ionization(ESI)source was operating in positive ion mode.Multiple reaction monitoring(MRM)was applied for the detection of the components:Methylprednisolone mass-to-charge ratio(m/z)375.4 → 339.4(qualitative ions),methylprednisolone m/z 375.4→357.3(quantitative ions),methylprednisolone-d3 m/z 378.2→360.3.The peak area ratio of methylprednisolone to methylprednisolone-d3 was used as the quantitative basis.The concentration of methylprednisolone in plasma was calculated and its performance was investigated.Results The linear range of methylprednisolone was 10～1 000ng/ml(r2=0.996 7),and the lower limit of quantification was 10 ng/ml.The RSDs of intra-day and inter-day precision results were less than 15%and the relative recovery ranged from 99.52%～104.79%.For methylprednisolone,the samples were stable at-20℃after three repeated freeze-thaw cycles.The prepared samples were stable at room temperature and 4℃for 24h(RSDs<15%).The steady-state blood drug concentrations of methylprednisolone in 16 patients were in the ranges of 1～258 ng/ml.Conclusion The HPLC-MS/MS method can accurately,rapidly and simply detect the concentration of methylprednisolone,and be suitable for clinical application.

Objective To establish a high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method for determining the plasma concentration of olverembatinib in leukemia patients,apply it to clinical drug monitoring,and provide reliable basis for rational drug use in clinical practice.Methods Ponatinib-d8 was used as an internal standard,and methanol was used to precipitate plasma proteins and extract olverembatinib.The chromatographic column was Welch Ultimate XB-C18 cloumn(50 mmx4.6 mm,5 μm),with a column temperature of 60 ℃.The mobile phase consisted of an aqueous solution(containing 0.1％formic acid+2 mmol/L ammonium acetate)-methanol solution(containing 0.1％formic acid),with a flow rate of 0.8 mL/min and gradient elution.Electrospray positive ion mode was used,with multiple reaction monitoring scanning.The quantitative ion pair of olverembatinib was m/z 533.3→260.1,the qualitative ion pair was m/z 533.3→433.3,and the internal standard ion pair was m/z 541.1 →260.2.The plasma samples of 40 leukemia patients taking olverembatinib were monitored and analyzed for concentration,and IBM SPSS Statistics 27.0 and OriginPro 2021 softwares were used for statistical analysis of the results.Results The linear range of olverembatinib was 1-250 ng/mL(r=0.998 0),the lower limit of quantification was 1 ng/mL,the extraction recovery rate was 100.28％～101.27％,the intra-day precision RSD was 1.15％～3.87％,and the inter-day precision RSD was 2.32％～3.68％.Conclusion This method is easy to operate,highly specific and sensitive,and can be used to determine the blood concentration of olverembatinib in leukemia patients.

Objective:To compare the efficacy of endoscopic submucosal dissection (ESD) and modified-endoscopic mucosal resection (M-EMR) for G1 rectal neuroendocrine tumors (RNETs) .Methods:Data of 121 patients with pathologically confirmed G1 RNETs treated with ESD ( n=105) or M-EMR ( n=16) in Nanjing Drum Tower Hospital from January 2017 to September 2020 were retrospectively analyzed. The complete resection rate, complication incidence, hospital stay, treatment cost and other indicators of the two groups were compared by using inverse probability of treatment weighting (IPTW). Results:There were significant differences in tumor number ( χ2=8.76, P=0.003), tumor invasion depth ( χ2=6.96, P=0.008), utilization of metal clips [82.9% (87/105) VS 93.8% (15/16), χ2=8.78, P=0.003], number of metal clips ( χ2=8.41, P=0.016), hemostasis using hot clamp [78.1% (82/105) VS 18.7% (3/16), χ2=20.64, P<0.001], traction procedure [2.9% (3/105) VS 18.7% (3/16), χ2=4.45, P=0.035] and treatment cost (17 568.6 ± 8 911.0 yuan VS 8 120.8±1 528.2 yuan, t=3.65, P<0.001) between the ESD group and the M-EMR group. After verifying the stability of the results using IPTW sensitivity analysis, there was still significant difference in the treatment cost ( t=2.07, P<0.001). Conclusion:Both ESD and M-EMR demonstrate comparable efficacy in treating G1 RNETs; however, M-EMR exhibites lower treatment costs.

The patient was a 55-year-old man. On February 16, 2024, he was admitted to Peking Union Medical College Hospital complaining of "weakness and poor appetite for more than half a year, and found creatinine increase for 1 week". The patient was diagnosed with multiple myeloma. During the treatment in our hospital, the patient sustained"hyponatremia"(Na 124-136 mmol/L measured by indirect ion selective electrode method), and combined with the patient′s clinical symptoms and serum osmotic pressure results (327 mOsm/kg H 2O), it was considered that hyperglobulinemia led to pseudohyponatremia. So no intervention was given. Subsequent failure to recognize pseudohyponatremia during treatment in other hospitals and the administration of hypertonic saline resulted in severe iatrogenic hypernatremia. By reviewing similar cases in our hospital, we found that hyperglobulinemia/hyperlipidemia associated pseudohyponatremia was not uncommon. This case reminds us that for patients whose serum solid phase ratio is higher than normal due to various reasons, the use of indirect ion selective electrode method to determine serum sodium is prone to false low, and direct ion selective electrode method can be used to re-test blood sodium to determine whether it is true, so as to avoid iatrogenic injury to patients.

Objective To investigate the clinical application of 3D printed bolus with specific density in breast cancer radiotherapy,and to evaluate its effects on dose distribution and positioning.Methods Forty post-mastectomy patients undergoing intensity-modulated radiotherapy were randomly enrolled for 3D printed bolus(n=20)and conventional bolus(n=20),and all patients were fixed in the supine position using styrofoam.Conventional positioning was performed based on in-room lasers and body markers,with daily Catalyst HD optical surface monitoring combined with weekly CBCT verification.The absolute dose,patients'skin surface dose,surgical incision,planned field,target area doses(VCTV50Gy,VPTV50Gy)and organs-at-risk doses in patients with different boluses were recorded,and the conformity index and homogeneity index were calculated,and the setup errors using CBCT and Catalyst HD were also analyzed.Results The difference in absolute dose between different boluses was trivial,but the skin surface dose with 3D printed bolus was significantly higher than with conventional bolus[(54.83±0.44)Gyvs(54.43±0.51)Gy,P<0.05].Patients with 3D printed boluses had a higher conformity index than with conventional boluses(0.69±0.04 vs 0.65±0.02).For different boluses,there was no significant difference in VCTV50 Gy,while the VPTV50 Gy and organs-at-risk doses were lower in those with 3D printed bolus than conventional boluses(P<0.05),with heart Vmean of 9.68%±3.24%vs11.43%±3.60%.In patients with 3D printed boluses,both planned field arrangement and surgical incision affected the target doses,and the doses of the target area without an internal breast wrap was greater than those with internal breast wrap(P<0.05).When the field was not wrapped around the internal breast,the surgical incisions only affected VPTV50 Gy,and the VPTV50 Gy was greater with the transverse fusiform incision than with the oblique vertical incision(P<0.05),which were 95.58%±0.51%vs95.44%±0.71%.The optical monitoring accuracies with different boluses differed only in the left-right direction(P<0.05),with(0.08±0.57)cm and(-0.15±0.46)cm for 3D printed and conventional boluses.Conclusion Compared with conventional bolus,3D printed bolus can improve dose distribution and optical monitoring accuracy.The surgical incision and planned field arrangement under 3D-printed bolus would exert effects on target doses.