OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

OBJECTIVE:The optimal non-surgical therapy for chronic ankle instability remains unclear due to the continuous introduction of novel treatment methods despite the availability of several non-surgical options for improving foot and ankle function and dynamic balance in chronic ankle instability patients.This study aims to investigate the most effective non-surgical therapy options to improve foot and ankle function and dynamic balance for patients with chronic ankle instability using a network meta-analysis. METHODS:Using"CAI,exercise,and randomized controlled trial"as search terms,a literature search of PubMed,Embase,Cochrane Library,and Web of Science databases was conducted through a computer network to collect information from the databases from their inception to March 2024 on non-surgical therapies for the treatment of chronic ankle instability randomized controlled trials on foot and ankle function or dynamic balance in patients.EndNote software was utilized for literature management.RevMan 5.4 software and Cochrane Risk of Bias Assessment Tool were used to evaluate the risk of bias of the included literature.Paired meta-analysis and network meta-analysis of the outcomes such as the Foot and Ankle Ability Measure in daily living subscale score,Foot and Ankle Ability Measure in sports activities subscale score,Star Excursion Balance Test-Anterior score,Star Excursion Balance Test-Posteromedial score,Star Excursion Balance Test-Posterolateral score and Cumberland ankle instability tool score were performed using the network commands of Stata 14.0 software.The strength of evidence rating of the outcome metrics was evaluated according to the GRADE Level of Evidence and Strength of Recommendation Grading Criteria. RESULTS:Of the 22 randomized controlled trials that met the inclusion criteria,1 study was rated as low risk,8 studies were rated as medium risk,and 13 studies were rated as high risk,enrolling a total of 952 patients and 25 treatments.(1)Network meta-analysis showed that compared with the control group,Isokinetic Strength Training,Balance Training,Balance+Stroboscopic Glasses Training,Strength Training,Joint Mobilizations Training,CrossFit Training,CrossFit Training+Self-Mobilization,Wobble Board Training,National Academy of Sport Medicine corrective exercise program,Trigger Point Dry Needling,and Neuromuscular Training had different significant enhancement effects on improving foot and ankle function and dynamic balance in patients with chronic ankle instability(P<0.05).(2)Cumulative probability ranking results showed that the three treatments with the highest ranked Cumberland ankle instability tool score were Joint Mobilizations Training(88.6%)>Visual Feedback Balance Training(83.1%)>CrossFit Training+Self-Mobilization(74.8%);the three treatments with the highest ranked Star Excursion Balance Test-Anterior score were Joint Mobilizations Training(88.4%)>Isokinetic Strength Training(86.9%)>National Academy of Sport Medicine corrective exercise program(65.0%);the three treatments with the highest ranked Star Excursion Balance Test-Posteromedial score were Balance+Stroboscopic Glasses Training(87.4%)>Neuromuscular Training(74.6%)>Strength Training(68.9%);the three treatments with the highest ranked Star Excursion Balance Test-Posterolateral score were CrossFit Training+Self-Mobilization(74.6%)>Balance+Stroboscopic Glasses Training(70.0%)>Neuromuscular Training(63.7%);the three treatments with the highest ranked Foot and Ankle Ability Measure in daily living subscale score were National Academy of Sport Medicine corrective exercise program(91.9%)>Balance+Stroboscopic Glasses Training(85.6%)>Wobble Board Training(82.2%);the three treatments with the highest ranked Foot and Ankle Ability Measure in sports activities subscale score were Balance+Stroboscopic Glasses Training(93.5%)>Balance Training(86.7%)>National Academy of Sport Medicine corrective exercise program(86.4%). CONCLUSION:Non-surgical therapies can significantly improve foot and ankle function and dynamic balance in patients with chronic ankle instability.National Academy of Sport Medicine corrective exercise program had the best efficacy in improving foot and ankle daily activity function in chronic ankle instability patients;Balance+Stroboscopic Glasses Training had the best efficacy in improving foot and ankle sports function and posterior medial dynamic balance;Joint Mobilizations Training had the best efficacy in improving anterolateral dynamic balance and ankle instability condition;and CrossFit Training+Self-Mobilization had the best efficacy in improving posterior lateral dynamic balance.The strength of evidence for each outcome was low,influenced by the risk of methodological bias and risk of publication bias of the included studies.Therefore,the above conclusions need to be validated by more high-quality pilot studies.

Objective:To investigate the effect of bed board of carbon fiber for treatment combined with fixed bottom board on verification results of Portal Dosimetry(PD)dose of intensity-modulated radiation therapy(IMRT)plan of fixed field for cervical cancer.Methods:A total of 15 patients with cervical cancer who admitted to Nanjing First Hospital from January 2019 to January 2020 were retrospectively selected,and the IMRT plans of fixed field for all patients were designed.The radiation field with 180° gantry angle was selected for each case to make the corresponding PD dose verification plan,and each verification plan included two subfields:AA180_0 and AA180_1.Three types of materials were placed between the accelerator head and the electronic portal imaging device(EPID),which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,when the Clinac iX accelerator was used to conduct verification plan for each case.The γ passing rates of the subfields(AA180_0 and AA180_1)and the total field(AA180)among three kinds of conditions,which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,were compared and analyzed.Results:For the subfield AA180_0,the γ passing rates under three different material conditions were respectively(96.09±1.38)%,(90.48±2.24)%and(81.85±2.46)%.For the subfield AA180_1,the γ passing rates under the above conditions were respectively(96.05±1.06)%,(91.86±2.22)%and(86.26±2.74)%.For the total field AA180,the γ passing rates were respectively(90.78±1.40)%,(84.82±2.56)%and(78.49±3.18)%.The γ passing rates of the subfield AA180_0,subfield AA180_1,and the total field AA180 showed statistically significant differences among the three different material conditions(F=177.80,80.00,91.42,P<0.01).Compared with materials without carbon fiber,the γ passing rate of the total field AA180 of the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber significantly decreased by 12.29%.Conclusion:In the PD dose verification of IMRT for cervical cancer,the bed board with carbon fiber for treatment combined with the fixed bottom board will produce adverse effect for the verification results.The effect of the single use of bed board for treatment is relatively small.The combined use of the bed board with carbon fiber for treatment and the fixed bottom board will lead to a significant deterioration in the verification result of PD dose.

Objective To propose a novel method for verifying the isocenter in radiotherapy based on markers and conduct a preliminary test. Methods A feasibility experiment was conducted on wooden box phantom for radiotherapy resetting. Fifteen groups of displacement data were randomly generated,corresponding to the position deviations of the isocenter in the radiotherapy plan relative to the original isocenter. According to each set of displacement data,with the aid of movable lasers and a CT scanning couch,CT scanning was performed with two sets of markers (3 per set) affixed to the phantom which were corresponding to the original and treatment isocenters,respectively. In the Eclipse treatment planning system,the coordinate data of the original and treatment isocenters were manually verified,and the difference of coordinate data was calculated to obtain the actual displacement value. The treatment isocenter position was finally confirmed by comparing with the actual displacement. In addition,the study attempts to use threshold segmentation algorithm to automatically detect metal markers and obtain coordinate values of the original isocenter on patient-positioned CT images. In the wooden box experiment,the absolute value of the difference between the actual displacement value and the planned displacement value (?d) was used to represent the position accuracy of treatment isocenter,and the deviation value obtained with threshold segmentation algorithm for isocenter detection was ?s. Results The ?d in the X (left-right),Y (superior-inferior) and Z (anterior-superior) directions was (0.83±0.37) mm,0 (0,0.5) mm and (0.45±0.29) mm,respectively. The ?s in the X,Y and Z directions was (0.46±0.22) mm,0 (0,0.5) mm and (0.33±0.29) mm,respectively. The mean values of ?s in 3 directions were all lower than 2 mm,within the range of permissible clinical positioning error. Conclusion The method of automatically verifying treatment isocenter position based on markers is feasible,and the study provides a useful reference for radiotherapy resetting using CT simulator.

Objective:To investigate the effect of bed board of carbon fiber for treatment combined with fixed bottom board on verification results of Portal Dosimetry(PD)dose of intensity-modulated radiation therapy(IMRT)plan of fixed field for cervical cancer.Methods:A total of 15 patients with cervical cancer who admitted to Nanjing First Hospital from January 2019 to January 2020 were retrospectively selected,and the IMRT plans of fixed field for all patients were designed.The radiation field with 180° gantry angle was selected for each case to make the corresponding PD dose verification plan,and each verification plan included two subfields:AA180_0 and AA180_1.Three types of materials were placed between the accelerator head and the electronic portal imaging device(EPID),which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,when the Clinac iX accelerator was used to conduct verification plan for each case.The γ passing rates of the subfields(AA180_0 and AA180_1)and the total field(AA180)among three kinds of conditions,which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,were compared and analyzed.Results:For the subfield AA180_0,the γ passing rates under three different material conditions were respectively(96.09±1.38)%,(90.48±2.24)%and(81.85±2.46)%.For the subfield AA180_1,the γ passing rates under the above conditions were respectively(96.05±1.06)%,(91.86±2.22)%and(86.26±2.74)%.For the total field AA180,the γ passing rates were respectively(90.78±1.40)%,(84.82±2.56)%and(78.49±3.18)%.The γ passing rates of the subfield AA180_0,subfield AA180_1,and the total field AA180 showed statistically significant differences among the three different material conditions(F=177.80,80.00,91.42,P<0.01).Compared with materials without carbon fiber,the γ passing rate of the total field AA180 of the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber significantly decreased by 12.29%.Conclusion:In the PD dose verification of IMRT for cervical cancer,the bed board with carbon fiber for treatment combined with the fixed bottom board will produce adverse effect for the verification results.The effect of the single use of bed board for treatment is relatively small.The combined use of the bed board with carbon fiber for treatment and the fixed bottom board will lead to a significant deterioration in the verification result of PD dose.

Objective To propose a novel method for verifying the isocenter in radiotherapy based on markers and conduct a preliminary test. Methods A feasibility experiment was conducted on wooden box phantom for radiotherapy resetting. Fifteen groups of displacement data were randomly generated,corresponding to the position deviations of the isocenter in the radiotherapy plan relative to the original isocenter. According to each set of displacement data,with the aid of movable lasers and a CT scanning couch,CT scanning was performed with two sets of markers (3 per set) affixed to the phantom which were corresponding to the original and treatment isocenters,respectively. In the Eclipse treatment planning system,the coordinate data of the original and treatment isocenters were manually verified,and the difference of coordinate data was calculated to obtain the actual displacement value. The treatment isocenter position was finally confirmed by comparing with the actual displacement. In addition,the study attempts to use threshold segmentation algorithm to automatically detect metal markers and obtain coordinate values of the original isocenter on patient-positioned CT images. In the wooden box experiment,the absolute value of the difference between the actual displacement value and the planned displacement value (?d) was used to represent the position accuracy of treatment isocenter,and the deviation value obtained with threshold segmentation algorithm for isocenter detection was ?s. Results The ?d in the X (left-right),Y (superior-inferior) and Z (anterior-superior) directions was (0.83±0.37) mm,0 (0,0.5) mm and (0.45±0.29) mm,respectively. The ?s in the X,Y and Z directions was (0.46±0.22) mm,0 (0,0.5) mm and (0.33±0.29) mm,respectively. The mean values of ?s in 3 directions were all lower than 2 mm,within the range of permissible clinical positioning error. Conclusion The method of automatically verifying treatment isocenter position based on markers is feasible,and the study provides a useful reference for radiotherapy resetting using CT simulator.

Objective:To analyze the risk factors for infection after surgery for complex kidney stones and to investigate their correlation with the expressions of microRNA (miRNA)-451 and miRNA-218, as well as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.Methods:A total of 213 patients with complex kidney stones who were admitted to Ningbo Fourth Hospital from March 2021 to March 2024 were included in this study. All patients underwent percutaneous nephrolithotomy (PCNL), and the occurrence of postoperative infections was recorded. The expression levels of serum miRNA-145 and miRNA-218 were measured using quantitative real-time PCR (qRT-PCR), while the expression of PI3K and Akt proteins was determined using Western blot assay. Multivariate logistic regression was performed to analyze the risk factors associated with infection after surgery for complex kidney stones. The expression levels of serum miRNA-145 and miRNA-218, as well as the grayscale values of PI3K and Akt proteins, were compared between the infection and non-infection groups. Pearson correlation analysis was conducted to assess the correlation between the expression of miRNA-145, miRNA-218, PI3K, and Akt and the occurrence of postoperative infections.Results:Among the 213 patients with complex kidney stones, 46 (21.60%) developed infections after PCNL, while 167 (78.40%) did not. There were no statistically significant differences between the two groups in terms of sex, age, history of hypertension, history of coronary heart disease, and history of smoking (all P > 0.05). The proportion of patients in the infection group with stone diameters ≥ 3 cm was higher than that in the non-infection group [78.26% (36/46) vs. 47.31% (79/167)]. The proportion of patients with diabetes in the infection group was higher than that in the non-infection group [30.43% (14/46) vs. 10.79% (18/167)]. Moreover, the incidence of moderate to severe hydronephrosis in the infection group was higher than that in the non-infection group [ 89.13% (41/46) vs. 68.86% (115/167)]. The proportion of patients with a surgical duration of ≥ 60 minutes in the infection group was higher than that in the non-infection group [86.96% (40/46) vs. 61.68% (103/167)]. Additionally, the proportion of patients in the infection group with a duration of postoperative urinary catheterization of ≥ 7 days was significantly higher than that in the non-infection group [69.57% (32/46) vs. 23.95% (40/167)]. The differences in stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days between the two groups were statistically significant ( χ2 = 13.91, 10.91, 7.55, 10.44, 33.53, all P < 0.05). Factors such as stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days were identified as independent risk factors for infection after surgery for complex kidney stones ( OR = 7.192, 4.870, 5.089, 12.988, 9.007). In the infection group, the relative expression levels of serum miRNA-145 and miRNA-218 were (1.37 ± 0.38) and (0.76 ± 0.21), respectively, which were significantly lower than those in the non-infection group [(2.86 ± 0.62), (1.97 ± 0.38), t = 15.50, 20.71, both P < 0.001]. In the infection group, the grayscale values of PI3K protein expression and Akt protein expression were (1.23 ± 0.31) and (0.98 ± 0.23), respectively, which were significantly higher than those in the non-infection group [(0.68 ± 0.20), (0.42 ± 0.12), t = 14.49, 22.36, both P < 0.001]. Pearson correlation analysis revealed that the expressions of miRNA-145 and miRNA-218 were negatively correlated with postoperative infections, while the expressions of PI3K and Akt were positively correlated with postoperative infection ( r = -0.57, -0.48, 0.62, 0.59, all P < 0.001). Conclusions:Postoperative infection in complex kidney stones is influenced by multiple factors, among which stone diameter, presence of diabetes, degree of hydronephrosis, surgical duration, and duration of postoperative urinary catheterization are independent risk factors. Additionally, patients with postoperative infection exhibit low expression levels of miRNA-145 and miRNA-218, while PI3K and Akt proteins show high expression levels.

With the latest development of information and communication technology, mobile applications for health care have attracted much attention to help cancer patients better manage their diseases. Digital therapeutics is an evidence-based intervention driven by high-quality software programs that prevent, manage, or treat medical disorders or diseases. This paper summarizes the origin, concept and characteristics of digital therapeutics and the application form, effect, challenge and opportunity of symptom management in cancer patients, in order to provide reference for the scientific and efficient application of Digital therapeutics to cancer patients.

Objective To investigate the current status of adverse drug reaction(ADR)monitoring in medical institu-tions under China's pharmacovigilance framework in Guangdong Province,and to propose evidence-based strategies for enhancing institutional monitoring capabilities.Methods A cross-sectional survey was conducted using a structured questionnaire devel-oped in alignment with national regulatory requirements and expert consensus.Data were collected from 65 medical institutions,including general hospitals,traditional Chinese medicine hospitals,and maternal/children's hospitals,across 21 prefecture-level cities in Guangdong.Descriptive and comparative analyses were performed to evaluate institutional practices.Results All 65 in-stitutions submitted valid responses.Among them,63(96.9％)had established standardized ADR reporting protocols,with 93.8％(61/65)delegating oversight to pharmacy departments.ADR data were predominantly collected via institutional informa-tion systems(67.7％,44/65),though these systems focused on passive reporting and basic data aggregation,lacking functional-ities for active signal detection or risk alert mechanisms.Significant disparities(P＜0.05)were observed across hospitals of dif-ferent tiers in reporting modalities,system sophistication,analytical frequency,and early warning implementation.Notably,mo-nitoring practices for conditionally approved drugs(e.g.,emergency-authorized therapeutics)exhibited systemic deficiencies.Conclusions To address these gaps,the following measures are recommended:Accelerating the adoption of intelligent monito-ring systems to enable real-time ADR detection and predictive analytics;Implementing tiered resource allocation policies to ensure equitable capability development;Establishing specialized protocols for high-risk pharmaceuticals,particularly conditionally ap-proved and fast-tracked drugs;Strengthening interdisciplinary training programs to improve pharmacovigilance literacy among healthcare practitioners.These interventions aim to foster a proactive risk management culture and advance patient safety within China's evolving healthcare landscape.