BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

Objective:To analyze the CT and MRI manifestations of hepatic angiomyolipoma (HAML) to improve the diagnostic accuracy of HAML.Methods:A retrospective analysis was conducted on the clinical data of 46 cases of HAML confirmed by tumor surgery or biopsy in Yueqing People's Hospital of Zhejiang and Rui'an People's Hospital of Zhejiang from November 2015 to June 2024. Among them, there were 20 males and 26 females, with an average age of (40±18) years. The CT and MRI manifestations of the patients were recorded, and the tumor location, size, shape, boundary, CT density, T 1-weighted imaging, T 2-weighted imaging, diffusion-weighted imaging (DWI), fat suppression sequence, and inverse phase signal were observed. Results:29 cases underwent plain CT scan combined with enhanced scan. Among them, 4 cases (13.8%) had a round shape, 22 cases (47.8%) had a nearly round shape, and 3 cases (10.3%) had an irregular shape. 26 cases (89.7%) had clear boundaries, and 3 cases (10.3%) had unclear boundaries. 5 cases (17.2%) had uniform density, and 24 cases (82.8%) had non-uniform density. The CT value of the tumor was (32±6.8) Hu. 25 cases (86.2%) contained fat tissue within the tumor. Among them, 13 cases (44.8%) were mixed type. After enhancement, the fat tissue and necrotic cystic changes did not enhance, and the soft tissue components showed varying degrees of enhancement in the arterial phase. Among them, 6 cases continued to enhance in the portal venous phase and delayed phase, showing " fast in and slow out" , and 7 cases showed decreased enhancement in the portal venous phase and delayed phase, showing " fast in and fast out" . 17 cases underwent plain MRI scan combined with enhanced scan. Among them, 12 cases were mixed type. On T 2-weighted imaging with fat suppression, it was a mixed high signal, on T 1-weighted imaging, it was an isointense/low signal or mixed low signal, and on DWI, it was a high signal, with partial signal reduction on the inverse phase. 9 cases of tumor septation showed isointense signals on T 1-weighted imaging, 7 cases showed isointense signals on T 2-weighted imaging, and 2 cases showed high signals on T 2-weighted imaging. After enhancement, the mass showed heterogeneous enhancement, with 7 cases showing " fast in and fast out" and 5 cases showing " fast in and slow out" . Conclusion:Plain CT scan shows that HAML is round or nearly round, with non-uniform low density or uniform isodensity. Plain MRI scan shows isointense or slightly high signal on T 2-weighted imaging, low signal on T 1-weighted imaging, and high signal on T 2-weighted imaging with fat suppression. After enhancement, there is significant or mild to moderate enhancement in the arterial phase, with " fast in and fast out" or " fast in and slow out" as the characteristics.

Objective To observe hierarchical differences in brain functional networks in unilateral mesial temporal lobe epilepsy(mTLE)patients with different outcomes after surgery.Methods A total of 69 unilateral mTLE patients who underwent resection of epileptogenic lesion on the affected side were retrospectively enrolled.Based on Engel classification 1 year after surgery,the patients were divided into seizure free(SF)group and non-seizure free(NSF)group.Functional connectivity gradient analysis was employed to extract principal gradient explaining the highest variance on preoperative resting-state functional MRI(rs-fMRI),then the whole-brain gradient characteristics and principal gradient values within specific functional networks were compared between groups.Results Principal gradient connected default mode network(DMN)with sensorimotor network(SMN)along a continuous axis.Compared to SF group,NSF group showed a contracted gradient range at both ends(DMN and SMN)of the functional network and weakened hierarchical differentiation,and principal gradient value of DMN was higher,while that of SMN was lower than those in SF group(both P＜0.05).Conclusion Hierarchical differences in brain functional networks in unilateral mTLE patients with different outcomes after surgery mainly present as enhanced DMN and weakened SMN in NSF ones,and the latter two might serve as important neuroimaging markers for evaluating postoperative seizure recurrence.

Objective To observe the value of machine learning(ML)models based on brain functional network features combining clinical indicators for predicting postoperative outcomes of patients with drug-resistant mesial temporal lobe epilepsy(DR-mTLE).Methods Totally 84 patients with unilateral DR-mTLE who underwent surgery were retrospectively enrolled and classified into seizure free(SF)group(n=55)and non-seizure free(NSF)group(n=29)according to one-year postoperative follow-up.Clinical data were analyzed to screen independent predictors of postoperative outcomes.Based on brain preoperative resting-state functional MRI,brain functional networks were constructed using graph theory analysis,and 587 features were extracted.Five-fold cross validation was used to divide the data into training set and test set,then the optimal brain functional network features related to postoperative outcomes of DR-mTLE patients were selected.Combining with clinically relevant independent predictors,ML models were constructed using classifiers including Gaussian process(GP),logistic regression(LR),support vector machine(SVM)and quadratic discriminant analysis(QDA),respectively,and the prediction efficacy,calibration and clinical value of each ML model were evaluated.Results Both course of disease and lesion location were clinically relevant independent predictors of postoperative outcome of DR-mTLE patients(OR=0.928,5.710,P=0.010,0.016).Four optimal brain function network features were selected,including betweenness centrality of the third zone of cerebellar vermis,degree centrality of right globus pallidus,nodal efficiency of temporal left inferior temporal gyrus and nodal clustering coefficient of left inferior parietal lobule.The average area under the curve(AUC)of GP,LR,SVM and QDA models in test set was 0.868,0.864,0.875 and 0.870,respectively.Calibration curves and decision curve analysis indicated that each ML model had good calibration and high clinical net benefit.Conclusion ML models based on brain functional network features combining with clinical indicators could be used to effectively predict postoperative outcomes in DR-mTLE patients.

Objective To explore the clinical value of inflammatory prognostic index combined with dual-source CT perfusion imaging in predicting early response of hepatocellular carcinoma(HCC)after transcatheter hepatic artery chemoembolization(TACE).Methods A total of 25 patients with HCC,who met the inclusion criteria and received initial TACE at the First Affiliated Hospital of Dali University of China from November 2022 to November 2023,were prospectively collected.CT perfusion scan was performed before TACE as well as in 30-40 days after TACE,and blood routine and blood biochemical data were collected.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to evaluate postoperative enhanced CT manifestations.Patients obtaining complete remission(CR)or partial remission(PR)were classified as effective group(n=14),and patients obtaining stable disease(SD)or progression disease(PD)were classified as ineffective group(n=11).The differences in CT perfusion imaging parameters and inflammatory parameters between the two groups were analyzed,and the predictive values of preoperative CT perfusion imaging parameters and inflammatory parameters for postoperative early response of HCC were evaluated.The cutoff value was taken at the maximum Youden index.Univariate analysis and multivariate analysis were used to analyze the effect of CT perfusion imaging parameters,inflammatory parameters and clinical features on the prognosis.The nomogram prediction model was constructed by using R software.Results The post-TACE arterial liver perfusion(ALP),hepatic perfusion index(HPI),blood flow(BF)and blood volume(BV)were significantly lower than their pre-TACE values(all P＜0.05).Afer TACE portal vein perfusion(PVP)was obviously higher than that before operation(P＜0.05).No statistically significant differences in the mean transit time(MTT),flow extraction product(FED),C-reactive protein(CRP),albumin(ALB),neutrophil/lymphocyte ratio(NLR)and inflammatory prognosis index(IPI)existed between the pre-TACE values and post-TACE values(all P＞0.05).The pre-TACE ALP,BF and FED in the effective group were significantly higher than those in the ineffective group,while the pre-TACE CRP and IPI in the effective group were remarkably lower than those in the ineffective group(P＜0.05).There were no statistically significant differences in pre-TACE PVP,HPI,MTT,BV,ALB and NLR between the effective group and the ineffective group before(all P＞0.05).In the effective group,the pre-TACE ALP,HPI,BF,BV and FED were obviously higher than their post-TACE values(all P＜0.05)preoperative PVP was significantly lower than postoperation(P＜0.05),while no statistically significant differences in MTT,CRP,ALB,NLR and IPI existed between the pre-TACE values and the post-TACE values(all P＞0.05).In the ineffective group,the pre-TACE HPI was prominently higher than the post-TACE value(P＜0.05),while no statistically significant differences in ALP,PVP,BF,BV,MTT,FED,ALB,CRP,NLR and IPI existed between the pre-TACE values and the post-TACE values(all P＞0.05).The pre-TACE ALP,BF,BV,FED,CRP and IPI had high predictive values in judging early response of HCC after TACE(all P＜0.05),the AUC values were 0.831,0.779,0.740,0.753,0.779 and 0.805 respectively,and the optimal cutoffs were 33.280 mL/100 mL min,61.860 mL/100 mL min,5.885 mL/100 mL,29.725 mL/100 mL min,30.465 mg/L,1.885 respectively.ALP combined with CRP had the highest predictive value for post-TACE early response of HCC,with an AUC of 0.968(95％CI:0.906-1.000,P＜0.05),ALP combined with IPI could significantly improve the predictive value,with an AUC of 0.961(95％CI:0.894-1.000,P＜0.05),with the sensitivity and specificity being 0.929 and 0.909 respectively.Multivariate analysis showed that pre-TACE ALP and CRP were the independent influencing factors for post-TACE early response of HCC(P＜0.05).The nomogram prediction model constructed based on the pre-TACE ALP and CRP could effectively predict the post-TACE early response of HCC,and the AUC value was 0.968(95％CI:0.908-1.000).Conclusion ALP and CRP can be used to predict the post-TACE early response of HCC,and the combination use of ALP and CRP can significantly improve the predictive value.

Objective To observe hierarchical differences in brain functional networks in unilateral mesial temporal lobe epilepsy(mTLE)patients with different outcomes after surgery.Methods A total of 69 unilateral mTLE patients who underwent resection of epileptogenic lesion on the affected side were retrospectively enrolled.Based on Engel classification 1 year after surgery,the patients were divided into seizure free(SF)group and non-seizure free(NSF)group.Functional connectivity gradient analysis was employed to extract principal gradient explaining the highest variance on preoperative resting-state functional MRI(rs-fMRI),then the whole-brain gradient characteristics and principal gradient values within specific functional networks were compared between groups.Results Principal gradient connected default mode network(DMN)with sensorimotor network(SMN)along a continuous axis.Compared to SF group,NSF group showed a contracted gradient range at both ends(DMN and SMN)of the functional network and weakened hierarchical differentiation,and principal gradient value of DMN was higher,while that of SMN was lower than those in SF group(both P＜0.05).Conclusion Hierarchical differences in brain functional networks in unilateral mTLE patients with different outcomes after surgery mainly present as enhanced DMN and weakened SMN in NSF ones,and the latter two might serve as important neuroimaging markers for evaluating postoperative seizure recurrence.

Objective To observe the value of machine learning(ML)models based on brain functional network features combining clinical indicators for predicting postoperative outcomes of patients with drug-resistant mesial temporal lobe epilepsy(DR-mTLE).Methods Totally 84 patients with unilateral DR-mTLE who underwent surgery were retrospectively enrolled and classified into seizure free(SF)group(n=55)and non-seizure free(NSF)group(n=29)according to one-year postoperative follow-up.Clinical data were analyzed to screen independent predictors of postoperative outcomes.Based on brain preoperative resting-state functional MRI,brain functional networks were constructed using graph theory analysis,and 587 features were extracted.Five-fold cross validation was used to divide the data into training set and test set,then the optimal brain functional network features related to postoperative outcomes of DR-mTLE patients were selected.Combining with clinically relevant independent predictors,ML models were constructed using classifiers including Gaussian process(GP),logistic regression(LR),support vector machine(SVM)and quadratic discriminant analysis(QDA),respectively,and the prediction efficacy,calibration and clinical value of each ML model were evaluated.Results Both course of disease and lesion location were clinically relevant independent predictors of postoperative outcome of DR-mTLE patients(OR=0.928,5.710,P=0.010,0.016).Four optimal brain function network features were selected,including betweenness centrality of the third zone of cerebellar vermis,degree centrality of right globus pallidus,nodal efficiency of temporal left inferior temporal gyrus and nodal clustering coefficient of left inferior parietal lobule.The average area under the curve(AUC)of GP,LR,SVM and QDA models in test set was 0.868,0.864,0.875 and 0.870,respectively.Calibration curves and decision curve analysis indicated that each ML model had good calibration and high clinical net benefit.Conclusion ML models based on brain functional network features combining with clinical indicators could be used to effectively predict postoperative outcomes in DR-mTLE patients.

Objective:To analyze the CT and MRI manifestations of hepatic angiomyolipoma (HAML) to improve the diagnostic accuracy of HAML.Methods:A retrospective analysis was conducted on the clinical data of 46 cases of HAML confirmed by tumor surgery or biopsy in Yueqing People's Hospital of Zhejiang and Rui'an People's Hospital of Zhejiang from November 2015 to June 2024. Among them, there were 20 males and 26 females, with an average age of (40±18) years. The CT and MRI manifestations of the patients were recorded, and the tumor location, size, shape, boundary, CT density, T 1-weighted imaging, T 2-weighted imaging, diffusion-weighted imaging (DWI), fat suppression sequence, and inverse phase signal were observed. Results:29 cases underwent plain CT scan combined with enhanced scan. Among them, 4 cases (13.8%) had a round shape, 22 cases (47.8%) had a nearly round shape, and 3 cases (10.3%) had an irregular shape. 26 cases (89.7%) had clear boundaries, and 3 cases (10.3%) had unclear boundaries. 5 cases (17.2%) had uniform density, and 24 cases (82.8%) had non-uniform density. The CT value of the tumor was (32±6.8) Hu. 25 cases (86.2%) contained fat tissue within the tumor. Among them, 13 cases (44.8%) were mixed type. After enhancement, the fat tissue and necrotic cystic changes did not enhance, and the soft tissue components showed varying degrees of enhancement in the arterial phase. Among them, 6 cases continued to enhance in the portal venous phase and delayed phase, showing " fast in and slow out" , and 7 cases showed decreased enhancement in the portal venous phase and delayed phase, showing " fast in and fast out" . 17 cases underwent plain MRI scan combined with enhanced scan. Among them, 12 cases were mixed type. On T 2-weighted imaging with fat suppression, it was a mixed high signal, on T 1-weighted imaging, it was an isointense/low signal or mixed low signal, and on DWI, it was a high signal, with partial signal reduction on the inverse phase. 9 cases of tumor septation showed isointense signals on T 1-weighted imaging, 7 cases showed isointense signals on T 2-weighted imaging, and 2 cases showed high signals on T 2-weighted imaging. After enhancement, the mass showed heterogeneous enhancement, with 7 cases showing " fast in and fast out" and 5 cases showing " fast in and slow out" . Conclusion:Plain CT scan shows that HAML is round or nearly round, with non-uniform low density or uniform isodensity. Plain MRI scan shows isointense or slightly high signal on T 2-weighted imaging, low signal on T 1-weighted imaging, and high signal on T 2-weighted imaging with fat suppression. After enhancement, there is significant or mild to moderate enhancement in the arterial phase, with " fast in and fast out" or " fast in and slow out" as the characteristics.

Objective:To explore the efficacy of long intramedullary nails versus short intramedullary nails in the treatment of AO/OTA 31-A3 intertrochanteric fractures.Methods:A retrospective analysis was conducted on 60 patients with AO/OTA 31-A3 intertrochanteric femur fractures treated between March 2019 and August 2022. The patients were randomly divided into two groups (the long nail group and the short nail group). Thirty-four patients were treated with long intramedullary nails, including 16 males and 18 females, aged 68.41±17.84 years old (range 31-96 years). Twenty-six patients were treated with short intramedullary nails, including 13 males and 13 females, aged 72.23±13.97 years old (range 31-90 years). The causes of injury, fracture classification (AO/OTA classification), intraoperative blood loss, operation time, fracture healing time, imaging indexes (fracture reduction quality, postoperative neck trunk angle, and medial support), Harris score of the hip joint at the last follow-up, one-year mortality rates and complications were compared between the two groups.Results:The follow-up time was 24.26±6.67 months in the long nail group and 24.31±5.60 months in the short nail group, and the general information of the two groups were comparable. Between the long nail and short nail group, the intraoperative blood loss was 281.47±235.28 ml vs. 121.92±84.14 ml and the operation time was 110.44±24.63 min vs. 81.15±28.54 min with significant differences ( P<0.05). While the length of hospital stay was 12.35±4.81 d vs. 10.89±4.30 d, the good rate of fracture reduction was 55.9% vs. 61.53%, the fracture healing time was 120.44±16.43 d vs. 128.07±18.33 d, the presence rate of medial support was 67.6% vs. 79.4%, and the excellent rate of Harris score was 65.4% vs. 65.4% with no significant difference between the two groups ( P>0.05). One-year mortality rates was 5.3% vs. 7.1% and complications was 11.7% vs. 15.4% with no significant difference between the two groups ( P>0.05). Conclusion:Both long intramedullary nails and short intramedullary nails are effective in the treatment of AO/OTA 31-A3 intertrochanteric femur fractures. However, surgical time and intraoperative blood loss was less in the short nail group.

Pharmacy practice in e-hospital is an innovative form that greatly enhances the accessibility,efficiency,and convenience of medical services,providing continuous health management and chronic disease drug treatment management for patients.To ensure the quality of pharmacy practice in e-hospitals,the standard formulation team for pharmacy practice in e-hospitals adhered to the principles of scientific,universal,instructive,and operability.They comb through key management content from national policy documents,domestic and international standards and regulations,and literature analysis.Combined with the actual work situation of pharmacy practice in e-hospitals,the standard is formulated through multiple rounds of opinion collection and expert verification.This paper interprets the key content of the standard,including basic requirements,service content and processes,and quality management and evaluation improvement,to provide guidance and reference for managers and pharmacists to deeply understand the standard and further enhance the quality of pharmacy practice in e-hospitals.