1.The Regulatory Role of Glucose Transporter 1 on the Function of Human Umbilical Vein Endothelial Cells Under Ischemia-hypoxic Conditions
Meiling LI ; Siqi GAO ; Zhefu LIU ; Huanyan LIAO ; Fanmao LIU ; Wenhao XIA ; Jun GUO ; Yan LI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):444-455
Abstract: ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 (GLUT1) on the proliferation, migration, adhesion, and angiogenesis of human umbilical vein endothelial cells (HUVECs) under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment (1% O2, 5% CO2, 94% N2). The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability, proliferation capacity, and examining the expression changes of GLUT1, HIF-1α, and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further, GLUT1 was overexpressed using plasmid transfection and the proliferation, migration, adhesion, and angiogenic capabilities of HUVECs were evaluated through scratch assays, cell adhesion assays, and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy,and oxygen consumption rate (OCR) was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions, the ischemia-hypoxic environment significantly inhibited the proliferation, cell viability, migration, and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1, HIF-1α and VEGFA proteins were also markedly reduced. However, when GLUT1 expression was upregulated, the migration, adhesion, and angiogenic capabilities of HUVECs were significantly improved, and the protein expression levels of HIF-1α, VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage, while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions, potentially through modulating cellular energy metabolism and signal transduction pathways, thereby affecting cell proliferation, migration, adhesion, and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.
2.Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
Ming XU ; Wenhao ZHU ; Siyu HOU ; Hongzhi XU ; Jingwen XIA ; Liyu LIN ; Hao FU ; Mingyu YOU ; Jiafeng WANG ; Zhi XIE ; Xiaohong WEN ; Yingwei WANG
Chinese Medical Journal 2025;138(17):2170-2179
BACKGROUND:
Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.
METHODS:
PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.
RESULTS:
PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.
CONCLUSIONS:
The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.
TRIAL REGISTRATION
ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult
;
Aged
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Female
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Humans
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Male
;
Middle Aged
;
Algorithms
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Lung Diseases/etiology*
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Machine Learning
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Neurosurgical Procedures/adverse effects*
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Postoperative Complications/diagnosis*
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Risk Factors
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ROC Curve
3.Evaluating the effectiveness of immediate vs. elective thoracic endovascular aortic repair for blunt thoracic aortic injury.
Zhaohui HUA ; Baoning ZHOU ; Wenhao XUE ; Zhibin ZHOU ; Jintao SHAN ; Lei XIA ; Yunpeng LUO ; Yiming CHAI ; Zhen LI
Chinese Journal of Traumatology 2025;28(1):22-28
PURPOSE:
To evaluate the relationship between the timing of thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injury (BTAI) and prognosis.
METHODS:
This is a single-center retrospective cohort study. Patients who received TEVAR for BTAI at our institution from October 2016 to September 2023 were divided into 2 categories depending on the injury severity score (ISS) (≤ 25 vs. > 25) and when the TEVAR was performed for BTAI (within 24 h vs. after 24 h), respectively. The analysis included all patients who received TEVAR treatment after being diagnosed with BTAI through whole-body CT angiography. Patients treated with open repair and non-operative management were excluded. After propensity-score matching for various factors, outcomes during hospitalization and follow-up were compared. These factors included demographics, comorbidities, concomitant injuries, cause and location of aortic injury, Glasgow coma scale score, society for vascular surgery grading, hemoglobin concentration, creatinine concentration, shock, systolic blood pressure, and heart rate at admission. The comparison was conducted using SPSS 26 software. Continuous variables were presented as either the mean ± standard deviation or median (Q1, Q3), and were compared using either the t-test or the Mann-Whitney U test. Categorical variables were expressed as n (%), and comparisons were made between the 2 groups using the χ2 test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05.
RESULTS:
In total, 110 patients were involved in the study, with 65 (59.1%) patients having ISS scores > 25 and 32 (29.1%) receiving immediate TEVAR. The perioperative overall mortality rate in the group with ISS > 25 was significantly higher than that in the group with ISS ≤ 25 (11 (16.9%) vs. 2 (4.4%), p < 0.001). Upon admission, the elective group exhibited a notably higher Glasgow coma scale score (median (Q1, Q3)) compared to the immediate group (15 (12, 15) vs. 13.5 (9, 15), p = 0.039), while the creatinine concentration (median (Q1, Q3)) at admission was significantly higher in the immediate group (90.5 (63.8, 144.0) vs. 71.5 (58.3, 80.8), p = 0.012). The final sample included 52 matched patients. Complications occurred significantly less frequently in the elective group compared to the immediate group (16 (50.0%) vs. 3 (10.0%), p < 0.001). Single-factor analysis of variance showed that complications in hospitalized patients were significantly associated with immediate TEVAR as the sole independent risk factor (odds ratio: 9.000, 95% confidence interval: 2.266-35.752, p = 0.002).
CONCLUSION
In this propensity-score matched analysis of patients undergoing TEVAR for BTAI, elective TEVAR was significantly associated with a lower risk of complication rates. In this study using propensity-score matching, patients who underwent elective TEVAR for BTAI had lower complication rates than immediate TEVAR.
Humans
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Retrospective Studies
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Male
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Aorta, Thoracic/surgery*
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Female
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Endovascular Procedures/methods*
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Wounds, Nonpenetrating/mortality*
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Middle Aged
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Adult
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Aged
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Injury Severity Score
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Elective Surgical Procedures
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Time Factors
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Treatment Outcome
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Endovascular Aneurysm Repair
4.Short-term outcomes of transcatheter pulmonary valve replacement with Venus-P valve in patients with moderate-to-severe pulmonary regurgitation and right ventricular systolic dysfunction.
Haiyue XIE ; Wenhao ZHU ; Zhiyuan XIA ; Gejun ZHANG
Journal of Zhejiang University. Medical sciences 2025;54(3):390-398
OBJECTIVES:
To evaluate the short-term outcomes of transcatheter pulmonary valve replacement (TPVR) using the Venus-P valve in patients with moderate-to-severe pulmonary regurgitation and right ventricular systolic dysfunction (RVSD) following surgical repair of complex congenital heart disease.
METHODS:
A retrospective analysis was conducted on patients undergoing Venus-P valve implantation (TPVR group, n=28) or surgical pulmonary valve replacement (SPVR group, n=19) at Fuwai Hospital between February 2014 and February 2024. All patients had moderate-to-severe pulmonary regurgitation with right ventricular ejection fraction less than 45% preoperatively. Postoperative pulmonary valve function and ventricular parameters were assessed at discharge and during a 6-month follow-up.
RESULTS:
All procedures were successfully completed with no early mortality. At 6 months, the TPVR group demonstrated significantly lower pulmonary valve transvalvular pressure gradients compared to the SPVR group (P<0.05). Both groups exhibited significant improvements from baseline in New York Heart Association (NYHA) functional class, biventricular ejection fractions, and right ventricular end-diastolic volume index (all P<0.05). The reduction in right ventricular end-diastolic diameter differed between the two groups (P<0.01). However, multivariable analysis revealed no association between this difference and surgical approach (β=4.4, P>0.05). In the TPVR group, QRS duration was significantly shortened postoperatively (P<0.01), with improvements in left ventricular end-diastolic volume index and cardiac index (both P<0.01), but these improvements did not differ significantly from the SPVR group (all P>0.05). During the follow-up, one patient in each group developed infective endocarditis within 1-month post-procedure; both were successfully treated with antibiotics. No other major complications were observed.
CONCLUSIONS
For patients with moderate-to-severe pulmonary regurgitation and RVSD, TPVR using the Venus-P valve effectively improves short-term pulmonary valve function and ventricular performance with a favorable safety profile, demonstrating potential as a minimally invasive alternative to SPVR .
Humans
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Pulmonary Valve Insufficiency/surgery*
;
Retrospective Studies
;
Pulmonary Valve/surgery*
;
Heart Valve Prosthesis Implantation/methods*
;
Ventricular Dysfunction, Right/physiopathology*
;
Treatment Outcome
;
Female
;
Male
;
Child
;
Adult
;
Heart Valve Prosthesis
;
Adolescent
;
Cardiac Catheterization/methods*
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Child, Preschool
5.Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis
Jintao SHAN ; Zhaohui HUA ; Peng XU ; Hui CAO ; Zhouyang JIAO ; Likun SUN ; Shirui LIU ; Lei XIA ; Wenhao XUE ; Zhen LI
Chinese Journal of Surgery 2024;62(3):229-234
Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.
6.Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis
Jintao SHAN ; Zhaohui HUA ; Peng XU ; Hui CAO ; Zhouyang JIAO ; Likun SUN ; Shirui LIU ; Lei XIA ; Wenhao XUE ; Zhen LI
Chinese Journal of Surgery 2024;62(3):229-234
Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.
7.Identification of spontaneous age-related cataract in Microtus fortis
Tianqiong HE ; Junkang ZHOU ; Yixin WEN ; Qian LIU ; Wenling ZHI ; Wenhao YANG ; Shuangyan HE ; Lingxuan OUYANG ; Xiaobo XIA ; Zhijun ZHOU
Journal of Central South University(Medical Sciences) 2024;49(4):553-561
Objective:Age-related cataract is the most common type of adult cataract and a leading cause of blindness.Currently,there are few reports on the establishment of animal models for age-related cataract.During the experimental breeding of Microtus fortis(M.fortis),we first observed that M.fortis aged 12 to 15 months could naturally develop cataracts.This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M.fortis. Methods:The 12-month-old healthy M.fortis were served as a control group and 12-month-old cataractous M.fortis were served as an experimental group.The lens transparency was observed using the slit-lamp biomicroscope.Hematoxylin and eosin staining was used to detect pathological changes in the lens.Biochemical detection methods were applied to detect blood routine,blood glucose levels,the serum activities of superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in both groups.Finally,real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. Results:Compared with the control group,the lens of cataract M.fortis showed severely visible opacity,the structure of lens was destroyed seriously,and some pathological damage,such as swelling,degeneration/necrosis,calcification,hyperplasia,and fiber liquefaction were found in lens epithelial cells(LECs).The fibrous structure was disorganized and irregularly distributed with morgagnian globules(MGs)aggregated in the degenerated lens fibers.There was no statistically significant difference in blood glucose levels between the experimental and control groups(P>0.05).However,white blood cell(WBC)count(P<0.05),lymphocyte count(P<0.01),and lymphocyte ratio(P<0.05)were significantly decreased,while neutrophil percentage(P<0.05)and monocyte ratio(P<0.01)were significantly increased.The serum activities of SOD and GSH-Px(both P<0.05)were both reduced.The mRNAs of cataract-related genes,including CRYAA,CRYBA1,CRYBB3,Bsfp1,GJA3,CRYBA2,MIP,HspB1,DNase2B,and GJA8,were significantly downregultaed in the lenses of the experimental group(all P<0.05). Conclusion:There are significant differences in lens pathological changes,peroxidase levels,and cataract-related gene expression between cataract and healthy M.fortis.The developed cataract spontaneously in M.fortis is closely related to age,the cataract M.fortis might be an ideal animal model for the research of age-related cataract.
8.Association of Estimated Glucose Disposal Rate With the Stenosis Severity of Coronary Artery Disease: A Cross-sectional Study
Yubin WU ; Zhiteng CHEN ; Maoxiong WU ; Wenhao LIU ; Qian CHEN ; Shiyi ZHOU ; Yan-xin CHEN ; Min XIA
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):136-145
ObjectiveTo investigate the association between estimated glucose disposal rate (eGDR) and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients (mean age: 62(53-68) years) who underwent coronary angiography for suspected coronary artery disease (53.9% were male). Insulin resistance level (IR) was calculated according to eGDR formula: eGDR = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [hypertension (yes = 1 / no = 0), HbA1c = HbA1c (%)]. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels: no-obstructive CAD group (all coronary stenosis were<50%, n=704), Single-vessel CAD group (only one involved major coronary artery stenosis≥50%, n=205), Multi-vessel CAD group (two or more involved major coronary arteries stenosis≥50%, n=349); Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic (ROC) curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). In multivariate logistic regression models, individuals with the lowest quantile of eGDR (T1) were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR (T3) (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD (P-nonlinear>0.05). In non-diabetic patients, compared with the reference group (T3), the T1 group had a significantly increased risk of CAD (OR: 1.42; 95% CI: 1.00~2.01; P<0.05) and multi-vessel CAD (OR: 1.86; 95%CI: 1.21~2.86; P<0.05). No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis, when eGDR was added to traditional model for CAD, significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR, as a non-insulin measure to assess IR, could be a valuable indicator of CAD severity for population.
9.Management and prognosis of spontaneous splenorenal shunt in liver cirrhosis
Wenhao XUE ; Lei XIA ; Shirui LIU ; Yunpeng LUO ; Baoning ZHOU ; Jintao SHAN ; Shichang DU ; Yiming CHAI ; Zhen LI
Chinese Journal of General Surgery 2024;39(5):344-349
Objective:To analyze the clinical characteristics of patients with spontaneous splenorenal shunt (SSRS) in liver cirrhosis, and to compare the effects and prognosis of different treatments.Methods:The data of cirrhotic patients with SSRS at the First Affiliated Hospital of Zhengzhou University between 2016-2022 were retrospectively analyzed.Patients were divided into Group A receiving conservative treatment, Group B by simple embolization, Group C undergoing TIPS combined with embolization, and Group D given liver transplantation. Life status, liver function changes, incidences of adverse events, and survival between groups were compared.Results:SSRS diameter was positively correlated with blood ammonia ( R=0.478) and negatively correlated with portal vein diameter ( R=-0.301). SSRS diameter is a protective factor for gastrointestinal hemorrhage and ascites and a risk factor for hepatic encephalopathy; Blood ammonia decreased and prothrombin time prolonged after treatment in group A ( P<0.05), blood ammonia decreased and albumin increased in group B ( P<0.05). Hemoglobin and bilirubin increased in group C ( P<0.05), blood ammonia and bilirubin decreased and platelets and albumin increased in group D ( P<0.05); Survival analysis showed that the prognosis of groups A and C was related to liver function, and the survival rate of group D was the highest of all ( P<0.05). Conclusions:SSRS embolization is safe and effective, and liver transplantation improves patient survival. Individualized treatment should be selected based on patient symptoms, liver function, and shunt diameter.
10.Application and Considerations on"Internet+"Healthcare in Outpatient Special Disease Management
Mingge XIA ; Qi LIU ; Luwei ZHU ; Wenhao WANG ; Min LI
Journal of Medical Informatics 2023;44(12):34-39
Purpose/Significance According to the experience of Sichuan Provincial People's Hospital in implementing the internet outpatient special disease services,the paper puts forward some thoughts and suggestions,so as to provide references for further promoting the application of"internet+"healthcare in outpatient special disease management.Method/Process Based on the operational data of the internet hospital,the paper analyzes the operation status and existing problems of internet outpatient special disease services from the aspects of patient visits,departments,and complaints feedback.Result/Conclusion At present,there are problems such as low utiliza-tion rate of internet outpatient special disease services,poor prescription circulation,and untimely drug delivery.It is necessary to opti-mize online service for key groups,establish the regional electronic prescription sharing platform,improve the drug distribution system,strengthen cooperation between medical institutions at different levels,and build a regional outpatient special disease management system.

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