Ischemic cholangiopathy （IC） is a severe clinical condition resulting from blood supply impairment in bile ducts， and its etiology includes vascular causes and non-vascular factors. The pathogenesis of IC mainly involves microcirculatory disturbance of the peribiliary blood plexus and biliary epithelial necrosis and fibrosis induced by ischemia-reperfusion injury. The clinical manifestations of IC are highly heterogeneous. The typical symptoms include jaundice， abdominal pain， and cholangitis， while non-specific symptoms， such as fatigue and fever， often cause delays in diagnosis. The diagnosis of IC mainly relies on radiological examination for identifying characteristic stenosis and microcirculatory disturbance， assisted by cholestasis biomarkers including alkaline phosphatase and gamma-glutamyl transferase. Therapeutic strategies include conventional pharmacotherapy， endoscopic intervention， and innovative techniques. Prognostic evaluation emphasizes the dynamic monitoring of alkaline phosphatase and bilirubin and classification based on radiological examination， and long-term management requires individualized monitoring regimens to prevent complications.

Hepatic angiosarcoma is a rare,highly malignant tumor originating from liver blood vessels or lymphatic vessels.Its clinical manifestations and imaging examinations are not specific,and pathological biopsy is needed to confirm the diagnosis.This article reports a 47-year-old male patient with hepatic angiosarcoma,who has clinical manifestations of abdominal pain,jaundice,and disseminated intravascular coagulation.The CT and MRI findings of this patient are similar to hepatic sinusoidal obstruction syndrome.Relevant literature on hepatic angiosarcoma in recent years was reviewed.The manifestations,diagnosis and treatment of hepatic angiosarcoma were summarized to improve clinicians'understanding of the disease.

Hepatic angiosarcoma is a rare,highly malignant tumor originating from liver blood vessels or lymphatic vessels.Its clinical manifestations and imaging examinations are not specific,and pathological biopsy is needed to confirm the diagnosis.This article reports a 47-year-old male patient with hepatic angiosarcoma,who has clinical manifestations of abdominal pain,jaundice,and disseminated intravascular coagulation.The CT and MRI findings of this patient are similar to hepatic sinusoidal obstruction syndrome.Relevant literature on hepatic angiosarcoma in recent years was reviewed.The manifestations,diagnosis and treatment of hepatic angiosarcoma were summarized to improve clinicians'understanding of the disease.

Objective:To understand the current clinical practice status of evidence on blood glucose management in ICU patients with insulin intravenous infusion, analyze barriers and formulate action strategies, so as to provide reference for the translation of evidence into clinical practice.Methods:Based on the clinical evidence application model of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center, clinical nursing problems were identified, literature search, evaluating and summarizing evidence were carried out, and review indicators and methods were developed. From July to August 2023, convenience sampling was used to select 42 nurses and 80 patients with insulin intravenous infusion from the comprehensive ICU of Wuxi Second People's Hospital as participants for baseline review. Barriers were analyzed and change strategies were developed based on baseline review results.Results:A total of 16 pieces of evidence were introduced regarding blood glucose management in ICU patients with insulin intravenous infusion. Nineteen review indicators were formulated, of which 13 had a compliance rate of less than 60%. Analysis identified 18 barriers and 13 facilitators. Sixteen change strategies were developed based on barriers and facilitators.Conclusions:There is still a significant gap between the evidence of ICU insulin intravenous infusion blood glucose management and clinical practice. Evidence-based practice programs should be constructed based on intervention strategies to effectively promote the application of evidence in clinical practice.

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

To investigate the cellular target selectivity of small molecules targeting thioredoxin reductase 1, we reported the construction and functional research of a stable TrxR1 gene (encode thioredoxin reductase 1) knockout HCT-116 cell line. We designed and selected TrxR1 knockout sites according to the TrxR1 gene sequence and CRISPR/Cas9 target designing principles. SgRNA oligos based on the selected TrxR1 knockout sites were obtained. Next, we constructed knockout plasmid by cloning the sgRNA into the pCasCMV-Puro-U6 vector. After transfection of the plasmid into HCT-116 cells, TrxR1 knockout HCT-116 cells were selected using puromycin resistance. The TrxR1 knockout efficiency was identified and verified by DNA sequencing, immunoblotting, TRFS-green fluorescent probe, and cellular TrxR1 enzyme activity detection. Finally, the correlation between TrxR1 expression and cellular effects of drugs specifically targeting TrxR1 was investigated by CCK-8 assay. The results demonstrated that the knockout plasmid expressing the sgRNA effectively knocked-out TrxR1 gene within HCT-116 cells, and no expression of TrxR1 protein could be observed in stable TrxR1 knockout HCT-116 (HCT116-TrxR1-KO) cells. The TrxR1-targeting inhibitor auranofin did not show any inhibitory activity against either cellular TrxR1 enzyme activity or cell proliferation. Based on these results, we conclude that a stable TrxR1 gene knockout HCT-116 cell line was obtained through CRISPR/Cas9 techniques, which may facilitate investigating the role of TrxR1 in various diseases.
CRISPR-Cas Systems/genetics* ; Gene Editing ; Gene Knockout Techniques ; HCT116 Cells ; Humans ; RNA, Guide/metabolism*

The portal vein system is the main blood supply system of the liver, and damage to the portal vein system caused by cirrhotic portal hypertension may be the second hit to the liver. Protection of the portal vein will ensure sufficient blood supply of the liver and maintain its structure and function. Starting from the physiological structure and pathological changes of the portal vein, this article elaborates on the adverse effect of portal hypertension on the liver from the three new perspectives of thrombosis of the portal system, abnormal angiogenesis, and disturbance of hepatic sinusoidal homeostasis. It is suggested to change the current status of passive treatment of portal hypertension complications and encourage scientific exploration to reduce portal hypertension from multiple angles as early as possible to avoid repeated endoscopic devascularization of collateral circulation and splenectomy, so as to reduce various factors for the damage of the portal system, maintain the homeostasis of the portal system, and protect the liver.

Objective:To develop an diagnostic equipment with artificial intelligence (AI) real-time assistance under endoscopy (endoscopic AI equipment) for the detection of gastrointestinal protruding lesions, and to evaluate its performance and safety.Methods:From January to December 2017, at Endoscopy Center of West China Hospital, Sichuan University, the endoscopic images of individuals who underwent routine gastroscopy and colonoscopy were collected. The model was established based on convolutional neural network and the endoscopic AI equipment was developed. From June to December 2019, a prospective, single center, blinded and parallel controlled study was conducted to compare the differences in evaluation of protruding lesions of the same patient under gastroscopy or colonoscopy between endoscopist and the endoscopic AI equipment and to evaluated the impact of lesion size (lesions <5 mm and ≥5 mm) on the detection of endoscopic AI equipment. The main outcome measure was the detection time difference in reporting the protruding lesion between endoscopic AI equipment and endoscopist; and the secondary indicator was the accuracy of endoscopic AI equipment in detecting the protruding lesion. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:A total of 71 582 white light endoscopy images were used for endoscopic AI equipment training, which included 41 376 images of protruding lesions. The endoscopic AI equipment was successfully developed and obtained the registration certificate of medical devices of the People′s Republic of China (Sichuan Instrument Standard, 20202060049). The accuracy, sensitivity, and specificity of endoscopic AI equipment in detecting protruding lesions were 96.4%, 95.1% and 92.8%, respectively. The detection time of each protruding lesions under gastroscopy of endoscopic AI equipment was 1.524 seconds faster than that of endoscopist; but the detection time of each protruding lesions under colonoscopy was 0.070 seconds slower than that of endoscopist, and the differences were statistically significant ( Z=-5.505 and -4.394, both P<0.01). The detection time of each protruding lesions under gastroscopy or colonoscopy of endoscopic AI equipment was not inferior to that of endoscopist. The detection rate of protruding lesions under colonoscopy by endoscopic AI equipment was 89.9% (249/277) and the sensitivity was 89.9%; the detection rate of protruding lesions under colonoscopy was 87.0% (450/517) and the sensitivity was 86.9%. There were no statistically significant differences in the detection time difference, sensitivity and missed diagnostic rate between the lesions <5 mm and ≥5 mm detected by endoscopic AI equipment under gastroscopy (all P>0.05). The sensitivity of endoscopic AI equipment in detecting the lesions ≥5 mm under colonoscopy was higher than that of lesions <5 mm (96.8% vs. 84.9%), and the missed diagnostic rate was lower than that of lesions <5 mm (3.2%, 3/94 vs. 15.1%, 61/405), and the differences were statistically significant ( χ2=9.615 and 9.612, both P=0.002). No adverse events on patients and medical staffs occurred, and there were no cases of equipment electricity leakage, and abnormal work reported during the use of endoscopic AI equipment. Conclusions:The endoscopic AI equipment can report the protruding lesions simultaneously with endoscopists, and the accuracy is close to 90%, which is expected to be a practical assistant for endoscopists to avoid missed detection of protruding lesions.

Objective To establish a preoperative nomogram model in predicting microvascular invasion (MVI) and to test its predictive effectiveness in hepatocellular carcinoma (HCC).Methods This retrospective study was conducted on 798 patients with HCC,including 690 males and 108 females,aged (49.8± 10.9) years old who underwent curative hepatectomy in the Guangxi Medical University Affiliated Tumor Hospital between January 2014 and December 2017 were retrospectively analyzed.The patients were divided into the model group (n=579) and the validation group (n=219) according to the periods of the operation time.Independent risk factors of MVI were identified by univariate and multivariate logistic regression analysis in the model group,and a nomogram model was established according to the independent risk factors.The accuracy of the nomogram model in predicting MVI was detected in the two groups by the computer consistency coefficient (C-index) and calibration graph method.The predictive value was evaluated by receiver operating characteristic curve.Results Histopathological diagnosis revealed 278 patients with MVI and no MVI in the 301 patients of HCC out of the 579 patients in the model group.In the validation group,there were 119 patients with MVI and 100 patients with no MVI out of the 219 patients.Total bilirubin ＞15 μmol/L(OR=1.519,95％ CI:1.041 ～ 2.217),alkaline phosphatase ＞60 U/L(OR =1.681,95％CI:1.059～2.670),alpha-fetoprotein ＞200 ng/L (OR=2.192,95％CI:1.531 ～3.134) and tumor maximum diameter (OR =1.120,95％CI:1.057 ～ 1.187) were the independent risk factors of MVI on multivariate analysis.After establishment of the nomogram model using the independent risk factors,the C-indexes were 0.680 and 0.773 respectively in the model group and the validation group.In the calibration graph,the standard curve properly fitted with the predicting calibration curve.The predicted value of MVI obtained was in good agreement with the observed value.The ROC curve analysis nomogram model predicted the low performance of MVI.Conclusion The nomogram model in predicting MVI in patients with HCC was successfully established.The model offered certain guiding significance in the clinical treatment of HCC.