Objective To investigate the influencing factors for acute multiple vessels occlusion(MVO)and its impact on the prognosis of patients with anterior circulation acute large vessel occlusion stroke(ALVOS)who achieved successful recanalization after endovascular treatment(EVT).Methods Patients with anterior circulation ALVOS who received successful EVT at the Yijishan Hospital of Wannan Medical College between July 2015 and April 2023 were retrospectively analyzed.Baseline data,including age,sex,onset-to-puncture time(OTP),onset-to-recanalization time(OTR),medical history(including atrial fibrillation,diabetes,hypertension),alcohol and smoking history,admission blood pressure(systolic and diastolic),Alberta stroke program early CT score(ASPECTS),National Institutes of Health stroke scale(NIHSS)score,trial of Org 10172 in acute stroke treatment(TOAST)classification(atherosclerotic type,cardioembolic type,and other etiology types),and 90-day modified Rankin scale(mRS)score were collected.Collateral circulation was assessed based on the degree of contrast agent reflux observed in the occluded arterial supply area during delayed DSA,and patients were classified into poor and good collateral circulation groups.Malignant cerebral edema was defined as a midline shift of ≥5 mm on the follow-up CT scan performed on day 3 post-surgery.The primary endpoint(efficacy indicator)was the 90-day mRS score,with mRS score≤ 2 considered as a good prognosis and mRS score＞2 considered as a poor prognosis.The secondary endpoint(safety indicator)was the 90-day mortality rate.All patients were divided into MVO and non-MVO groups based on whether they had single or multiple intracranial vessel occlusions.Acute MVO was defined as the detection of acute occlusion of other large or medium vessels,in addition to the main vessels(internal carotid artery or M1/M2 segments of the middle crebral artery[MCA]),in CT angiography,MR angiography,or DSA,resulting in ischemia in brain regions distinct from the main occlusion area.Factors that showed statistically significant differences in univariate analysis were further analyzed using multivariate Logistic regression to identify the risk factors for the occurrence of acute MVO and the factors associated with the prognosis of ALVOS patients.Results A total of 846 patients with ALVOS were included,with ages ranging from 26 to 94 years(mean age[69±11]years).The proportion of male patients was 57.2％(484/846).The median admission ASPECTS was 8(7,9)and the median admission NIHSS score was 14(12,18).The incidence of malignant cerebral edema at 3 days post-surgery was 13.4％(112/835),and the 90-day mortality rate was 19.1％(162/846).(1)Among the 846 ALVOS patients,810(95.7％)were in the non-MVO group and 36(4.3％)were in the MVO group.Univariate analysis showed significant differences between the MVO and non-MVO groups in terms of atrial fibrillation,malignant cerebral edema,admission ASPECTS,admission NIHSS scores,TOAST classification,collateral circulation,rate of complete recanalization,and 90-day poor prognosis rate(all P＜0.05).However,there was no statistically significant difference in 90-day mortality between the two groups(P=0.193).Multivariate Logistic regression analysis showed that TOAST classification of cardioembolic type(OR,16.089,95％CI 1.835-141.061,P=0.012)and other etiology types(OR,9.768,95％CI 1.078-88.540,P=0.043)were associated with the occurrence of MVO.(2)Among the 846 ALVOS patients,445 had a good prognosis at 90days,and 401 had a poor prognosis.Univariate analysis showed that,compared to the good prognosis group,the poor prognosis group had a lower proportion of males and smokers,and a higher proportion of patients with older age,higher baseline systolic blood pressure,hypertension,diabetes,and atrial fibrillation(all P＜0.01).Additionally,the poor prognosis group had higher admission NIHSS scores(P＜0.01),lower admission ASPECTS,lower rates of good collateral circulation and complete recanalization,higher rates of malignant cerebral edema and MVO,and statistically significant differences in TOAST classification distribution(all P＜0.01).Multivariate Logistic regression analysis showed that MVO was associated with poor 90-day prognosis in ALVOS patients after EVT(OR,3.368,95％CI 1.149-9.878,P=0.027).Furthermore,older age(OR,1.045,95％CI 1.025-1.066),diabetes(OR,1.719,95％CI 1.080-2.734),higher baseline systolic blood pressure(OR,1.012,95％CI 1.004-1.019),lower admission ASPECTS(OR,0.746,95％CI 0.674-0.826),higher admission NIHSS score(OR,1.115,95％CI 1.070-1.162),without immediate postoperative complete recanalization(OR,0.413,95％CI 0.290-0.592),poor collateral circulation(OR,0.594,95％CI 0.415-0.851),and malignant cerebral edema(OR,6.191,95％CI 3.026-12.670)were all associated with poor 90-day prognosis after EVT in ALVOS patients(all P＜0.05).Conclusions The TOAST classification of cardioembolic type and other etiology types is associated with MVO.MVO is a risk factor for poor outcomes after successful EVT in ALVOS patients.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.

Traditional Chinese Medicine (TCM) shows unique advantages in the field of adjuvant treatment of gastric cancer. The main mechanism of TCM in improving gastric cancer includes regulating cell proliferation and apoptosis, reversing cell resistance, reducing the ability of invasion and metastasis and epithelial-mesenchymal transformation, regulating immune function, inhibiting neovascularization, regulating autophagy exosome, and ferroptosis.

【Objective】 To compare the effects of low flux and high flux hemodialysis on insulin resistance (IR), inflammatory factors and coronary artery calcification(CAC) in patients with non-diabetic end-stage renal disease (ESRD), and analyze the related factors affecting the prognosis survival of patients. 【Methods】 A total of 217 patients with non-diabetic ESRD treated in our hospital from February 2015 to April 2017 were selected and randomly divided into control group (n=108) and observation group (n=109) according to the random number table. Low flux and high flux hemodialysis were adopted respectively. Baseline data, renal function, lipid metabolism, inflammatory factors, IR, CAC, complications, outcomes and health and economic benefits of the two groups were compared. The patients were followed up for 3 years and divided into survival group (n=130) and death group (n=75). The clinical data of the two groups were compared and related factors affecting the prognosis and survival were analyzed. 【Results】 Scr, BUN, UAER, TC, TG and LDL-C in the two groups were significantly lower than those before treatment [control group: Scr (μmol/L)349.62±37.16 vs 201.73±24.58, BUN (mmol/L) 28.43±5.39 vs20.81±3.47, UAER(μg /min)60.14±11.52 vs 55.73±9.86, TC (mmol/L)5.46±0.93 vs 4.75±0.69, TG (mmol/L)2.58±0.64 vs 2.13±0.57, LDL-C(mmol/L)3.69±0.73 vs 2.45±0.60; observation group: Scr (μmol/L) 352.14±38.29 vs 136.85±16.47, BUN (mmol/L) 27.96±5.25 vs17.56±3.68, UAER(μg /min) 60.32±12.07 vs 49.85±7.42, TC (mmol/L)5.48±0.97 vs 4.27±0.56, TG (mmol/L) 2.55±0.62 vs 1.49±0.35, LDL-C(mmol/L) 3.72±0.74 vs1.91±0.48), and eGFR and HDL-C were significantly higher than those before treatment [control group: eGFR(mL/min/1.73m)29.32±3.25 vs 72.54±7.86, HDL-C(mmol/L)1.13±0.24 vs1.28±0.31, observation group: eGFR(mL/min/1.73m)30.05±3.29 vs 121.63±13.34, HDL-C(mmol/L)1.09±0.22 vs 1.57±0.46), differences between groups were statistically significant (P<0.05); FBG, FINS, HOMA-IR, IL-6, IL-8, TNF-α and hs-CRP in the two groups were significantly lower than those before treatment [control group: FBG(mmol/L)4.99±0.95 vs 4.52±0.63, FINS(mU/L)12.93±2.54 vs10.15±2.21, HOMA-IR 2.87±0.54 vs 2.04±0.43, IL-6(pg/mL)120.16±13.54 vs 75.94±9.28, IL-8(mg/L)56.83±6.15 vs 41.52±5.38, TNF-α(ng/L)50.03±5.42 vs 45.62±4.81, hs-CRP(mg/L)26.75±2.79 vs 14.37±2.19; observation group: FBG(mmol/L)5.01±0.97 vs 4.11±0.56, FINS(mU/L)13.07±2.62 vs 8.86±1.79, HOMA-IR 2.91±0.55 vs 1.62±0.31, IL-6(pg/mL)119.85±12.91 vs 31.07±4.46, IL-8(mg/L)57.04±6.09 vs 32.65±4.27, TNF-α(ng/L)49.78±5.36 vs 40.15±4.27, hs-CRP(mg/L)23.04±2.82 vs 7.56±1.03], and the CACS score was significantly higher than that before treatment(control group: 26.75±2.79 vs 53.68±26.93, observation group: 27.04±2.82 vs 75.49±7.66), differences between groups are statistically significant (all P<0.05). Compared with the control group, the total incidence of complications during dialysis was significantly lower in the observation group (P<0.05), and has more economic advantages.Venerable age(OR=1.893, P<0.05), low HDL-C level(OR=0.575, P<0.05), high CACS score(OR=2.384, P<0.05), and high hs-CRP level(OR=3.526, P<0.05) were independent risk factors affecting the survival rate of non-diabetic ESRD patients after dialysis treatment (P<0.05). 【Conclusion】 Compared with low-flux hemodialysis, high-flux hemodialysis has significant effects in improving renal function, lipid metabolism, IR, micro-inflammatory state, and reducing CAC progression and complications, with more prominent cost-effectiveness advantages. HDL-C and Hs-CRP levels and CACS scores of patients should be closely monitored during clinical application, and active preventive measures should be taken to improve the survival rate of patients.

Neuroendocrine tumors(NET) is a rare tumor with high heterogeneity.Pancreatic NET is the most common type in China. European Neuroendocrine Tumor Society(ENETS) has launched the ENETS guidelines since 2006 and published the ENETS standard of care in 2009. With the newly targeted therapies and further research on NET, 2017 new edition of the ENETS standard of care has changed a lot in the diagnosis and treatment of NET. This article explains the update of pancreatic NET in the 2017 edition of the ENETS standard of care, and introduces pancreatic NET from pathology, imaging examination, surgery, systemic therapy, etc., and deepens the understanding of the diagnosis and treatment of pancreatic NET.

Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.
Apoptosis ; Autophagy* ; Cell Cycle Checkpoints ; Cell Death ; Colon* ; Colonic Neoplasms* ; Heterografts ; HT29 Cells ; Humans ; Protein Processing, Post-Translational

Objective: To study the segment of liver according to the large amount of three-dimensional(3D) reconstructive images of normal human livers and the vascular system, and to recognize the basic functional liver unit based on the anatomic features of the intrahepatic portal veins. Methods: The enhanced CT primitive DICOM files of 1 260 normal human livers from different age groups who treated from October 2013 to February 2017 provided by 16 hospitals were analyzed using the computer-aided surgery system.The 3D liver and liver vascular system were reconstructed, and the digital liver 3D model was established.The vascular morphology, anatomical features, and anatomical distributions of intrahepatic portal veins were statistically analyzed. Results: The digital liver model obtained from the 3D reconstruction of CAS displayed clear intrahepatic portal vein vessels of level four.Perform a digital liver segments study based on the analysis of level four vascular distribution areas.As the less anatomical variation of left hepatic portal vein, the liver was classified into four types of liver segmentation mainly based on right hepatic portal vein.Type A was similar to Couinaud or Cho′s segmentation, containing 8 segments(537 cases, 42.62%). Type B contained 9 segments as there are three ramifications of right-anterior portal vein(464 cases, 36.82%). The main difference for Type C was the variation of right-posterior portal vein which was sector shape(102 cases, 8.10%). Type D contained the cases with special portal vein variations, which needs three-dimensional simulation to design individualized liver resection plan(157 cases, 12.46%). These results showed that there was no significant difference in liver segmental typing between genders(χ²=2.179, P=0.536) and did not reveal any significant difference in liver segmental typing among the different age groups(χ²=0.357, P=0.949). Conclusions The 3D digital liver model can demonstrate the true 3D anatomical structures, and its spatial vascular variations.The observation of anatomic features, distribution areas of intrahepatic portal veins and individualized liver segmentation achieved via digital medical 3D visualization technology is of great value for understand the complexity of liver anatomy and to guide the precise hepatectomy.

Objective To screen cardiac-specific short-acting peptides on live myocardial slices using phage display technology,so as to improve the targeted delivery efficiency of drugs in myocardium and provide effective candidates for the targeted therapy of Duchenne muscular dystrophy (DMD) and other cardiomyopathies.Methods Myocardial tissue slices were prepared and cultured in vitro.The protein activities of the tissues were examined by immunohistochemistry.The in vitro cultured myocardial tissue slices were co-incubated with phage library (1×1012 pfu),and the phages that bound to the myocardium were recovered and amplified.The cardiac-specific targeting phages were identified by five rounds of in vitro phage biopanning.The candidate phage-related insertion sequence was sequenced,and the in vivo tissue distribution of the highly enriched phages was verified.Results A platform for in vitro culturing of live myocardial slices was established.Myocardial slices with good biological activity were obtained.After 48 hours of culturing,the normal expression and localization of Dystrophin protein were detected.Using phage library,candidate phages were screened after five rounds of phage biopanning.The results of the sequencing analyses and in vivo tissue distribution verification indicated that the selected candidate phages showed significant enrichment in myocardium and skeletal muscle,and showed low levels in liver and kidney tissues.Conclusions The candidate phages showed higher binding efficiency in both myocardium and skeletal muscle,indicating that the candidate peptides had myocardial targeting property,and that can provide a new method for myocardial targeting therapy of DMD.

To develop a low-cost, reliable, easy-to-maintain and practical instrument for protein purification. Some ultraviolet luminescent diode was used to provide 280 nm light source, and high-sensitivity S1336 photo-electric detector was employed for real-time monitoring of purified protein solution flowing through quartz cell to supervise the concentration of the protein. The instrument gave voice alarm and stopped working in case the protein concentration was less than the standard one. The lower SCM monitored the liquid level of the protein collecting cup and the position of loading arm through laser infrared distance sensor, so that a cup full of protein might be replaced by another empty cup. The instrument involved in Samsung S5PV210 embedded master computer, Wince6.0 operating system, Keil4.0 and VS2005. Trials proved that the instrument could perform real-time monitoring and curve display of dual-channel ultraviolet absorption, and could realize auto collection of 735 ml protein solution and up to 5-hour standby. The instrument developed has simple structure, high reliability and easy maintenance, and meets the desired require-ments.

Objective To analyze age-related changes in fractional anisotropy(FA) in sub-regions of corpus callosum on diffusion tensor imaging(DTI).Methods DTI was obtained from 171 healthy individuals(80 men,91 women; age 12 to 73 years; median age 44 years).All the subjects were stratified into the following seven age groups(10-19,20-29,30-39,40-49,50-59,60-69,70-79 years).Corpus callosum was divided into 5 subregions(Ⅰ-Ⅴ region).DTI FA values of sub-regions of corpus callosum were measured.Mean FA values changes in corpus callosum sub-regions with advancing age were evaluated with hierarchical polynomial regression analyses.Results The mean FA value in the Ⅴ region was the highest within the same age group.The corresponding values from group 1 to 7 were 0.77±0.06,0.80±0.03,0.79±0.03,0.79±0.03,0.78±0.03,0.77±0.03,0.77±0.03,respectively.The mean FA value in the Ⅲ region was the lowest within the same age group.The corresponding values from group 1 to 7 were 0.51 ±0.08,0.59± 0.06,0.59±0.06,0.56±0.07,0.55±0.07,0.52±0.07,0.43±0.07,respectively.The change of FA values in subregions of the corpus callosum on DTI followed an inverted U-shaped curve with advancing age(ROI1-ROI5,R2=0.162,0.214,0.164,0.098,0.070,respectively,all P＜0.05).FA peak appeared at 20 to 30 years old in all regions.Conclusions The study demonstrated age-related changes in FA value in sub-regions of the corpus callosum on DTI as following a curve,reflecting the age-related changes of physiological processes,which could serve as a basis for corpus callosum research.