OBJECTIVE To investigate the potential mechanism of epigallocatechin gallate （EGCG） enhancing the sensitivity of hepatocellular carcinoma （HCC） cells to lenvatinib based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS Five human HCC cell lines （HepG2， Huh-7， SMMC-7721， SNU-368 and SNU-739） were used to evaluate the effects of lenvatinib alone and in combination with EGCG on survival rates， clone number， proliferation rate， invasion number and the expressions of mRNAs and proteins related to the PI3K/Akt signaling pathway. The PI3K activator insulin-like growth factor-1 （IGF-1） was introduced to investigate the effect of activating the PI3K/Akt signaling pathway on the sensitization effect of EGCG. RESULTS Compared with the control group， lenvatinib （10 μmol/L） and different concentrations of EGCG+ lenvatinib （1， 5 and 10 μg/mL EGCG+10 μmol/L lenvatinib） significantly reduced the survival rates and clone numbers of all five HCC cell lines in a dose-dependent manner （P＜0.05）. Lenvatinib （10 μmol/L） and EGCG+lenvatinib （10 μg/mL EGCG+10 μmol/L lenvatinib） also markedly inhibited the proliferation rate and invasion numbers of these cells， and decreased the mRNA expressions of PI3K， Akt， mammalian target of rapamycin （mTOR）， P70S6K and 4EBP， and the phosphorylation levels of PI3K and Akt， as well as the protein expressions of mTOR and B cell lymphoma-2 （Bcl-2） in HepG2 cells or all five HCC cells； conversely， the mRNA and protein expressions of phosphatase and tensin homologue deleted on chromosome 10（PTEN）， and the protein expressions of caspase-3 and cleaved caspase-3 were significantly upregulated， with more pronounced effects observed in the EGCG+lenvatinib group than in the lenvatinib group （P＜0.05）. Compared with the lenvatinib group and the EGCG+lenvatinib group， the clone number， proliferation rate and invasion number of HepG2 cells in the EGCG+lenvatinib+IGF-1 group （10 μg/mL EGCG+10 μmol/L lenvatinib+50 ng/mL IGF-1） were significantly increased （P＜0.05）. CONCLUSIONS EGCG can enhance the sensitivity of HCC cells to lenvatinib， and its underlying mechanism may be related to the inhibition of the activation of PI3K/Akt signaling pathway activation.

Objective To investigate the mechanism of E26 transformation-specific sequence 4(ETV4)affecting the proliferation and migration of colon cancer cells through the nuclear factor-κB(NF-κB)signaling pathway.Methods The expression level of ETV4 in normal colon tissues and cancer tissues was analyzed by the user-friendly interactive cancer transcriptome data analysis resource(UALCAN)database.Reverse transcription quantitative polymerase chain reaction(qRT-PCR)and Western blot were used to detect the expression level of ETV4 in normal intestinal epithelial cells and colon cancer cell lines.After silencing ETV4 in SW480 cells,qRT-PCR and Western blot were per-formed to detect the expression of ETV4 to assess transfection efficiency;colony formation and Tran-swell assays were conducted to explore the effects of ETV4 silencing on the proliferation and migration of colon cancer cells;the Western blot was used to detect the effects of ETV4 silencing on the protein expression of protein 65(p65)and phosphorylated protein 65(p-p65)in the NF-κB pathway.Results The UALCAN database analysis revealed high expression of ETV4 in colon cancer tissues.The qRT-PCR and Western blot showed that ETV4 expression was significantly higher in the colon cancer cell lines SW480,Lovo,Caco-2,and SW620 than in normal intestinal epithelial cells HIEC-6,with the highest expression in SW480 cells(P＜0.001).Colony formation and Transwell assay results indicated that silencing ETV4 significantly inhibited the proliferation and migration of colon cancer SW480 cells(P＜0.001).Western blot results showed that silencing ETV4 significantly inhibited the expression of p-p65 protein in the cells(P＜0.001).Conclusion Silencing ETV4 may inhibit the activation of the NF-κB signaling pathway,thereby inhibiting the proliferation and migration of colon cancer cells.

Objective To investigate the safety and efficacy of bybrid surgery in the treatment of cerebral arteriovenous malformation(CAVM)and possible factors for postoperative symptom progression.Methods A total of 61 patients with CAVM admitted to the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University from January 1,2016 to December 31,2021 who underwent bybrid surgery were retrospectively included.Demographic information(sex,age),incidence(first diagnosis of CAVM by imaging and/or first appearance of CAVM-related symptoms such as hemorrhage and epilepsy),time from onset to hybrid surgery,modified Rankin scale(mRS)score at admission,history of previous CAVM treatment(surgical removal of previous CAVM and intravascular treatment),CAVM imaging data(lesion location,size,drainage),Spetzler-Martin grade,lesion density(loose,dense),CAVM combined with aneurysm or aneurysmal structure,surgical method(microsurgery+intraoperative DSA,microsurgery+intraoperative DSA+endovascular embolism),treatment-related complications(intracranial hemorrhage and/or ischemic events and/or edema in surgery-related areas,puncture site hematoma and/or fistula and/or pseudoaneurysm,gastrointestinal and/or gingival bleeding and/or epistaxis,contrast hypersensitivity,all-cause death),clinical and radiological follow-up data were recorded.The safety(treatment-related complications,symptom progression[positive difference between the mRS score at 6 months postoperatively and the baseline mRS score])and effectiveness(occlusion,complete absence of the malformation on DSA at 6 months postoperatively;good prognosis,mRS score≤2 at 6months postoperatively)of hybrid surgery treatment were evaluated.Based on the clinical follow-up results at 6 months after surgery,patients who underwent hybrid surgery for CAVM were divided into the progressive group and the non-progressive group,and their baseline and clinical characteristics were compared.Results(1)Among the 61 patients who underwent hybrid surgery for CAVM,37(60.7％)were male,with a median age of 25(13,42)years;11(18.0％)were asymptomatic,and 39(63.9％)had hemorrhage as their initial symptom,while 11(18.0％)had seizures as their initial symptom.At admission,54(88.5％)patients had an mRS score of ≤2,including 38(62.3％)patients who had undergone previous endovascular embolization and had residual or recurrent CAVM;the Spetzler-Martin grade of the CAVM lesion was Ⅰ,Ⅱ,Ⅲ,or Ⅳ in 13(21.3％),22(36.1％),21(34.4％),and 5(8.2％)patients,respectively;24 patients underwent DSA verification during surgery using a hybrid surgical platform,and 37 patients underwent DSA verification and assisted endovascular embolization using a hybrid surgical platform.(2)Clinical follow-up completion rate was 77.0％(47/61);the follow-up time ranged from 6 to 24 months and the median follow-up time was 12(6,24)months.The good prognosis rate was 91.5％(43/47),there was no death.The incidence of treatment-related complications was 10.6％(5/47).The completion rate of imaging follow-up was 72.1％(44/61)and the median follow-up time was 15(10,22)months.There were 40(90.9％)of CAVM occlusion,2(4.5％)of residual CAVM and 2(4.5％)of recurrent CAVM.(3)Among the 47 patients who completed clinical follow-up,15 patients developed symptoms and 32 patients did not develop symptoms.There were no significant differences in sex,age,onset symptoms,mRS score at admission,lesion location,lesion density and aneurysm or aneurysmal structure between the two groups(all P＞0.05).In the progressive group,the proportion of lesions with the largest diameter＜3 cm,3-6 cm and＞6 cm were 3/15,10/15 and 2/15,respectively,and the largest diameter was mainly 3-6 cm.In the non-progressive group,the proportion of the largest diameter＜3 cm and 3-6 cm were 18/32 and 14/32,respectively,and the largest diameter＜3 cm was the main proportion(x2=8.321).Deep venous drainage(x2=11.937)and residual and/or recurrence(x2=8.507)were present in the progressive group,and the differences between the groups were statistically significant(all P＜0.05).Conclusions Hybrid surgery has certain safety and effectiveness in the treatment of CAVM.Patients with CAVM who experienced progression after undergoing composite surgery have characteristics such as larger maximum diameter,the presence of deep venous drainage and residual and/or recurrence,and the factors affecting progression need to be further explored in the future.

Objective:To introduce the standard screw implantation methods and to analyze the biomechanical stability of the second-generation dynamic anterior plate-screw system for quadrilateral area (DAPSQ).Methods:Six adult formalin-preserved corpses were selected to make a complete pelvic specimen. Further, the left high double-column fracture models were made and randomly fixed with second-generation DAPSQ or anterior reconstruction titanium plate and 1/3 tube buttress-plate (ARTPB). The specimens of intact pelvis (IP) group, DAPSQ group and ARTPB group were fixed on a Zwick Z100 material machine and loaded vertically with 200 N, 300 N, 400 N, 500 N, 600 N, 700 N, and 800 N in a simulated sitting position, respectively. The axial displacement and strain changes in the anterior and posterior columns were tested in the three groups. The stiffness was calculated accordingly.Results:The axial compression displacement in the three groups showed an increase trend as well with the vertical load increased from 200 N to 800 N ( F=68.581, P<0.001; F=91.795, P<0.001; F=33.819, P=0.002). The axial displacement in ARTPB group was significantly larger than that in DAPSQ group and IP group ( P<0.05), while the difference between DAPSQ and IP groups was not significant ( P>0.05). Under the vertical load of 600 N, the pelvic axial stiffness of IP group, DAPSQ group, and ARTPB group were 220.72±70.33 N/mm, 185.68±48.49 N/mm and 135.83±60.58 N/mm, respectively. The axial stiffness of ARTPB group was significantly lower than that in DAPSQ group and IP group ( t=5.345, P=0.003; t=6.443, P=0.001), while the difference between DAPSQ and IP groups was not significant ( t=2.138, P=0.086). There were no significant differences of the strain values in anterior column among the three groups during the load increasing from 200 N to 800 N ( P>0.05). With the load increasing from 500 N to 800 N, the strain values of the posterior column in ARTPB group were significantly greater than those of IP and DAPSQ groups ( P<0.05). However, the differences between IP and DAPSQ groups were not statistically significant in strain values of the posterior column ( P>0.05). Conclusion:Compared with anterior reconstruction titanium plate and 1/3 tube buttress-plate, acetabular double-column fracture model fixed with the second-generation DAPSQ has less axial compression displacement but with greater axial stiffness. The stress change in the posterior columns of the acetabulum is like in IP. Therefore, the second-generation DAPSQ has reliable biomechanical stability.

Objective:To explore the association between suboptimal health status (SHS) and plasma IgG N-glycans levels among undergraduates in a college in Shandong Province.Methods:A case-control study was conducted from September to November 2017, 100 college students who underwent physical examinations at Weifang University in Shandong, were selected as study participants based on the inclasion and exclusion criteria of the study. According to the criteria of SHS, the participants were divided into an SHS group ( n=50) and a health control group ( n=50). Plasma IgG N-glycosylaton levels were analyzed by means of ultra-high liquid chromatography (UPLC), and 24 glycan peaks were obtained. The Mann-Whitney U-test and binary logistic regression analysis were performed to investigate the association between IgG N-glycans and SHS. P<0.05 was considered statistically significant. Receiver operating characteristic (ROC) curve analyses were used to evaluate the possibility of plasma IgG N-glycans being a biomarker of SHS. Results:The results of univariate and multivariate analysis showed that GP17 was associated with SHS ( P<0.05), and the relative abundance of initial glycan peaks (GP17) was higher in the SHS group compared with the control group. ROC curve analysis showed that the area under the curve (AUC) of the baseline model was 0.826 (95% confidence interval [ CI]: 0.747-0.905, P<0.001); the AUC of the glycan-based model was 0.631 (95% CI: 0.519-0.744, P=0.002), and the AUC of the combined model was 0.848 (95% CI: 0.763-0.912, P<0.001). Compared with the baseline model, the diagnostic efficiency of the combined model revealed a trend of improvement. Conclusions:The SHS of the students in a college in Shandong Province was associated with an IgG N-glycan level of GP17, which was significantly higher than that of the control group.

Objective: To investigate the clinical efficacy of reduced port laparoscopic radical resection on colorectal cancer. Methods: Clinical data of 46 patients with colorectal cancer undergoing reduced port laparoscopic radical resection were retrospectively analyzed. Results: All of 46 patients underwent laparoscopic surgery, with an average operation time of 206 minutes, an average intraoperative bleeding of 56 ml, an average number of lymph nodes removement of 12/case (ranged from 6 to 21). One case had incision infection, 2 cases had anastomotic leakage, and they all recovered and discharged after treatment. Conclusions Reduced port laparoscopic radical resection of colorectal cancer is safe and feasible, reduces labor costs, and has a good clinical efficacy, which is worthy of clinical promotion.

To investigate the effects of Yupingfeng granule (YPF) on immune factors of the rats with allergic rhinitis (AR) induced by ovalbumin(OVA). OVA 0.3 mg, Al(OH)3 30 mg and saline 1 mL were mixed and intraperitoneally injected for the initial immunization, 4% OVA 200 μg (50 μL) was given to the nose on the 15th day for the second immunization to establish the allergic rhinitis model. Sixty male SD rats were randomly divided into allergic rhinitis(AR) model group, Yupingfeng granule three dose (2.7,1.35,0.68 g•kg⁻¹) groups, control drug Biyankang (0.4 g•kg⁻¹) and normal control group. After 14 days, efforts were made to collect blood from abdominal aorta, and take nasopharynx tissues and fasten them into 10% formaldehyde for a pathological examination. The levels of HIS, IgE, IL-4 and TNF-α in serum were examined by radioimmunoassay, and nasal mucosa tissues were examined by HE staining. According to the results, the levels of HIS, IgE, IL-4 and TNF-α in serum of Yupingfeng granule groups were significantly lower than that of AR model group (P<0.05, P<0.01). Nasal mucosa tissues showed slight morphological changes and inflammatory cell infiltration, with unobvious necrosis. Yupingfeng granule can improve the pathological changes of nasal mucosa tissues, and reduce the production and release of immune factors during allergic rhinitis (AR) process in vivo by OVA, which may be the important curative mechanism of allergic rhinitis.

Objective To compare differences of SRS-22 scores between male and female AIS patients.Methods From October 2007 to April 2009,298 AIS patients from 7 spine centers completed simplified Chinese edition of SRS-22 questionnaire,including 62 males and 236 females with an average age of 15.7 years old,and the average Cobb angle was 52.8°.Of 62 male patients,34 were from urban areas and 28 rural areas.Among 236 female patients,132 were from urban areas and 104 rural areas.A comparison was conducted in terms of age,Cobb angle,the ratio of urban population to rural population,and the scores of all domains and the subtotal scores of SRS-22 questionnaire between male and female patients.Results There was no difference of age,Cobb angle and the ratio of urban population to rural population between male and female patients(P＞0.05).The scores of four domains and subtotal scores of SRS-22 questionnaire were significantly higher in male patients when compared with female patients(P＜0.05).Conclusion Gender difference should be taken into the consideration when estimating the quality of life in AIS patients by SRS-22 questionnaire.The quality of life in male patients with AIS was better than that of female patients.

OBJECTIVETo assess the value of stent-assistant angioplasty for intracranial vascular diseases.

METHODSThirteen patients with intracranial vascular diseases were treated consecutively by stent-assistant angioplasty for different purposes. Of these patients 7 had symptomatic intracranial artery stenosis, 3 intracranial wide-neck aneurysms, 2 intracranial pseudoaneurysms, and 1 bilateral transverse sinus stenosis. Clinical procedures and technical data of the patients were retrospectively analyzed.

RESULTSIn the 7 patients, the degree of intracranial artery stenosis reduced from 83% to 5%. Three months after the operation they exhibited good patency of stented lesions. Intracranial wide neck aneurysms (with 2 pseudoaneurysms) were successfully embolized with GDC in 5 patients. The patients with bilateral transverse sinus stenosis were implanted a self-expanded stent in the right transverse sinus. One patient failed because of the tortuous configuration of the left jugular bulb, but the patient's symptoms were improved quickly after the procedure.

CONCLUSIONStent-assistant angioplasty is a useful technique for selected intracranial vascular diseases, and it needs further investigation.

Adult ; Angioplasty, Balloon ; methods ; Cerebrovascular Disorders ; therapy ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stents ; Treatment Outcome

Objective To review the experience of multiple modality endovascular treatment for intracranial venous thrombosis, and to evaluate the efficacy and risk of endovascular thrombolysis for intracranial venous thrombosis.Methods From October, 2000 to October, 2001, 12 patients with intracranial venous thrombosis confirmed by CT, MRI, MRV, and/or DSA were treated with multiple modality endovascular thrombolysis including intravenous thrombolysis, mechanical thrombus maceration, intraarterial thrombolysis, and stenting.After thrombolysis, treatment aimed at the primary diseases was continued and warfarin was used for 6 months.The patients were followed-up for 17-29 months, averaged 23 months.Results Of the twelve patients, all underwent transvenous thrombolysis, ten underwent combined transvenous thrombolysis and clot maceration, seven underwent transvenous infusion of urokinase combined with transarterial infusion of urokinase.Two underwent transvenous infusion of urokinase combined with transarterial infusion of urokinase.The thrombolysis duration was from one to three days.The infusion dose of urokinase was 800 000 to 2 900 000 IU, the averaging dosage of urokinase was less than 1 000 000 IU per day.All patients achieved from recanalization of sinuses as confirmed on postprocedural angiography, MRI, and MRV studies prior to hospital discharge.At discharge, all the patients improved neurologically, and GCS improved from averaged 12 of pre-operation to 14 of post-operation.During the averaging 23 months follow-up, no patient recurred. Conclusion Combined multiple modality endovascular treatment is an effective and safe procedure for potentially catastrophic intracranial venous thrombosis.