Objective To make a preliminary investigation and summary of the technique and efficacy of the novel intracranial stent, Enterprise, together with hydro-detachable coils for the treatment of very small intracranial wide-necked aneurysms (diameter<3 nun and body-to-neck ratio<1.5). Methods Six cases with very small intracranial wide-necked aneurysms were treated with Enterprise stents and hydro-detachable coils. In 5 cases the Enterprise stent was implanted to cover the neck of the aneurysm, which was followed by the introduction of a microcatheter into the aneurysmal sac through the stent mesh to stuff hydro-detachable coils in order to fill the aneurysmal sac. In the remaining case, the microcatheter was placed into the aneurysmal sac before the Enterprise stent was inserted to embolize the aneurysm. Postoperative follow-up was conducted for 3-6 months. Results The operation was successfully completed in all 6 patients, with the implanted stents being in right place. The parent arteries remained patency in all patients. No complications occurred. Complete occlusion of aneurysmal cavity was obtained in four cases, and the occlusion degree of the aneurysmal cavity above 95% was seen in 2 cases. After the procedure, all the patients recovered well. Neither rebleeding nor symptoms related to thrombosis occurred during a clinic follow-up of 3-6 months. Conclusion Endovasculur embolization with Enterprise stent together with hydro-detachable coils is a safe and effective method for the treatment of very small intracranial wide-necked aneurysms. However, its long-term effect needs to be further observed.

Objective:To research the effect of lumbar spinal nerve block combined with ultrashort wave on the pain and biomechanics of lumbar back muscle of patients biomechanics with lumbar disc.Methods:98 patients with lumbar disc herniation in our hospital from February 2014 to August 2016,according to the lottery method divided into control group and research group.The control group was treated with Lumbar spinal nerve block.The research group was based on the control group treated with ultrashort wave,clinical curative effect,changes of the visual analogue scale (VAS),60 ° /s angular velocity,120° /s average apical power (AP),peak torque (PT),lumbar dorsiflexion / dorsal flexion (F/E),serum levels of substance P (SP),β-endorphin (β-EP),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α) before and after treatment,and adverse reactions were compared between two groups.Results:The total effective rate of research group was95.91％,which was significant higher than that of the control group,the difference was statistically significant (P＜0.05).After treatment,The VAS,F/E,serum levels of SP,IL-6 and TNF-α of two groups were significantly lower than those before treatment,the above indicators of research group were significantly lower than those of the control group.The AP,PT and serum levels of β-EP between two groups were significantly higher than those before treatment,the above indicators of research group were significantly higher than those of the control group (P＜0.05).No statistical difference was found in the incidence of adverse effects between the two groups (P＞0.05).Conclusion:Umbar spinal nerve block combined with ultrashort wave was more effective than lumbar paravertebral nerve block treatment alone in the treatment of lumbar disc herniation,it could effectively relieve the pain and improve the low back muscle biological mechanics performance and reduce the inflammatory response.

Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare and enhanced CT or MRI can be used for its diagnosis. Surgical procedure is the main treatment for HCC with BDTT. The authors introduce the experiences of recurrent patient with HCC and BDTT who was treated with targeted therapy plus immunotherapy, in order to provide reference for its clinical diagnosis and treatment.

Objective:To evaluate the clinical outcome of 3D printing titanium cage combined with Masquelet technology for the treatment of calcaneus infective defect.Methods:Data of 5 cases with chronic calcaneus infectivedefect treated with regional flap, 3D printing titanium cage combined with Masquelet technology with rib autograft from January 2017 to January 2019 were retrospectively analyzed. There were 3 males and 2 females, with an average age of 37 years old (range, 17-52 years). The mechanism of the five patients included two motor vehicle incidents, two high fall injuries and one rolling compaction. All patients were treated by two-stage procedures. First stage included debridement, polymethyl methacrylate (PMMA) filling and regional flap coverage. The soft tissue defect of the 5 cases included 10 cm×8 cm in 2 cases, 8 cm×7 cm, 8 cm×5 cm, and 5 cm×3 cm each in one case. Bone defect included 4 cm×3 cm×2 cm in two cases, 3 cm×3 cm× 2 cm in two cases and 3 cm×1 cm×1 cm in one case. Second stage was 3D printing titanium cage combined with masquelet technology of rib autograft. Time of bone union, morphology of calcaneus, position of implant, Maryland score and AOFAS hind foot score were recorded to evaluate the clinical outcome.Results:All five patients were followed up for an average time of 18.2 months (range, 12-30 months). Infection happened in one patient 2 months after first stage operation and successfully treated by debridement and PMMA replacement. Incision of the rest 4 cases all healed successfully. Germiculture of the five cases included Methicillin-resistant Staphylococcus aureus (MRSA) in three cases, Staphylococcus epidermidis in one case and Bacterium coli in one case. All five patients got calcaneus bone union after second stage operation. The average time for bone union was 4.32 (range, 3-8) month. Bone trabecular were observed in CT scan 13 (range, 10-22) month post-operation. Average Maryland score in 12 months post-operation was 92 (range, 86-98) and average AOFAS ankle hind foot score was 89.8 (range, 83-100).Conclusion:3D printing titanium cage and Masquelet technology maybe an effective treatment for calcaneus infective defect.

Objective To investigate effects of polyphylin Ⅰ on the proliferation and apoptosis of human melanoma cell line A375,and to explore their mechanisms.Methods Normal human melanocytes isolated from healthy human foreskin were divided into 6 groups to be treated with 0,1.5,3.0,6.0,9.0,12.0 mg/L polyphyllin Ⅰ respectively.A375 melanoma cells were divided into 4 groups,i.e.,control group,1.5-,3.0-,6.0-mg/L polyphyllin Ⅰ groups,to be treated with 0,1.5,3.0,6.0 mg/L polyphyllin Ⅰ,respectively.Cell counting kit-8 (CCK8) assay was performed to evaluate the effect of polyphyllin Ⅰ on the proliferation of normal human melanocytes and A375 cells.Hoechst 33258 fluorescent staining was conducted to observe the morphology of apoptotic cells,flow cytometry to estimate cell cycle phase distribution and apoptosis rate,dichloro-dihydro-fluorescein diacetate (DCFH-DA) fluorescent probe assay to detect the level of reactive oxygen species (ROS),rhodamine-123 staining to evaluate changes of mitochondrial membrane potential,spectrophotography to detect the level of ATP in A375 cells,as well as levels of lactic acid and glucose in the culture supernatant of A375 cells,and Western blot analysis to determine the protein expression of Bcl-2,Bcl-2-related X protein (Bax),cleaved-caspase-3,cyclin D1 and pyruvate kinase isozyme type M2 (PKM2).Statistical analysis was carried out by using one-way analysis of variance (ANOVA) for comparisons among groups and Student-Newman-Keuls-q (SNK-q) test for multiple comparisons.Results CCK8 assay showed that the treatment with polyphyllin Ⅰ at concentrations of 1.5,3.0,6.0 mg/L for 48 hours had no effects on the proliferation of normal human melanocytes,but significantly inhibited the proliferation of A375 cells.The survival rate of A375 cells was significantly lower in the 1.5-,3.0-,6.0-mg/L polyphyllin Ⅰ groups than in the control group (P ＜ 0.01).After the treatment with polyphyllin Ⅰ,distinct apoptotic morphology of A375 cells was observed under fluorescence microscope.Additionally,along with the increase of polyphyllin Ⅰ concentrations (0,1.5,3.0,6.0 mg/L),there were gradual increasing trends in the apoptosis rate of A375 cells (4.25％ ± 1.27％,10.03％ ± 1.49％,36.62％ ± 1.97％,44.11％ ± 2.47％ respectively,F =665.7,P ＜ 0.01),the percentage of A375 cells at G0/G1 phase (54.13％ ± 2.57％,67.35％ ± 3.79％,74.39％ ± 3.29％,82.29％ ± 3.99％ respectively,F =71.81,P ＜ 0.01),the level of ROS in A375 cells (P ＜ 0.01),the level of glucose in the culture supernatant (P ＜ 0.01),and the protein expression of Bax and cleaved-caspase-3 (both P ＜ 0.01),while gradual decreasing trends were found in the levels of mitochondrial membrane potential and ATP in A375 cells (both P ＜ 0.01),the level of lactic acid in the culture supernatant (P ＜ 0.01),and the protein expression of Cyclin D1,Bcl-2 and PKM2 (all P ＜ 0.01).Conclusion Polyphyllin Ⅰ can effectively induce A375 cell apoptosis by promoting the production of ROS in A375 cells and decreasing the mitochondrial membrane potential,and arrest A375 cells at G0/G1 phase by inhibiting the expression of PKM2 and Cyclin D1.

【Objective】 To investigate the expression of pyruvate kinase M2 (PKM2) in intrahepatic cholangiocarcinoma (ICC) and the effect of PKM2 on the proliferation and epithelial-to-mesenchymal transition (EMT) of ICC cells. 【Methods】 PKM2 expression was evaluated in ICC tissues and cell lines by Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry assays. In vitro, we knocked down PKM2 expression in ICC cell lines and investigated the biological function and the underlying mechanism of PKM2 in ICC. 【Results】 RT-PCR results showed that PKM2 was highly expressed in ICC (P<0.05). Moreover, PKM2 knockdown inhibited cell proliferation and the invasive capacities of ICC cells, and inhibited Wnt/ β-Catenin signaling, which subsequently regulated EMT signaling pathway in vitro. 【Conclusion】 PKM2 expression in cholangiocarcinoma is significantly higher than that in adjacent tissues. PKM2 can regulate EMT and invasion and metastasis of ICC via the Wnt/β-Catenin signal.

OBJECTIVE： To mine and evaluate the post-marketing safety alert signals of pegaspargase （PEG-ASP） and L-asparaginase （L-ASP），and compare the safety differences between them ，so as to provide reference for clinical safe and rational drug use. METHODS ： The adverse drug event （ADE） reports of PEG-ASP and L-ASP issued by FDA adverse event reporting system from Jan. 1st，2004-Jun. 30th，2020 were retrieved. BCPNN method was used to mine the safety signals of these two drugs under the condition that the lower limit of information component （IC－2SD）＞0 and the number of events ≥3. The medium and strong signals of two drugs with IC －2SD≥1.5 were evaluated and compared in 8 system organ class，such as gastrointestinal system ，hepatobiliary system ，blood and lymphatic system ，blood vessels and lymphatic vessels ， nervous system ，immune system ，metabolism and nutrition ，various examinations. IC value of specific ADE signal and its 95％ confidence interval were analyzed by time scanning spectrum. RESULTS & CONCLUSIONS ：The reports of PEG-ASP and L-ASP as suspected drugs were 2 324 and 3 824；67 and 68 medium and strong signals were included ，respectively. In gastrointestinal system，the common strong signal of PEG-ASP and L-ASP was necrotic pancreatitis. In hepatobiliary system ，both of them showed strong signal in venoocclusive liver disease ，and this ADE was not included in the drug instruction. In blood and lymphatic system ， common strong signals of the two drugs were febrile neutropenia ，coagulation disorder ，neutropenia and febrile bone marrow regeneration disorder ；in blood vessels and lymphatic vessels ，in addition to haemodynamic instability ，IC values of other signals of L-ASP were higher than those of PEG-ASP. In nervous system ，IC values of other signals of L-ASP were higher than those of PEG-ASP except for intracranial haemorrhage. In immune system ，anaphylactic reaction was a medium signal for L-ASP but was a strong signal for PEG-ASP. In metabolism and nutritional diseases ，except for tumor lysis syndrome ，IC values of other signals of L-ASP were higher than those of PEG-ASP. The results of time scanning spectrum showed that the signals of necrotic pancreatitis and coagulation disorder of PEG-ASP were stable ，while the signals of veno occlusive liver disease and hypersensitivity were unstable and needed to be observed ；above four signals of L-ASP were stable signals. When using PEG-ASP or L-ASP clinically ， close attention should be paid to the safety problems such as hypersensitivity ，coagulation disorder ，thrombosis，necrotic pancreatitis，venoocclusive liver disease and hypoproteinemia.