N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl₄) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.

Objective:To summarize the clinical researches of Wumei Pill and provide reference for clinical application and follow-up research.Methods:The databases CNKI, VIP, Wanfang, CBM, PubMed, Embase were retrieved from the inception to June 30,2022. CiteSpace 6.1.R3 software was used to analyze the research hotspots and keywords in the literature. Using EndNote X9 software and Microsoft Office Excel 2013, we recorded and analyzed the published year, literature type, affiliated journal, disease treated, TCM syndrome type, single drug dose and treatment duration of the included articles.Results:212 articles were included. Diarrhea, gastritis, diabetes, insomnia were the research hotspots. The types of diseases treated by Wumei Pill mainly include digestive system, endocrine system and tumor, mainly for cold-heat syndrome and Jueyin syndrome. The average dosage of Mume Fructus was the largest, 21 g. The average treatment time was 5.78 weeks. Conclusion:At present, the overall clinical research of Wumei pill shows an increasing tendency, mainly involving gastrointestinal disease.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective:To assess the efficacy and safety of acupuncture compound anesthesia(ACA)for traditional thyroidectomy. Methods:Randomized controlled trials(RCTs)studying the use of ACA for traditional thyroidectomy were retrieved from PubMed,Excerpta Medica Database(EMBASE),Cochrane Library,Web of Science,China National Knowledge Infrastructure(CNKI),Chongqing VIP Database(CQVIP),Wanfang Academic Journal Full-text Database(Wanfang),and China Biology Medicine Disc(CBM)from inception to September 30,2021.Two investigators independently extracted data and assessed the risk of bias and quality of the studies.Anesthesia effectiveness was the primary outcome,while the secondary outcomes included various pain scales,vital signs,analgesic consumption,and adverse events.Review Manager 5.3 was used for meta-analysis.Weighted mean difference(WMD),standardized mean difference(SMD),and confidence interval(CI)were used for statistical descriptions. Results:A total of 16 papers were included,involving 1228 patients.Meta-analysis showed that anesthesia effectiveness was significantly improved after adding acupuncture as an adjunct[SMD=0.62,95%CI(0.40,0.83),P<0.0001,I2=36%].Besides,ACA can also moderate vital signs and reduce the feeling of pain[SMD=-1.61,95%CI(-2.61,-0.61),P<0.00001,I2=95%],analgesic consumption,and adverse events.Subgroup analysis of the electroacupuncture(EA)group further revealed that the effectiveness of low-frequency EA[WMD=0.43,95%CI(0.30,0.55),P<0.00001,I2=15%]and the entire operative stimulation of EA[WMD=0.55,95%CI(0.33,0.77),P<0.00001,I2=0%]was significantly better than high-frequency EA and short-time stimulation of EA during the operation.Further,no significant difference existed between conventional analgesia and acupuncture analgesia. Conclusion:ACA is beneficial to traditional thyroidectomy regarding efficacy and safety when acupuncture is applied as an adjunct.However,additional high-quality studies with larger sample sizes are needed to verify the findings.

Objective:To evaluate the application of intraoperative optical coherence tomography (iOCT) in vitreoretinal surgery.Methods:An observational case series study was conducted.A total of 316 patients (316 eyes) who received vitreoretinal surgery and iOCT from January 2015 to December 2017 in Hangzhou Branch of Eye Hospital, Wenzhou Medical University were enrolled.The iOCT scanning time and result, the consistency between iOCT result and observation under the operating microscope as well as the influence of iOCT on surgical strategy were recorded.The postoperative adverse reactions and complications were observed.The study protocol was approved by an Ethics Committee of Eye Hospital, Wenzhou Medical University(No.2019-168-K-160). Written informed consent was obtained from all patients prior to any medical examination.Results:There were 85.8% (271/316) of patients who successfully completed iOCT scanning, with an average scanning time of (3.54±2.30)minutes.Among the 271 successful eyes, there were 51 with idiopathic macular hole (IMH), 95 with epiretinal membrane, 50 with dense vitreous hemorrhage (VH), 30 with macular lamellar hole, 12 with vitreous macular traction syndrome, 33 with myopic maculopathy.There were 45 eyes, accounting for 16.6%, the iOCT results of which were inconsistent with the observation of operator under the operating microscope.There were 27 eyes, accounting for 10.0%, the surgical strategy of which was changed.The iOCT results of IMH showed that intra-retinal bridge connection appeared in 2 eyes after ILM peeling, then air tamponade was used.High-reflection strips on the edge of the MH after ILM peeling, called the Hole-door phenomenon, were found in 15 eyes, accounting for 32.6%.In MH with a diameter >400 μm, the postoperative best corrected visual acuity and continuity of outer limiting membrane were better in eyes with Hole-door phenomenon than eyes without Hole-door phenomenon.There were 8 eyes, accounting for 8.4%, showing residual membrane, 3 eyes of which received extra ERM peeling.There were 56 eyes, accounting for 58.9%, showing the secondary changes after membrane peeling.For 50 eyes with dense VH, there were 17 eyes showing the normal macular structure, accounting for 34%, and 33 eyes showing the abnormal macular structure, accounting for 66.0%.In addition, the macular structures of 14 eyes, accounting for 28.0%, observed in iOCT image were inconsistent with the intraocular microscope finding, and 11 of them received extra ERM peeling.Conclusions:The application of iOCT in vitreoretinal surgery can guide the selection of reasonable surgical methods during operation, predict postoperative recovery as well as improve postoperative outcomes.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To evaluate the effect of down-regulating lncRNA LINC00263 targeting miR-4458 on the proliferation, migration, invasion and radiosensitivity of breast cancer SK-BR-3 cells.Methods:The expression differences of LINC00263 in breast cancer tissues, adjacent tissues, normal breast epithelial cells and breast cancer cells were determined by qRT-PCR. Transfection of LINC00263 shRNA in breast cancer SK-BR-3 cells down-regulated the expression of LINC00263, and the cloning experiment was used to detect the radiosensitivity. Breast cancer SK-BR-3 cells were treated with 6 Gy irradiation. CCK-8 assay was employed to detect cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Transwell chamber test was performed to detect cell migration and invasion. Western blot was used to detect the expression levels of C-Caspase-3 and C-Caspase-9, MMP-2 and MMP-9 proteins. Bioinformatics software predicted that LINC00263 and miR-4458 had complementary binding sites, and the luciferase reporter system was utilized determine the targeting relationship between LINC00263 and miR-4458. LINC00263 shRNA and miR-4458 inhibitor were co-transfected into breast cancer SK-BR-3 cells, and 6 Gy irradiation was given to detect the changes in cell proliferation, apoptosis, invasion and migration.Results:The expression level of LINC00263 in breast cancer tissues was higher than that in adjacent tissues. The expression level of LINC00263 in breast cancer cells was higher compared with that in normal breast epithelial cells. The radiosensitivity of breast cancer SK-BR-3 cells was increased after transfection of LINC00263 shRNA. Transfection of LINC00263 shRNA and radiation exerted a synergistic effect, jointly inhibited breast cancer cell proliferation, migration and invasion, promoted cell apoptosis, up-regulated the expression levels of C-Caspase-3 and C-Caspase-9 proteins in cells, and down-regulated those of MMP-2 and MMP-9 proteins. Down-regulation of LINC00263 targetedly up-regulated miR-4458 expression. miR-4458 inhibitor reversed the inhibitory effect of LINC00263 shRNA combined with radiation on the proliferation, migration, invasion and apoptosis promotion of breast cancer SK-BR-3 cells.Conclusion:Down-regulating lncRNA LINC00263 targeting miR-4458 inhibits the proliferation, migration and invasion of breast cancer SK-BR-3 cells, and improves cell radiosensitivity.

BACKGROUND: Hemolysis is an important problem in the design and development of artificial heart pumps. Hemolysis is associated with the shear force of blood cells in the pump and the movement time in the pump. OBJECTIVE: To analyze the relationship between the operating parameters of blood pump (flow rate of blood pump), the structure of blood pump (outlet width of blade) and the shear stress of blood cells in artificial heart pump. METHODS: The basic structure of the centrifugal blood pump was designed according to the velocity coefficient method. The three-dimensional model of the blood pump, mesh division and flow field simulation were established by using CFturbo, ANSYS ICEM and FLUENT software respectively to study the best mesh division method. The results of the numerical simulation corrected the diameter of the impeller outlet to finally obtain an artificial heart pump meeting the needs of the human heart. In order to reduce the shear stress and movement time of blood cells in the heart pump, the optimal design and analysis of the impeller inlet flow rate Q (2, 3, 4, 5, 6, 7 L/min) and the operating parameter blade outlet width b2 (2.0, 2.1, 2.2, 2.3, 2.4, 2.5 mm) of the centrifugal artificial heart pump were designed to reduce the probability of hemolysis. RESULTS AND CONCLUSION: (1) As the flow rate increased, the shear stress of the blood cells in the blood pump gradually increased, and the movement time gradually decreased. As the flow rate increased, the standard hemolysis value in the blood pump gradually decreased, and the damage to the blood cells in the blood pump alleviated. When the flow rate was 7 L/min, the standard hemolysis value in the blood pump was the lowest. (2) With the increase of blade outlet width, the shear stress of the blood in the pump decreased, and the movement time of the blood in the pump increased. When the blade outlet width was 2.0-2.5 mm, the hemolysis value in the blood pump decreased with the increase of the blade outlet width. When the blade outlet width was about 2.5 mm, the hemolysis value in the blood pump was the lowest.

Objective The objective of this study was to investigate the abnormal expression of Notch signaling pathway members in pancreatic cancer and its important effect on the development of pancreatic carcinoma. Methods Affymetrix gene expres-sion microarray was used to screen the differentially expressed members of Notch signal pathway in 10 cases of pancreatic carcinoma and its adjacent tissues,and verified by real-time quantitative PCR and Western blotting. The lentivirus expression vector carrying the siRNA fragment of Jagged 2(JAG2)gene was transfected into the pancreatic cancer primary cells to construct the JAG2 gene re-pression-expressing pancreatic cancer cell line. MTT,flow cytometry and Transwell assays were used to analyze cell proliferation, changes of cell cycle and invasive transfer capabilities. Results A total of 512 differentially expressed genes were detected by Affy-metrix gene expression microarray,including 419 up-regulated genes and 93 down-regulated genes. JAG2( up-regulated expres-sion 8. 20 times),NOTCH1(up-regulated expression 3. 74 times),HES1(up-regulated expression 3. 27 times),and NOTCH2(up-regulated expression 3. 16 times)were differentially expressed in Notch signaling pathway. The results of PCR and Western blotting were consistent with those of gene chip. The growth curves of JAG2 gene repressed pancreatic cancer cells and pancreatic cancer pri-mary cells were drawn by the standard OD490 value of d1-d5 by MTT assay. JAG2 gene repressor expression vector could signifi-cantly inhibit the proliferation of pancreatic cancer cells. The cell cycle analysis showed that the apoptosis and the arrested cell cycle at the S phase were significantly increased in pancreatic cancer cells with JAG2 gene repressor expression. The invasive ability was significantly reduced in JAG2 gene repressor expression pancreatic cancer cells(P<0. 05). Conclusion Some members of the Notch signaling pathway are significantly differentially expressed in pancreatic cancer tissues,and repression of this member can affect the growth,cell cycle,invasion and metastasis of pancreatic cancer cells.

Objective To evaluate the assistant effect ofintraoperative OCT (iOCT) in vitreous retinal surgery for macular disease.Methods A retrospective case study.A total of 71 patients (71 eyes) with macular disease who underwent vitrectomy in Eye Hospital of Wenzhou Medical University at Hangzhou from June 2015 to September 2016 were collected.There were 24 males (24 eyes) and 47 females (47 eyes),aged from 25 to 78 years,with the mean age of 63.35± 10.01 years.Among 71 eyes,there were 26 eyes with idiopathic macular hole,42 eyes with idiopathic epiretinal membrane,3 eyes with vitreomacular traction syndrome.The examination of iOCT was performed on the patients during 23G minimally invasive vitreoretinal surgery combined with internal limiting membrane peeling.Use observational method to compare the difference between result of iOCT and observation under the microscope,record the change of treatment strategy.Results Eight eyes (11.27％) iOCT results were different from the surgeon's observation,which including 5 eyes (62.50％) with idiopathic macular hole,2 eyes (25.00％) with idiopathic epiretinal membrane,1 eye (12.50％) with vitreomacular traction syndrome.The treatment strategy was changed in 8 eyes (11.27％) based on iOCT result,which including 5 eyes (62.50％) with idiopathic macular hole,2 eyes (25.00％) with idiopathic epiretinal membrane,1 eye (12.50％) with vitreomacular traction syndrome.Conclusions iOCT can help the surgeon find some subtle morphological changes which can hardly be seen by eyes.The surgeon can change and optimize the treatment strategy based on the result of iOCT.