Objective:To explore the correlation between the characteristics of contrast-enhanced sonography of intraoperative glioblastoma multiform (GBM) and molecular markers of isocitrate dehydrogenase-1(IDH1).Methods:A retrospective analysis were performed in 30 patients who underwent neurosurgery and pathologically confirmed to be GBM at Beijing Tiantan Hospital from May 2018 to April 2019. All neurosurgical glioblastoma patients after craniotomy underwent conventional ultrasound and contrast-enhanced ultrasound(CEUS) guided navigation. The characteristics of the ultrasound imaging (whether the tumor involves the structure of the corpus callosum, the clarity of the tumor boundary after enhanced ultrasound and whether the tumor has necrotic areas with enhanced ultrasound images) were analyzed. The ratio between tumor necrosis area and whole tumor area (N/W) was measured, and the correlation with IDH1 gene expression was analyzed.Results:There were statistical differences in clarity of tumor boundary after CEUS and tumor necrosis after CEUS between positive IDH1 and negative IDH1 groups(all P<0.05). The positive expression of IDH1 was negatively correlated with the N/W area of the contrast-enhanced ultrasound mode( r=-0.756, P<0.05), suggesting that the expression level of IDH1 gene was negatively correlated with the area of tumor necrosis. Conclusions:Ultrasound contrast agent examination can more accurately distinguish the active proliferation area, hemorrhagic necrosis area and peripheral edema area of glioblastoma. Accurately identifying the extent of tumor necrosis area through ultrasound contrast agent examination can predict expression of IDH1.

Objective:To systematically evaluate the volumetric changes of upper airway after rapid maxillary expansion using Meta analysis.Methods:All literatures about volumetric changes in the upper airway after rapid maxillary expansion were searched from the database in general.The literatures were screened according to the correlation and the inclusion criteria,included the literatures were analyzed by Rev Man 5.3.Results:11 literatures were finally selected.Meta analysis indicated that,after treatment nasopharyngeal volume increased by 0.62 cm3(P=0.000 2),palatopharyngeal volume increased by 0.62 cm3(P=0.02),glossopharyngeal volume increased by 0.39 cm3(P=0.11),oropharyneal volume increased by 0.40 cm3(P=0.27).Conclusion:The existing evidence indicates that rapid maxillary expansion can increase the volume of nasopharynx and retropalatal part of upper airway.

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

OBJECTIVETo detect potential mutation of EXT1 gene in a pedigree affected with multiple osteochondroma and explore its pathogenic mechanism.

METHODSThe coding regions and their flanking sequences of the EXT1/EXT2 genes were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified by excluding possible single nucleotide polymorphisms and bioinformatics analysis. Transcripts of the EXT1 gene in the proband were analyzed by TA clone-sequencing, with its abundance compared with that of healthy controls.

RESULTSDNA sequencing has identified in the proband a novel heterozygous point mutation (c.1164+1G to A) at the 5'splice sites of intron 3 of the EXT1 gene. The same mutation was not found in the healthy controls. Bioinformatics analysis indicated that the mutation is highly conserved and can lead to skipping of exon 3 or aberrant splicing. TA clone-sequencing indicated that the numbers of transcripts with skipping of exon 3 has significantly increased in the proband (< 0.05) compared with the controls.

CONCLUSIONThe c.1164+1G to A mutation has resulted in skipping of exon 3 in a proportion of EXT1 gene transcripts. As the result, the number of transcripts with tumor suppressing function is relatively reduced and has ultimately led to the tumors.

Adult ; Base Sequence ; Child ; Exostoses, Multiple Hereditary ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; N-Acetylglucosaminyltransferases ; genetics ; Point Mutation ; RNA Splice Sites ; RNA Splicing

Objective:To explore the efficacy, safety, and feasibility of single port laparoscopic liver resection via umbilical cord, and summarize its surgical experience.Method:A retrospective analysis was conducted on 39 patients who underwent liver resection surgery at the Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University from February 2022 to September 2023. There were 19 patients in the transumbilical single-port laparoscopic group, including 5 males and 14 females, aged (49.6±2.5) years. There were 20 patients in the multi-port laparoscopic group, including 7 males and 13 females, aged (49.9±3.1) years. The intraoperative blood loss, operation time, intestinal recovery time, postoperative hospital stay and postoperative complications were compared between the single-port group and multi-port group.Results:All 39 patients successfully completed the surgery without any additional foramen or conversion to open surgery. The operation time of the single hole group (166.3±59.0) min was longer than that of the multi-port group (123.2±48.0) min, and the difference was statistically significant ( t=2.50, P=0.020). There were no statistically significant differences in intraoperative blood loss, intestinal recovery time, postoperative hospital stay, and postoperative complications between these two groups (all P>0.05). All patients had no postoperative complications such as bleeding, infection, or bile leakage. Follow up for 3~21 months showed no recurrence of primary diseases such as hepatic hemangioma, hepatic adenoma, and intrahepatic bile duct stones. The aesthetic effect of the umbilical incision in the single orifice group was significant, and patient satisfaction was 100%. Conclusion:Umbilical single-port laparoscopic liver resection surgery is safe and feasible, with significant minimally invasive and aesthetic effects.

Objective To explore the anti-inflammatory effect of Qingre Jiedu(QRJD)formula on mice with gout and its effect on gut microbiota.Methods Forty C57BL/6 mice weighing 20～22 g were divided into control(CON),model(MOD),allopurinol(ALLO),and QRJD formula(QRJD)groups,and i.g.10 g/0.1 mL carboxymethyl cellulose was administered to the CON every morning from 1 to 35 days.A hyperuricemia mouse model was prepared by intragastric injection of a potassium oxalic acid(500 mg/kg)and yeast extract(10 g/kg)suspension.On day 29,50 μL sterile carboxymethyl cellulose was injected into the right ankle of mice in the CON group under isoflurane-induced anesthesia,and a gouty arthritis model was prepared by injecting the same volume of sodium urate(50 mg/mL)into the right ankle of mice in the other groups.Each group was treated with corresponding drugs every day.On day 35,samples were collected from mice that had been fasted for 6 hours without water.Blood indexes,such as uric acid,creatinine,and urea nitrogen,were assessed.Hematoxylin-eosin and saffranine O-fast green staining was performed on ankle joints.Anti-inflammatory indexes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)were detected by ankle joints immunohistochemical assay.The cecum contents of mice were collected,and changes in gut microbiota were analyzed by high-throughput sequencing of 16S rDNA.Results(1)After 7 days of treatment,compared with the MOD group,QRJD formula effectively reduced the blood concentrations of uric acid(P＜0.001),creatinine(P＜0.01),and urea nitrogen(P＜0.05),and effectively protected renal functions.(2)Compared with the MOD group,HE staining showed that synovial hyperplasia and inflammatory cell infiltration were reduced in the QRJD formula group after treatment.The cartilage arrangement of the compound was more orderly than before,cartilage destruction was less than that in the MOD group,and no matrix loss was observed.(3)Immunohistochemical analysis of the ankle joint indicated that IL-10 and TGF-β1 were not significantly increased in CON and MOD groups.Compared with the MOD group,IL-10 and TGF-β1 expression in the QRJD formula group were increased(P＜0.05).(4)In terms of biodiversity,the number of MOD-specific OTUs increased by 75 compared to the CON group,while the QRJD was able to reduce the number of MOD-specific OTUs to more closely resemble the CON group;no significant difference was found in α-diversity among the four groups(P＜0.05),whereas β-diversity was more similar to the CON group(P=0.001).(5)Compared with the CON group,the MOD group exhibited increased abundances(P＜0.05)of Ruminococcaceae spp.,Dubosiella sp.,Tyzzerella sp.,Ileibacterium sp.,and Bacteroidales spp..In contrast to the MOD group,the QRJD formula group showed elevated abundances(P＜0.05)of Lactobacillus sp.,Ligilactobacillus sp.,and Bacteroides sp..Furthermore,an interaction network of gut microbiota indicated mutual interactions among these microorganisms.(6)In the correlation analysis between gut microbiota and renal functions as well as anti-inflammatory factors,the relative abundances of Dubosiella sp.,Tyzzerella sp.,and Bacteroidales spp.were significantly positively correlated to SUA and SCR(P＜0.05).However,Lactobacillus sp.,Ligilactobacillus sp.,and Mitochondria spp.exhibited a positive correlation to anti-inflammatory factors IL-10 and TGF-β1 with a more significant association observed for TGF-β1(P＜0.05).(7)COG function prediction suggested that the functions of the QRJD formula group were concentrated on inorganic ion transport and metabolism,and carbohydrate transport and metabolism.Conclusions QRJD effectively modulates immune inflammation and gut microbiota dysbiosis,thereby treating gout.Its mechanism of gout prevention and treatment may involve regulation of gut microbiota diversity and abundance,as well as the control of the abundance of differential bacterial species,such as Ruminococcaceae spp.,Dubosiella sp.,and Lactobacillus sp.,to achieve gout therapy.

Objective:To investigate the effects of of anti tumor necrosis factor-α (TNF-α) in adjuvant treatment of strangulated intestinal obstruction combined with ischemic intestinal necrosis.Methods:From February 2011 to August 2016 in Huadu District People′s Hospital Affiliated with Southern Medical University, 122 patients with strangulated intestinal obstruction combined with ischemic intestinal necrosis were selected and were equally divided into the experimental group and control group with 61 cases in each group according to the random draw envelope principle. Conventional surgical resection and anastomosis was used in control group, the postoperative anti TNF-α therapy was given for 2 weeks based on the treatment in control group.Results:All patients completed surgery and there were no serious complications during operation.The postoperative anal exhaust time and symptom remission time in experimental group were significantly lower than those in control group: (2.14 ± 0.41) d vs. (6.24 ± 1.28) d and (3.54 ± 0.77) d vs. (6.99 ± 0.91) d ( P<0.05). The incidence of postoperative 14 d complications such as anastomotic leakage, wound infection, anastomotic stenosis and pulmonary infection in the experimental group was 4.9%(3/61), and that of the control group was 18%(11/61), and the incidence of postoperative complications in the experimental group was significantly lower than that in the control group ( P<0.05). The postoperative 1d and 7 d serum TNF-α content in the experimental group was significantly lower than that in the control group ( P<0.05). The postoperative 14 d anal function in the experimental group was significantly better than that in the control group ( P<0.05). MRASP and MSP of postoperative 14 d in experimental group were all significantly higher than those in the control group: (80.24 ± 11.39) mmHg (1 mmHg=0.133 kPa) vs. (76.24 ± 12.11) mmHg, (231.98 ± 45.29) mmHg vs. (226.39 ± 41.87) mmHg ( P<0.05). Conclusions:The anti TNF-α in adjuvant treatment of strangulated intestinal obstruction combined with ischemic intestinal necrosis can promote the recovery of clinical symptoms and inhibit the release of TNF-α. It also can reduce the incidence of postoperative complications and improve gastrointestinal motility of patients.

BACKGROUND:Piezo1,a mechanosensitive protein,is tightly connected to osteogenic differentiation,and it has been demonstrated that TAZ has a role in regulating osteogenic differentiation.It is unclear whether TAZ participates in the regulation of osteogenic differentiation of human bone marrow mesenchymal stem cells by Piezo1,so it is crucial to investigate its unique mechanism to prevent osteonecrosis of the femoral head. OBJECTIVE:To elucidate what function Piezo1 plays in osteogenic differentiation and TAZ expression in human bone marrow mesenchymal stem cells. METHODS:The siRNA targeting Piezo1 was constructed and transfected into 293T cells.The silencing efficiency was detected by RT-qPCR.The selected Piezo1-Home-2337 was packaged according to the silencing efficiency,and its optimal multiplicity of infection value was assayed by immunofluorescence staining.The packaged Piezo1 silencing recombinant lentivirus was transfected into human bone marrow mesenchymal stem cells,and its silencing effect was detected by RT-qPCR and western blot assay.Alizarin red staining,alkaline phosphatase activity analysis,immunofluorescence staining,RT-qPCR and western blot assay were utilized to analyze the effect of silencing Piezo1 on the osteogenic differentiation of human bone marrow mesenchymal stem cells. RESULTS AND CONCLUSION:(1)The mRNA and protein levels of Piezo1 in human bone marrow mesenchymal stem cells transfected by si-Piezo1 were decreased significantly,with a statistically significant difference compared with normal and negative control groups.(2)The alkaline phosphatase activity in the si-Piezo1 group was much lower and the calcium deposition in the si-Piezo1 group was significantly reduced compared with the negative control group.(3)The mRNA levels of osteogenesis-related genes including Runt-related transcription factor 2(Runx2),osteopontin(OPN),distal-less homeobox 5(DLX5),osteocalcin,β-catenin and Tafazzin(TAZ)in the si-Piezo1 group were significantly decreased compared with the negative control group.Afterward,the expression levels of TAZ and β-catenin protein in the si-Piezo1 group were down-regulated significantly compared with the negative control group,whereas the expression levels of p-TAZ and p-β-catenin protein in the si-Piezo1 group had the opposite condition.(4)The results of immunofluorescence staining showed that the expression of TAZ and β-catenin in human bone marrow mesenchymal stem cells in the si-Piezo1 group was less compared with the negative control group.(5)These findings indicate that Piezo1 can promote the osteogenic differentiation of human bone marrow mesenchymal stem cells.The osteogenic ability of human bone marrow mesenchymal stem cells is significantly reduced after silencing Piezo1,and the expression of TAZ is also reduced.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.