The ezrin,radixin,moesin(ERM)protein family plays a pivotal role in cell morphology,migration,and signal transduction.Ezrin,as a prominent member of this family,is highly involved in these processes.Ezrin phosphorylation is particularly crucial,by regulating the interaction between ezrin and the actin cytoskeleton.This interaction is a key mediator of cytotoxicity in host cells infected with Helicobacter pylori,significantly impacting cell morphology.In this review,we comprehensively summarize the multifaceted role of ezrin protein in H.pylori-induced nodular gastritis.We consider the relationships between ezrin's structure,function,signaling pathways,and phosphorylation in the context of nodular gastritis.Moreover,this review highlights the role of ezrin protein as a potential therapeutic target,offering novel insights for the prevention and treatment of nodular gastritis.

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.

BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches. METHODS: We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs. RESULTS: The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling. CONCLUSION We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.
Humans ; Thymoma ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins/genetics* ; China ; Thymus Neoplasms/pathology* ; Prognosis ; Neuroendocrine Tumors/pathology* ; Mutation/genetics*

Objective:To investigate the status of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) in emergency department.Methods:Participants of a national emergency conference from August 1st to August 4th in 2019 from hospitals of different levels in different regions were interviewed by online questionnaire to collect data about the current status and limitations of the application of RCA in emergency CRRT by convenient sampling.Results:Totally 407 questionnaires were collected through internet, and the completeness of the answers was as high as 100%. Twenty-three responses with logic errors were excluded, and 384 questionnaires were finally retrieved, with an effective rate of 94.35%. Representatives from 29 provinces, autonomous regions and municipalities directly under the Central Government participated in the questionnaire survey, and the hospitals in which they worked were mainly class Ⅲ grade A [70.31% (270/384)]. The survey showed that 61.46% (236/384) of the emergency departments could carry out CRRT independently. There were less than 10 CRRT cases per month in most emergency departments [52.87% (166/314)]. In the emergency departments where CRRT were carried out, heparin was a widely used and well-applied anticoagulant [82.17% (258/314)], and 199 emergency departments (63.38%) were proficient in RCA. In clinical practice, heparin [49.68% (156/314)] was preferred to RCA [25.80% (81/314)] and low molecular weight heparin [23.56% (74/384)]. In the emergency departments where RCA could be used skillfully, 4% sodium citrate was the main regional anticoagulant [68.34% (136/199)]. Anticoagulation protocol came from different sources, most of which were from nephrology or dialysis center (29.65%). Most departments could adjust the ionized calcium before the filter to the target safety level [0.9-1.2 mmol/L, 88.94% (177/199)], and adjust the ionized calcium after the filter to the target ideal anticoagulation level [0.2-0.4 mmol/L, 93.47% (186/199)] within 4 hours. The common complications that emergency physicians concerned were accumulation of citrate [58.29% (116/199)], metabolic alkalosis [54.77% (109/199)] and metabolic acidosis [37.19% (74/199)]. In 281 emergency departments that could not use RCA, there were kinds of factors that limited the use of citrate, such as higher cost than heparin (31.67%), unskilled personnel (21.00%), limited source of citrate (17.08%), concerns of complications (11.74%). At present, the substitution fluids used in clinical practice were mainly the commercial products (45.54%). In most cases, emergency CRRT filters had a life span of 12-23 hours (39.49%).Conclusions:The use of RCA in domestic emergency CRRT is low. Compared with the international peers, we are still lacking of adequate understanding of RCA. Therefore, it is necessary to develop an anticoagulation protocol of RCA for emergency departments in China, and promote training of CRRT.

OBJECTIVE: To study the effect of nano-cerium oxide on the early development of zebrafish embryos. METHODS: The well-developed zebrafish embryos were randomly divided into the control group and the 50, 100, 200, 400 and 800 mg/L dose groups, with 40 embryos in each group. The dose groups were treated with nano-cerium oxide at the corresponding mass concentration for 5 days. The control group received no treatment. The death and malformation of embryos were observed. The heart rate of zebrafish embryos was recorded using confocol microscope. The protein expression of microtubule-associated protein 1 light chain 3(LC3) and cleaved Caspase-3 and were observed by Western blot technology. RESULTS: The death and embryonic malformation rate of zebrafish embryos increased with the increase of doses, showing statistical significance(P<0.01). The heart rate of the 800 mg/L dose group was decreased compared with the control group [(77±8) vs(93±4) beats/min, P<0.01]. There was no statistical significant difference in LC3-Ⅱ protein expression in each groups(P>0.05). The cleaved Caspase-3 protein expression increased in all dose groups compared with the control group(P<0.05). The cleaved Caspase-3 protein expression in the 200 mg/L dose group was higher than that in the 50 mg/L dose group(P<0.05). CONCLUSION: The nano-cerium oxide may induce cell apoptosis, causing toxic effect in early development of zebrafish embryos.

Objective To compare the planned radiation dose and the actual dose received after 125I radioactive seeds implantation supported by coplanar template (CPT) in lung cancer patients with mediastinal node metastases 4R,and to evaluate the clinical efficacy.Methods Totally 32 patients with lung cancer with mediastinal lymph node metastases 4R who had been diagnosed via cellular pathology studies were selected from January 2008 to December 2014.The mediastinal lymph node metastases were treated by CPT-assisted 125I radioactive seed implantation.Digital imaging and communications in medicine (DICOM) data were acquired by chest CT scan before implantation,brachytherapy radiation treatment planning system (BTPS) was introduced to carry out the plan,and the prescribed dose(PD) was 120 Gy.CPT was used to control the precision of needle penetration and implantation of radioactive seeds.Computer tomography (CT) was used to ensure the correct position of needles and radioactive seeds.Dose evaluation was performed immediately after implantation and was compared with planned dose using paired t-test.The 6-months postoperative chest CT was conducted to evaluate treatment efficacy according to response evaluation criteria in solid tumors(RECIST Version 1.1).Results All patients went through implantation procedure successfully.Dose evaluation after implantation was as followed.The average dose received (231.9 ±29.6)Gy,the dose received by 90％ of the target(D90) (150.8 ± 16.6) Gy,the dose received by 100％ of the target(D100) (100.4 ± 12.6)Gy,the volume of 100％PD covering the target(V100)(94.1 ± 2.6) ％,the volume of 200％ PD covering the target(V200) (33.0 ± 5.7) ％,the conformal index (CI) 0.75 ±0.06,the external index(EI) (22.7 ± 5.8)％,the average dose received by the superior vena cava (19.3 ± 7.2)Gy,and the average dose received by aorta (12.1 ± 5.1)Gy.Efficacy was followed for 6 months after implantation and the effective rate was 84.37％.There was no serious complications (such as radioactive lung injury,major vascular injury,bleeding,and et al.) occurred in follow-up period.Conclusions CPT assisted CT guided 125I radioactive seed imnplantation in treating mediastinal node metastases 4R can achieve preoperative BTPS,minimize major vascular or organ injury.It is an accurate,effective and safe treatment approach and may be of great value to standardize the procedure of radioactive seed implantation in mediastinal metastases.

Objective To observe the effects of nonylphenol(NP)on the intracellular calcium concentration changes and cell proliferation,and the involvement of GPR30 receptor in H9c2 cell. Methods The intracellular calcium concentration changes were recorded by using intracellular calcium determination method and cell proliferation was observed by MTT method in H9c2 cell. Results NP(1×10-10 mol/L)increased the intra?cellular calcium concentration changing amplitude and promoted the proliferation of H9c2 cells,while NP(1×10-6 mol/L)decreased intracellular calcium concentration changing amplitude and suppressed cell proliferation. G15 could block the promoting effect of 1×10-10 mol/L NP on the intracel?lular calcium concentration and cell proliferation,but could not block the inhibition of 1×10-6 mol/L NP on the intracellular calcium increase and cell proliferation. Conclusion The results indicate that NP affect rapid calcium signal changes and cell proliferation in non?monotonic dose dependent manner,and its mechanism may be due to the different involvement of GPR30 receptor in different concentrations.

BACKGROUNDAnterior cruciate ligament reconstruction (ACLR) has developed dramatically in the last century. Now, ACLR has become a reliable and productive procedure. Patients feel satisfied in >90% cases. The aim of this study was to evaluate the feasibility of allogenetic cortical bone cross-pin (ACBCP) used as a clinical fixation method in anterior cruciate ligament reconstruction on the femoral side based on biomechanical tests in vitro.

METHODSThe specimens were provided by the bone banks of the First Affiliated Hospital of People's Liberation Army of General Hospital from September 2011 to June 2012. Fresh deep frozen human allogenetic cortical bone was machined into cross-pins which is 4.0 mm in diameter and 75.0 mm in length. Biomechanical parameters compared with Rigidfix were collected while cross-pins were tested in double-shear test. The load-to-failure test and cycling test were carried out in a goat model to reconstruct anterior cruciate ligament with Achilles tendon autograft on the femoral side fixed by human 4.0 mm ACBCP and 3.3 mm Rigidfix served as control. Maximum failure load, yield load, and stiffness of fixation in single load-to-failure test were compared between the two groups. Cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 were also compared in between.

RESULTSIn double-shear test both maximum failed load and yield load of 4.0 mm human ACBCP were (1 236.998±201.940) N. Maximum failed load and yield load of Rigidfix were (807.929±110.511) N and (592.483±58.821) N. The differences of maximum failed load and yield load were significant between ACBCP and Rigidfix, P < 0.05. The shear strength of ACBCP and Rigidfix were (49.243±8.039) MPa and (34.637±3.439) MPa, respectively, P < 0.05. In the load-to-failure test ex vivo, yield load and maximum failed load of ACBCP fixation complexity ((867.104±132.856)N, (1 032.243±196.281) N) were higher than those of Rigidfix ((640.935±42.836) N, (800.568±64.890) N, P < 0.05). However, stiffness did not differ significantly between ACBCP group ((247.116±31.897)N/mm) and Rigidfix group ((220.413±51.332) N/mm, P > 0.05). In the cycling test, the cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 did not differ significantly between the ACBCP group and Rigidfix group, P > 0.05.

CONCLUSIONSAllogenetic cortical bone cross-pin possesses satisfactory biomechanical profile which is safe for ACLR and suitable for an aggressive rehabilitation program. Animal and clinical tests should be recommended before clinical use to secure the ACBCP could successfully substituted by host new bone in vivo.

Achilles Tendon ; surgery ; Adult ; Anterior Cruciate Ligament ; surgery ; Anterior Cruciate Ligament Reconstruction ; Female ; Femur ; surgery ; Humans ; Male ; Materials Testing ; Middle Aged ; Orthopedic Fixation Devices

Objective To investigate clinical efficacy of different ventilator parameters on acute left heart failure.Methods One hundred and nineteen patients with acute left heart failure were randomly divided into A,B,C,D group.Patients in A,B,C,D groups were treated separately with higher air pressure,high pressure,medium pressure or low pressure respectively.In each group,clinical efficacy,heart rate (HR),arterial partial pressure of oxygen (PaO2),pulse oxygen saturation (SpO2),partial pressure of carbon dioxide (PaCO2) and pH were measured.Results There were significant differences among the four groups in terms of HR,PaO2,SpO2,PaCO2 and pH (F =32.21,29.46,12.34,36.47,18.38 ; P ＜ 0.05).Compared with that in A,C and D group,the levels of HR,PaO2,SpO2,PaCO2 and pH in B group were significant difference (P ＜ 0.05).Meanwhile those indices in B group were difference among before and after treatment (t =12.25,13.46,8.75,9.83,2.58 ;P ＜ 0.05).The efficacy rates of four groups were significant different (x2 =0.97,P =0.012),and in B group was 93.1％,higher than that of other 3 groups(71.0％,65.6％,51.8％ ;P ＜0.05).Condusion The ventilator parameters(10-15 cmH2O,55％-75％ FiO2 at beginning and later revised the FiO2 to 30％-40％) was proved to be worthy in treating acute left heart failure.