BACKGROUND:Due to the treatment of cervical spondylosis,the Zero-P system of the anterior cervical interbody fusion system will have problems such as screw loosening and fracture after operation,so a novel Low-P system has been developed. OBJECTIVE:To compare the effects of the novel Low-P and Zero-P anterior cervical intervertebral fusion systems on the biomechanical properties of adjacent segments of the cervical spine and to perform stress analysis on the internal fixation system,so as to provide a theoretical reference for clinical treatment. METHODS:A complete model of the C1-C7 segment of the cervical spine was established.Based on the effectiveness of the model,a finite element model of Low-P(type Z Low-P and type H Low-P)and Zero-P system implanted in C4-C5 segments was established.The stress distribution of implanted devices and adjacent vertebral nucleus pulposus,fibrous rings and end plates was analyzed under the conditions of forward flexion,posterior extension,lateral bending and rotation. RESULTS AND CONCLUSION:(1)After implantation of Low-P and Zero-P internal fixation devices,the range of motion of the type H Low-P system was large;the maximum stress value of type Z Low-P system was small;the maximum stress of Zero-P on the nucleus pulposus of adjacent segments was large;the maximum stress of end plate was small.(2)The influence of three internal fixation systems on adjacent segment fiber rings was close.(3)The screw stress of the Zero-P internal fixation system was much greater than that of the Low-P system.(4)It is indicated that compared with Zero-P type internal fixation system,the novel Low-P system reduces the stress value of steel plate and screw,which can reduce screw loosening and internal fixation system failure.The Low-P system has less stress on the nucleus pulposus of adjacent discs and reduces disc degeneration in adjacent segments.This paper provides a theoretical basis for the clinical study of a Low-P type internal fixation system.

Objective:To evaluate the diagnostic value of rapid on-site evaluation (ROSE) performed by endoscopists for solid pancreatic lesions requiring tissue for immunohistochemistry (IHC) staining with different approach of endoscopic ultrasound-guided tissue acquisition (EUS-TA).Methods:After screening 1 573 cases who underwent EUS-TA operation at the Endoscopy Center of Peking Union Medical College Hospital between August 2018 and October 2022, a total of 65 cases of solid pancreatic lesions whose diagnosis rely on IHC staining was collected and summarized with clinical data of each case. Among 65 cases, there were 46 cases of pancreatic neuroendocrine tumors (PNETs), 13 cases of pancreatic solid pseudo-papillary tumors (SPTs), and 6 cases of lymphomas and mesenchymal. Patients were categorized into ROSE group (36 cases) and non-ROSE group (29 cases) according to the presence or absence of endoscopists performed ROSE during EUS-TA operation. They were further divided into subgroups of FNA-ROSE (26 cases), FNB-ROSE (10 cases), FNA-non-ROSE (24 cases) and FNB-non-ROSE (5 cases) according to the type of EUS-TA. Diagnostic accuracy and IHC success rate were compared between different groups and subgroups. Binomial logistic multifactorial regression analysis was used to evaluate the influence of ROSE and EUS-TA type on diagnostic accuracy and IHC success rate.Results:There were no statistically significant differences between ROSE group and non-ROSE group in terms of age, gender, bilirubin level, CA19-9 level, lesion site, lesion size, composition ratio of diagnosis, and surgical rate. The differences in mean size of lesions, needle gauge, location of puncturation, and number of needle pass between subgroups were not statistically significant. The diagnostic accuracy was 88.9% in ROSE group and 79.3% in non-ROSE group, and the difference between the two groups was statistically significant ( P=0.023). The diagnostic accuracy of FNA-ROSE group was higher than that of FNA-non-ROSE group (88.5% vs 75.0%), but the difference was not statistically significant ( P>0.100). The differences in diagnostic accuracy and success rate of IHC between FNB-ROSE group and FNB-non-ROSE group were not statistically significant. Binomial logistic multifactorial regression analysis did not reveal any independent influences on diagnostic accuracy. Conclusions:ROSE performed by endoscopists improved diagnostic accuracy of EUS-TA in solid pancreatic lesions requiring IHC staining, and therefore is potentially valuable for improving the diagnostic efficiency of EUS-TA for such diseases.

Objective:To investigate the diagnostic value of nucleic acid matrix-assisted laser desorption ionization-time of flight mass spectrometry（MALDI-TOF MS）in sputum smear-negative patients with nontuberculous Mycobacterial（NTM）pulmonary disease.Methods:Clinical data of 123 patients suspected of NTM pulmonary disease admitted in Public Health Clinical Center Affiliated to Shandong University between July 2022 and November 2023 were retrospectively analyzed. Bronchoalveolar lavage fluid（BALF）specimens were collected for MALDI-TOF MS assay and MGIT 960 culture. The diagnostic efficacy of MALDI-TOF MS for NTM pulmonary disease in patients with negative sputum smears for acid-fast bacilli was evaluated with receiver operating characteristic（ROC）curve. Statistical analysis was performed using SPSS 26.0 software and MedCalc statistical software.Results:Diagnosis of NTM pulmonary disease was finally confirmed in 66 out of the 123 suspected patients. It took 8 to 24 h for MALDI-TOF MS to identify NTM species and resistance. By MALDI-TOF MS，72 NTM strains were identified，with the Mycobacterium avium complex being the most prevalent（34 strains，47.22%），followed by the Mycobacterium abscessus complex（13 strains，18.06%）；resistance to macrolides was detected in 6 cases，while no resistance to aminoglycosides was found. It took 9 to 45 days for BALF MGIT 960 culture to identify NTM，and took 7 to 15 days for NTM typing and drug sensitivity testing. By BALF MGIT 960 culture，28 NTM strains were identified；and 1 case was found to be resistant to macrolides. Using confirmed diagnosis as the gold standard，MALDI-TOF MS demonstrated higher sensitivity，negative predictive value，and agreement rate compared to MGIT 960 culture（84.85% vs. 42.42%，81.13% vs. 56.32%，80.49% vs. 62.60%， χ2=25.667，8.998，9.664， P<0.05 or <0.01）. The area under ROC curve（AUC）for MALDI-TOF MS was significantly higher than that of MGIT 960 culture（0.801 vs. 0.642， Z=3.300， P=0.001）. Conclusion:Compared to MGIT 960 culture，MALDI-TOF MS exhibits superior diagnostic efficiency in detecting NTM pulmonary disease in patients with acid-fast bacilli smear-negative sputum，with advantage of rapidly identifying NTM species and resistance.

Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Takeda G protein-coupled receptor 5(TGR5)is a bile acid receptor located on the surface of cell membrane,widely distributed in many tissues and cells in the body,and can be directly activated by most bile acids in vivo.TGR5 plays an important role in various physiological and pathophysiological processes,including cellular Ca2+transport,oxidative stress,cell proliferation,inflammatory responses,and mitochondrial metabolism,thereby maintaining mitochondrial homeostasis and vascular endothelial function,and inhibiting the progression of cardiovascular diseases such as atherosclerosis,myocardial hypertrophy,and cardiac remodeling after myocardial infarction.Currently,with the gradual clinical application of numerous bile acid and bile acid derivatives drugs,it is necessary to further investigate the role of TGR5 in the cardiovascular system,which is an important basis for clinical application of these new drugs.This review discusses the relationship between TGR5 and cardiovascular system from five perspectives:TGR5's involvement in regulating macrophages,endothelial function,vascular smooth muscle cells,cardiomyocytes,and mitochondrial metabolism.It summarizes the recent research progress,aiming to provide the theoretical basis for TGR5 as a novel therapeutic target for cardiovascular diseases.

Objective To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation,and to establish a nomogram prediction model.Methods A total of 167 patients with femoral neck fracture from Jan-uary 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period.There were 21 males and 17 females in the necrosis group,aged from 33 to 72 years old,with an average of(53.49±10.96)years old,and the time from injury to operation ranged from 40 to 67 hours,with average time of(53.46±7.23)hours.There were 72 males and 57 females in the non-necrosis group,aged from 18 to 83 years,with an average of(52.78±12.55)years old,and the time from injury to operation was 18 to 65 hours,with an aver-age time of(39.88±7.79)hours.The potential influencing factors,including patient gender,diabetes mellitus,hypertension,chronic liver disease,posterior inclination angle of the femoral head,operation mode,fracture displacement,fracture line loca-tion,preoperative braking traction,screw arrangement mode,reduction quality,age,body mass index(BMI),and injury to operation time were subjected to single factor analysis.Logistic multivariate regression analysis was conducted for factors with a significance level of P＜0.05.Results The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76％.The following factors were identified as independent risk factors for early postoperative femoral head necrosis in pa-tients with femoral neck fractures:coexisting diabetes[OR=5.139,95％CI(1.405,18.793),P=0.013],displaced fracture[OR=3.723,95％CI(1.105,12.541),P=0.034],preoperative immobilization[OR=3.444,95％CI(1.038,11.427),P=0.043],quality of reduction[OR=3.524,95％CI(1.676,7.411),P=0.001],and time from injury to surgery[OR=1.270,95％CI(1.154,1.399),P=0.000].The Hosmer-Lemeshow goodness-of-fit test(x2=3.951,P=0.862),the area under the receiver operator characteristic(ROC)curve was 0.944[P＜0.001,95％CI(0.903,0.987)],with a sensitivity of 89.50％,the specificity was 88.40％,the maxi-mum Youden index was 0.779,and the overall trend of the model correction curve was close to the ideal curve.Model regres-sion equation was Z=1.637 × diabetes+1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduc-tion quality+0.239 ×injury to operation time-18.310.Conclusion The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors.The risk early warning model established according to the factors has good predictive efficacy.

An innovative on-site real-time avian influenza virus(AIV)detection method was estab-lished by integratingrecombinase-aided amplification(RAA)with the clustered regularly inter-spaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)system.After analy-zing 120 sequences of the M gene of avian influenza viruses of different subtypes publicly available on NCBI,the RAA primers and crRNA were designed based on the identified highly conserved segment and used for RAA nucleic acid amplification.After the amplified products were transferred to a CRISPR/Cas13a detection system,the fluorescence values were monitored throughout the re-action process to indicate the results.The sensitivity and specificity of the RAA-CRISPR/Cas13a method were validated using gradient dilutions(106-100 copies/μL)of positive plasmids and sev-en other avian viruses.Fifty clinical samples were tested using this method and compared with the national standard fluorescence RT-PCR method.The results indicated that the detection limit for RAA-CRISPR/Cas13a method was 102 copies/μL,a two-fold improvement over the standard RAA.Specificity assay showed the established method only detected AIV with no cross-reactivity with other seven avian viruses.Compared to the national standard fluorescence RT-PCR method,this method exhibited 100％specificity,95.24％accuracy,and 98.00％consistency in detection of clinical samples.In conclusion,a universal and rapid RAA-CRISPR/Cas13a for detection of AIV was established with the capacity of achieving detection within 60 minutes at 37 ℃,which provides a rapid,sensitive,and specific on-site detection method for AIV.

Aim To explore the role of Takeda G pro-tein-coupled receptor 5(TGR5)in the proliferation and migration of vascular smooth muscle cells(VSMCs)within the intimal layer of mice.Methods Mouse VSMCs were stimulated for proliferation and migration with PDGF-BB,followed by administration of INT-777 for activation of TGR5.CCK-8 assay and Ki-67 immunofluorescence staining were employed to eval-uate cell proliferation.The scratch assay was utilized to assess migration.Western blot analysis was conducted to monitor TGR5 protein expression.To further investi-gate the role of TGR5 in intimal hyperplasia in vivo,20 male wild-type C57BL/6J mice were randomly divided into four groups:sham group,carotid artery endothelial injury group,sham+UDCA(ursodeoxy-cholic acid,a TGR5 agonist)group,and carotid artery endothelial injury+UDCA group(n=5 in each group).After the establishment of endothelial injury model,mice were orally fed with regular maintenance feed containing 0.5％UDCA for 21 days.Subsequent-ly,samples were collected for Hematoxylin and Eosin(HE)staining to assess the neointimal hyperplasia.Immunofluorescence(IF)staining was used to exam-ine the proliferation of VSMCs within the carotid inti-ma.Results The specific activation of TGR5 marked-ly diminished cell viability,the proportion of Ki-67-positive cells,and slowed down the rate of wound-heal-ing.Notably,the specific activation of TGR5 increases the expression of UCP2 in cells and reduces the levels of reactive oxygen species(ROS).The inhibitory effect of TGR5 on VSMC proliferation and migration was neutralized upon the restoration of intracellular ROS level with H2O2.Activation of TGR5 was found to mitigate intimal thickening following carotid artery inju-ry.Conclusion TGR5 may inhibit the proliferation and migration of mouse VSMCs by attenuating intracel-lular oxidative stress.