BACKGROUND:Intramedullary nail has achieved a good clinical result in the treatment of femoral shaft fractures,but some patients still have aseptic nonunion due to mechanical instability.The femur is the longest and largest bone in the human body,but there are few studies on whether the fracture of the femur has different biomechanical results in different areas and the influence of different inserting methods on the stability of fracture fragments in different areas. OBJECTIVE:To analyze the biomechanical characteristics of anterograde and retrograde intramedullary nails in the treatment of different areas of femoral shaft fractures,and to evaluate the best way of insertion to reduce the incidence of nonunion. METHODS:CT data of a healthy volunteer were selected to import into the software of Mimics 19.0 and Geomagic studio 2017 to extract and optimize the three-dimensional model of the right femur.The anterograde and retrograde intramedullary nail models were built with Solidworks 2017 software and assembled with femoral shaft fracture models at different fracture areas according to standard surgical techniques.The models were imported into Abaqus 2017 software in STEP format to set material attribute parameters,boundary conditions,load and submit calculation,and the results were viewed in the visualization module.Among them,the antegrade and retrograde intramedullary nails of the upper femoral shaft fracture were A1 and A2 models,B1 and B2 models in the middle segment,and C1 and C2 models in the lower segment. RESULTS AND CONCLUSION:(1)In models A1,B1 and C2,the overall stress distribution of the femur was more uniform,and the placement,the displacement and angle of the fracture site,and inversion angle of the proximal femoral bone fragment were smaller.(2)For the upper and middle femoral shaft fractures,the anterograde intramedullary nail has a better biomechanical effect.For lower femoral shaft fractures,a retrograde intramedullary nail is preferable.

ObjectiveTo observe the effect of bee acupuncture therapy on clinical symptoms and signs， as well as the level of inflammatory cytokine interleukin-6 （IL-6） in synovial fluid of patients with knee osteoarthritis. MethodsThe 94 patients with knee osteoarthritis were divided into the control group and the trial group by the random number table method， with 47 cases in each group. Both groups were given one tablet （60 mg） of etoricoxib orally every morning for 2 weeks. The control group also received microneedle shallow acupuncture therapy， once a day for 5 consecutive times followed 2-day pause， and continued 5 consecutive times， as a course of treatment； the trial group was treated with bee acupuncture therapy once every 2 days， 2 times a week， and 4 times as a course of treatment. Both groups have a course of treatment for 2 weeks. The changes in clinical symptoms and signs of patients in the two groups were observed and evaluated before treatment， after 1- and 2-week treatment， and 12-week follow-up and the differences in Lequesne index scores， HSS scores， Visual Analogue Scale （VAS） scores and IL-6 levels in knee synovial fluid between the two groups of patients were also compared. ResultsNo patients lost to follow up in either group. The Lequesne index scores and VAS scores were lower， and the HSS scores were higher in both groups at all time points after treatment compared with those before treatment （P＜0.05）. Compared at the same time after treatment， the Lequesne index scores and VAS scores of the trial group were lower than those of the control group， and the HSS scores were higher than those of the control group （P＜0.05）. IL-6 in synovial fluid was lower in the trial group at the 12-week follow-up than before treatment （P＜0.05）， but there was no significant difference between two groups at each time point（P＞0.05）. ConclusionBee acupuncture therapy for knee osteoarthritis can significantly improve clinical signs and symptoms， but has no significant effect on the level of IL-6 in knee synovial fluid.

Allergic rhinitis(AR)is a type Ⅰ allergic reaction,which mediated by immunoglobulin E immediately when an individual with a special constitution is exposed to a same allergen for second time,whose pathogenesis has not been clarified yet,and closely related to genes,immune cells and cytokines.Pathogenesis of AR become more deeper and more accurate due to rapid develop-ment of molecular biology and second-generation gene sequencing technology.Current studies have found that miR-155 and transcrip-tion factor GATA3 have important regulatory effects on occurrence and development of AR,then affect dominant differentiation of CD4+T lymphocytes and proliferation of ILC2.This article discusses and reviews pathogenesis of AR,which mainly focuses on miR-155/GATA3 pathway and effects of related upstream genes and downstream regulatory substances.

Objective To analyze the spatial relationship between the roots of maxillary anterior premolars and the maxillary sinus,thus providing an anatomical basis for timing,planning,surgical approaches,and implant selection at this site.Methods Cone beam CT(CBCT)images were collected from 264 patients(aged 20-65 years)who visited the Ruihua Dental Clinic between January 2017 and March 2023.The minimum distance from the apex of the maxillary an-terior premolar roots to the lower wall of the maxillary sinus was measured on the coronal plane.The classification of the vertical relationship between the tooth root and the lower wall of the maxillary sinus was performed,and comparisons were made bilaterally,between genders,and among different age groups.Results The minimum distance(Q50)from the apex of the first maxillary premolar root to the lower wall of the maxillary sinus was 7.34 mm for the single-root type,7.80 mm for the buccal root of the double-root type,and 7.36 mm for the palatal root.For the second maxillary premo-lar,the median distance was 2.56 mm for the single root type,1.73 mm for the buccal root type,and 1.23 mm for the palatal root type.There was a significant difference in the shortest distance from the apex of the right second maxillary premolar single root to the lower wall of the maxillary sinus among the different age groups(P＜0.05),with the 20-29-year-old group having the smallest median distance(1.52 mm)and the≥40-year-old group having the largest(4.44 mm).There was no significant difference in the effect of sex or laterality on distance(P＞0.05).The most common vertical relationship between the apex of the maxillary anterior premolar roots and the lower wall of the maxillary sinus was non-contact.There was no significant difference in the vertical relationship classification between the single-root and dou-ble-root types(P＞0.05).Conclusion Most maxillary first premolar roots can provide sufficient bone height,which makes it easy to achieve immediate implantation.The maxillary second premolar root frequently involves insufficient bone,which is necessary to make full use of the bone wall of the extraction socket or the sinus floor cortical bone to achieve initial stability.The vertical relationship between the premolar root and maxillary sinus was influenced by age and dental position.Younger age groups often exhibit inadequate bone height,and the indication for immediate implan-tation should be carefully considered.The number of roots does not significantly affect the relationship between the sinus and root;however,double-rooted premolars offer more support for immediate implantation and socket healing due to the small root diameter and bony separation between the roots.

Objective To analyze the routine test parameter levels of patients with colorectal adenoma and colorectal cancer,and develop a prediction model.Methods A total of 580 patients diagnosed with colorectal adenoma(117 patients)and colorectal cancer(463 patients)were included in the retrospective study.The patients were randomly divided into two groups according to a 7:3 ratio:a training set with 406 cases and a validation set with 174 cases.Logistic regression analysis was used to establish a prediction model,and a nomogram was drawn.The model′s discrimination,calibration,and clinical applicability were evaluated using receiver operating characteristic curve(ROC),calibration plot,and decision curve analysis(DCA).Results Univariate logistic regression analysis identified 13 potential predictors:age,fecal occult blood test(FOBT),fibrinogen(FIB),thrombin time(TT),albumin(ALB),white blood cell value(WBC),neutrophil count(NEUT#),hematocrit value(HCT),mean corpuscular hemoglobin(MCH),red cell distribution width(RDW),platelet count(PLT),mean platelet volume(MPV),and activated partial thromboplastin time(APTT).Multivariate logistic regression analysis showed MPV,FIB,ALB,FOBT,TT,and HCT were risk factors for colorectal cancer in patients with colorectal adenoma(P<0.05).A nomogram was constructed based on these predictors to build a prediction model.The AUC of the ROC curve was 0.915 for colorectal cancer in the training set and 0.836 in the validation set.Calibration plots demonstrated high prediction accuracy and good model calibration.DCA results indicated the prediction model provided greater net benefit compared with the extreme models at threshold probabilities of approximately 55%-95%.Conclusion The developed prediction model exhibits satisfactory discrimination,calibration,and clinical applicability.The model can serve as an auxiliary tool in distinguishing between colorectal adenoma and colorectal cancer in patients.

Objective To explore the mechanism of ginsenoside Rg1 in alleviating heat stress-induced testicular injury in mice.Methods A total of 20 C57BL/6 male mice(6～8 weeks old)were randomly divided into 4 groups(n=5).The mice from the control group and heat stress(HS)group were intraperitoneally injected with 10 mL/(kg·d)0.9％normal saline for 14 d,while those in the HS+Rg1 group and the Rg1 group were given an intraperitoneal injection of 20 mg/(kg·d)for 14 d,and then on the 7th day after administration,the mice in the HS group and the HS+Rg1 group had the lower abdomen put into a 43 ℃ water bath for 30 min as a single heat stress after being anesthetized with 4％chloral hydrate.Mouse spermatocytes GC-2spd(ts)were divided into control group(routine culture for 48 h),HS group(placed in a 43 ℃ water bath for 30 min after 36 h of conventional culture,and cultured till the end of 48 h),HS+Rg1 group(50 μmol/L Rg1 treatment followed by heat stress injury),and Rg1 group(no heat stress injury).In 1 d after modeling,the eyeball blood samples were collected to detect serum testosterone with ELISA,and the testicles were extracted to observe the morphology and weighed to calculate the testicular index.HE staining was used to observe the histopathology of testis,and corresponding reagents and kits was employed to detect the content of malondialdehyde(MDA)and activities of catalase(CAT)and superoxide dismutase(SOD)in testis tissue.After the epididymal sperm were collected,the sperm concentration and motility were analyzed by computer-assisted sperm analysis(CASA)system.In in vitro experiments,cell apoptosis was detected with TUNEL staining,the protein levels of Nrf2,Keap1,HO-1,Bax,Bcl-2 and Caspase3 were detected with Western blotting,and the mRNA levels of GCLC,GCLM and NQO1 were detected by RT-qPCR.Results Rg1 prevented the decreases in testicular weight and testicular index caused by heat stress,reduced the damage of testicular tissue structure,prevented the decrease of sperm concentration and vitality,antagonized the decreasd number of Leydig cells and serum testosterone level,reduced the accumulation of MDA in testicular tissue,and enhanced the activities of CAT and SOD.Rg1 treatment alleviated the apoptosis of GC-2spd(ts)cells,down-regulated the expression of Bax,Caspase3 and Keap1 proteins,enhanced the expression of Bcl-2,Nrf2 and HO-1 proteins,and increased the transcriptional levels of Nrf2 target genes GCLC,GCLM and NQO1.Conclusion Rg1 has no significant effect on the structure and function of mouse testes,but it can effectively improve the ability of mouse testes to resist heat stress injury,which may be related to the activation of Nrf2 signaling pathway,the improvement of antioxidant enzyme activity,and the reduction of apoptosis of spermatogenic cells.

Background and purpose:Epidermal growth factor receptor exon 20 T790M(EGFR T790M)mutation is one of the acquired resistance mechanisms in non-small cell lung cancer(NSCLC)against first-/second-generation EGFR tyrosine kinase inhibitors(EGFR TKIs).Additionally,EGFR T790M mutation can also be observed in NSCLC patients who have not undergone EGFR TKIs treatment.This study aimed to compare the clinical pathological characteristics and prognostic differences between NSCLC patients with de novo and acquired EGFR T790M mutation,and further explore the immune microenvironment features of acquired T790M mutation in NSCLC.Methods:This study retrospectively included 3 762 cases of NSCLC diagnosed at Fudan University Shanghai Cancer Center from April 2020 to September 2022.Among them,2 070 cases(55.02%)exhibited EGFR mutations,and 556 cases(14.77%)received EGFR TKIs treatment.Specifically,there were 119 cases(3.16%)of NSCLC with EGFR T790M mutation,including 51 cases(1.35%)of de novo T790M mutation and 68 cases(1.81%)of acquired EGFR T790M mutation.Clinical data of the patients were collected for comparative analysis between NSCLC patients with de novo and acquired T790M mutation.Multiple immunofluorescence histochemistry(mIHC)was employed to explore the immune microenvironment characteristics of NSCLC patients with acquired T790M mutation.Results:The proportion of de novo and acquired T790M mutations was higher in female patients compared to males.Patients with de novo T790M mutation tended to be younger.Both de novo and acquired T790M mutations were more commonly found in poorly differentiated carcinomas.Among NSCLC patients with de novo T790M mutation,there was a higher rate of programmed death ligand-1(PD-L1)expression(60.00%).In contrast,among NSCLC patients with acquired T790M mutation,the rate of PD-L1 expression was lower(22.39%).Acquired T790M mutation in NSCLC was often accompanied by TP53 alterations(39.7%).Cox regression analysis results indicated that mesenchymal to epithelial transition(MET)factor alteration was a risk factor for the occurrence of acquired T790M mutation(P=0.000 5).The average overall survival(OS)showed no significant difference between de novo and acquired T790M mutations(35.4 and 37.3 months respectively).However,patients with acquired T790M mutation exhibited a higher proportion of recurrence and metastasis.In acquired T790M mutation,there was a higher presence of immune cell infiltration within the stromal compartment,such as CD20+B cells,CD23+B cells,CD8+T cells,CD8+PD-1-/+cells,CD20+PD-1-/+cells and CD23+PD-1-/+cells.Additionally,the study found that when EGFR was accompanied by tumor suppressor gene(TSG)alterations,the average distance between tumor cells and CD8+T cells,CD20+B cells,CD8+PD-1+cells,CD20+PD-1+cells and CD23+PD-1+cells was closer compared to cases with only EGFR mutations.Conclusion:In comparison to patients with de novo T790M mutation,patients with acquired T790M mutation exhibit a lower rate of PD-L1 positivity.Acquired T790M mutation often accompanies TP53 alterations,and MET alteration is identified as a risk factor triggering acquired T790M mutation.Although patients with acquired T790M mutation face higher risk of recurrence and metastasis,their average OS does not significantly differ from those with de novo T790M mutation.In cases of acquired T790M mutation,the presence of TSG mutations can alter the spatial distribution of immune cells,potentially leading to benefits from immunotherapy.

Objective: To investigate the relationship between multi-dimensional myocardial strain and global cardiac function in different stages of cardiac dysfunction in spontaneously hypertensive rats (SHR) by two-dimensional strain echocardiography. Methods: According to cardiac function measurements, SHR of 28 to 102 weeks were divided into 3 groups: Normal group[Group A, normal left ventricular ejection fraction(LVEF) and left ventricular end-diastolic pressure(LVEDP), n=13], diastolic dysfunction group (Group B, normal LVEF but increased LVEDP, n=24), and systolic dysfunction group (Group C, decreased LVEF and increased LVEDP, n=17), with WKY rats at similar weeks of age as controls (group a, n=7; group b, n=12; and group c, n=16). Morphological parameters of left ventricular were measured by echocardiography. Using EchoPac workstation, systolic peak longitudinal strain, circumferential and radial strain were calculated at the left ventricular middle levels. Extracellular collagen content was observed histologically. Results: Left atrial dimension increased in group B and larger in group C, and dilated left ventricular and thickened wall were only found in group C. Systolic peak longitudinal strain of group B was significantly lower than group A and group a(all P<0.05), and deteriorated in group C(P<0.05), while systolic peak circumferential and radial strain and LVEF were only significantly decreased in group C (all P<0.05), while there was no significant difference between Group A and Group B(all P>0.05). Collagen content in endocardial and mid-layer myocardium increased in group B and C, and increased epicardial collagen occurred in group C. Systolic peak longitudinal strain, circumferential and radial strain were correlated positively with LVEF(r=0.65, 0.80, 0.80, all P<0.01). Conclusions In SHR, systolic peak longitudinal strain obtained by echocardiography is decreased in the period of diastolic dysfunction, while the damage of systolic peak circumferential and radial strain leads to the systolic dysfunction.

Objective To investigate the relationship between multi‐dimensional myocardial strain and global cardiac function in different stages of cardiac dysfunction in spontaneously hypertensive rats ( SHR ) by two‐dimensional strain echocardiography . MethodsAccording to cardiac function measurements ,SHR of 28 to 102 weeks were divided into 3 groups :Normal group[ Group A , normal left ventricular ejection fraction( LVEF) and left ventricular end‐diastolic pressure( LVEDP) , n ＝13] ,diastolic dysfunction group ( Group B , normal LVEF but increased LVEDP , n ＝24) ,and systolic dysfunction group ( Group C ,decreased LVEF and increased LVEDP , n ＝ 17 ) ,with WKY rats at similar weeks of age as controls ( group a , n ＝ 7 ;group b , n ＝ 12 ; and group c , n ＝ 16 ) . Morphological parameters of left ventricular were measured by echocardiography . Using EchoPac workstation ,systolic peak longitudinal strain ,circumferential and radial strain were calculated at the left ventricular middle levels . Extracellular collagen content was observed histologically . Results Left atrial dimension increased in group B and larger in group C ,and dilated left ventricular and thickened wall were only found in group C .Systolic peak longitudinal strain of group B was significantly lower than group A and group a ( all P ＜ 0 .05 ) ,and deteriorated in group C( P ＜ 0 .05 ) ,while systolic peak circumferential and radial strain and LVEF were only significantly decreased in group C ( all P＜ 0 .05 ) ,w hile there was no significant difference between Group A and Group B( all P ＞0 .05) . Collagen content in endocardial and mid‐layer myocardium increased in group B and C , and increased epicardial collagen occurred in group C . Systolic peak longitudinal strain , circumferential and radial strain were correlated positively with LVEF( r ＝0 .65 ,0 .80 ,0 .80 ,all P ＜0 .01) . Conclusions In SHR ,systolic peak longitudinal strain obtained by echocardiography is decreased in the period of diastolic dysfunction ,w hile the damage of systolic peak circumferential and radial strain leads to the systolic dysfunction .

OBJECTIVE： To study the mechanism of Prunus persica-Carthamus tinctorius couplet medicine in the treatment of osteonecrosis of the femoral head （ONFH）. METHODS： The network pharmacology was adopted. The active components of P. persica -C. tinctorius couplet medicine and ONFH target were screened through TCM systematic pharmacological analysis platform target （TCMSP）， DRAR-CPI， hnuman gene database （GeneCards） and online medelian inheritance in man （OMIM） using oral availability of compounds （OB）＞30％ and drug like （DL）＞0.18 as standard. Network topology attribute analysis software Cytoscape 3.6.0 was utilized to construct the active components-ONFH targets network. Target protein interaction network was established on the basis of STRING database， and top 5 target proteins in the list of connectivity were screened， and molecular docking server was used to predict the combination activity of active components from P. persica -C. tinctorius couplet medicine. The biological processes of target gene ontology （GO） and metabolic pathways in Kyoto encyclopedia of genes and genomes （KEGG） were enriched and analyzed by DAVID. RESULTS： A total of 44 active components were screened from P. persica -C. tinctorius couplet medicine， including baicalin， quercetin， etc.， and 78 targets related to ONFH including VEGF， VEGI， CRP， etc. Through analysis of molecular docking server， binding activity of active components of P. persica -C. tinctorius couplet medicine to target protein was strong. GO and KEGG pathway enrichment analysis showed that biological process of P. persica -C. tinctorius couplet medicine for ONFH was related with negative regulation of apoptosis process and positive regulation of nuclear factor-κB transcription factor， mainly through regulating secretory glycoprotein signaling pathway， melanogenesis signaling pathway， VEGF signaling pathway， signaling pathway of basal cell carcinoma， adenosine-activated protein kinase signaling pathway. CONCLUSIONS： This study preliminarily validates the major targets and pathways of P. persica -C. tinctorius couplet medicine for ONFH， which lay a foundation for further study on their pharmacological action.