Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective:To observe the effects of shoulder-three-needle therapy plus joint mobilization and extracorporeal shock wave therapy(ESWT)in improving symptoms and pain mediators in patients with scapulohumeral periarthritis.Methods:A total of 82 patients with scapulohumeral periarthritis were randomized into a control group and an observation group by the random number table method,with 41 cases in each group.The control group was treated with ESWT.The observation group was treated with additional shoulder-three-needle therapy plus joint mobilization based on the treatment in the control group.After 4 weeks of treatment,shoulder joint function,pain mediators,inflammatory factor levels,and clinical efficacy were compared between the two groups.Results:The total effective rate and the score of shoulder joint function in the observation group were higher than those in the control group(P<0.05).After treatment,the levels of serum pain mediators substance P(SP),5-hydroxytryptamine(5-HT),and prostaglandin E2(PGE2),as well as inflammatory factors interleukin(IL)-6,tumor necrosis factor(TNF)-α,and C-reactive protein(CRP)decreased significantly in both groups(P<0.05).And,the serum pain mediators SP,5-HT,and PGE2,and the levels of inflammatory factors IL-6,TNF-α,and CRP in the observation group were all lower than those in the control group(P<0.05).Conclusion:Shoulder-three-needle therapy plus joint mobilization and ESWT has a better curative effect than ESWT alone in treating scapulohumeral periarthritis.It can effectively improve the clinical symptoms,reduce the levels of pain mediators and inflammatory factors,and increase shoulder joint function.

Objective To discuss the value of the multi-parameter imaging of dual-energy computed tomography(DECT)combined with apparent diffusion coefficient(ADC)value of brain metastases in predicting lung adenocarcinoma with epidermal growth factor receptor(EGFR)gene mutation.Methods The DECT and MRI parameters of 90 patients with lung adenocarcinoma and brain metastases were collected.DECT parameters included normalized iodine concentrations in the arterial and venous phases(N1CA,NICV)and slope of the energy spectrum curves in the arterial and venous phases(kA,kv).The MRI parameters of brain metastases included ADC and relative ADC(rADC)of solid area,necrotic area,and peritumoral edema.Predictive model were constructed for EGFR gene mutation according to the parameters above.Results NICV,kv,ADC and rADC of solid area and peritumoral edema in the EGFR positive group were higher than those in the EGFR negative group,which had statistical significances(P＜0.05).Model1 and model2 were established by combining DECT or MRI parameters,while model3 was established by combining DECT and MRI parameters,which had the best predictive efficiency for EGFR gene mutation,with an area under the curve(AUC)of 0.846.Conclusion The predictive model combining DECT parameters with ADC value of brain metastases can improve the prediction efficiency of EGFR gene mutation in advanced lung adenocarcinoma.

Objective Tetanus is a serious infectious diseases with high mortality,which is an important global public health issue.This study aims to analyze the epidemiological burden and changing trends of tetanus in China from 1990 to 2021,providing a basis for disease prevention and control.Methods Epidemiological indicators and global socio-demographic index(SDI)related to tetanus in China were retrieved and collected from the 2021 Global Burden of Disease database(GBD 2021).The trend analysis of the incidence rate,mortality rate and disability-ad-justed life years(DALYs)rate of tetanus in China from 1990 to 2021 was conducted by Joinpoint 5.3 software.Results From 1990 to 2021,the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized disability-adjusted life years(DALYs)rate of tetanus in China decreased significantly(average annual percent change[AAPC]＜0,P＜0.001),with males being significantly higher than females.The crude incidence rate,crude mortality rate,and crude DALYs rate for all age groups showed overall declining trends,with the lar-gest decline in the 0-14 years age group.In 2021,the crude incidence rate,crude mortality rate,and crude DALYs rate of tetanus in the population aged 70-years were higher than those in the population aged 0-14,15-49,and 50-69 years groups.The ASIR,ASMR,and age-standardized DALYs rate of tetanus in China in 2021 were lower than the global level,only higher than those in the high SDI regions.Conclusion From 1990 to 2021,the disease burden of tetanus in China varied with gender and age,with an overall declining trend over time.It is necessary to strengthen tetanus health education for males and the ≥70 years population,and to improve the overall level of pri-mary prevention measures for tetanus.

Objective To explore the roles of the mechanoreceptor Yes-associated protein 1(YAP1)and piezo type mechanosensitive ion channel component 2(PIEZO2)in mechanotransduction in mouse bladder urothelial cells.Methods Mouse bladder urothelial cells were subjected to mechanical stretching using the FX-6000T cell stretching system and treated with the YAP1-specific inhibitor verteporfin(VP).The expressions of PIEZO2,YAP1 and connective tissue growth factor(CTGF)at the mRNA and protein levels,as well as changes in cellular adenosine triphosphatase(ATP)concentration,were detected using reverse transcription quantitative PCR(RT-qPCR)and Western blotting(WB).Results After stretching stimulation,under the fluorescence microscope,it was observed that the diameter length of the stretched cells were longer than that before stretching,and the difference was statistically significant(P＜0.05).The expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels were increased in the stretched group compared to those of the non-stretched group(P＜0.05).VP effectively reduced the expressions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels after stretching stimulation(P＜0.05).Stretching stimulation significantly increased the intracellular ATP concentration,while VP was able to inhibit the increase in ATP concentration,with a statistically significant difference(P＜0.000 1).Conclusion Stretching stimulation increased the expressions of YAP1 and PIEZO2 in bladder urothelial cells and promoted the release of ATP;verteporfin inhibited the increase in YAP1 activity and the overexpression of PIEZO2 caused by stretching,thereby reducing the release of ATP.It is suggested that mouse bladder urothelial cells may primarily sense mechanical signals through the YAP1-PIEZO2-ATP pathway.

Objective:To observe the effects of shoulder-three-needle therapy plus joint mobilization and extracorporeal shock wave therapy(ESWT)in improving symptoms and pain mediators in patients with scapulohumeral periarthritis.Methods:A total of 82 patients with scapulohumeral periarthritis were randomized into a control group and an observation group by the random number table method,with 41 cases in each group.The control group was treated with ESWT.The observation group was treated with additional shoulder-three-needle therapy plus joint mobilization based on the treatment in the control group.After 4 weeks of treatment,shoulder joint function,pain mediators,inflammatory factor levels,and clinical efficacy were compared between the two groups.Results:The total effective rate and the score of shoulder joint function in the observation group were higher than those in the control group(P<0.05).After treatment,the levels of serum pain mediators substance P(SP),5-hydroxytryptamine(5-HT),and prostaglandin E2(PGE2),as well as inflammatory factors interleukin(IL)-6,tumor necrosis factor(TNF)-α,and C-reactive protein(CRP)decreased significantly in both groups(P<0.05).And,the serum pain mediators SP,5-HT,and PGE2,and the levels of inflammatory factors IL-6,TNF-α,and CRP in the observation group were all lower than those in the control group(P<0.05).Conclusion:Shoulder-three-needle therapy plus joint mobilization and ESWT has a better curative effect than ESWT alone in treating scapulohumeral periarthritis.It can effectively improve the clinical symptoms,reduce the levels of pain mediators and inflammatory factors,and increase shoulder joint function.

Objective To analyze the characteristics of facial and tongue chromaticity parameters in patients with gastrointestinal tumors by setting the inspection image characteristics of patients with gastrointestinal tumors as the main research content;To establish an auxiliary diagnostic model for gastrointestinal tumors.Methods One-way ANOVA,t-test,Mann-whitney U test,canonical correlation analysis and Spearman statistical methods were used to analyze the characteristics of inspection image indexes and correlation of tumor markers of the 391 cases in the control group and 359 patients with gastrointestinal tumors.Machine learning methods such as SVM,Random Forest,KNN,Naive Bayes,XG Boost and Ada Boost were used to establish an auxiliary diagnostic model for gastrointestinal tumors.Results In terms of facial indicators,there were differences in F-R,F-G and F-B indicators among the control group,early-stage gastrointestinal cancer patients,and mid-to late-stage gastrointestinal cancer patients,in the comparison of tongue features among,TC-L,TB-L and TB-a of the control group,patients with early gastrointestinal tumors,and patients with intermediate and advanced gastrointestinal tumors showed a gradual downward trend;the AUC of the auxiliary diagnosis model of gastrointestinal tumor disease based on the chromaticity parameters of face tongue image constructed by Ada Boost algorithm was 0.930.Conclusion The auxiliary diagnostic model of gastrointestinal diseases constructed by facial and tongue images has good diagnostic effect,which can provide objective data support for in-depth exploration of the complex relationship between diagnosis and disease.

Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for diagnosing malignant adnexal tumors.Methods Totally 112 patients with single adnexal masse were retrospectively enrolled and divided into benign adnexal tumor group(benign group,n=73)and malignant adnexal tumor group(malignant group,n=39).Clinical data,laboratory indicators,ovarian-adnexal ultrasound reporting and data system(O-RADS)classification based on conventional ultrasound(US),CEUS manifestations and CEUS classification of benign and malignant tumors were compared between groups.Multivariable logistic regression analysis of clinical and laboratory indicators being statistically different between groups,as well as US O-RADS classification and CEUS classification was performed to screen the independent predictors of malignant adnexal tumors,and combined models were constructed using forward stepwise regression method.The efficacy of each independent predictor and combined model for diagnosing malignant adnexal tumors was analyzed.Results Statistical differences of carbohydrate antigen 125(CA125),US O-RADS classification,enhancement time and level of CEUS,as well as CEUS classification were found between groups(all P＜0.05).CA125,US O-RADS classification and CEUS classification were all independent predictors of malignant adnexal tumors(all P＜0.05).Combined model Ⅰ,Ⅱ and Ⅲ were constructed based on CA125+CEUS classification,US O-RADS classification+CEUS classification and CA125+US O-RADS classification+CEUS classification,respectively.The area under the curve(AUC)of single CA125 level,US O-RADS classification,CEUS classification and combined model Ⅰ,Ⅱ and Ⅲ for diagnosing malignant adnexal tumor was 0.708,0.809,0.908,0.918,0.945 and 0.954,respectively.AUC of combined model Ⅲ was higher than that of combined model Ⅰ(Z=-2.142,P=0.032),while no significant difference of AUC was found between combined model Ⅱ and Ⅰ nor Ⅱ and Ⅲ(both P＞0.05).Conclusion CEUS could be used to effectively diagnose malignant adnexal tumor.Combining with CA125 level and US O-RADS classification could significantly improve its diagnostic efficacy.