Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

In audiovisual emotion recognition, representational learning is a research direction receiving considerable attention, and the key lies in constructing effective affective representations with both consistency and variability. However, there are still many challenges to accurately realize affective representations. For this reason, in this paper we proposed a cross-modal audiovisual recognition model based on a multi-head cross-attention mechanism. The model achieved fused feature and modality alignment through a multi-head cross-attention architecture, and adopted a segmented training strategy to cope with the modality missing problem. In addition, a unimodal auxiliary loss task was designed and shared parameters were used in order to preserve the independent information of each modality. Ultimately, the model achieved macro and micro F1 scores of 84.5% and 88.2%, respectively, on the crowdsourced annotated multimodal emotion dataset of actor performances (CREMA-D). The model in this paper can effectively capture intra- and inter-modal feature representations of audio and video modalities, and successfully solves the unity problem of the unimodal and multimodal emotion recognition frameworks, which provides a brand-new solution to the audiovisual emotion recognition.
Emotions ; Humans ; Attention ; Algorithms

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

Chylothorax is one of the complications of surgery and lymphatic diseases. The incidence rate of chylothorax has been increasing in recent years. X-ray-guided interventional therapy is a new method for treating chylothorax, and its curative effect is no less than the traditional surgical treatment. Based on discussing the aetiology and diagnosis of chylothorax, this paper briefly summarizes the application progress of X-ray-guided interventional therapy for chylothorax to provide further reference and a basis for clinical practice.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

The delivery of exogenous insulin is very important for the treatment of type 1 and advanced type 2 diabetes.Traditional injectable administration is prone to cause hypoglycemia, while the intelligent insulin system has the advantages of safety, long-term effectiveness, and high responsiveness.Glucose oxidase (GOx) can consume O2 and catalyze glucose to produce gluconic acid and H2O2.Therefore, the O2 level, H2O2 content and pH of GOx system are closely related to the glucose level in the system.This review introduces the application of GOx in closed-loop insulin delivery systems at home and abroad in recent years, which can be divided into single response and multiple response of pH-response, hypoxia-response, and H2O2-response according to the mechanism.It also discusses the opportunities and challenge facing by the application of GOx in the future.

Objective To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).Methods The retrospective case-control study was conducted.The clinicopathological data of 305 patients with primary GBC who underwent radical Ro resection in the First Affiliated Hospital of Xi'an Jiaotong University from 2013 to 2017 were collected,including 108 males and 197 females,aged from 30 to 88 years,with a median age of 62 years.According to the different tumor staging,patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy.Observation indicators:(1) results of imaging and laboratory examinations;(2) treatment situations:① surgical situations,② postoperative adjuvant treatment;(3) results of postoperative pathological examination;(4) followup;(5) prognostic factors analysis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5,2018,and death was used as the end point.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.Results (1) Results of imaging and laboratory examinations:results of imaging examination showed that diagnostic rates of ultrasound,CT and MRI examination were respectively 84.06％ (174/207),85.71％ (168/196) and 63.11％ (65/103).Results of laboratory examination showed that the positive rates of CA19-9,CA125 and carcinoembryonic antigen (CEA) were respectively 55.34％ (145/262),48.06％ (124/258) and 46.15％ (126/273).(2) Treatment situations:① surgical situations:305 patients underwent radical R0 resection for primary GBC,including 145 undergoing liver wedge resection + D2 lymph node dissection,61 undergoing liver wedge resection + D1 lymph node dissection,55 undergoing liver Ⅳ B and Ⅴ segmentectomy + D2 lymph node dissection,11 undergoing liver Ⅳ B and Ⅴ segrnentectomy + D1 lymph node dissection,9 undergoing right hepatectomy + D2 lymph node dissection,5 undergoing liver wedge resection + D2 lymph node dissection + partial colectomy,4 undergoing pancreaticoduodenectomy,3 undergoing simple cholecystectomy in Tis stage,3 undergoing right hepatectomy + D1 lymph node dissection,2 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial colectomy,1 undergoing liver Ⅳ B and Ⅴ segmentectomy + resection and reconstruction of portal vein + D2 lymph node dissection,1 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial resection of the stomach or duodenum,1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein,1 undergoing right hepatectomy + pancreaticoduodenectomy,1 undergoing right hepatic lobectomy + partial gastrectomy + D2 lymph node dissection,1 undergoing right hepatic lobectomy + D1 lymph node dissection and 1 undergoing right hepatic trilobectomy + D2 lymph node dissection.Of 94 patients with unsuspected GBC,78 who were diagnosed in the other hospitals received salvage surgery in the authors' center.Twenty-one patients had postoperative surgery-related complications,including 11 with bile leakage,8 with pulmonary infection and 2 with abdominal bleeding.Two patients died in the perioperative period.② Postoperative adjuvant treatment:26 patients underwent postoperative adjuvant chemotherapy.Chemotherapy regimen:gemcitabine + oxaliplatin were used in 12 patients,gemcitabine + tegafur in 7 patients,gemcitabine + cisplatin in 6 patients,oxaliplatin + tegafur in 1 patient.(3) Results of postoperative pathological examination.The postoperative pathological type of 305 patients:257,23,6,5,4,3,3,2,1 and 1 patients were respectively confirmed as pure adenocarcinoma,adenocarcinoma combined with squamous cell carcinoma,adenocarcinoma combined with neuroendocrine carcinoma,mucinous adenocarcinoma,neuroendocrine carcinoma,adenocarcinoma combined with mucinous carcinoma,squamous cell carcinoma,sarcomatoid carcinoma,adenocarcinoma combined with sarcomatoid carcinoma,adenocarcinoma combined with signet-ring cell carcinoma.Degree of tumor differentiation:highdifferentiated,moderate-differentiated and low-differentiated tumors were detected in 37,130 and 121 patients,respectively,17 with unknown differentiated degree.Of 305 patients,16 and 32 patients had respectively vascular invasion and nerve invasion.The number of lymph node dissected of 305 patients was 8±5,with positive lymph node of 0 (range,0-9),including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis).TNM staging of 305 patients:stage 0,Ⅰ,Ⅱ,ⅢA,ⅢB,ⅣA and ⅣB were detected in 7,18,13,137,57,11 and 62 patients,respectively.(4) Follow-up:245 of 305 patients were followed up for 18.0 months (range,6.0-70.0 months).The survival time,1-and 3-year survival rates were respectively 29.5 months (range,0.5-69.9 months),71.6％ and 45.8％.One hundred and twenty-two patients died during the follow-up.(5) Prognostic factors analysis:the results of univariate analysis showed that preoperative level of bilirubin,pathological type,degree of tumor differentiation,liver invasion,vascular invasion,nerve invasion,T staging,N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (x2 =10.26,3.96,45.89,34.64,12.75,27.05,35.09,39.44,4.40,P＜0.05).The results of multivariate analysis showed that low-differentiated tumor,liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC [odds ratio (OR)=1.90,1.71,1.46,95％ confidence interval (CI):1.34-2.70,1.15-2.52,1.17-1.82,P＜0.05],and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35,95％ CI:0.15-0.82,P＜0.05).Conclusions For patients with primary GBC undergoing radical resection,D2 lymph node dissection should be performed routinely.The low-differentiated tumor,liver invasion and N2 staging are independent risk factors affecting prognosis of patients,and postoperative chemotherapy is a protective factor.

Objective: To study the correlation between pancreatic duct stent placement and postoperative pancreatic fistula in patients undergoing pancreaticoduodenectomy. Methods: We performed a retrospective review on 298 patients who underwent pancreaticoduodenectomy from Jan 2011 to Dec 2016. Patients were divided into none stent group, external stent group and internal stent group according to the placement and drainage of the pancreatic duct stent. Results: There were 60 cases in none stent group, 103 cases in external stent group and 135 cases in internal stent group. Altogether there were 52 cases suffering from biochemical pancreatic fistula, 52 cases of grade B fistula and 9 cases of grade C pancreatic fistula. There were three factors with statistical significance: 1, the operative method (χ²=20.947, P=0.000), 2, the diameter of main pancreatic duct (χ²=8.662, P=0.013), and 3, the intraoperative blood loss (χ²=14.03, P=0.001). There were no statistical significance difference between no stenting group and external/ internal stent group in the incidence of pancreatic fistula (P>0.05). The difference between internal stent group and external stent group was of statistical significance (χ²=9.948, P=0.019). The incidence of clinically relevant pancreatic fistula in external stent group was lower than the internal stent group (14.5% vs. 26.6%)(χ²=9.777, P=0.002). Conclusions The pancreatic duct stenting is not a risk factor for pancreatic fistula. The external drainage of pancreatic juice is associated with a lower incidence of pancreatic fistula compared to the internal drainage.

Objective To investigate the application value of the anatomical location of positive nodes (N staging) from TNM staging systems published by American Joint Committee on Cancer (AJCC) (7th edition),number of metastatic lymph nodes (NMLN),lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) as prognostic predictors in advanced gallbladder carcinoma(GBC).Methods The retrospective crosssectional study was conducted.The clinicopathological data of 176 patients who underwent radical resection of advanced GBC in the First Affiliated Hospital of Xi'an Jiaotong University between January 2008 and December 2014 were collected.According to preoperative assessment,intraoperative exploration and frozen section biopsy,staging and surgical procedure were confirmed.Observation indicators and evaluation criteria:(1) surgical and postoperative situations;(2) follow-up and survival situations;(3) N staging related indicators based on TNM staging systems of AJCC (7th edition):LNR =NMLN / total number of lymph node dissection,LODDS =Log (NMLN+0.5) / (total number of lymph node dissection-NMLN+0.5);(4) lymph node staging based on NMLN,LNR and LODDS:LODDS ＜-1.0 as LODDS 1 staging,-1.0 ≤ LODDS ＜ 0 as LODDS 2 staging,LODDS ≥0 as LODDS 3 staging;(5) prognostic comparisons of patients with different lymph node staging;(6) accuracy of 4 different types of lymph node staging predicting the prognosis of patients.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 31,2017.Measurement data with normal distribution were represented as x-±s.Measurement data with skewed distribution were described as M (range),and comparisons were done using the nonparametric test.The survival rate was calculated by the Kaplan-Meier method,and the Log-rank test was used for survival comparison.Correlation analysis was done using the Spearman correlation analysis,r ≥ 0.800 as a high correlation,0.500 ≤ r ＜ 0.800 as a moderate correlation and 0.300 ≤ r ＜ 0.500 as a low correlation.The receiver operating characteristic (ROC) curve and area under the curve (AUC) were respectively drawn and calculated based on 4 kinds of binary logistic regression model.Akaike information criterion (AIC) and Harrell concordance index (Harrell c-index) were respectively calculated based on 4 kinds of COX proportional hazard regression model.The larger values of AUC and Harrell c-index caused a smaller value of AIC,but a lymph node staging standard correlated with greater prognostic accuracy.Harrell c-index ＜ 0.50 was no prediction,and 0.50 ≤ Harrell c-index ≤ 1.00 was an obvious prediction.Results (1) Surgical and postoperative situations:176 patients underwent successful radical resection of GBC,including 161 in R0 resection and 15 in R1 resection,99 with D1 lymph node dissection and 77 with D2 lymph node dissection.Of 176 patients,9 with postoperative complications were improved by symptomatic treatment,including 6 with bile leakage,2 with hepatic dysfunction and 1 with intra-abdominal hemorrhage.Results of postoperative pathological examination:total number of lymph node dissection,NMLN and LNR were respectively 6.7±4.4,0 (range,0-12.0) and 0 (range,0-1.00);high-differentiated,moderate-differentiated and low-differentiated tumors were respectively detected in 16,81 and 79 patients;162 and 14 patients were in T3 and T4 stages;60 patients were combined with infiltration of the liver.(2) Follow-up and survival situations:176 patients were followed up for l-118 months,with a median time of 33 months.The 1-,3-and 5-year overall survival rates were respectively 63.1％,42.0％ and 32.0％.(3) N staging related indicators based on TNM staging systems ofAJCC (7th edition):95,45 and 36 patients were respectively detected in staging N0,N1 and N2.NMLN,LNR and LODDS were respectively 2.0 (range,1.0-7.0),0.40 (range,0.08-1.00),-0.15 (range,-0.99-1.04) in staging N1 and 4.0 (range,1.0-12.0),0.57 (range,0.13-1.00),0.11 (range,-0.70-1.04) in staging N2,with a statistically significant difference in NMLN (Z=-3.888,P＜0.05) and with no statistically significant difference in LNR and LODDS (Z=-1.492,-1.689,P＞0.05).(4) Lymph node staging based on NMLN,LNR and LODDS:NMLN and LNR as a cut-off point were respectively 4.0 and 0.70,NMLN 1 staging (NMLN=0) was detected in 95 patients,NMLN 2 staging (1.0 ≤ NMLN ≤ 4.0) in 61 patients and NMLN 3 staging (NMLN＞4.0) in 20 patients;LNR 1 staging (LNR=0) was detected in 95 patients,LNR 2 staging (0 ＜ LNR ≤ 0.70) in 58 patients and LNR 3 staging (LNR＞0.70) in 23 patients.LODDS 1,2 and 3 stagings was detected in 61,70 and 45 patients,respectively.The lymph node staging based on NMLN and LNR was significantly correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r =0.949,0.922,P＜0.05);the lymph node staging based on LODDS was moderately correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r =0.758,P＜ 0.05).(5) Prognostic comparisons of patients with different lymph node staging:1-,3-and 5-year overall survival rates were respectively 86.3％,65.3％,52.2％ in N0 staging patients and 44.4％,22.2％,13.3％ in N1 staging patients and 25.0％,5.6％,2.8％ in N2 staging patients,with a statistically significant difference (x2=88.895,P＜0.05).The 1-,3-and 5-year overall survival rates were respectively 86.3％,65.3％,52.2％ in NMLN 1 staging patients and 47.5％,19.7％,11.1％ in NMLN 2 staging patients and 0,0,0 in NMLN 3 staging patients,with a statistically significant difference (x2=121.086,P＜0.05).The 1-,3-and 5-year overall survival rates were respectively 86.3％,65.3％,52.2％ in LNR 1 staging patients and 41.4％,17.2％,11.8％ in LNR 2 staging patients and 17.4％,8.7％,0 in LNR 3 staging patients,with a statistically significant difference (x2 =86.503,P＜ 0.05).The 1-,3-and 5-year overall survival rates were respectively 85.2％,65.5％,51.8％ in LODDS 1 staging patients and 65.7％,40.0％,31.3％ in LODDS 2 staging patients and 28.9％,13.3％,5.9％ in LODDS 3 staging patients,with a statistically significant difference (x2=59.195,P＜0.05).(6) Accuracy of 4 different types of lymph node staging predicting the prognosis of patients:according to N staging of TNM staging systems of AJCC (7th edition),NMLN,LNR and LODDS,AUC,AIC and Harrell c-index of lymph node staging were respectively 0.878,0.881,0.870,0.864 and 1 047.5,1 026.4,1 044.2,1 063.6 and 0.77,0.78,0.77,0.76.AIC value was smaller with increased values of AUC and Harrell c-index based on NMLN,showing a greatest accuracy predicting the prognosis of patients.Conclusion Among N staging of TNM staging system of AJCC (7 edition),NMLN,LNR and LODDS as prognostic predictors,NMLN can more precisely predict radical resection of advanced GBC.

Objective: To evaluate left atrial (LA) function and synchrony in lone atrial fibrillation (LAF) patients by two-dimensional speckle tracking echocardiography (2D-STE) and to explore the predictive value of 2D-STE parameters for AF recurrence after ablation procedure. Methods: Our research included in 2 groups: LAF group,n=50 patients diagnosed in our hospital from 2013-06 to 2015-05; it was further divided into 2 subgroups as Non-LA enlargement subgroup,n=34 and LA enlargement subgroup,n=16 and Control group,n=35 healthy subjects. With sinus rhythm, 2D-STE was conducted to obtain LA peak ventricular systolic longitudinal strain (PALS), strain rate (SRs) and atrial contraction longitudinal strain (ACLS), strain rate (SRa). Standard deviation for the time to peak (TPSD) of regional strain was calculated. TPSD during ventricular systole was named as SDs and TPSD during ventriculardiastole was named asSDa. Results: Compared with Control group, LAF group had reduced PALS (28.34±8.57) vs (38.73±6.13), SRs (1.17±0.31) vs (1.57±0.25), ACLS (14.11±4.91) vs (18.86±3.57 ) and SRa (-1.41±0.58) vs (-1.90±0.30), allP<0.05; while elevated SDs (8.11±3.00) % vs (4.67±1.48) % and SDa (5.57±2.26) % vs (3.11±1.13) %, bothP<0.05. Furthermore, Compared with Control group, Non-LA enlargement subgroup had decreased PALS, SRs, ACLS and SRa, allP<0.05; while increased SDs and SDa, bothP<0.05. Logistic regression analysis indicated that compared with traditional parameters, SDs and SDa could more effectively distinguish LAF patients from normal subjects (SDs with the sensitivity 83%, speciifcity 72% and SDa with the sensitivity 81%, speciifcity 76%). Elevated SDa and SDs were the best predictors for post-operative AF recurrence (SDs with the sensitivity 80%, speciifcity 71% and SDa with the sensitivity 86%, speciifcity 79%). Conclusion: 2D-STE may detect LA dysfunction and dyssynchrony in LAF patients, abnormal parameters could be found in LAF patients without LA enlargement. SDs and SDa were the best predictors for post-operative AF recurrence.