OBJECTIVES: To evaluate the feasibility, efficacy and safety of Sentinel cerebral embolic protection device (CEPD) during transcatheter aortic valve replacement (TAVR). This study is a subgroup analysis of the China Moderate to Severe Valvular Heart Disease Registry, which has been registered at the Chinese Clinical Trial Registry (ChiCTR2300075006). METHODS: Patients undergoing TAVR with the Sentinel CEPD from October 2023 to September 2024 were retrospectively enrolled. A total of 80 patients were included, with a median age of 72 (68, 76) years, including 52 males (65.0%) and 28 females (35.0%); 62 patients (77.5%) with tricuspid valves, and 18 patients (22.5%) with bicuspid valves; 34 patients (42.5%) with type Ⅰ aortic arch, 24 patients (30.0%) with type Ⅱ aortic arch, 12 patients (15.0%) with type Ⅲ aortic arch, and 10 patients (12.5%) with bovine-type aortic arch. Clinical data of the patients were summarized and analyzed. The primary endpoints were success rate of Sentinel CEPD implantation, as well as all-cause death, symptomatic stroke, transient ischemic attack, and Sentinel CEPD access vessel complications during hospitalization and within 30 days postoperatively. RESULTS: In the 80 patients, self-expanding valves were used in 68 cases (85.0%) and balloon-expandable valves in 12 cases (15.0%). Seventy-nine patients (98.8%) successfully underwent TAVR with Sentinel CEPD deployment. Macroscopically visible debris was captured in 92.5% (74/80) by filters of Sentinel CEPD. Although the procedure time for Sentinel CEPD placement was slightly longer in patients with bovine-type aortic arch, there was no statistically significant difference in deployment time among different aortic arch types (P>0.05). During hospitalization and within 30 days postoperatively, only one case of transient ischemic attack occurred, and there was no all-cause mortality, symptomatic stroke, or access-site vascular complications related to the Sentinel CEPD observed. CONCLUSIONS The Sentinel CEPD demonstrates high feasibility across aortic arch types, potential efficacy in embolic capture, and excellent safety in TAVR.
Humans ; Transcatheter Aortic Valve Replacement/adverse effects* ; Male ; Female ; Aged ; Embolic Protection Devices ; Retrospective Studies ; Intracranial Embolism/prevention & control* ; Aged, 80 and over ; Aortic Valve Stenosis/surgery* ; Aortic Valve/surgery*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.

Objective:To explore the correlation between time in range (TIR) after short-term treatment and glycated hemoglobin after 3 months (HbA lc-3m) in patients with newly-diagnosed type 2 diabetes mellitus (T2DM). Methods:In this cross-sectional study, a total of 94 patients with newly-diagnosed T2DM who received treatment in the Department of Endocrinology of Inner Mongolia Autonomous Region People′s Hospital were enrolled from January 2018 to September 2022. The patients were followed-up for 3 months and had complete medical record. TIR was divided into three groups according to different target ranges of blood glucose (TIR1: TIR with blood glucose between 3.9 and 10.0 mmol/L, TIR2: TIR with blood glucose between 3.9 and 7.8 mmol/L, TIR3: TIR with fasting, premeal or bedtime blood glucose <6.1 mmol/L and 2 h postprandial blood glucose <8.0 mmol/L). The patients were divided into two groups based on whether their HbA 1c-3m level was less than 6.5%, and the baseline data and variations in TIR for distinct target glucose levels were compared between the two groups. Spearman′s correlation analysis and binary logistic regression analysis were used to analyze the relationship between baseline indicators, TIR after short-term treatment and HbA 1c-3m. Receiver operating characteristic curve (ROC) was drawn to evaluate the predictive ability of different TIR after short-term therapy for HbA 1c-3m. Results:There were statistically significant differences in TIR1 [81.0 (67.5, 94.6)% vs 71.4 (51.7, 85.7)%], TIR2 [57.7 (29.7, 70.8)% vs 40.9 (22.4, 52.3)%] and TIR3 [23.8 (10.2, 39.5)% vs 13.0 (4.8, 25.0)%] between patients with a HbA 1c-3m<6.5% and patients with a HbA 1c-3m≥6.5% (all P<0.05). Spearman correlation analysis showed that among all the patients with newly-diagnosed T2DM, TIR1, TIR2 and TIR3 were all negatively correlated with HbA 1c-3m [6.4 (6.1, 6.9)%] ( r=-0.322, -0.348, -0.303, respectively, all P<0.01). Logistic regression analysis showed that after adjusting for the confounding factors, TIR1 ( OR=1.021, 95% CI: 1.002-1.041; P=0.034), TIR2 ( OR=1.024, 95% CI: 1.006-1.043; P=0.011), TIR3 ( OR=1.037, 95% CI: 1.010-1.065; P=0.008) were all independently related to HbA 1c-3m. When HbA lc-3m<6.5% was taken as the target value, the area under the ROC curve: TIR1 was 0.639 (95% CI: 0.528-0.751), TIR2 was 0.671 (95% CI: 0.560-0.782), TIR3 was 0.659 (95% CI: 0.549-0.770), respectively. When HbA lc-3m<7.0% was taken as the target value, the area under the ROC curve: TIR1 was 0. 730 (95% CI: 0.619-0.841), TIR2 was 0.744 (95% CI: 0.642-0.846), TIR3 was 0.701 (95% CI: 0.588-0.814). There was no significant difference in the area among the three statistics ( P>0.05). Conclusions:For newly-diagnosed T2DM patients, TIR after short-term treatment is negatively correlated with HbA 1c after 3 months and has good predictive value for it.

BACKGROUND:Repetitive magnetic stimulation of either S3 nerve root or M1 area can improve the urination function of patients with urinary retention after spinal cord injury,but there are few reports on the repetitive magnetic stimulation of both sites in patients with urinary retention after spinal cord injury. OBJECTIVE:To observe the effect of repetitive magnetic stimulation of both S3 nerve root and M1 area on urinary retention after spinal cord injury. METHODS:Forty patients with urinary retention after spinal cord injury were enrolled and were randomly divided into two groups(n=20 per group):group A(repetitive magnetic stimulation in both S3 nerve root and M1 area)and group B(repetitive magnetic stimulation in the S3 nerve root and sham stimulation in the M1 area).Patients in both groups were given 4-week repetitive magnetic stimulation based on conventional bladder function intervention.The stimulation time and duration of treatment were same in both groups,with a treatment time of 21 minutes daily,5 days per week,for 4 weeks in total.The urination diary and urodynamics were compared between two groups. RESULTS AND CONCLUSION:Before treatment,there were no statistically significant differences in the average daily catheterization times,average daily catheterization volume,average single urinary volume,urinary storage period(maximum bladder volume,bladder pressure),and urinary voiding period(detrusor pressure,residual urine volume)between the two groups(P>0.05).After 4 weeks of treatment,the average daily catheterization times in group A were lower than before treatment(P<0.05),while the average single urination volume in group A was higher than that before treatment(P<0.05);and the average daily catheterization times in group B were lower than before treatment(P<0.05).After 4 weeks of treatment,the average daily catheterization times in group A were lower than those in group B,and the average single urination volume was higher than that in group B(P<0.05).After 4 weeks of treatment,the maximum bladder volume and detrusor pressure during urination were increased in both groups compared with before treatment(P<0.05),while the bladder pressure and residual urine volume at the maximum volume of the two groups were decreased compared with those before treatment(P<0.05).Compared with group B,the maximum bladder volume and detrusor pressure during urination were higher in group A,while the bladder pressure and residual urine volume at maximum volume were lower in group A(P<0.05).To conclude,two treatments can both improve the urination function of patients with urinary retention after spinal cord injury,and repetitive magnetic stimulation of both S3 nerve root and M1 area is superior to repetitive magnetic stimulation of S3 nerve root alone.Repetitive magnetic stimulation of both S3 nerve root and M1 area can effectively improve the urination function of patients with urinary retention after spinal cord injury.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective To analyze the effects of glucocorticoid stent implantation combined with nasal endoscopic surgery on nasal ventilation function and serum levels of eosinophil cationic protein(ECP),fibronectin(Fn)and aquaporin-1(AQP-1)in patients with chronic sinusitis with nasal polyp(CSwNP).Methods 60 patients with CSwNP from January 2022 to February 2023 were included in the study,and then they were divided into experimental group and control group,with 30 cases in each,using random number table method.The experimental group was treated with glucocorticoid stent implantation based on the original nasal endoscopic surgery,and the control group was treated with nasal endoscopic surgery,and both groups were treated until 12 weeks after surgery.The two groups of nasal symptoms,quality of life,nasal structure and ventilation function,serum levels of ECP,Fn,AQP-1,and adverse reactions were compared.Results Compared before the treatment,scores of nasal mucosal structure(Lund-Mackay scale),nasal symptom visual analogue scale(VAS)(including:nasal obstruction,runny nose,stuffy head,decreased sense of smell,nasal dryness/scab)and serum levels of ECP were decreased,distance from minimum nasal cross section to anterior nostril(DCAN)was shortened in two groups 12 weeks after treatment,and the experimental group was lower than the control group,the differences were statistically significant(P<0.05).Compared before the treatment,12 weeks after treatment,the nasal minimum cross-sectional area(NMCA),score of world health organization abbreviated quality of life(WHOQOL-100),nasal cavity volume(NCV),serum levels of Fn,AQP-1 were increased in two groups,and the experimental group was higher than the control group,the differences were statistically significant(P<0.05).During treatment,the incidence of adverse reactions was similar between the two groups(P>0.05).Conclusion Glucocorticoid stent implantation combined with nasal endoscopic surgery can control nasal symptoms in patients with CSwNP,improve nasal structure and ventilation function,regulate serum levels of ECP,Fn,AQP-1,and improve patients'quality of life.

Objective:A novel anatomic posterior malleolus locking plate for Chinese people was designed, researched, developed, and tested biomechanically.Methods:An anatomic parameter database of posterior malleolus of Chinese people was established by collecting CT images of ankle joints from 100 healthy volunteers in Shanghai Tongji hospital from June 2022 to May 2023. Combined with relevant computer-aided technologies, a novel anatomic posterior malleolus locking plate for Chinese people was designed and produced. In addition, model verification and biomechanical test were carried out on vertical displacements under different fixation modes and different axial loads (500, 1 000, and 1 500 N). Failure loads at a displacement of 2 mm and maximum failure loads at the complete failure of internal fixation were also tested and recorded.Results:Based on the imaging anatomic measurement, the width quartile of posterior malleolus was 19.4, 26.6, 35.0 mm. The 3D reconstruction models of ankle joint CT corresponded to small, medium, and large basic posterior malleolus plates. Height of the screw safety zone was 5.5(5.3, 5.7) mm. The tip-back angle was 153.0°(148.5°, 157.5°) and tip-back height was 20.0(19.7, 20.9) mm. The novel anatomic posterior malleolus locking plate based on tibiofibular and ankle joint CT scan and relevant computer-aided technologies fit well with posterior malleolus of tibia, showing anatomic fitting. Based on the associate biomechanical test, the novel plate fixation had smaller vertical displacements of posterior malleolus fragment under axial loads of 500, 1 000, and 1 500 N compared with the control plate, but greater failure loads when the vertical displacement of the posterior malleolus fragment was 2 mm and greater maximum failure loads at complete failure of the internal fixation. At an axial load of 500 N, the vertical displacements of the posterior malleolus fragment after posterior malleolus fixation with a control plate, a 6-hole anatomical locking plate, and a 5-hole anatomical locking plate were 0.60±0.02, 0.45±0.04, and 0.52±0.04 mm, respectively with significant difference ( F=88.287, P<0.001); at an axial load of 1 000 N, the vertical displacements were 2.22±0.03, 1.10±0.03, and 1.15±0.03 mm for the three fixation modes, respectively, and the difference was statistically significant ( F=10 061.890, P<0.001); At an axial load of 1 500 N, the vertical displacements were 2.81±0.04, 1.50±0.03 and 1.67±0.03 mm for the three fixation modes, respectively with significant difference ( F=9 774.019, P<0.001). When the vertical displacement of the posterior malleolus fragment was 2 mm, the failure loads for the three fixation modes were 0.80(0.73, 0.80)、2.00(1.93, 2.00) and 1.70(1.70, 1.70) kN, respectively with significant differences ( H=54.245, P<0.001). The maximum failure loads at complete failure of the internal fixation for the three fixation modes were 1.90(1.90, 1.98)、4.30(4.30, 4.30) and 3.70(3.63, 3.70) kN, respectively with significant differences ( H=53.863, P<0.001). Conclusions:The novel anatomic posterior malleolus locking plate for Chinese people was well matched to the posterior malleolus with high mechanical strength and good stability, showing a promising future for clinical application.

Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.
Humans ; Female ; Ovarian Neoplasms/genetics* ; Cell Proliferation ; Cytokines ; Endoplasmic Reticulum Stress/genetics*