Weissella viridescens(W.viridescens)was used as the trained immunity inducer.We mo-nitored the protective efficacy against lethal infection of Candida albicans.After W.viridescens training,inflammatory mediator level was measured by NO assay kit upon re-stimulation,and the bacterial killing ability of peritoneal macrophages(PMs)was detected by counting CFU after Staphylococcus aureus(S.aureus)infection.The expression proteins in the classical signaling pathway of trained immunity were detected.Meanwhile,the PMs were pretreated with the corre-sponding inhibitors for the corroborative mechanism.The results showed that W.viridescens could induce trained immunity.The survival rate of Galleria mellonella treated with W.viridescens was still as high as 70％at 48 h,which protected against lethal infection of Candida albicans.W.viri-descens-trained PMs presented immune-enhancing activity,producing more inflammatory mediator(NO)after LPS stimulation and accelerating the clearance of S.aureus.To our delight,the high ex-pression levels of AKT/mTOR/HIF1α were observed under W.viridescens training.Moreover,in-hibiting the AKT/mTOR/HIF1α signaling with inhibitors dampened the trained response to LPS after W.viridescens training.Altogether,these results suggested that W.viridescens induces trained immunity through the AKT-mTOR-HIF-1α pathway to enhance the pro-inflammatory and anti-in-fective capacities of host cells.

In order to explore the role of signal transducer and activator of transcription 3(STAT3)in the infection process of porcine hemagglutinating encephalomyelitis virus(PHEV),Western blot,qRT-PCR and indirect immunofluorescence experiments were used to detect the phosphoryla-tion level and subcellular localization changes of STAT3 after PHEV infection.The replication of PHEV were examined in cells with STAT3 knockdown or overexpression,respectively.The results showed the phosphorylation level of STAT3 at tyrosine 705 was significantly increased after PHEV infection,and the expression of STAT3 in the nucleus increased.In addition,STAT3 knock-down in cells can significantly inhibit PHEV replication.The above results further reveal the path-ogenic mechanism of PHEV and provide a theoretical basis for the research of anti-PHEV drugs.

Objective To systematically evaluate the effect of hysteroscopic uterine septum resection on the pregnancy live birth rate in patients with septate uterus.Methods The randomized controlled studies and cohort studies on the impact of hysteroscopic uterine septum resection on the pregnancy live birth rate in the patients with septate uterus were retrieved from PubMed,Web of Science,CNCN.cn,and Wanfang databases.The retrieval time was from the establishment of the database to March 2024.The NOS scale was used to con-duct the literature quality evaluation.The Statal0.0 statistical software was used for conducting the meta a-nalysis,and the main evaluation index was the pregnancy live birth rate.Results A total of 9 articles on the treatment of septate uterine were included,involving 821 subjects,including 528 septate uterine patients with hysteroscopic uterine septum resection and 293 septate uterine patients with conservative treatment.The meta analysis showed that the live birth rate in the patients with septate uterine undergoing hysteroscopic uterine septum resection was higher than that in the patients with septate uterine undergoing the conservative treat-ment(I2=38.0％,OR=1.60,95％CI:1.05-2.44,P=0.028).Conclusion Hysteroscopic uterine septum resection could improve the pregnancy outcome and increase the live birth rate.It is a minimally invasive sur-gery with good effect and high safety,which has good clinical application prospects and is worth popularizing.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Objective:To compare the anticoagulant efficacy and safety between argatroban and heparin in patients with liver failure complicated with hepatic encephalopathy undergoing artificial liver treatment.Methods:A total of 207 patients with liver failure complicated with hepatic encephalopathy who received artificial liver treatment in the intensive care unit (ICU) of Wuxi No.5 People′s Hospital from January 2021 to October 2024 were enrolled, including 105 cases in the argatroban group and 102 cases in the heparin group. Changes in coagulation function, hemoglobin (Hb), platelet (PLT) count, and model for end-stage liver disease (MELD) score before and after artificial liver treatment were compared between the two groups. The formation of deep vein thrombosis in the lower extremities, coagulation in the extracorporeal circulation circuit and plasma separator, bleeding at the deep venous catheter site were compared between the two groups. The 28-day survival outcome of the patient were recorded. Two independent sample t-test, rank sum test, and chi-square test were used for statistical comparisons, and the Kaplan-Meier method and log-rank test were used to analyze the survival rate of patients. Results:There were no statistically significant differences in activated partial thromboplastin (APTT), international normalized ratio (INR), Hb and PLT count before and after artificial liver treatment in the argatroban group ( Z=-1.74, -1.80, -1.26 and -0.52, respectively, all P>0.05), while the MELD score after treatment was lower than that before treatment and the difference was statistically significant ( t=6.49, P<0.001). After artificial liver treatment, the APTT in the argatroban group was 47.10(42.65, 51.90) s, which was shorter than that in the heparin group (56.05(50.02, 63.00) s). The INR, Hb, and PLT count in the argatroban group were 2.00(1.65, 2.54), 98.00(88.00, 112.00) g/L, and 92.00(75.50, 106.00)×10 9/L, respectively, which were all higher than those in the heparin group, which were 1.56(1.22, 1.93) g/L, 90.50(80.00, 104.75) g/L, and 74.00(64.75, 99.50)×10 9/L, respectively. The differences were all statistically significant ( Z=-7.16, -5.28, -3.05 and -3.32, respectively, all P<0.05). There was no statistically significant difference in MELD scores between the two groups ( P=0.250). The incidence of coagulation in the extracorporeal circulation circuit and plasma separator and bleeding at the deep venous catheter site in the argatroban group was 5.71%(6/105) and 1.90%(2/105), respectively, which were both lower than those in the heparin group (14.71%(15/102) and 9.80%(10/102), respectively). The differences were both statistically significant ( χ2=4.59 and 5.91, respectively, both P<0.05). At the end of the 28-day follow-up, the mortality rates in the argatroban group and the heparin group were 22.9%(24/105) and 34.3%(35/102), respectively, and the difference was not statistically significant ( χ2=3.33, P=0.068). There was no statistically significant difference in the 28-day survival rate between the argatroban group and the heparin group ( χ2=2.09, P>0.05). Conclusions:Argatroban has a relatively minor impact on PLT count and Hb when it is used in artificial liver treatment for patients with liver failure complicated with hepatic encephalopathy. The incidence of coagulation in extracorporeal circulation circuits and plasma separators is low, and the risk of bleeding at the deep venous catheters is low. Argatroban is highly safe, which provides a new anticoagulation option for patients with a high risk of bleeding.

Objective This review aims to investigate the application of eye tracking(ET)in patients with speech impairment in the ICU.The review summarizes the current status and prospects of ET technology applications.Methods Following the scoping reviews framework,a systematic search was conducted across Web of Science,PubMed,Cochrane Library,Embase,CINAHL,CNKI,Wanfang Data,Chinese Medical Database,and Chinese biomedical database.The search covered publications from the inception of each database to October 29th,2024.The included studies were comprehensively analyzed.Results A total of 12 pieces of the literature were included,including 4 prospective cohort studies,4 experimental studies,3 prospective observational studies,and 1 randomized controlled trial.The application population of ET in the ICU mainly includes patients on mechanical ventilation,those at high risk of delirium,patients with spinal cord injury,etc.The types of integrated ET system equipment are mainly head-mounted and fixed;the types of ET involve gaze,blinking,etc.;the functions include standardized scale assessment,free interaction,and eye-movement model recognition.The main outcome indicators of the research are feasibility,physical symptoms and social-psychological status.Conclusion ET is applicable to a specific group of ICU patients with aphasia,and has shown good feasibility and effectiveness in the expression of patients'basic needs,self-assessment of symptoms and improvement of psychosocial status.

Weissella viridescens(W.viridescens)was used as the trained immunity inducer.We mo-nitored the protective efficacy against lethal infection of Candida albicans.After W.viridescens training,inflammatory mediator level was measured by NO assay kit upon re-stimulation,and the bacterial killing ability of peritoneal macrophages(PMs)was detected by counting CFU after Staphylococcus aureus(S.aureus)infection.The expression proteins in the classical signaling pathway of trained immunity were detected.Meanwhile,the PMs were pretreated with the corre-sponding inhibitors for the corroborative mechanism.The results showed that W.viridescens could induce trained immunity.The survival rate of Galleria mellonella treated with W.viridescens was still as high as 70％at 48 h,which protected against lethal infection of Candida albicans.W.viri-descens-trained PMs presented immune-enhancing activity,producing more inflammatory mediator(NO)after LPS stimulation and accelerating the clearance of S.aureus.To our delight,the high ex-pression levels of AKT/mTOR/HIF1α were observed under W.viridescens training.Moreover,in-hibiting the AKT/mTOR/HIF1α signaling with inhibitors dampened the trained response to LPS after W.viridescens training.Altogether,these results suggested that W.viridescens induces trained immunity through the AKT-mTOR-HIF-1α pathway to enhance the pro-inflammatory and anti-in-fective capacities of host cells.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

Objective This review aims to investigate the application of eye tracking(ET)in patients with speech impairment in the ICU.The review summarizes the current status and prospects of ET technology applications.Methods Following the scoping reviews framework,a systematic search was conducted across Web of Science,PubMed,Cochrane Library,Embase,CINAHL,CNKI,Wanfang Data,Chinese Medical Database,and Chinese biomedical database.The search covered publications from the inception of each database to October 29th,2024.The included studies were comprehensively analyzed.Results A total of 12 pieces of the literature were included,including 4 prospective cohort studies,4 experimental studies,3 prospective observational studies,and 1 randomized controlled trial.The application population of ET in the ICU mainly includes patients on mechanical ventilation,those at high risk of delirium,patients with spinal cord injury,etc.The types of integrated ET system equipment are mainly head-mounted and fixed;the types of ET involve gaze,blinking,etc.;the functions include standardized scale assessment,free interaction,and eye-movement model recognition.The main outcome indicators of the research are feasibility,physical symptoms and social-psychological status.Conclusion ET is applicable to a specific group of ICU patients with aphasia,and has shown good feasibility and effectiveness in the expression of patients'basic needs,self-assessment of symptoms and improvement of psychosocial status.