Objective To construct a nomogram model for prediction of constipation risk in adult patients with cardiovascular disease (CVD). Methods A total of 780 adult patients with CVD admitted to Zhongshan Hospital, Fudan University from June 15, 2025 to August 15, 2025 were prospectively enrolled and randomly divided into a training set and a validation set at a 7∶3 ratio. Risk factors for constipation were identified using the least absolute shrinkage and selection operator (LASSO) and Firth logistic regressions, and a nomogram model was subsequently constructed in the training set. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the discrimination ability of the model. Calibration curve and decision curve analysis (DCA) were used to assess calibration and clinical applicability. The value of model was evaluated in the validation set. Results Among 780 adult patients with CVD, 391 patients (50.1%) developed constipation. Eleven variables were selected by LASSO regression and Firth logistic regression, and a nomogram model was constructed. The ROC curve showed that the AUCs of the model to predict constipation in adult patients with CVD in training and validation sets were 0.881 and 0.883, respectively. Calibration curves and DCA demonstrated good calibration and predictive performance of the model in training and validation sets. Conclusions The nomogram model based on LASSO-Firth logistic regression demonstrates good predictive performance and may serve as a useful tool for identifying adult patients with CVD at high risk of constipation.

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 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: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:To analyze the main chemical components of Lanqin Granules based on UPLC-Q-TOF-MS/MS; To explore the potential targets, core components and related pathways of Lanqin Granules in the treatment of respiratory tract infection through network pharmacology.Methods:Using UPLC-Q-TOF-MS/MS secondary fragment cleavage information, combined with literature and database, the chemical components of Lanqin Granules were analyzed; the related action targets of Lanqin Granules were obtained by PharmMapper; The related targets of respiratory tract infection were obtained from GeneCards and OMIM databases, and the common targets were selected by intersection with the relevant action targets of Lanqin Granules. The common targets were imported into string database, and the protein interaction data were downloaded and input into Cytoscape 3.7.2 software to obtain hub gene; Go function and KEGG pathway enrichment analysis were carried out on DAVID platform, and chemical components closely related to hub gene were obtained by using the Network Anlyzer plug-in.Results:53 chemical constituents of Lanqin Granules were obtained, including 11 alkaloids, 20 flavonoids, 5 terpenoids, 7 organic esters, 2 amino acids and 8 other compounds. 28 hub genes and 38 related core components were obtained. The results of GO analysis showed that the treatment of respiratory tract infection with Lanqin Granules was related to neutrophil degranulation, negative regulation of apoptosis, protein hydrolysis and other biological processes; extracellular exosomes, cytoplasm, extracellular components and other cellular components; the same protein binding, RNA polymerase Ⅱtranscription factor activity, ligand activated sequence specific DNA binding, protein serine/ threonine/ tyrosine kinase activity and other molecular processes. KEGG analysis results mainly involved cancer pathway, lipid and atherosclerosis, metabolic pathway and other signaling pathways.Conclusion:Lanqin Granules can treat respiratory tract infection through multi-component, multi-target and multi-channel, and play the role of anti-inflammatory, antibacterial and anti-virus.

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.

Objective:To compare the efficacy and safety of continuous venetoclax combined azacitidine (VA) chemotherapy and intermedium/high-dose cytarabine (I/HDAC) consolidation in patients with acute myeloid leukemia (AML) fit for standard chemotherapy (transform from UNFIT) .Methods:Clinical data of patients who were fit for standard chemotherapy were collected among those with AML who underwent VA induction in the Department of Hematology, the Second Hospital of Hebei Medical University. The overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), and incidence of adverse events were analyzed retrospectively.Results:This study enrolled 69 patients, consisting of 46 cases in the VA group and 23 cases in the I/HDAC group. We revealed the following. ① The median OS, RFS, EFS were 26.18, 24.69, 20.34 months in the VA group, and 34.14, 30.99, 28.42 months in the I/HDAC group, respectively, with no statistically significant difference (all P>0.05). Median OS of patients who underwent I/HDAC consolidation with European Leukemia Net (ELN) favorable-risk, positive measurable residual disease (MRD), wild type FLT3, or IDH1/2 mutation was significantly longer than those who received VA ( P<0.05). ②Adverse events rate of grade 3 - 4 neutropenia, grade 3 - 4 thrombocytopenia, and bacteremia were significantly lower in the VA group than in the I/HDAC group ( P<0.05) . Conclusions:I/HDAC consolidation was more likely to help get survival benefits for patients with ELN favorable-risk, positive MRD, wild type FLT3, or IDH1/2 mutation. Continuous VA chemotherapy exhibited superior safety than I/HDAC consolidation.

The ribosomal protein S11(RPS11)from Enterococcus faecalis is was heterologously ex-pressed using the Pichia pastoris system.The RPS11 gene sequence was optimized to match the yeast codon preference,and the recombinant expression vector pPIC9K-RPS11 was constructed.Electroporation was used to transform the vector into the Pichia pastoris GS115 strain,and high-copy recombinant strains were selected through G418 resistance screening.Protein expression was induced with methanol,and the expression was verified by SDS-PAGE.The recombinant protein was applied in a mouse melanoma treatment model to evaluate its therapeutic effects.The results showed that the recombinant expression vector pPIC9K-RPS11 successfully expressed the target protein with an approximate molecular weight of 14 kDa in Pichia pastoris.The optimal fermenta-tion conditions were determined to be an induction temperature of 30 ℃,induction time of 72 h,and methanol concentration of 1％.Analysis using a mouse peritoneal macrophage trained immuni-ty model revealed that recombinant RPS11 possessed biological activity capable of inducing trained immunity.Additionally,therapeutic experiments in a mouse melanoma model demonstrated that recombinant RPS11 significantly inhibited tumor growth.These findings suggest that the recombi-nant RPS11 secreted by Pichia pastoris not only possesses biological activity in inducing trained immunity but also inhibits tumor cell growth in a mouse melanoma model,providing theoretical support for the heterologous expression and potential applications of recombinant RPS11.

Objective:To explore the subtypes and duration of postoperative delirium in elderly hip fracture patients and analyze the impact of delirium in 6 months postoperative mortality.Methods:A convenience sampling method was used to select elderly hip fracture patients who underwent surgery at Taizhou Hospital of Zhejiang Province from April 2021 to October 2023. General information and cognitive status were assessed using a demographic survey and the Mini-Mental State Examination. Postoperative delirium was evaluated and recorded twice daily for one week after surgery, distinguishing delirium subtypes. The differences in all-cause mortality within 6 months post-surgery among patients with different delirium subtypes were compared. Time-dependent Cox regression analysis was conducted to examine the impact of each subtype and duration of delirium on mortality.Results:A total of 662 questionnaires were distributed, with 659 valid responses (valid response rate was 99.55%). Among the 659 elderly hip fracture patients, 249 cases (37.78%) experienced delirium. Based on the occurrence and subtype of postoperative delirium, patients were divided into four groups: non-delirium group ( n=410), hyperactive group ( n=95), hypoactive group ( n=66), and mixed group ( n=88). At the end of the 6 months follow-up, 91 patients had died. The mortality rates were 8.05% (33/410) in the non-delirium group, 11.58% (11/95) in the hyperactive group, 39.39% (26/66) in the hypoactive group, and 23.86% (21/88) in the mixed group, with statistically significant differences among the groups ( P<0.01). Time-dependent Cox regression analysis indicated that the duration of delirium was independently associated with 6 months postoperative mortality in the hypoactive group [ HR=2.420, P<0.01] and the mixed group [ HR=3.049, P<0.01] . Conclusions:The incidence of postoperative delirium in elderly hip fracture patients is moderately high, with hyperactive delirium being the most common subtype. Hypoactive and mixed delirium subtypes are independently associated with increased 6 months postoperative mortality. Prolonged delirium duration further increases the risk of death.