Objective: To investigate the regulatory role of miR-6824-3p in macrophage function and its molecular mechanism in inhibiting hepatitis B virus (HBV) replication, thereby providing experimental evidence to elucidate the immune regulatory mechanisms underlying persistent HBV infection. Methods: miR-6824-3p mimic and inhibitor were transfected into human THP-1-induced macrophages. Real-time quantitative PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), neutral red uptake, reactive oxygen species (ROS) production, and fluorescent latex particle phagocytosis assays were employed to evaluate the effects of miR-6824-3p on macrophage phenotype and function. Through a combination of bioinformatics analysis, dual luciferase reporter assays, western blot, and siRNA interference techniques, we identified the target gene of miR-6824-3p and examined their effects on downstream signaling pathways. qRT-PCR and western blot analyses were performed to assess the impact of miR-6824-3p-regulated macrophages on HBV DNA, pgRNA, cccDNA, and HBV-associated antigen levels in HepAD38 cells. Key effector molecules were identified through neutralization assays. Results: miR-6824-3p mimic significantly promoted the expression and secretion of proinflammatory factors, such as TNF-α and IL-1β, in macrophages (P<0.001), while concurrently reducing ROS production and phagocytosis (P<0.05). Furthermore, miR-6824-3p downregulated NRAS expression in macrophages, which was accompanied by a reduction in MAPK signalling path-way activity (p-MEK, p-ERK). Compared to the control group, the medium of macrophages with overexpressed miR-6824-3p inhibited the expression of HBV DNA, pgRNA, cccDNA, and HBV-associated antigens HBsAg, HBeAg, and HBcAg in HepAD38 cells (P<0.01). Similar results were also observed in the co-culture system of macrophages with HepAD38 cells. The addition of TNF-α neutralizing antibodies markedly attenuated the aforementioned antiviral effects (P<0.001). Conclusion: miR-6824-3p targets NRAS to affect the downstream MAPK signaling pathway, regulating the immune function of macrophages. The TNF-α induced by miR-6824-3p is one of the key molecules that suppress HBV replication. This study provides evidence for further elucidating the molecular mechanisms by which miRNAs influence HBV replication via modulating the host immune microenvironment.

OBJECTIVE To construct a classification prediction model for vancomycin blood concentration， and to optimize its precision dosing strategies. METHODS Patient records meeting inclusion criteria were extracted from the Medical Information Mart for Intensive Care database. Following data cleaning and preprocessing， a final cohort of 9 902 patient was analyzed. Feature selection was performed through correlation analysis and the Boruta feature selection algorithm. Vancomycin blood concentrations were discretized into three categories based on clinical therapeutic windows： low （＜10 μg/mL）， intermediate （10-20 μg/mL）， and high （≥20 μg/mL）. Six machine learning algorithms were employed to construct classification models： tabular prior-data fitted network （TabPFN）， logistic regression （LR）， random forest （RF）， extreme gradient boosting （XGBoost）， support vector machine （SVM）， K-nearest neighbors （KNN）. Model performance was evaluated using 10-fold cross-validation （10-CV）， with primary metrics including： accuracy， balanced accuracy， precision macro， recall macro， macro F1， area under the receiver operating characteristic curve （OvR-AUC）. Shapley Additive Explanations （SHAP） was adopted to analyze the direction and magnitude of the impact that different features had on the model’s predictive outcomes. RESULTS The results showed that the RF and TabPFN models performed the best （with accuracy of 0.741 4 and 0.737 7， and OvR-AUC of 0.907 0 and 0.895 8， respectively）. XGBoost model exhibited moderate performance， while LR， SVM， and KNN models demonstrated relatively poor performance. Confusion matrix heatmap analysis revealed that both RF and TabPFN achieved higher accuracy in predicting high- concentration cases but exhibited slightly lower performance in the low and medium concentration categories. Bootstrap with 10-CV revealed that the RF model demonstrated stable performance across various evaluation metrics （accuracy： 0.741 4； balanced accuracy： 0.740 3； precision macro： 0.732 1； recall macro： 0.736 0； macro F1： 0.736 0； OvR-AUC： 0.907 0）， indicating good classification performance and generalization ability. SHAP analysis revealed that creatinine， urea nitrogen， daily cumulative dose and administration frequency of vancomycin， which were key predictors， had a significant impact on the prediction results. CONCLUSIONS RF and TabPFN models demonstrate certain advantages in the classification prediction of vancomycin trough blood concentrations； however， their performance in the low to moderate concentration categories still requires improvement.

Objective: To investigate the current status and influencing factors for cognitive frailty among the elderly in community, so as to provide the evidence for early identification and prevention of cognitive frailty among the elderly. Methods: Residents aged 60 years and above with local household registration from 11 counties (cities, districts) in Zhejiang Province from 2021 to 2023 were selected as study participants using a multistage random sampling method. Demographic information, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were assessed using the Patient Health Questionnaire. Cognitive frailty was evaluated using the FRAIL Scale and the Mini-Mental State Examination. Factors affecting cognitive frailty among the elderly in community were identified using a multivariable logistic regression model. Results: A total of 16 613 individuals were surveyed, including 7 465 males (44.93%) and 9 148 females (55.07%). The average age was (70.97±7.29) years. A total of 784 individuals were detected with depressive symptoms, with a detection rate of 4.72%. A total of 724 individuals were detected with cognitive frailty, with a detection rate of 4.36%. Multivariable logistic regression analysis showed that females (OR=1.419, 95%CI: 1.179-1.708), aged ≥70 years (70-<80 years old, OR=1.869, 95%CI: 1.490-2.345; ≥80 years old, OR=5.017, 95%CI: 3.935-6.398), without a spouse (OR=1.495, 95%CI: 1.234-1.810), sedentary (OR=2.420, 95%CI: 1.829-3.202), chronic diseases (1 type, OR=1.456, 95%CI: 1.175-1.804; ≥2 types, OR=1.639, 95%CI: 1.314-2.045), and depressive symptoms (OR=4.191, 95%CI: 3.361-5.225) were associated with a higher risk of cognitive frailty among the elderly in community. Conversely, a lower risk of cognitive frailty was seen among the elderly in community who had primary school or above (primary school, OR=0.512, 95%CI: 0.389-0.676; junior high school or above, OR=0.464, 95%CI: 0.354-0.608), engaged in physical exercise (OR=0.396, 95%CI: 0.291-0.539), and were reported average or good self-rated health status (average, OR=0.641, 95%CI: 0.475-0.866; good, OR=0.150, 95%CI: 0.109-0.208). Conclusions The detection rate of cognitive frailty among the elderly in community is relatively low and is influenced by demographic factors such as gender, age, education level, as well as lifestyle like sedentary and physical exercise, and health status. It is recommended to reduce the risk of cognitive frailty among the elderly through multidimensional interventions, including health education, promotion of healthy lifestyles, and enhanced mental health support.

OBJECTIVE To investigate the distribution and drug resistance of pathogens isolated from the children with bloodstream infection in pediatric intensive care unit(PICU)so as to provide guidance for empirical clinical treatment of infections.METHODS Based on the Pediatric Intensive Care Database(PIC,http://pic.nbscn.org),the etiological data were collected from the PICU children of Children's Hospital,Zhejiang University School of Medicine by R software in 2010-2019 and were retrospectively analyzed.The species,distribution and drug resist-ance of the pathogens isolated from the children were observed.RESULTS Totally 991 strains of pathogens were isolated,727(73.36％)of which were gram-positive bacteria,213(21.49％)were gram-negative bacteria,and 51(5.15％)were fungi.Staphylococcus epidermidis(320 strains,32.29％)was the predominant species of the gram-positive bacteria,followed by Staphylococcus hominis(118 strains,11.91％),Staphylococcus capitis(55 strains,5.55％)and Enterococcus faecium(Group D,33 strains,3.33％);Klebsiella pneumoniae(59 strains,5.95％),Escherichia coli(58 strains,5.85％),Acinetobacter baumannii(25 strains,2.52％)and Pseudo-monas aeruginosa(18 strains,1.82％)were the major species of gram-negative bacteria.The analysis of drug re-sistance showed that the gram-positive bacteria were generally resistant to β lactams and maintained sensitive to vancomycin and linezolid;the gram-negative bacteria showed high drug resistance rates,especially,A.baumannii and P.aeruginosa,showed multi-drug resistance.CONCLUSIONS The gram-positive bacteria are dominant among the pathogens isolated from the PICU children with bloodstream infections.The empirical treatment should be performed based on the distribution and drug resistance data of the pathogens,and sensitive drugs should be cho-sen for optimization of the treatment regimen.

Objective To explore the application value of CT fusion navigation technology in Stanford B-type aortic dissection endovas-cular isolation surgery.Methods Nineteen patients who underwent Stanford B-type aortic dissection endovascular isolation surgery were selected.Prior to surgery,all patients underwent chest and abdominal CT plain scan and enhanced scan,and three-dimensional vascular reconstruction was performed at the post-processing workstation;During the operation,a chest(region of interest)digital subtraction angiography(DS A)3D-CT scan was first performed as the intraoperative matching localization image.Then,a thin-layer(1.0 mm)CT enhanced tomographic image of the chest and abdomen was extracted from the picture archiving and communication system(PACS).At the same time,the DSA 3D-CT image and the thin-layer CT enhanced image were opened for overlapping regis-tration of bony landmarks.After registration,the three-dimensional vascular volume rendering(VR)image of the aorta from the thin-layer CT was fused with the DSA 3D-CT,and the positioning and release of the covered stent were guided by the newly fused multimodal real-time image.Results All 19 patients underwent guided surgery with precise positioning of the covered lesions and successful release of the covered stents,with a success rate of 100％ for the guided technique.The intraoperative placement time of the covered stent was(5.4±2.4)s,the exposure time was(12.8±3.2)min,the surgical duration was(53.9±25.3)min,the intraopera-tive contrast agent dosage was(125.8±25.3)mL,the X-ray fluoroscopy dose was(221.3±155.7)mGy,and the total X-ray exposure dose was(1 056.4±330.3)mGy.There were no serious complications during the operation,and all patients received 1-3 months of follow-up which found they all recovered well.Conclusion The use of CT and DSA fusion navigation technology in guiding the treat-ment of Stanford B-type aortic dissection with covered stents provides real-time three-dimensional fusion images for the operator,which can quickly and accurately locate and release the stent,and has certain clinical value.

Objective:To study the current situation of the operating room nurses′ flourishing, and to explore the mediating role of self-compassion between forgiveness and flourishing, so as to provide a basis for improving the level of flourishing of operating room nurses.Methods:From September to November 2023, a total of 1 182 operating room nurses from 20 hospitals in Henan province were investigated by convenient sampling method. General data questionnaire, the Heartland Forgiveness Scale, Self-Compassion Scale and the Flourishing Scale were used to conduct an online cross-sectional survey. The mediating role of self-compassion in the relationship between forgiveness and flourishing was analyzed.Results:A total of 1 182 valid questionnaires were collected, including 261 males and 921 females. The age ranged from 21 to 54 (33.21 ± 5.72) years. In operating room nurses, the score of the forgiveness was (111.88 ± 18.77) points, the score of the self-compassion was (76.60 ± 10.75) points, the score of the flourishing was (43.48 ± 8.72) points. Forgiveness was positively correlated with self-warmth and flourishing ( r=0.545, 0.590, both P<0.05), forgiveness was negatively correlated with self-cold ( r=-0.365, P<0.05). The flourishing was positively correlated with self-warmth ( r=0.608, P<0.05), and negatively correlated with self-cold ( r=-0.509, P<0.05). self-warmth and self-cold played a mediating role between forgiveness and flourishing. The indirect effects of self-warmth and self-cold were 23.97% and 20.93% of the total mediating effects. Conclusions:The level of flourishing of the operating room nurses is at a relatively high level. Nurses′ forgiveness can affect their flourishing directly as well as indirectly through self-warmth and self-cold.

Objective To investigate the efficacy of extracorporeal shock wave therapy(ESWT)combined with ultrasound-guided corticosteroid injection(CSI)for the treatment of primary frozen shoulder(PFS).Methods Ninety-nine patients with PFS who visited the pain department of the Affiliated Hospital of Xuzhou Medical University between April 2024 and July 2024 were enrolled and randomly divided into three groups according to the randomized number table method:ESWT group(T group),CSI group(I group),and combined treatment group(TI group),with 33 patients in each group.Visual analogue scale(VAS)scores,shoulder range of motion(SROM),and Constant-Murley shoulder scores(CMS)were recorded before treatment and at 1,4,8,and 12 weeks post-treatment.Additionally,the patients'Ascens Insomnia Scale(AIS)scores were recorded before treatment and 1 month after treatment.The occurrence of adverse effects and the use of remedial medications during the treatment period were also documented.Results Compared with pre-treatment,VAS scores decreased,and SROM and CM scores improved at all time points after treatment in all three groups(P<0.05).AIS scores also decreased in all three groups at 1 month post-treatment(all P<0.05).Intergroup comparisons revealed that the TI group exhibited signifi-cantly lower VAS pain scores,greater SROM(forward flexion and backward extension),and higher CM scores at 4,8,and 12 weeks post-treatment compared to the T and I groups(Bonferroni-corrected P<0.05).No statistically significant differences were observed between the T and I groups for these measures(Bonferroni-corrected P>0.05).Additionally,there were no statistically significant differences in AIS scores or adverse effects occurrence among the three groups at 1 month post-treatment(P>0.05).Conclusion The combined treatment demonstrated greater efficacy compared to trigger point extracorporeal shock wave therapy alone and periapical steroid injection alone,resulting in significant improvement in the patient's clinical symptoms and quality of life.

Objective To investigate the efficacy of extracorporeal shock wave therapy(ESWT)combined with ultrasound-guided corticosteroid injection(CSI)for the treatment of primary frozen shoulder(PFS).Methods Ninety-nine patients with PFS who visited the pain department of the Affiliated Hospital of Xuzhou Medical University between April 2024 and July 2024 were enrolled and randomly divided into three groups according to the randomized number table method:ESWT group(T group),CSI group(I group),and combined treatment group(TI group),with 33 patients in each group.Visual analogue scale(VAS)scores,shoulder range of motion(SROM),and Constant-Murley shoulder scores(CMS)were recorded before treatment and at 1,4,8,and 12 weeks post-treatment.Additionally,the patients'Ascens Insomnia Scale(AIS)scores were recorded before treatment and 1 month after treatment.The occurrence of adverse effects and the use of remedial medications during the treatment period were also documented.Results Compared with pre-treatment,VAS scores decreased,and SROM and CM scores improved at all time points after treatment in all three groups(P<0.05).AIS scores also decreased in all three groups at 1 month post-treatment(all P<0.05).Intergroup comparisons revealed that the TI group exhibited signifi-cantly lower VAS pain scores,greater SROM(forward flexion and backward extension),and higher CM scores at 4,8,and 12 weeks post-treatment compared to the T and I groups(Bonferroni-corrected P<0.05).No statistically significant differences were observed between the T and I groups for these measures(Bonferroni-corrected P>0.05).Additionally,there were no statistically significant differences in AIS scores or adverse effects occurrence among the three groups at 1 month post-treatment(P>0.05).Conclusion The combined treatment demonstrated greater efficacy compared to trigger point extracorporeal shock wave therapy alone and periapical steroid injection alone,resulting in significant improvement in the patient's clinical symptoms and quality of life.

OBJECTIVE To investigate the distribution and drug resistance of pathogens isolated from the children with bloodstream infection in pediatric intensive care unit(PICU)so as to provide guidance for empirical clinical treatment of infections.METHODS Based on the Pediatric Intensive Care Database(PIC,http://pic.nbscn.org),the etiological data were collected from the PICU children of Children's Hospital,Zhejiang University School of Medicine by R software in 2010-2019 and were retrospectively analyzed.The species,distribution and drug resist-ance of the pathogens isolated from the children were observed.RESULTS Totally 991 strains of pathogens were isolated,727(73.36％)of which were gram-positive bacteria,213(21.49％)were gram-negative bacteria,and 51(5.15％)were fungi.Staphylococcus epidermidis(320 strains,32.29％)was the predominant species of the gram-positive bacteria,followed by Staphylococcus hominis(118 strains,11.91％),Staphylococcus capitis(55 strains,5.55％)and Enterococcus faecium(Group D,33 strains,3.33％);Klebsiella pneumoniae(59 strains,5.95％),Escherichia coli(58 strains,5.85％),Acinetobacter baumannii(25 strains,2.52％)and Pseudo-monas aeruginosa(18 strains,1.82％)were the major species of gram-negative bacteria.The analysis of drug re-sistance showed that the gram-positive bacteria were generally resistant to β lactams and maintained sensitive to vancomycin and linezolid;the gram-negative bacteria showed high drug resistance rates,especially,A.baumannii and P.aeruginosa,showed multi-drug resistance.CONCLUSIONS The gram-positive bacteria are dominant among the pathogens isolated from the PICU children with bloodstream infections.The empirical treatment should be performed based on the distribution and drug resistance data of the pathogens,and sensitive drugs should be cho-sen for optimization of the treatment regimen.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.