ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

Objective: To investigate the awareness of knowledge about hepatitis C prevention and control among outpatients in Ningbo City, Zhejiang Province, and its influencing factors, so as to provide the evidence for strengthening health education on hepatitis C prevention and control. Methods: Based on sentinel surveillance of hepatitis C, the outpatients aged 15 to 65 years at seven hospitals in Yinzhou District, Cixi City and Xiangshan County of Ningbo City were selected using the convenient sampling method from April to June during 2020 and 2022. Demographic information, knowledge and behaviors related to hepatitis C prevention and control were collected through questionnaire surveys. The influencing factors for knowledge about hepatitis C prevention and control were analyzed using a multivariable logistic regression model. Results: A total of 2 792 participants were surveyed, including 1 157 males (41.44%) and 1 635 females (58.56%). The awareness rate of knowledge about hepatitis C prevention and control was 56.23%, and was lower in knowledge about hepatitis C vaccine and treatment. The awareness rates of knowledge about hepatitis C prevention and control among outpatients from 2020 to 2022 were 47.11%, 53.22% and 70.65%, respectively, showing an upward trend (P<0.05). Multivariable logistic regression analysis showed that participants aged 25 to <50 years (OR=1.358, 95%CI: 1.073-1.719), with an educational level of high school or junior college (OR=1.431, 95%CI: 1.134-1.806) or above junior college (OR=3.728, 95%CI: 2.958-4.699), with household monthly income per capita of 3 000 to <5 000 yuan (OR=1.828, 95%CI: 1.344-2.486) or ≥5 000 yuan (OR=1.858, 95%CI: 1.366-2.526), without a history of invasive treatments such as pedicure in public places (OR=1.287, 95%CI: 1.024-1.618), without a history of contact with family members' blood-contaminated items (OR=2.050, 95%CI: 1.552-2.707), and always using condoms during sexual contacts (OR=1.740, 95%CI: 1.273-2.378) had higher awareness of knowledge about hepatitis C prevention and control. Conclusions The awareness of knowledge about hepatitis C vaccine and treatment among outpatients in Ningbo City needs to be improved. Age, educational level, household monthly income per capita, history of invasive treatments such as pedicure in public places, history of contact with family members' blood-contaminated items and frequency of condom use during sexual contacts are associated with outpatients' awareness of knowledge about hepatitis C prevention and control.

Objective To investigate the analgesic effect of ultrasound-guided quadratus lumborum block combined with patient-controlled intravenous analgesia after lower abdominal surgery.Methods A total of 134 patients who underwent lower abdominal surgery in General Hospital of Central Theater Command from April 2021 to April 2024 were prospectively selected and randomly divided into the observation group and the control group,with 67 patients in each group.Patients in the observation group received ultrasound-guided quadratus lumborum block combined with patient-controlled intravenous analgesia.Patients in the control group underwent only patient-controlled intravenous analgesia.The number of analgesic pump compressions and the cumulative sufentanil consumption 4 hours,6 hours,12 hours,and 24 hours after surgery,the visual analogue score(VAS)of pain at rest and exercise,and the incidence of adverse reactions during postoperative analgesia were compared between the two groups.Results Compared with the control group,the number of analgesic pump compressions and the cumulative sufentanil consumption of patients were fewer/less at 6 hours,12 hours and 24 hours after surgery in the observation group(P<0.05).The VAS scores of patients at exercise 4 hours,6 hours,12 hours and 24 hours after surgery in the observation group were significantly lower than those in the control group(P<0.05).The incidence of nausea,vomiting and vertigo in the observation group was significantly lower than that in the control group(P<0.05).Conclusion Compared with patient-controlled intravenous analgesia,ultrasound-guided quadratus lumborum block combined with patient-controlled intravenous analgesia can significantly reduce the number of analgesia pump compressions and the cumulative sufentanil consumption in postoperative analgesia of lower abdominal surgery,and has a better effect in relieving exercise pain,it can also reduce the occurrence of adverse reactions such as nausea and vomiting.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

Objective To assess the clinical feasibility of a self-developed augmented reality(AR)system in surgeries for cerebral arteriovenous malformation(AVM),dural arteriovenous fistula(DAVF),moyamoya,and internal carotid artery stenosis.This system integrates preoperative vascular imaging(CTA,MRA,DSA)with intraoperative real-time visualization through high-precision patient-image registration and virtual-real integration technology.Methods A retrospective analysis was conducted on 6 patients(1 cerebral AVM,1 DAVF,3 moyamoya and 1 internal carotid artery stenosis)collected between March 2023 and April 2024.AR with three-dimensional reconstruction was used for preoperative precise localization and intraoperative navigation guidance.Clinical feasibility was evaluated and analyzed using an intraoperative self-controlled method.Results All 6 patients with diverse etiologies successfully underwent preoperative precise localization and intraoperative navigation guidance under AR three-dimensional reconstruction modeling.This technology achieved visualization of intracranial arteriovenous structures and precise lesion locations,providing surgeons with a visual reference for accurate planning of the surgical approach and operative field.Conclusion The application of AR with three-dimensional reconstruction is safe and feasible in neurosurgical procedures for cerebrovascular diseases.It demonstrates satisfactory effectiveness in preoperative localization and intraoperative navigation guidance.

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.

AIM:To observe the effect of opioid-free anesthesia with esketamine on delirium after hip replacement surgery in elderly patients.METH-ODS:One hundred and fourteen elderly patients who underwent hip replacement were randomly di-vided into two groups:opioid-free anesthesia(OFA)group and opioid anesthesia(OA)group(n=57).During anesthesia induction and maintenance,es-ketamine was administered in OFA group,and that fentanyl and remifentanil were administered in OA group.Delirium was mainly recorded within 3 days after the surgeries,and the patients'delirium sta-tus was evaluated using the Chinese Revised Deliri-um Diagnostic Scale(CAM-CR).RESULTS:The pa-tients in OFA group had lower CAM-CR scores and delirium incidence compared to those in the OA group at 2 days after surgery.CONCLUSION:Opioid-free anesthesia based on esketamine can effective-ly reduce delirium after hip replacement in elderly patients.

Parkinson's disease is a neurodegenerative disease that mainly affects dopamine neurons in the substantia nigra region of the brain,and its clinical manifestations include shaking and slowness of movement.The means of clinical medicine treatment are limited,but traditional Chinese medicine,with its advantages of low cost and high safety,shows great potential in the prevention and treatment of Parkinson's disease.Our team proposed that the core pathogenesis of Parkinson's disease was"earth deficiency and wood multiplication",that is,spleen(soil)deficiency and liver(wood)dysfunction.Among them,"earth deficiency"was the basis of the disease,and"wood multiplication"was the core of the disease.The treatment advocated"strengthening spleen and soothing liver",the specific methods included strengthening spleen and resolving phlegm,Tonify qi and cultivate the middle and soothing liver and relieve depression,and subdue wind and unblock the meridians,etc.Representative recipes were Lianmei Siwu decoction,Zhengan Xifeng decoction,Huangya decoction and Shenzhu decoction.In the treatment,we should pay attention to the whole concept and syndrome differentiation and treatment,and combine the three factors to improve the clinical effect.At the same time,the advantages and mechanisms of TCM in the prevention and treatment of Parkinson's disease deserve further research and verification.

BACKGROUND:In recent years,the application of exosomes of periodontal ligament stem cells in periodontal tissue regeneration engineering has been widely studied,but the effect of exosomes on periodontal ligament stem cells derived from inflammatory environment is still unclear.OBJECTIVE:To investigate the effects of exosomes secreted by periodontal ligament stem cells from healthy and inflammatory environments on the proliferation and differentiation of periodontal ligament stem cells from inflammatory environments.METHODS:Human periodontal ligament stem cells from healthy and inflammatory tissues were isolated and cultured by enzyme digestion method.Exosomes were extracted from two kinds of periodontal ligament stem cells using ultracentrifugation.Passage 3 periodontal ligament stem cells derived from inflammatory tissue were selected and cultured in three groups.Cells in the blank group were cultured routinely.The healthy exosome group was added with exosomes secreted by peripheral ligament stem cells derived from healthy tissue.The inflammatory exosome group was added with exosomes secreted by human periodontal ligament stem cells derived from inflammatory tissue.Cell proliferation and cloning were detected.The expression of alkaline phosphatase,the formation of mineralized nodules,and the expression of mRNA and protein of genes related to osteogenesis were detected under osteogenic differentiation.RESULTS AND CONCLUSION:(1) CCK-8 assay and clonal formation test showed that compared with the blank group,two kinds of exosomes could promote the proliferation and colony formation of periodontal ligament stem cells from inflammatory tissue (P<0.05),and the effect of the healthy exosome group was stronger than that of the inflammatory exosome group (P<0.05).(2) Alkaline phosphatase and alizarin red staining showed that compared with the blank group,the two kinds of exosomes could promote the expression of alkaline phosphatase and the formation of mineralized nodules in periodontal ligament stem cells from inflammatory tissue,and the promoting effect of the healthy exosome group was stronger than that of the inflammatory exosome group.RT-PCR and western blot assay showed that compared with the blank group,the two kinds of exosomes could promote the expression of alkaline phosphatase,RUNX2,and type Ⅰ collagen mRNA and protein in periodontal ligament stem cells from inflammatory tissue (P<0.05).The promoting effect of the healthy exosome group was stronger than that of the inflammatory exosome group (P<0.05).(3) The results showed that exosomes secreted by human periodontal ligament stem cells could promote the proliferation and osteogenic differentiation of periodontal ligament stem cells derived from inflammatory environments,and the promoting effect of exosomes secreted by human periodontal ligament stem cells derived from healthy tissues was better than that from human periodontal ligament stem cells derived from inflammatory tissues.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.