Objective: To prepare platelet membrane biomimetic liposomes loaded with vincristine sulfate (VCR) for targeted delivery to tumor. Methods: Vincristine sulfate liposomes (LIPO) were prepared using the pH-gradient method, followed by the fusion of platelet membranes and subsequent drug loading to obtain platelet membrane biomimetic liposomes (PLM-LIPO). The particle size, polydispersity index (PDI), Zeta potential, and drug encapsulation efficiency (EE%) of both liposomes were characterized. The tumor-targeting capability was evaluated through in vitro cellular experiments and in vivo biodistribution studies. Results: The optimal preparation conditions for LIPO were determined as follows: DPPC-to-cholesterol molar ratio of 1∶1, internal aqueous phase of 0.3 M pH 4.0 citrate buffer, external aqueous phase of 1 M Na HPO solution, drug-to-lipid ratio of 1∶10, drug loading temperature of 60℃, and loading time of 10 minutes. The LIPO exhibited a mean particle size of (147.3±2.24) nm, PDI of 0.078±0.014, Zeta potential of (-3.54±0.75) mV, and EE% of 91.37±0.47. For PLM-LIPO, prepared via membrane fusion followed by drug loading, the mean particle size was (185.3±3.61) nm, PDI was 0.075±0.022, Zeta potential was (-18.91±1.54) mV, and EE% was 63.36±2.45. In the CD62P validation experiment, the fluorescence intensity of PLM-LIPO was five times higher than that of LIPO. In vitro cellular uptake experiments revealed that PLM-LIPO showed 1.3-fold and 1.2-fold higher uptake rates compared to LIPO at 6 h and 12 h, respectively. In vivo experiments demonstrated that 1h after administration, the accumulation of PLM-LIPO at tumor sites was 4-fold higher than that of LIPO and 6-7 times higher than that in healthy mice. Conclusion: The platelet membrane biomimetic liposomes loaded with vincristine sulfate were successfully developed. Both cellular uptake and tissue distribution studies confirmed the PLM-LIPO enhanced tumor-targeting capability.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H₂O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min^-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS² data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

【Objective】 To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. 【Methods】 LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. 【Results】 The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL^-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL^-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. 【Conclusion】 The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

Objective To explore the association between visceral adiposity index(VAI)and nonalcoholic fatty liver disease(NAFLD)in lean population and the predictive value of VAI.Methods A total of 2 576 healthy subjects,body mass index(BMI)＜24 kg/m2,from The Second Affiliated Hospital of Xi'an Jiaotong University from June 2020 to May 2021 were randomly included and divided into lean NAFLD(n=213)and healthy control group(n=2 363).According to the VAI quartiles,they were divided into Q1-Q4 groups from low to high.The differences in biochemical parameters and the prevalence of NAFLD were compared among groups.The correlation between VAI and lean NAFLD was analyzed with restricted cubic spline(RCS),and the predictive value of VAI was explored by Logistic regression and receiver operating characteristic(ROC)curve.Results A total of 2 576 participants were included,and the prevalence of lean NAFLD was 8.3％(213 cases).The mean age,male ratio,BMI and waist circumference(WC)from group Q1 to group Q4 were significantly increased in a dose-response relationship(all P＜0.001).Compared with those in group Q1,systolic blood pressure,diastolic blood pressure,white blood cell count,hemoglobin concentration,alanine aminotransferase,aspartate aminotransferase,γ-glutamyl transpeptidase,alkaline phosphatase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,blood uric acid,and fasting blood glucose levels in groups Q2 to Q4 were significantly increased,while direct bilirubin and high-density lipoprotein cholesterol levels were gradually decreased(both P＜0.001).The prevalence rate of NAFLD in groups Q1-Q4 was 0.6％,3.3％,7.0％and 22.2％,respectively(P＜0.001).RCS showed that the risk of NAFLD in lean population rose significantly with the increase of VAI(P＜0.001),and there was a nonlinear relationship between them(P for nonlinear＜0.001).Logistic regression showed that after adjusting other confounding factors,the risk of lean NAFLD in groups Q2,Q3 and Q4 was still 2.926 times(95％CI:0.971-8.811),3.435 times(95％CI:1.154-10.230),and 5.920 times(95％CI:1.873-18.719)that Q1 group.ROC curve showed that VAI had a good predictive value for lean NAFLD,with area under the curve of 0.815,critical value of 1.532,diagnostic sensitivity of 77.9％and specificity of 72.8％,which were better than BMI and WC.Conclusion VAI is significantly associated with the risk of NAFLD in lean population,and thus has a good predictive value.It can be used for early screening and diagnosis of lean NAFLD.

Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09％)were diagnosed with STB,and 54(40.91％)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68％and 66.67％,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95％CI:1.847-9.974,P＜0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56％,higher than 67.42％of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.

Objective To investigate a suspected outbreak of carbapenem-resistant Klebsiella pneumoniae(CRKP)healthcare-associated bloodstream infection(HA-BSI),provide reference for effective control of CRKP in-fection.Methods The characteristics of CRKP infected patients and the risk factors for the event transmission in an adult hematology department of a teaching hospital in June 2022 were obtained by field epidemiological investigation.The specimens of environmental target strains were co-llected by blood nutrient agar inoculation,the removal status of environmental microorganisms and the effect of infection control after implementing control measures were com-pared.Results There were a total of 6 cases of CRKP HA-BSI,with an attacking rate of 1.29％(6/464),which was significantly higher than 0 during the same period in 2021,and difference was statistically significant(P=0.011).In environmental hygiene monitoring,the detection rate of CRKP was 2.27％(1/44),which was from the surface of bed curtain in the living unit of infected patients,homology analysis with CRKP detected from 2 patients revealed that the 16s RNA of 3 CRKP strains was completely identical,with a similarity of 100％.Seven house-keeping genes of 3 CRKP strains were all identical and belonged to the ST11 type.Comprehensive control measures were taken:appropriate closure of the ward,centralized isolation of patients,terminal disinfection of the ward,reg-ular health care workers and relative restriction of their activity areas.After the measures were taken,the qualified rate of microbial colony count in the ward increased compared to before taking the measures(2.27％vs 68.89％,P＜0.001),with a statistically significant difference,there were no more CRKP infected cases after the intervention,indicating that the control measures were effective.Conclusion This outbreak was caused by ST11 type of common CRKP in China,and laminar bed curtains are carriers of pathogen transmission.It is speculated that non-standard cleaning and disinfection,as well as inadequate implementation of hand hygiene are the main causes for transmis-sion.Adopting an appropriate strategy of closing the ward and concentrating patient isolation can quickly and effec-tively prevent the transmission of the event.