To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

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.

Objective To explore the clinical efficacy of applying exoskeleton robots in lower limb functional rehabilitation for patients after minimally invasive surgery for cervical spondylotic myelopathy(CSM).Methods A retrospective analysis was conducted on the clinical data of 56 patients who underwent spinal endoscopic minimally invasive surgery between April 2021 and October 2022.Based on the rehabilitation methods,patients were divided into the observation group(robot-assisted rehabilitation group)and the control group(conventional rehabilitation group).The Japanese Orthopaedic Association(JOA)scores for cervical spinal cord function,lower limb somatosensory evoked potential amplitudes,and gait analysis indicators(step frequency,walking speed,and stance phase ratio)were assessed preoperatively,4 weeks postoperatively,and 8 weeks postoperatively.Results In 4 and 8 weeks after surgery,both groups showed significant improvements in JOA scores,lower-limb somatosensory evoked potential amplitudes,and gait parameters(step frequency,walking speed,and stance phase ratio)com-pared with preoperative data(P<0.05).Furthermore,the improvements in JOA scores,somatosensory evoked potential amplitudes,and gait parameters in the observation group were significantly greater than those in the control group at both 4 and 8 weeks postoperatively(P<0.05).However,at the 2-year follow-up,there were no statistically significant differences(P>0.05)between the two groups in any of these measures.Conclusions Rehabilitation using lower limb exoskeleton robots can accelerate spinal cord function recovery and improve lower limb walking ability in patients after minimally invasive surgery for CSM,demonstrating superior short-term clinical efficacy com-pared to conventional rehabilitation.However,no significant differences were observed between the two methods during long-term follow-up.

Objective:To compare the differences in breastfeeding rates and the incidence of clinical complications in very/extremely low birth weight infants with and without the use of donor milk banks.Methods:Before and after the establishment of the donor milk bank,a total of 279 very/extremely low birth weight infants who were hospitalized in neonatal intensive care unit in a tertiary hospital in Beijing were selected.In the study,136 infants who did not receive donated breast-feeding were included in con-trol group and 143 infants who received donated breast-feeding were included in observation group.The clinical data of mothers and their infants were collected.The mother's information included gestational age,maternal comorbidities,and mode of delivery.Infant information includes gender,weight,gesta-tional age,duration of breastfeeding,total enteral feeding time,hospitalization time and incidence of complications(feeding intolerance,necrotizing enterocolitis,retinopathy of prematurity).Results:The maternal ages were(33.5±4.2)years in the observation group and(32.5±3.9)years in the con-trol group.Cesareans were performed in 95 cases(70.4％)and 81 cases(66.9％),respectively.The gestational ages of preterm infants were(29.2±2.1)weeks and(29.1±2.2)weeks,with birth weights of(1 140.5±247.1)g and(1 169.4±228.6)g,respectively.Newborn boys accounted for 72 cases(50.3％)in the observation group and 63 cases(46.3％)in the control group.No statistically significant differences were found in baseline characteristics between the two groups(all P＞0.05).After the use of donor milk banks,the rate of exclusive breastfeeding in very/low birth weight infants increased from 3.1％to 10.5％(x2=5.778,P=0.016)during hospitalization,the time to full enteral feeding was shortened from 13dto10d(Z=-4.567,P＜0.001),the first breastfeeding time was shortened from the third day of admission to the first day of admission(Z=-11.812,P＜0.001),the first breastfeeding of mother's own milk was extended from the third day of admission to the fourth day of admission(Z=-4.652,P＜0.001),and the incidence of feeding intolerance during hospitalization was reduced from 34.0％to 10.0％(x2=17.015,P＜0.001).There were no significant differences in the incidence of necrotizing enterocolitis,late-onset sepsis,retinopathy of prematurity and total length of hospital stay(P＞0.05).Conclusion:The use of donor milk bank can improve the breastfeeding rate,shorten the time to first breastfeeding,and reduce the incidence of feeding intolerance in very/extremely low birth weight infants,which provides a reference for the clinical treatment of very/extremely low birth weight infants.

AIM To evaluate the quality of Croci Stigma from different producing areas.METHODS The analysis was performed on a 25 ℃ thermostatic Waters Acquity UPLC HSS T3 column(2.1 mm× 100 mm,1.8μm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 0.35 mL/min in a gradient elution manner,and the detection wavelengths were set at 254,440 nm.The UPLC fingerprints were established,after which orthogonal partial least squares discriminant analysis was performed,picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅲ,crocin-Ⅳ contents and chromaticity values(L*,a*,b*,E*ab)were determined,Pearson correlation analysis was adopted in the investigation of correlations between chromaticity values and internal constituent contents.RESULTS There were 14 common peaks in the fingerprints for 22 batches of medicinal materials with the similarities of more than 0.98.Various batches of medicinal materials were clustered into 2 types,7 quality difference components were screened.crocin-Ⅰ content in medicinal materials from different producing areas demonstrated significant differences(P＜0.05);the redder the color of medicinal material,the higher the contents of crocins.Picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅳ contents displayed highly significant correlations with colorimetric values(P＜0.01),while crocin-Ⅲ content exhibited no significant correlation with the latter(P＞0.05).CONCLUSION This accurate and reliable method can provide references for the quality control and color-quality relationship elucidation of Croci Stigma.

40 patients with choronic periodontitis underwent periodontal basic treatment were randomly divided into 2 groups(n=20).The patients in control group used special toothpaste and toothbrush to brush their teeth after meals,those in the experimental group brushed their teeth with special toothpaste and toothbrush in the morning,evening and after meals,and wore personalized film pressing trays containing cymene care solution while sleeping at night.Gingival bleeding,periodontal pocket depth and attachment loss were ob-served after 4,6 and 10 weeks respectively.The personalized tray combined with cymbidium reduced the depth of periodontal pocket(P＜0.05)and the rate of probing bleeding sites(P＜0.05)more effectively,and showed no statistical significance in the change of attachment loss(P＜0.05).Cymene care solution is effective in the improvement of periodontal health.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To survey the awareness and intended adoption of patient-based real-time quality control(PBRTQC)among medical laboratories,thereby providing a basis for subsequent research and promotion efforts.Methods An electronic questionnaire was distributed via the Questionnaire Star system to collect participants' general information,their knowledge,attitudes,and practices regarding PBRTQC,as well as their implementation willingness.Results A total of 161 valid questionnaires were collected.The sur-vey revealed that fewer than 50％of laboratory staff had basic knowledge of PBRTQC,and their confidence in establishing and applying PBRTQC in their own laboratories was low.However,they acknowledged its potential to enhance quality management.Key concerns and support needs for PBRTQC promotion include professional implementation guidelines and policy support,reliable third-party evalu-ations,software and hardware support,and user training.Conclusion The laboratory staff accepted the value of PBRTQC and gener-ally held a positive attitude toward its application.Future efforts should focus on developing standardized guidelines,refining evaluation methods,advancing software and hardware,and enhancing knowledge dissemination,technical training and other actions related to guiding the practical implementation thereby facilitating the wider adoption of PBRTQC.

This study was aimed at providing basic data for the control and prevention of Yersinia enterocolitica(Ye)infections.Ye isolates from stool samples collected from patients with diarrhea in a Beijing district between January 2019 and June 2024 were studied.Basic patient information and stool samples were collected,and quantitative polymerase chain reaction(qPCR)was applied to enriched cultures.Further analyses included virulence gene detection,whole-genome sequencing,and drug resistance detection.The detection rate of Ye was 0.76%(11/1 439),according to culture methods,thus yielding 12 Ye strains from distinct patients:11 isolated during the study period and 1 from 2017.The 12 Ye positive patients were 6-41 years of age,and their clinical presentations predominantly featured watery stools(66.67%,8/12)and loose stools(33.33%,4/12).The frequencies of nausea,vomiting,and fever were 41.67%(5/12),41.67%(5/12),and 8.33%(1/12),respectively.The drug resistance rates of Ye to TET,AMP,and NAL were 50.00%(6/12),33.33%(4/12),and 25.00%(3/12),respectively.One Ye strain exhibited multidrug resistance to ETP,MEM,TET,CIP,NAL,and AMP.According to qPCR detection of five common virulence genes,two Ye strains were identified as ystA+/ystB-type(ystA+/ystB-/ail+/yadA+/virF+),whereas ten strains were identified as ystA-/ystB+type(ystA-/ystB+/ail-/yadA-/virF-).VFDB database analysis based on genome sequences indicated that 12 Ye strains carried an average of 11 key virulence genes associated with adhesion,invasion,protease activity,and flagellar movement,and predicted 106 virulence genes and 12 virulence gene profiles.Only the two ystA+/ystB-Ye strains contained elements related to the TTSS and ABC transporter function.Detection of ystA-/ystB+Ye in stool isolation and culture of diarrhea cases might potentially have been missed in some cases,thus highlighting the importance of fluorescence PCR screening of fecal growth solutions to enhance isolation efficiency.Moreover,our findings revealed the genetic diversity of Ye isolated from diarrhea cases,thereby indicating the presence of multiple types of virulence genes within this pathogen.