Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective To investigate the correlation between untreated premenopausal women with sys-temic lupus erythematosus(SLE)and 25 hydroxyvitamin D[25(OH)D]levels.Methods A total of 80 newly diagnosed premenopausal female SLE patients admitted to our hospital from July 2020 to June 2023 were se-lected as the SLE group,and 80 healthy premenopausal women were selected as the control group during the same period.Chemiluminescence method was used to detect the level of 25(OH)D,ELISA to detect autoanti-bodies in SLE patients,and the proportion of SLE patients with 25(OH)D deficiency or insufficiency was ana-lyzed.Pearson correlation analysis was used to investigate the correlation between 25(OH)D and 24-hour uri-nary protein quantification,complement 3(C3),complement 4(C4),systemic lupus erythematosus activity(SLEDAI)score,and specific lupus autoantibody titers in SLE patients.Multiple logistic regression was used to analysis the risk factors for developing SLE in premenopausal women.The receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to analyze the value of various indicators in predic-ting the occurrence of SLE in premenopausal women.Results The serum 25(OH)D level in the SLE patient group was lower than that in the control group(P＜0.05).According to the diagnostic criteria for vitamin D deficiency and insufficiency,the proportion of patients with vitamin D deficiency in the SLE group was 22.50％(18/80),and the proportion of patients with vitamin D deficiency was 63.75％(51/80).The serum levels of C3 and C4 in SLE patients were lower than those in the control group(P＜0.05).The levels of anti-double stranded DNA(dsDNA)antibody and anti-cardiolipin IgG(CL IgG)antibody were higher than those in the control group(P＜0.05).Pearson correlation analysis showed that serum 25(OH)D levels in SLE pa-tients were negatively correlated with anti-CL IgG antibody,anti-dsDNA antibody,24-hour urine protein quan-tification,and SLEDAI scores(r=-0.339,-0.294,-0.328,-0.392,P＜0.05),and positively correlated with complement C3 and C4 levels(r=0.241,0.178,P＜0.05).Multivariate logistic regression analysis showed that 25(OH)D,anti-dsDNA antibody,anti-CL IgG antibody,C3,C4,24-hour urinary protein quantifi-cation level,and SLEDAI score were independent influencing factors for the occurrence of SLE in premenopa-usal women(OR=1.125,0.413,0.203,99.791,33.162,0.045,0.096,P＜0.05).The AUC of each indicator predicting the occurrence of SLE in premenopausal women were 0.911,0.800,0.768,0.978,0.893,and 0.893,re-spectively.Conclusion 25(OH)D plays an important role in the onset and development of SLE and can be used as a predictive indicator of disease activity.It is recommended to screen for 25(OH)D in newly diagnosed SLE patients and treat patients with deficiency or insufficiency.

Objective To satisfy the normalized disinfection in the orthopedic ward,an air sterilizer based on low-temperature plasma has been developed to investigate its sterilization results in a dynamic environment of hospitalization where patients,companions and medical workers are involved.Methods This study took an orthopedics ward in the Secondary Affiliated Hospital of Xi'an Jiaotong University,as the research object,where a home-made low-temperature plasma air sterilizer was utilized.A six-stage viable Andersen cascade impactor was used to sample the natural bacteria in the ward before and after machine operation for three hours.The species and quantity of bacteria in the ward were analyzed.Results The ozone concentration in the indoor dynamic environment decreased to below 5 ppbv.After three-hour disinfection,the elimination rate of natural bacteria reached 92.35％.The final colony forming unit decreased to～150 CFU/m3;the extinction rates of Staphylococcus hominis,Bacillus cereus,molds,and Micrococcus luteus were 90.48％,80.90％,87.50％,and 92.82％respectively.Even all Haemophilus massiliensis disappeared after two-hour treatment.Conclusion Intermittent disinfection of the dynamic environment in the ward using low-temperature plasma synergistic catalyst has enabled the indoor ozone concentration to reach the first-level national standard line,effectively suppressing secondary pollution caused by ozone leakage while efficiently killing suspended microorganisms in the air,which is close to the disinfection level Ⅰenvironment specified in Hygienic Standard for Disinfection in Hospitals(GB 15982-2012).The results also show that the plasma catalytic synergistic disinfection and sterilization has the technical advantages of efficient disinfection and human-machine coexistence,which can ensure indoor air quality safety,reduce the workload of nursing staff,and thus is an effective method to assist or even replace the existing physical and chemical means.

As the "main force" for providing health services, there has been a constant increase in the number of health service and management graduates in recent years, but with a lack of satisfactory quality. The concept of outcome-based education (OBE) takes the needs of all parties as the starting point and foothold for practice, which can ensure the consistency between the goal of talent training and the learning achievements of students to the greatest extent. This article proposes to integrate the educational concept of OBE into the training path of health service and management talents, clarify talent training objectives by understanding the needs of all parties, optimize the curriculum system according to training objectives, and construct a diversified evaluation system with the organic combination of process evaluation and summative assessment, in order to continuously optimize the training path of health service and management talents and cultivate applied health management talents with knowledge, ability, and quality.

Objective To satisfy the normalized disinfection in the orthopedic ward,an air sterilizer based on low-temperature plasma has been developed to investigate its sterilization results in a dynamic environment of hospitalization where patients,companions and medical workers are involved.Methods This study took an orthopedics ward in the Secondary Affiliated Hospital of Xi'an Jiaotong University,as the research object,where a home-made low-temperature plasma air sterilizer was utilized.A six-stage viable Andersen cascade impactor was used to sample the natural bacteria in the ward before and after machine operation for three hours.The species and quantity of bacteria in the ward were analyzed.Results The ozone concentration in the indoor dynamic environment decreased to below 5 ppbv.After three-hour disinfection,the elimination rate of natural bacteria reached 92.35％.The final colony forming unit decreased to～150 CFU/m3;the extinction rates of Staphylococcus hominis,Bacillus cereus,molds,and Micrococcus luteus were 90.48％,80.90％,87.50％,and 92.82％respectively.Even all Haemophilus massiliensis disappeared after two-hour treatment.Conclusion Intermittent disinfection of the dynamic environment in the ward using low-temperature plasma synergistic catalyst has enabled the indoor ozone concentration to reach the first-level national standard line,effectively suppressing secondary pollution caused by ozone leakage while efficiently killing suspended microorganisms in the air,which is close to the disinfection level Ⅰenvironment specified in Hygienic Standard for Disinfection in Hospitals(GB 15982-2012).The results also show that the plasma catalytic synergistic disinfection and sterilization has the technical advantages of efficient disinfection and human-machine coexistence,which can ensure indoor air quality safety,reduce the workload of nursing staff,and thus is an effective method to assist or even replace the existing physical and chemical means.

As the "main force" for providing health services, there has been a constant increase in the number of health service and management graduates in recent years, but with a lack of satisfactory quality. The concept of outcome-based education (OBE) takes the needs of all parties as the starting point and foothold for practice, which can ensure the consistency between the goal of talent training and the learning achievements of students to the greatest extent. This article proposes to integrate the educational concept of OBE into the training path of health service and management talents, clarify talent training objectives by understanding the needs of all parties, optimize the curriculum system according to training objectives, and construct a diversified evaluation system with the organic combination of process evaluation and summative assessment, in order to continuously optimize the training path of health service and management talents and cultivate applied health management talents with knowledge, ability, and quality.

Objective:To study the correlation between different body weight metabolic phenotypes and their changes and new-onset hyperuricemia in physical examination population.Methods:This study was a retrospective cohort study. A total of 31 956 people who underwent routine physical examination and met the inclusion and exclusion criteria at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 1, 2014 to August 31, 2022 were selected as the study subjects to establish a dynamic physical examination cohort. The end point of follow-up was new-onset hyperuricemia or the end of follow-up period. Cox regression stepwise fitting model was used to analyze the risk of different body weight metabolic phenotypes and hyperuricemia, and stratified analysis was performed for gender. According to body weight metabolic phenotype, the subjects were divided into normal metabolism and normal weight(NMNW) group, normal metabolism and obesity (NMO) group, abnormal metabolism and normal weight (AMNW) group and abnormal metabolism and obesity (AMO) group. The risk of hyperuricemia was calculated according to the changes of body weight metabolic phenotype during the follow-up period. In the sensitivity analysis, the robustness of the results was verified by changing the diagnostic criteria for hyperuricemia, removing patients with hyperuricemia at the first year of follow-up, and removing subjects aged ≥65 years.Results:Compared with the NMNW group, the risk of hyperuricemia in the NMO group, AMNW group and AMO group increased by 78.9%, 61.3%, 115.4%, respectively ( χ2=272.88, 128.15, 496.12, all P<0.001). Patients who were initially classified as NMNW at baseline, if transitioned to NMO or AMO by the follow-up endpoint, their risk of hyperuricemia increased by 122.5% ( χ2=8.01, P<0.05) and 137.4% ( χ2=15.99, P<0.001), respectively. When the baseline AMNW group changed to AMO, the risk of hyperuricemia was increased by 119.2% ( χ2=6.63, P<0.05). For patients with AMO as baseline, if they turned into NMNW and AMNW at the end of follow-up, their risk of hyperuricemia would decrease by 58.3% ( χ2=43.67, P<0.001) and 27.2% ( χ2=16.07, P<0.001). Patients with a baseline of NMO who transitioned to NMNW and AMNW at the follow-up endpoint had their risk of developing hyperuricemia decreased by 36.7% ( χ2=25.35, P<0.001) and 30.9% ( χ2=9.70, P<0.05), respectively. Conclusions:The transition from metabolic health and non-overweight obesity to metabolic abnormalities and overweight obesity is associated with an increased risk of hyperuricemia, and improvements in metabolic health or weight are associated with a decreased risk of hyperuricemia.

Objective:To explore the relationship between weight change and the development of hyperuricemia (HUA) in adults receiving health checkups.Methods:A retrospective cohort study. A total of 37 722 subjects who underwent two or more health checkups at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2022 were included, and the general information and laboratory findings at the time of the initial health checkups and follow-up were collected. Weight change was defined as the ratio of difference between the weight at the last follow-up and the baseline weight to baseline weight. The subjects were grouped with weight change: significant weight loss group (weight change ≤-5.0%), mild weight loss group (-5.0%

Objective:By conducting a retrospective analysis of the clinical data of 14 patients diagnosed with invasive fungal rhinosinusitis (IFRS) confirmed by metagenomics next generation sequencing (mNGS) technology, we aim to explore the rapid diagnosis value of mNGS in IFRS.Methods:The clinical data of 14 IFRS patients admitted to TianJin First Central Hospital were retrospectively analyzed from February 2021 to October 2023. The study cohort comprised 8 males and 6 females, with ages ranging from 14 to 77 years. All patients were diagnosed as IFRS by performing mNGS sequencing technology of nasal sinus lesion biopsy specimens. Clinical data such as laboratory examination, imaging examination, histopathological examination results, treatment plan and prognosis were summarized and analyzed.Results:All 14 patients were diagnosed as IFRS, with mNGS detecting pathogens such as Rhizopus (7 cases), Aspergillus (5 cases), Trichoderma (1 case), and Scedosporium apiospermum (1 case). Follow-up evaluations were conducted for a period ranging from 2 months to 2 years post-treatment. At the end of follow-up, 11 out of 14 IFRS patients achieved a complete cure with no signs of recurrence, while the symptoms of the remaining 3 patients significantly improved with comprehensive treatment. Conclusion:mNGS emerges as a highly effective diagnostic tool for IFRS, providing valuable microbiological evidence for clinical diagnosis and demonstrating promising clinical utility.

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.
Humans ; Hypoglycemic Agents/pharmacology* ; Circular Dichroism ; Cytokines ; Glucose ; Hep G2 Cells ; Insulin Resistance