AIM:Xiongshi Shiwei Wendan decoc-tion(SWD)comes from Xiong Jibai,a master of tra-ditional Chinese medicine,and has been widely used in the treatment of AS.ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS.The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacol-ogy,molecular docking and in vitro experiments,and explore the pathway mechanism of promoting reverse cholesterol transport(RCT).METHODS:The active components of SWD drugs were screened by TCMSP and HERB databases,RCT targets were pre-dicted,the component-target network map was constructed,the PPI network was constructed and the GO and KEGG pathways were enriched and ana-lyzed by STRING database,and the key active com-ponents of SWD were selected for molecular dock-ing with ABCA1 protein and miR-33 by AutoDockVi-na.In vitro,RAW264.7 was used to establish foam cell model,oil red O staining,NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells.Western blotting was used to de-tect the expression of ABCA1.RESULTS:According to network pharmacology,336 active components of SWD,267 targets of RCT and 46 targets of inter-section of RCT and SWD were obtained,which in-volved multiple signal pathways such as lipid and atherosclerosis.Molecular docking showed that the main active components had stable conforma-tion with ABCA1 and miR-33.In vitro experiment,it was found that the lipid content was significantly decreased(P＜0.01),the cholesterol outflow rate was significantly increased(P＜0.01)and the expres-sion of ABCA1 protein was up-regulated in SWD group(P＜0.01),but the expression of ABCA1 in miR-33 overexpression group was significantly de-creased(P＜0.01).CONCLUSION:SWD has the char-acteristics of multi-components and multi-targets,which can promote RCT and treat AS through miR-NA-33-ABCA1 pathway.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

AIM:Xiongshi Shiwei Wendan decoc-tion(SWD)comes from Xiong Jibai,a master of tra-ditional Chinese medicine,and has been widely used in the treatment of AS.ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS.The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacol-ogy,molecular docking and in vitro experiments,and explore the pathway mechanism of promoting reverse cholesterol transport(RCT).METHODS:The active components of SWD drugs were screened by TCMSP and HERB databases,RCT targets were pre-dicted,the component-target network map was constructed,the PPI network was constructed and the GO and KEGG pathways were enriched and ana-lyzed by STRING database,and the key active com-ponents of SWD were selected for molecular dock-ing with ABCA1 protein and miR-33 by AutoDockVi-na.In vitro,RAW264.7 was used to establish foam cell model,oil red O staining,NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells.Western blotting was used to de-tect the expression of ABCA1.RESULTS:According to network pharmacology,336 active components of SWD,267 targets of RCT and 46 targets of inter-section of RCT and SWD were obtained,which in-volved multiple signal pathways such as lipid and atherosclerosis.Molecular docking showed that the main active components had stable conforma-tion with ABCA1 and miR-33.In vitro experiment,it was found that the lipid content was significantly decreased(P＜0.01),the cholesterol outflow rate was significantly increased(P＜0.01)and the expres-sion of ABCA1 protein was up-regulated in SWD group(P＜0.01),but the expression of ABCA1 in miR-33 overexpression group was significantly de-creased(P＜0.01).CONCLUSION:SWD has the char-acteristics of multi-components and multi-targets,which can promote RCT and treat AS through miR-NA-33-ABCA1 pathway.

Objective:To explore the family function of childbearing period cervical cancer patients and their caregivers based on the McMaster Family Functioning Theory, providing a reference for developing scientific and effective family support programs.Methods:This qualitative study employed a purposive sampling method to recruit 15 pairs of childbearing period cervical cancer patients and their caregivers from Wuxi Maternity and Child Health Hospital between March and April 2024. Face-to-face semi-structured interviews were conducted, and data were analyzed using Colaizzi's seven-step method to extract themes.Results:A total of five main themes were identified: role transitions and family structure changes; alterations in family interaction dynamics; evolving caregiving needs and distress; emotional disengagement in disease experiences among family members; family behavioral isolation.Conclusions:The cancer diagnosis posed threats to all six dimensions of family function (role distribution, problem-solving, communication, emotional involvement, emotional responsiveness, and behavioral control). Clinical practitioners should pay close attention to the family functioning of childbearing period cervical cancer patients and develop patient- and caregiver-centered family function intervention programs to help them better cope with the disease and improve clinical outcomes.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Objective:To explore the family function of childbearing period cervical cancer patients and their caregivers based on the McMaster Family Functioning Theory, providing a reference for developing scientific and effective family support programs.Methods:This qualitative study employed a purposive sampling method to recruit 15 pairs of childbearing period cervical cancer patients and their caregivers from Wuxi Maternity and Child Health Hospital between March and April 2024. Face-to-face semi-structured interviews were conducted, and data were analyzed using Colaizzi's seven-step method to extract themes.Results:A total of five main themes were identified: role transitions and family structure changes; alterations in family interaction dynamics; evolving caregiving needs and distress; emotional disengagement in disease experiences among family members; family behavioral isolation.Conclusions:The cancer diagnosis posed threats to all six dimensions of family function (role distribution, problem-solving, communication, emotional involvement, emotional responsiveness, and behavioral control). Clinical practitioners should pay close attention to the family functioning of childbearing period cervical cancer patients and develop patient- and caregiver-centered family function intervention programs to help them better cope with the disease and improve clinical outcomes.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration(cmin)of voriconazole(VRZ)in patients with invasive fungal infection.METHODS The Cochrane Library,Embase,PubMed,Web of Science,China Biomedical Literature Database,CNKI,VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms andcmin of VRZ from inception to April 2024.After screening the literature,extracting data,and evaluating the quality of the literature,meta-analysis was performed using R 4.3.2 software.RESULTS A total of 21 studies with 2 454 patients were included.The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type,and the VRZ cmin of IM type was significantly lower than PM type(P＜0.01).The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type,and that of CYP3A5 rs776746 CC type was significantly higher than TT type(P＜0.01).The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types,and that of POR rs1057868 CT type was significantly lower than TT type(P＜0.01).The VRZ cminof ABCB1 rs1045642 CC type was significantly higher than TT type(P＜0.05).The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type,and rs7643645 AA type was significantly higher than AG type(P＜0.05).The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type,and the CT type was significantly lower than TT type(P＜0.01).CONCLUSIONS Mutant alleles in CYP2C19,CYP2C9 rs1057910,CYP3A5 rs776746,POR rs10954732,ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration,and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

Objective To identify the current research hotspots of global health training, and construct a global health talent training evaluation index system. Methods Publications pertaining to global health talent training evaluation were retrieved in China National Knowledge Infrastructure, Wanfang Database, and Web of Science Core Collection from 2003 to 2022, and keywords were extracted from eligible publications for co-occurrence and cluster analyses using the CiteSpace software. Based on keywords clustering results, a global health talent training evaluation index system was constructed using a context, input, process, and product (CIPP) evaluation model as a theoretical framework. Results A total of 692 Chinese publications and 1 264 English publications were included. Keyword co-occurrence and cluster analyses yielded 10 Chinese and 10 English keyword clusters, and the 10 Chinese keyword clusters included analytic hierarchy process, health diplomacy, personnel structure, crossdiscipline, educational assessment, global health discipline development, training needs, curriculum program, quality evaluation and logistics support, while the English keyword clusters included evidence-based practice, capacity building, global health, quality of life, machine learning, leadership, sub-Saharan Africa, health equity, global health security and global health diplomacy. Based on keyword clustering, a global health talent training evaluation index system was constructed with CIPP as the theoretical framework, which contained 4 primary indicators, 15 secondary indicators and 59 tertiary indicators, and the primary indicators included 4 dimensions of context evaluation, input evaluation, process evaluation and product evaluation. Conclusions A global health talent training evaluation index system has been constructed, which provides an effective evaluation tool and quantitative evidence for future global health talent training.

BACKGROUND:It has been found that vascular endothelial growth factor 165 and bone morphogenetic proteins interact with each other during hypoxia-reoxygenation and are involved in the repair process of osteoblast injury by regulating the activation of intracellular signaling pathways. OBJECTIVE:To further investigate the relationship between vascular endothelial growth factor 165/bone morphogenetic protein and hypoxic-reoxygenated osteoblast injury. METHODS:Osteoblasts were selected and the hypoxic-reoxygenated injury model was established.Vascular endothelial growth factor 165 and bone morphogenetic protein expressions at mRNA and protein levels were detected by real-time PCR and western blot before and after modeling.After modeling,osteoblasts were given different concentrations of vascular endothelial growth factor 165 and bone morphogenetic protein 2(10,20,40 ng/mL).Cell proliferation was detected by cell counting kit-8 method and apoptosis was detected by DAPI at 12,24,36,48,and 72 hours after treatment. RESULTS AND CONCLUSION:Compared with before modeling,the mRNA and protein expressions of vascular endothelial growth factor 165 and bone morphogenetic protein 2 in osteoblasts after modeling were significantly decreased(P＜0.05).The proliferation rate of osteoblasts was significantly increased with the increase of vascular endothelial growth factor 165 concentration(P＜0.05),while the apoptosis rate of osteoblasts decreased significantly with the increase of vascular endothelial growth factor 165 concentration(P＜0.05).The proliferation rate of osteoblast was significantly increased with the increase of bone morphogenetic protein 2 concentration(P＜0.05),while the apoptosis rate of osteoblast decreased significantly with the increase of bone morphogenetic protein 2 concentration(P＜0.05).To conclude,vascular endothelial growth factor 165 and bone morphogenetic protein are lowly expressed in hypoxic-reoxygenated osteoblast injury,and treatment with vascular endothelial growth factor 165 and bone morphogenetic protein can reduce the injury of hypoxic-reoxygenated osteoblast in a concentration-dependent manner,suggesting that vascular endothelial growth factor 165 and bone morphogenetic protein have a significant protective effect against the injury of hypoxic-reoxygenated osteoblasts.

Objective:To explore the influencing factors for compliance to colonoscopy screening for colorectal cancer in outpatients.Methods:Patients aged 40-74 years who visited the outpatient gastroenterology department of 7 tertiary hospitals in 7 regions of Xinjiang from January 2022 to June 2022 were enrolled. Recommendations for colonoscopy screening were made according to the patient's medical conditions, and the questionnaire was used to collect information. The Chi-square test was used to compare the differences of compliant and non-compliant patients. Multivariate logistic regression was used to analyze the influencing factors of compliance to colonoscopy screening.Results:A total of 463 valid questionnaires were obtained from 7 centers, in which, 427 outpatients (92.2%) followed the recommendation for colonoscopy screening, and 36 (7.8%) did not. Chi-square test results showed that there were statistically significant differences between the two groups in gender, age, education, subjective cognition of intestinal polyps, personal history of colorectal polyps, family history of colorectal cancer, family history of colorectal polyps, abdominal pain or distension, and defecation habit or stool changes ( P<0.05). The results of multivariate regression analysis showed that the screening compliance of patients aged 40-49 years ( P=0.005, OR=0.141, 95% CI: 0.036-0.549) and 50-59 years ( P=0.039, OR=0.257, 95% CI: 0.071-0.932) was lower than that of patients aged 60-74 years. The screening compliance of patients with high school education ( P=0.011, OR=3.121, 95% CI: 1.304-7.473) and college education or above ( P=0.016, OR=3.544, 95% CI: 1.270-9.890) was higher than those with primary school education and below. Patients with personal history of colorectal polyps ( P=0.015, OR=12.288, 95% CI: 1.629-92.719), family history of colorectal cancer ( P=0.038, OR=8.506, 95% CI: 1.124-64.351) and changes in defecation habit or stool trait ( P=0.039, OR=4.794, 95% CI: 1.085-21.192) also had higher compliance. Conclusion:Age, educational level, personal history of colorectal polyps, and family history of colorectal cancer are related to colonoscopy screening compliance in outpatients of 7 tertiary hospitals in 7 regions of Xinjiang. The independent risk factors affecting compliance to colorectal cancer screening in outpatients are age of 40-59 years, lower educational level, no previous history of polyps or family history of colorectal cancer, and no defecation habit or stool changes.