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.

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.

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 study the medication law of Professor Qian Ying in the treatment of primary liver cancer based on data mining technology;To provide ideas for the clinical treatment of primary liver cancer.Methods Outpatient TCM prescriptions of Professor Qian Ying for the treatment of liver cancer from November 2008 to August 2020 were collected,and a data table was established after sorting.The drug frequency,property and taste and tropism were analyzed using Excel 2019.The medical case analysis module of the Great Physician Inheritance Platform was used to analyze the core drugs,the symbiosis analysis between drug pairs,the drug association analysis,and the drug clustering analysis of the screened TCM prescriptions.Results Totally 108 prescriptions were included,involving 188 kinds of Chinese materia medica,with a total frequency of 1 322 times.High-frequency drugs included Hedyotis Sinensis,Angelicae Sinensis Radix,Visci Herba,Curcumae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.The medicinal properties were mainly cold,mild and warm,and the tastes were mainly bitter,sweet and pungent,and the main meridians were liver meridians,spleen meridians,kidney meridians and stomach meridians.There were 9 pairs of high frequency drug combinations in drug association,such as Curcumae Radix-Polygoni Orientalis Fructus,Visci Herba-Curcumae Rhizoma.In the correlation analysis of drug disease,the ones with higher correlations include"stomachache-Salviae Miltiorrhizae Radix et Rhizoma""abdominal mass-Paeoniae Radix Rubra and Citri Reticulatae Pericarpium""tinnitus-Adenophorae Radix,Lycii Fructus,Visci Herba""prolonged sublingual collaterals-Curcumae Rhizoma,Polygoni Orientalis Fructus,Salviae Miltiorrhizae Radix et Rhizoma"and so on.Drug clustering could be divided into three potential drug clusters.Conclusion Professor Qian Ying often uses heat-clearing drugs,tonifying drugs,and promoting qi and blood circulation drugs to treat liver cancer,with Huqi Powder as the main formula and modified according to the syndromes.Clearing heat and detoxifying,soothing liver and relieving depression,removing blood stasis and regulating collatrals are used to treat its symptoms,and tonifying qi and invigorating spleen,regulating liver and nourishing liver and kidney are used to treat its essence.

Objective To analyze and study the prescriptions of Chief Physician Chang Yalin for treating breast hyperplasia patients in the outpatient department,explores and summarizes the medication patterns for treating breast hyperplasia,and provides reference and dialectical medication ideas for clinical treatment of breast hyperplasia by using data mining technology.Methods Collect the prescriptions of Dr.Chang Yalin for treating breast hyperplasia patients at the Outpatient Department of Jiuquan Traditional Chinese Medicine Hospital from January 1,2017 to December 31,2022.After induction and organization,establish a data table,use Excel 2019 to statistically analyze the drug frequency and gender,taste,and meridian.Use SPSS Modoler 18.0 software April algorithm to analyze the association rules of the drugs,and use SPSS Statistics for cluster analysis.Results A total of 184 prescriptions were included,covering 140 types of traditional Chinese medicine,with a total frequency of use of 4059 times.Among them,Cornus officinalis,dried ginger,roasted licorice,Poria cocos,and jujube are commonly used drugs for the treatment of breast hyperplasia.The top three types of Chinese medicine that are commonly used are tonifying deficiency,warming internal medicine,and relieving external symptoms.The medicinal properties are mainly warm and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are spleen,lung,and heart meridians.Association rule analysis shows that roasted licorice white peony,poria cocos,licorice,and cornus flesh white peony,jujube,and ginger are equivalent.Classify commonly used drugs into 4 categories using Euclidean distance clustering and segmentation with 5.Conclusion Dr.Chang Yalin has always implemented the core idea of treating breast hyperplasia through the coordination of liver and spleen,the simultaneous application of attack and tonifying,and the simultaneous treatment of phlegm and blood stasis.In terms of the combination of latent drugs,the main focus is on tonifying qi and spleen,tonifying yin/blood and regulating liver,and resolving stasis/resolving phlegm and dispersing stagnation.In terms of the combination of"cold phlegm"and"blood stasis and toxin",as well as the combination of"eighteen contraindications"and"nineteen contraindications",his principles and methods are more distinctive and worthy of further research and promotion.

Objective:To construct and test the reliability and validity of an assessment scale for self-management of patients with dry eye, so as to help patients establish dry eye related health behaviors.Methods:Based on the knowledge attitude and practice theory, the initial scale was constructed on the basis of literature review and qualitative interview, and revised through Delphi expert consultation and expert argumentation. After the preliminary investigation, 211 dry eye patients treated in the dry eye nursing outpatient department of Beijing Tongren Hospital from August 2023 to January 2024 were selected by convenience sampling method for questionnaire investigation to test the reliability and validity of the scale.Results:Among 211 dry eye patients, there were 58 males and 153 females, aged (39.31 ± 12.81) years old. The scale of self-management of patients with dry eye included 27 items in 3 dimensions: knowledge, attitude and behavior. The authority coefficient of the two rounds of expert consultation was 0.86, and the Kendall coordination index increased from 0.175 to 0.223 (both P < 0.01). The cumulative variance contribution rates of the three dimensions were 41.843%, 54.219% and 44.273%, respectively. The Cronbach α coefficient of the scale was 0.787, and the Spearman-Brown coefficient was 0.641. Conclusions:The scale of self-management of patients with dry eye has good reliability and validity and can be used in the assessment of dry eye patients to provide a reference basis for targeted guidance and intervention.