OBJECTIVE To investigate the potential mechanism of Sanqi danshen tablets in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Core targets of Sanqi danshen tablets in the treatment of NAFLD were explored by network pharmacological methods. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were also performed. Based on the results obtained from network pharmacological studies， using SD rats as subjects， the NAFLD model was induced by feeding them high-fat diet. The effects of Sanqi danshen tablets on pathological changes such as lipid droplet vacuoles and lipid accumulation in the liver tissue of NAFLD rats， as well as its impact on relative indicators of lipid metabolism， inflammatory responses and oxidative stress， were investigated. RESULTS A total of 20 core targets for the treatment of NAFLD with Sanqi danshen tablets were screened， primarily involved in GO functions such as biological regulation， cellular membrane and binding， and enriched in signaling pathways related to inflammatory responses， oxidative stress and lipid metabolism. Compared with the model group， lipid droplet vacuoles were reduced significantly in low-dose， medium-dose， high-dose groups of Sanqi danshen tablets and positive control （simvastatin） group， the number of lipid droplets decreased significantly and the color became lighter. The contents of total cholesterol， triglyceride （except for medium- dose group of Sanqi danshen tablets）， aspartate transaminase， alanine transaminase， tumor necrosis factor-α （except for low-dose group of Sanqi danshen tablets）， interleukin-17 （except for Sanqi danshen tablets groups） and malondialdehyde （except for low- dose group of Sanqi danshen tablets） in liver tissue were significantly decreased， while the content of superoxide dismutase was significantly increased （P＜0.01 or P＜0.05）. CONCLUSIONS Sanqi danshen tablets exert anti-inflammatory， antioxidant and lipid metabolism regulating effects by influencing the levels of inflammation， oxidative stress and lipids metabolism-related indicators， thereby improving NAFLD in rats.

Objective To analyze the effectiveness of the digital medicine boosting county-town-village linkage diabetes mellitus(DM)management model.Methods A total of 135 patients with T2DM from 9 villages in 3 towns of Longyou County from June to September 2021 were selected and randomly grouped into a control(Con,n=45)group and an intervention(Exp,n=90)group at a ratio of 1∶2 by village.The Con group implements routine management.The Exp group implemented the internet+boosting county-town-village linkage DM management model.Both groups were followed up for one year.The body mass index(BMI),waist circumference(WC),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting plasma glucose(FPG),hemoglobin A1c(HbA1c),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),urine albumin/creatinine ratio(UACR),management compliance,and the proportion of new DM complications were compared between the two groups.Results All patients in the Con group completed follow-up,8 patients in the Exp group were lost to follow-up,and 82 patients were finally included.After the intervention,BMI,WC,SBP,DBP,FPG,HbA1c,TC,TG,LDL-C and UACR were significantly decreased in both groups(P<0.05),while HDL-C and DM self-management scale(SDSCA)scores increased(P<0.05).In Exp group,SBP,DBP,FPG,HbA1c,TC,TG,LDL-C and UACR were lower than those in Con group(P<0.05),while HDL-C and SDSCA scores and the compliance rates of FPG,HbA1c,TC,TG were higher than those in Con group(P<0.05).There was no statistically significant difference in the changes of medication methods,the incidence of diabetic kidney disease and diabetic peripheral neuropathy between the two groups(P>0.05).Conclusions The digital medicine boosting county-town-village linkage DM management model,which helps achieve glycolipid standards and opens up new ideas for the management of diabetes in rural areas.

Objective To analyze the effectiveness of the digital medicine boosting county-town-village linkage diabetes mellitus(DM)management model.Methods A total of 135 patients with T2DM from 9 villages in 3 towns of Longyou County from June to September 2021 were selected and randomly grouped into a control(Con,n=45)group and an intervention(Exp,n=90)group at a ratio of 1∶2 by village.The Con group implements routine management.The Exp group implemented the internet+boosting county-town-village linkage DM management model.Both groups were followed up for one year.The body mass index(BMI),waist circumference(WC),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting plasma glucose(FPG),hemoglobin A1c(HbA1c),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),urine albumin/creatinine ratio(UACR),management compliance,and the proportion of new DM complications were compared between the two groups.Results All patients in the Con group completed follow-up,8 patients in the Exp group were lost to follow-up,and 82 patients were finally included.After the intervention,BMI,WC,SBP,DBP,FPG,HbA1c,TC,TG,LDL-C and UACR were significantly decreased in both groups(P<0.05),while HDL-C and DM self-management scale(SDSCA)scores increased(P<0.05).In Exp group,SBP,DBP,FPG,HbA1c,TC,TG,LDL-C and UACR were lower than those in Con group(P<0.05),while HDL-C and SDSCA scores and the compliance rates of FPG,HbA1c,TC,TG were higher than those in Con group(P<0.05).There was no statistically significant difference in the changes of medication methods,the incidence of diabetic kidney disease and diabetic peripheral neuropathy between the two groups(P>0.05).Conclusions The digital medicine boosting county-town-village linkage DM management model,which helps achieve glycolipid standards and opens up new ideas for the management of diabetes in rural areas.

Objective:To explore the genetic background for a patient with refractory myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with co-morbid neutrophilia patient.Methods:A MDS/MPN patient who was admitted to the First Affiliated Hospital of Nanjing Medical University in May 2021 was selected as the study subject. RNA sequencing was carried out to identify fusion genes in his peripheral blood mononuclear cells. Fusion gene sequence was searched through transcriptome-wide analysis with a STAR-fusion procedure. The novel fusion genes were verified by quantitative real-time PCR and Sanger sequencing.Results:The patient, a 67-year-old male, had progressive thrombocytopenia. Based on the morphological and molecular examinations, he was diagnosed as MDS/MPN with co-morbid neutropenia, and was treated with demethylating agents and Bcl-2 inhibitors. Seventeen months after the diagnosis, he had progressed to AML. A novel fusion gene NCOR1: : GLYR1 was identified by RNA-sequencing in his peripheral blood sample, which was verified by quantitative real-time PCR and Sanger sequencing. The patient had attained morphological remission after a DCAG regimen (a combinatory chemotherapy of decitabine, cytarabine, aclarubicin and granulocyte colony-stimulating factors) plus Chidamide treatment. A significant decrease in the NCOR1: : GLYR1 expression was revealed by quantitative real-time PCR at post-chemotherapy evaluation. Conclusion:NCOR1: : GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.

This study aimed to assess the efficacy and safety of gilteritinib combined with chemotherapy in treating newly diagnosed FLT3-mutated acute myeloid leukemia (AML). We retrospectively collected clinical data from 16 patients newly diagnosed with FLT3-mutated AML at Jiangsu Province Hospital. Patients received induction therapy with the classic "3 + 7" regimen or the VA regimen, and all patients were immediately supplied with gilteritinib after detecting FLT3-ITD/TKD mutations. Of the 16 patients, 12 were male and 4 were female, with a median age of 52.5 years (range: 15-76 years). Additionally, 15 patients had FLT3-ITD mutations and 1 had FLT3-TKD mutation. The complete remission (CR/CRi) rate was 93.8% (15/16) after the first cycle of gilteritinib-based induction therapy, with 13 patients achieving MRD negativity detected with flow cytometry. All patients achieved a CR MRD- during the consolidation phase. FLT3 mutation clearance was achieved among all 14 patients who underwent next-generation sequencing (NGS) analysis. The 12-month overall survival and relapse-free survival rates were both 73.9%, respectively, with a median followup of 18 months. Nine (56.2%) patients experienced infectious fever during the induction therapy. Three patients had grade 3 QTc prolongation during consolidation and maintenance therapy. Treatment-related adverse events were generally tolerable.

The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs. MERT's excellent specificity, ultrahigh ligand density, and potential synergistic recognition ability enable it to target the different key regions of ADCs to overcome the deficiencies of traditional technologies. The binding capacity of MERT for antibodies is ten to hundred times higher than that of the mono-epitope or Fc-specific affinity technologies. Since MERT can efficiently capture target ADCs from serum, a novel bioanalytical platform based on MERT and RPLC‒QTOF-MS has been developed to monitor the dynamic changes of ADCs in serum, including the fast changes of drug-to-antibody ratio from 3.67 to 0.22, the loss of payloads (maytansinol), and the unexpected hydrolysis of the succinimide ring of the linker, which will contribute to clarify the fate of ADCs and provide a theoretical basis for future design. In summary, the MERT-based versatile platform will open a new avenue for in-depth studies of ADCs in biological fluids.

Dynamic tracking analysis of monoclonal antibodies(mAbs)biotransformation in vivo is crucial,as certain modifications could inactivate the protein and reduce drug efficacy.However,a particular chal-lenge(i.e.immune recognition deficiencies)in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen.To address this limitation,a multi-epitope affinity technology utilizing the metal organic framework(MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region(CDR)mimotope peptide(HH24)and non-CDR mimotope aptamer(CH1S-6T)onto the surface of MOF@Au nanocomposite.Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited signifi-cantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope af-finity technology.Moreover,the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry(LC-QTOF-MS).Therefore,multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb.Particularly,the novel bioanalytical platform can be suc-cessfully used for the tracking analysis of trastuzumab modifications in different biological fluids.Compared to the spiked phosphate buffer(PB)model,faster modification trends were monitored in the spiked serum and patients'sera due to the catalytic effect of plasma proteins and relevant proteases.Differences in peptide modification levels of trastuzumab in patients'sera were also monitored.In summary,the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb,contributing to improved understanding and paving the way for future research and clinical applications.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

This study aimed to assess the efficacy and safety of gilteritinib combined with chemotherapy in treating newly diagnosed FLT3-mutated acute myeloid leukemia (AML). We retrospectively collected clinical data from 16 patients newly diagnosed with FLT3-mutated AML at Jiangsu Province Hospital. Patients received induction therapy with the classic "3 + 7" regimen or the VA regimen, and all patients were immediately supplied with gilteritinib after detecting FLT3-ITD/TKD mutations. Of the 16 patients, 12 were male and 4 were female, with a median age of 52.5 years (range: 15-76 years). Additionally, 15 patients had FLT3-ITD mutations and 1 had FLT3-TKD mutation. The complete remission (CR/CRi) rate was 93.8% (15/16) after the first cycle of gilteritinib-based induction therapy, with 13 patients achieving MRD negativity detected with flow cytometry. All patients achieved a CR MRD- during the consolidation phase. FLT3 mutation clearance was achieved among all 14 patients who underwent next-generation sequencing (NGS) analysis. The 12-month overall survival and relapse-free survival rates were both 73.9%, respectively, with a median followup of 18 months. Nine (56.2%) patients experienced infectious fever during the induction therapy. Three patients had grade 3 QTc prolongation during consolidation and maintenance therapy. Treatment-related adverse events were generally tolerable.

Objective:To translate and revise the Arteriovenous Fistula Assessment Scale (AVF-AS), test the reliability and validity of the Chinese version of AVF-AS.Methods:The modified Brislin translation model was used to translate, back translate and cross culture adjust AVF-AS, forming the Chinese version of AVF-AS. Using the convenient sampling method, 220 hemodialysis patients from the First Affiliated Hospital of Zhengzhou University were selected for investigation from July to September 2022. Two weeks later, 30 patients were randomly selected for retesting. The valid data were used for project analysis and reliability and validity evaluation.Results:The Chinese version of AVF-AS consisted of 3 factors and 18 items. Consistency level between evaluators was 0.94, the item level content validity index was 0.83-1.00, average scale level content validity index was 0.94, and the calibration validity was 0.68.Three common factors(autogenous arteriovenous fistula blood flow, stenosis and ischemia, puncture location) were extracted from exploratory factors, and the cumulative variance contribution rate was 75.255%. The total scale's Cronbach α was 0.946, the half reliability of each dimension was 0.826 - 0.898, and the test-retest reliability was 0.907.Conclusions:The Chinese version of AVF-AS has good reliability and validity, and can be used as an effective tool to evaluate the autogenous arteriovenous fistula functional status of hemodialysis patients in China.