Objective: To explore the active components, key targets, and mechanism of action of turnip in alleviating pulmonary fibrosis(PF) based on network pharmacology and animal experiments. Methods: The active components and targets of Brassica rapa L. were screened using the traditional Chinese medicine systems pharmacology database and analysis platform database, and PF-related targets were obtained from disease databases such as online mendelian inheritance of man(OMIM) and DrugBank. The intersection targets were used to construct a protein-protein interaction(PPI) network to identify core targets, followed by gene oncology(GO)/Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. In the animal experiments, a bleomycin-induced PF mouse model was established. Pathological changes in lung tissue were evaluated using HE and Masson staining. qRT-PCR was used to detect the mRNA expression of tumor necrosis factor-α(TNF-α), phosphatidylinositol 3-kinase(PI3K), and akstrain transforming 1(AKT1), and immunofluorescence staining was used to measure the protein expression of TNF-α, PI3K, and AKT1. Results: The 68 active components identified in Brassica rapa L. may regulate PI3K-Akt signaling pathway by acting on 89 potential targets such as TNF-α and AKT1. The results of animal experiments showed that polysaccharide of Brassica rapa L.(BRPs) could significantly reduce the degree of bleomycin induced pulmonary fibrosis in mice; HE and Masson staining of lung tissue showed that compared with the model group, the damage of alveolar structure, the infiltration of inflammatory cells and the deposition of collagen fibers in the BRPs treatment group were significantly reduced. Further mechanism studies showed that BRPs could significantly down-regulate the mRNA and protein expression levels of TNF-α, PI3K and AKT1 in lung tissue of pulmonary fibrosis mice. Conclusion Brassica rapa L. can synergistically alleviate pulmonary fibrosis through “multi-component, multi-target and multi-channel” approach; BRPs is one of the main active components, and plays an anti-fibrosis role by inhibiting TNF-α/PI3K Akt signaling pathway.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective The purpose of this study is to utilize CiteSpace visualization software for literature analysis to investigate published literature concerning geriatric pharmacy outpatient services,create a knowledge graph,and analyze and discuss the developmental process and relevant hotspots of geriatric pharmacy outpatient services in China.Methods Utilizing the China National Knowledge Infrastructure(CNKI)as the source database,a search for literature containing the core phrases"pharmacy outpatient",'pharmacist outpatient","drug outpatient","drug consultation outpatient"and"elderly"was conducted from the inception of the database to March 2024 for data extraction.CiteSpace was employed to generate a visual knowledge graph,analyze,and discuss key nodes such as authors,institutions,and keywords within the realm of geriatric pharmacy outpatient services.Results After screening based on inclusion criteria,a total of 396 articles were included in the study.Scholars such as Ge Weihong,Wu Qiuhui and Liu Yang have made significant contributions to the research field of geriatric pharmacy outpatient services.Drum Tower Hospital affiliated with Nanjing University Medical School,the Sixth People's Hospital affiliated with Shanghai Jiao tong University,Dali University rank as the top three publishing institutions in terms of publication volume.The most frequently occurring keywords in the published literature include"pharmaceutical services","clinical pharmacists","pharmacy clinics","rational drug use"and"pharmacists".Conclusion"Drug safety","survey questionnaires"and"tertiary hospitals"have emerged as prominent and evolving topics within the realm of geriatric pharmacy outpatient services in China in recent years.In general,there remains considerable potential for further development in both the scope and depth of outpatient services for the elderly in the field of pharmacy in China.

Objective To investigate the protective mechanism of ergothioneine against oxidative stress and inflammatory damage in vascular dementia(VaD)neurons through activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.Methods A total of 15 VaD patients(VaD group)admitted in our hospital from December 2023 to April 2024 were prospectively recruited,and another 15 healthy individuals taking physical examination during same period were subjected and served as health group.Then,plasma ergothioneine levels in the two groups were quantified by liquid chromatography-tandem mass spectrometry(LC-MS/MS).In in vitro experiments,hippocampal neurons were isolated from neonatal rats,and then divided into control,oxygen-glucose deprivation model,ergothioneine,and ergothioneine+ML385 groups.The expression levels of key molecules of Nrf2/HO-1 signaling pathway,oxidative stress markers,inflammatory cytokines,and apoptosis-related proteins were detected with RT-qPCR and Western blotting.Results The VaD patients exhibited significantly reduced plasma ergothioneine level(694.71±106.87 vs 1268.84±152.87)and down-regulated mRNA levels of Nrf2(0.49±0.14 vs 1.00±0.17),HO-1(0.35±0.23 vs 1.00±0.14)and NQO1(0.39±0.16 vs 1.00±0.12)than the health group(P＜0.05,P＜0.01).Compared with the control group,the model group showed significant increases in inflammatory factor levels.Ergothioneine treatment resulted in significant decreases in malondialdehyde and reactive oxygen species contents,and neuronal apoptosis rate.The ergothioneine+ML385 group showed a significant increase in hippocampal neuronal apoptotic rate,when compared with the ergothionein group.Conclusion Ergothioneine protects VaD neurons against oxidative stress and inflammatory damage by activating the Nrf2/HO-1 signaling pathway.

Objective:To construct a nomogram model for predicting the incidence of hepatocellular carcinoma based on serum abnormal prothrombin and alpha-fetoprotein and evaluate the predictive effect.Methods:Retrospective analysis of data from 351 patients with liver disease who received treatment at the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023, including 285 males and 66 females, aged (52.9±11.9) years. Among the 351 patients, there were 229 cases (65.2%) of hepatocellular carcinoma, 87 cases (24.8%) of liver cirrhosis, and 35 cases (10.0%) of chronic hepatitis B. All patients were randomly divided into a training set ( n=245) and a testing set ( n=106) in a 7∶3 ratio without replacement sampling. The training set was used to construct the model, and the testing set was used to evaluate the model. At the same time, gender, age, disease type, and other indicators were compared between the two sets. The risk factors of hepatocellular carcinoma were analyzed by univariate and multivariate logistic regression based on the training set, and a nomogram was constructed to predict the incidence of hepatocellular carcinoma based on the multivariate results. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of nomogram, and decision curve analysis was used to evaluate the clinical applicability of the model. Results:There was no statistically significant difference in age, gender, disease type, etc. between the training and testing sets of patients (all P>0.05). Univariate logistic regression analysis showed that age, abnormal prothrombin logarithm (LnPIVKA-Ⅱ), alpha-fetoprotein logarithm (LnAFP), and diabetes were associated with hepatocellular carcinoma (all P<0.05). Multivariate logistic regression analysis showed that older age ( OR=1.07, 95% CI: 1.03-1.12), higher LnPIVKA-Ⅱ ( OR=2.97, 95% CI: 1.97-4.46), higher LnAFP ( OR=1.43, 95% CI: 1.11-1.84) and diabetes ( OR=5.17, 95% CI: 1.02-26.17) were risk factors for hepatocellular carcinoma (all P<0.05). Based on the above variables, a nomogram model for predicting the incidence of hepatocellular carcinoma was constructed. The area under the ROC curve analysis of the nomogram for predicting the incidence of hepatocellular carcinoma was 0.920 (95% CI: 0.886-0.953) in the training set and 0.934 (95% CI: 0.891-0.977) in the testing set. The calibration curve fit well with the standard curve, and the prediction was basically consistent with the actual situation. The decision curve analysis showed that the net benefit of the model was greater than 0 under most thresholds (0.1-1.0). Conclusion:The nomogram constructed based on age, LnPIVKA-Ⅱ, LnAFP and diabetes can effectively predict the incidence of hepatocellular carcinoma and has clinical applicability.

Objective To explore the correlation between serum homocysteine(Hcy),25-hydroxyvitamin D[25(OH)D]and frailty with type 2 diabites mellitus(T2DM)complicated with sarcopenia.Methods From September 2021 to March 2023,210 elderly T2DM patients were selected from the Department of Geriatrics of The First People's Hospital of Yunnan Province,and divided into simple T2DM(n=99)group,mild sarcopenia(M-Sar,n=59)group and severe sarcopenia(S-Sar,n=52)group.The"Elderly Comprehensive Assessment System"was used to evaluate subjects.The influencing factors of T2DM complicated with sarcopenia were analyzed by Logistic regression.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of Hcy,25(OH)D combined with frailty in evaluating T2DM with sarcopenia.Results In T2DM,M-Sar and S-Sar groups,the age,Hcy,the risk rate of balance gait work falling and the rate of weakness increased in turn(P<0.05),while BMI,hemoglobin,25(OH)D,the rate of good nutrition,the normal rate of basic daily living,the low risk rate of falling,the rate of good balance gait function and the rate of no weakness decreased in turn(P<0.05).Logistic regression analysis showed that serum Hcy,frailty and 25(OH)D were the influencing factors of senile T2DM complicated with sarcopenia.Hcy,25(OH)D and frailty combined to predict T2DM with sarcopenia had an area under ROC carve of 0.815,with a sensitivity of 0.811 and a specificity of 0.717.Conclusions Serum Hcy,25(OH)D and frailty are closely related to T2DM combined with sarcopenia.Detection of Hcy and 25(OH)D combined with frailty score is helpful for early diagnosis of sarcopenia in primary hospitals.

Objective To investigate the association between UGT1A1 inhibitors-induced liver injury(DILI)and UGT1A1 gene polymorphisms through a pharmacogenomics approach.Methods Information on relevant drugs that may induce liver injury,blood routine tests,and liver function tests was collected from hospitalized patients diagnosed with DILI between June 2022 and June 2024.Relevant databases were searched to categorize DILI-associated drugs into UGT1A1 enzyme inhibitors and those without interaction with UGT1A1.Sanger sequenc-ing or MassARRAY SNP typing technology was utilized to detect and genotype the UGT1A1 gene.Results A total of 219 patients with drug-induced liver injury(DILI)were enrolled,including 98 males,with a mean age of 46.32±14.95 years.A literature search of relevant databases revealed that 20 drugs(16.26%,20/123)associated with DILI had inhibitory effects on the UGT1A1 enzyme.The proportion of DILI cases related to UGT1A1 inhibitors was 60.73%(133/219).Compared to non-UGT1A1 inhibitor-related DILI group,the UGT1A1 inhibitor-related DILI group exhibited significantly higher levels of ALT,AST,ALP,and GGT(P<0.05),while no significant differences were observed in age,gender,TBIL,IBIL,WBC,Hb,PLT,injury type,or injury grade(P>0.05).The prevalence of UGT1A1 polymorphisms was significantly higher in the UGT1A1 inhibitor-related DILI group(68.42%)com-pared to the non-UGT1A1 inhibitor-related DILI group(51.16%),with an odds ratio(OR)of 2.068(95%CI:1.183 to 3.617;χ2=6.58,P=0.010).There was also a significant difference in the distribution of genotypes between the UGT1A1 inhibitor-related and non-UGT1A1 inhibitor-related DILI groups(χ2=9.60,P=0.022).Univariate logistic regression analysis indicated that ALT and UGT1A1*6 were associated with UGT1A1 inhibitor-related DILI,while multivariate analysis confirmed that UGT1A1*6 was independently associated with UGT1A1 inhibitor-related DILI[OR(95%CI)=3.143(1.398 to 7.067),P=0.006].Conclusion The UGT1A1*6 allele increases the susceptibility to drug-induced liver injury(DILI)associated with UGT1A1 inhibitory drugs.

Objective To explore the correlation between serum homocysteine(Hcy),25-hydroxyvitamin D[25(OH)D]and frailty with type 2 diabites mellitus(T2DM)complicated with sarcopenia.Methods From September 2021 to March 2023,210 elderly T2DM patients were selected from the Department of Geriatrics of The First People's Hospital of Yunnan Province,and divided into simple T2DM(n=99)group,mild sarcopenia(M-Sar,n=59)group and severe sarcopenia(S-Sar,n=52)group.The"Elderly Comprehensive Assessment System"was used to evaluate subjects.The influencing factors of T2DM complicated with sarcopenia were analyzed by Logistic regression.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of Hcy,25(OH)D combined with frailty in evaluating T2DM with sarcopenia.Results In T2DM,M-Sar and S-Sar groups,the age,Hcy,the risk rate of balance gait work falling and the rate of weakness increased in turn(P<0.05),while BMI,hemoglobin,25(OH)D,the rate of good nutrition,the normal rate of basic daily living,the low risk rate of falling,the rate of good balance gait function and the rate of no weakness decreased in turn(P<0.05).Logistic regression analysis showed that serum Hcy,frailty and 25(OH)D were the influencing factors of senile T2DM complicated with sarcopenia.Hcy,25(OH)D and frailty combined to predict T2DM with sarcopenia had an area under ROC carve of 0.815,with a sensitivity of 0.811 and a specificity of 0.717.Conclusions Serum Hcy,25(OH)D and frailty are closely related to T2DM combined with sarcopenia.Detection of Hcy and 25(OH)D combined with frailty score is helpful for early diagnosis of sarcopenia in primary hospitals.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective The purpose of this study is to utilize CiteSpace visualization software for literature analysis to investigate published literature concerning geriatric pharmacy outpatient services,create a knowledge graph,and analyze and discuss the developmental process and relevant hotspots of geriatric pharmacy outpatient services in China.Methods Utilizing the China National Knowledge Infrastructure(CNKI)as the source database,a search for literature containing the core phrases"pharmacy outpatient",'pharmacist outpatient","drug outpatient","drug consultation outpatient"and"elderly"was conducted from the inception of the database to March 2024 for data extraction.CiteSpace was employed to generate a visual knowledge graph,analyze,and discuss key nodes such as authors,institutions,and keywords within the realm of geriatric pharmacy outpatient services.Results After screening based on inclusion criteria,a total of 396 articles were included in the study.Scholars such as Ge Weihong,Wu Qiuhui and Liu Yang have made significant contributions to the research field of geriatric pharmacy outpatient services.Drum Tower Hospital affiliated with Nanjing University Medical School,the Sixth People's Hospital affiliated with Shanghai Jiao tong University,Dali University rank as the top three publishing institutions in terms of publication volume.The most frequently occurring keywords in the published literature include"pharmaceutical services","clinical pharmacists","pharmacy clinics","rational drug use"and"pharmacists".Conclusion"Drug safety","survey questionnaires"and"tertiary hospitals"have emerged as prominent and evolving topics within the realm of geriatric pharmacy outpatient services in China in recent years.In general,there remains considerable potential for further development in both the scope and depth of outpatient services for the elderly in the field of pharmacy in China.