OBJECTIVE: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. METHODS: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. RESULTS: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. CONCLUSION These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

Objective To prepare a dissolvable microneedle(DMN)with a tip-layer loaded with hyaluronic acid(HA)modified sinomenine hydrochloride liposomes(HA-SMH-Lip),as well as characterize,evaluate its in vitro transdermal permeability,cellular uptake ability,and anti-inflammatory ability.Methods HA-SMH-Lip-DMNs were prepared by a two-step casting method,and the drug loading capacity was determined using HPLC.The morphology,skin permeation properties and in vitro transdermal ability were investigated by scanning electron microscopy,puncture assay and Franz diffusion cell method.Fluorescent microneedles were prepared by replacing HA-SMH-Lip with fluorescein isothiocyanate liposomes(HA-FITC-Lip/FITC-Lip).The uptake behavior of inflammation cells on HA-FITC-Lip-DMNs/FITC-Lip-DMNs was investigated using a flow cytometer and a fluorescence microscope.To evaluate the anti-inflammatory activity of HA-SMH-Lip-DMNs,the levels of inflammatory factors including nitric oxide(NO),tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),and IL-10 in cell supernatants were measured using an ELISA kit.Results The prepared HA-SMH-Lip-DMNs have uniform shape and size,integral and visually pleasing array,and an average drug loading of(114.01±1.04)μg.Additionally,they have good puncture ability.The results of in vitro transdermal experiments showed that the accumulated amounts of HA-SMH-Lip-DMNs were(101.47±2.91)μg·cm-2 at 36 hours.Its transdermal ability was better than that of the SMH solution group and SMH liposome group.In vitro cellular uptake results indicated that HA-FITC-Lip-DMNs were more effectively taken up by RAW 264.7 cells(P＜0.01).Compared to the model group,HA-SMH-Lip-DMNs group significantly reduced TNF-α,IL-1β,and NO levels while increase IL-10 levels(P＜0.01).Conclusion The prepared HA-SMH-Lip-DMNs have a complete and beautiful morphology with excellent cellular uptake capability,remarkable in vitro transdermal performance,and potent anti-inflammatory properties.HA-SMH-Lip-DMNs are expected to become a new type of transdermal drug delivery system.

Objective:To investigate the mechanism of Wenjing Decoction in the treatment of hepatic fibrosis through network pharmacological methods, and conducting animal experiments to verify the core targets.Methods:The TCMSP database platform was used to screen the active components and related targets of Wenjing Decoction, and the Uniprot database was used to obtain the target genes corresponding to the active components of Wenjing Decoction. The network diagram of "Chinese materia medica-compound-target" was constructed in Cytoscape 3.7.2, and the GeneCards database was used to search liver fibrosis related targets. String database was used to construct a protein interaction network (PPI) to screen the core components and key targets of liver fibrosis, and GO analysis and KEGG pathway enrichment were performed. Animal experiments were conducted to verify the results of the analysis. 10 mice were selected as the blank group, and the remaining 45 rats were induced with carbon tetrachloride induced liver fibrosis model. After modeling, 40 successfully modeled rats were divided into model group and Wenjing Decoction high, medium-, and low-dosage groups using a random number table method, with 10 rats in each group. Wenjing Decoction high, medium-, and low-dosage groups were orally administered with 1.5×3.18, 3.18, and 0.5×3.18 g/kg Wenjing Decoction, respectively. The blank group was orally administered with equal volume distilled water once a day for 8 consecutive weeks. HE staining was used to observe the histopathological and morphological changes in the liver of rats. The serum GPT and GOT levels of rats were detected using a fully automated biochemical analyzer, and the expressions of TNF, AKT, and IL-6 proteins in rat liver tissue was detected using Western Blot.Results:A total of 188 active components of Wenjing Decoction were obtained, and the active components with higher degree values were β-sitosterol, quercetin, naringenin, etc. 799 liver fibrosis gene targets were collected, and the core target genes of the PPI network were TNF, AKT, IL6, etc. The key anti-hepatic fibrosis related pathways were obtained by GO function and KEGG analysis, including pathway in cancer, TNF, PI3K-Akt and other signalling pathways. Results of animal experiments showed that there were obvious inflammatory infiltration, collagen fibre and pseudo lobe generation in the liver tissue of rats in the model group, and the levels of inflammation and fibrosis in the liver tissue of rats in the Wenjing Decoction high, medium-, and low-dosage groups were improved to different degrees compared with that of the model group; compared with the model group, the levels of serum GPT and GOT decreased ( P<0.05); the protein expressions of TNF, AKT and IL6 in the Wenjing Decoction high, medium-, and low-dosage groups decreased ( P<0.05). Conclusion:Wenjing Decoction may exert anti-liver fibrosis effects by intervening in TNF, AKT, IL6 targets, regulating cancer pathways, TNF, PI3K Akt and other signaling pathways.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

OBJECTIVE To establish the fingerprints of Tianma jiannao granules （TJG） and the method for content determination to evaluate the quality of TJG comprehensively combined with chemometric analysis. METHODS High-performance liquid chromatography （HPLC） was used to establish the fingerprints of 13 batches （S1-S3） of TJG and determine the contents of inosine， gastrodin， parishin B and parishin E. Cluster analysis， principal component analysis， and orthogonal partial least squares- discriminant analysis were performed using SPSS 20.0 and SIMCA 18 software； using variable importance projection （VIP） value greater than 1 as a criterion， marker components that affected quality were screened. RESULTS A total of 28 common peaks were identified in the 13 batches of TJG with similarities greater than 0.9， and 7 common peaks were identified， which were gastrodin， p-hydroxybenzyl alcohol， parishin B， parishin E， rhynchophylline， inosine and salidroside. The 13 batches of TJG were clustered into 3 categories， S1-S2， S8-S10 and S12 were clustered into one category； S3 and S7 were clustered into one category； S4-S6， S11 and S13 were clustered into one category. VIP of inosine was greater than 1. The contents of inosine， gastrodin， parishin B and parishin E were 62.637-176.677， 17.821-37.642， 5.748-16.077 and 5.660-13.510 μg/g. CONCLUSIONS The established HPLC fingerprints and content determination method are stable， reliable and highly reproducible， which can be used to evaluate the quality of TJG in combination with chemometric analysis. Inosine may be a marker component that affects the quality of TJG. There are differences in the quality of 13 batches of TJG.

Objective This study aims to investigate the selection intention of nursing interns and their influencing fac-tors,providing a scientific basis for nursing human resource management in hospitals and departments.Methods A convenience sampling method was used to conduct a questionnaire survey A questionnaire survey was conducted concerning the selection inten-tion on departments and influencing factors of intern nurses from several tertiary hospitals affiliated to three medical universities from July 2022 to December 2023.General data investigation and self-developed scales were employed,and descriptive analysis,chi-square test and other statistical methods were used to analyze the differences in department selection and related influencing factors among nursing interns.Results Analysis of 652 valid questionnaires revealed that surgery(65.80％)and operating room(38.84％)were the most preferred departments for nursing interns.The primary influencing factors included the working environment and equipment of the department(54.60％),as well as its cohesion and cultural atmosphere(51.53％).Pediat-rics(51.23％)and infectious medicine(48.77％)were found to be less favored by nursing interns.Their main concerns re-volved around work-related risks and population characteristics of patients(67.02％),along with work pressure and labor intensi-ty(65.49％).Epidemic factors have an impact on the attitudes and expectations of nursing interns towards their future practice(P＜0.01).Conclusion The choice of departments by nursing interns is influenced by various environmental,societal and personal factors;primarily based on departmental environment quality and team culture atmosphere considerations.During the in-ternship,nursing interns require more professional education guidance from both hospital administration and individual depart-ments in order to make informed career choices and plans.

Objective This study aims to investigate the selection intention of nursing interns and their influencing fac-tors,providing a scientific basis for nursing human resource management in hospitals and departments.Methods A convenience sampling method was used to conduct a questionnaire survey A questionnaire survey was conducted concerning the selection inten-tion on departments and influencing factors of intern nurses from several tertiary hospitals affiliated to three medical universities from July 2022 to December 2023.General data investigation and self-developed scales were employed,and descriptive analysis,chi-square test and other statistical methods were used to analyze the differences in department selection and related influencing factors among nursing interns.Results Analysis of 652 valid questionnaires revealed that surgery(65.80％)and operating room(38.84％)were the most preferred departments for nursing interns.The primary influencing factors included the working environment and equipment of the department(54.60％),as well as its cohesion and cultural atmosphere(51.53％).Pediat-rics(51.23％)and infectious medicine(48.77％)were found to be less favored by nursing interns.Their main concerns re-volved around work-related risks and population characteristics of patients(67.02％),along with work pressure and labor intensi-ty(65.49％).Epidemic factors have an impact on the attitudes and expectations of nursing interns towards their future practice(P＜0.01).Conclusion The choice of departments by nursing interns is influenced by various environmental,societal and personal factors;primarily based on departmental environment quality and team culture atmosphere considerations.During the in-ternship,nursing interns require more professional education guidance from both hospital administration and individual depart-ments in order to make informed career choices and plans.