Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

The purpose of this study was to investigate the damage mechanism of pathogenic E.coli on mouse brain microvascular endothelial cells(BMEC cells)and mouse alveolar macrophages(MH-S cells),as well as the lung and brain of healthy mice.In this study,BMEC cells and MH-S cells were infected with pathogenic E.coli strains,and cell morphological changes were observed.Plate counting method was used to detect the adhesion and invasion ability of the strains to cells and the number of bacteria in the lungs and brains of mice.RT-qPCR was used to detect the ex-pression of TNF-α,IL-1β and IL-6 genes in cells and mouse organs at different time periods.West-ern blot was used to detect the expression of p-NF-κB,p-JAK2 and p-STAT3 proteins related to inflammation in cells and mouse organs after infection.The results showed that the cell culture medium of the infection group was turbid,the cell vision became dark and blurred,some cells shrank and died,and more fragments were produced.The adhesion rate and invasion rate of BMEC cells at 3 h were significantly lower than those at 6 h(P＜0.050),and the adhesion rate and inva-sion rate of MH-S cells at 3 h were significantly higher than those at 6 h(P＜0.010).Infected mice had a large area of swelling and bleeding in the brain,and the lungs had different degrees of swell-ing and bleeding.The bacterial load in the brain and lung was the highest at 12 h.Compared with the control group,the mRNA expression levels of IL-1β,IL-6 and TNF-α in the infection group were significantly increased at 3 h and 6 h(P＜0.050),and the mRNA expression levels of inflam-matory factors in BMEC cells and MH-S cells were the highest at 6 and 3 h,respectively.The mR-NA expression of inflammatory factors in the brain and lung of infected mice showed a trend of in-creasing first and then decreasing with time,with the highest expression at 12 h after infection.The expression levels of p-NF-κB protein in BMEC cells,MH-S cells,lung and brain tissues of mice in the infection group were significantly higher than those in the control group(P＜0.001),and the expression levels of p-JAK2 protein and p-STAT3 protein were significantly lower than those in the control group(P＜0.050).The above results showed that pathogenic E.coli could adhere and invade BMEC cells and MH-S cells,colonize in lung and brain tissues of mice,promote the expres-sion of NF-κB protein in cells and tissues,inhibit the expression of JAK2 protein and STAT3 pro-tein,and then stimulate cells and tissues to produce inflammatory response.

Objective To explore and establish preliminary methods for sampling,pretreatment,and detection of airborne etomidate and fentanyl.By finding and selecting source-marking molecules of illicit drugs,preliminarily elucidated the source characteristics of airborne etomidate and fentanyl.Methods Etomidate and fentanyl-containing flue gas have been produced via simulated smoking,while the flue gas has been collected through bubbling absorption or filter membrane;The collected PM have been extracted by ethanol for gas chromatography-mass spectrometry(GC-MS)analysis of etomidate,fentanyl and marking molecules(nicotine).Additionally,ultra-high performance liquid chromatography triple quadrupole mass spectrometry(UPLC-MS/MS)have been implemented to quantify concentration of etomidate and fentanyl in PM extraction solution for estimating content of airborne PM-containing etomidate and fentanyl.Results The estimated content of indoor PM-containing etomidate generated from smoking is 750.70 ng/m3,and the estimated content of indoor PM-containing fentanyl is 399.07 ng/m3.Conclusion Under the experimental conditions,the sampling efficiency of PM filtration is higher than that of flue-gas blubbing absorption.Nicotine can serve as a marker for the smoking or thermal-inhaling sources of PM-containing etomidate and fentanyl.The present research provides a new practical case for analyzing the source characteristics of airborne PM-containing illicit drugs.

Objective:To retrieve, evaluate, and integrate evidence related to balance function management in stroke patients with hemiplegia.Methods:A systematic search was conducted on BMJ Best Practice, UpToDate, National Institute for Health and Care Excellence, Guidelines International Network, Scottish Intercollegiate Guidelines Network, Australia Joanna Briggs Institute Evidence-Based Practice Center, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, VIP, China Biology Medicine disc, PubMed, Web of Science, Medlive, and other websites or data platforms for relevant guidelines, best practices, evidence summaries, systematic reviews, and Meta-analyses on balance function management in stroke patients with hemiplegia, with a retrieval period from March 2014 to March 2024. Two researchers trained in evidence-based practices evaluated the methodological quality of the literature and extracted and summarized the relevant evidence.Results:Based on the inclusion and exclusion criteria, a total of eight guidelines and seven systematic reviews were included, yielding 29 pieces of best evidence across nine aspects: the importance of balance function training, organizational management, assessment tools, assessment timing, assessment content, assessment frequency, balance exercise programs, exercise duration, and health education.Conclusions:This study summarizes the best evidence for balance function management in stroke patients with hemiplegia, providing accurate evidence-based support for clinical practice among medical professionals. It is recommended that healthcare providers appropriately apply this evidence based on clinical scenarios to improve measures related to balance function management in stroke patients with hemiplegia.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Objective:To analyze the frequency and characteristics of polymyositis (PM) in idiopathic inflammatory myopathy (IIM), and to investigate whether PM is over-diagnosed.Methods:Patients diagnosed as IIM according to the Bohan & Peter criteria of IIM hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2008 to 2019 were involved in the study. Definite PM (dPM) was defined as typical clinical and pathological features including elevated creatine kinase (CK) level, muscle weakness and muscle biopsy findings with endomysial CD8 + T cell infiltration and expression of MHC-1 on sarcolemma. Meanwhile, dermatomyositis (DM), anti-synthase syndrome(ASS), immune-mediated necrotic myopathy(IMNM), sporadic inclusion body myositis(sIBM) and other myopathies were excluded according to the new classification criteria of IIM subtypes respectively. Statistical analysis was performed using SPSS software 24.0. The Kruskal-Wallis test and χ2 test were used to compare the clinical characteristics between the dPM group and other IIM subtypes. Results:A total of 1 259 patients with IIM including 1 015 (80.6%) DM and 244(19.4%) PM were enrolled in this study. According to the strict definition of PM criteria, only 0.5% of patients (6/1 259) in IIM could be diagnosed as dPM. Most PM patients were IMNM and ASS according to the new IIM subtypes criteria, of which 48.0% (117/244) were IMNM and 32.0% (78/244) were ASS. 66.7%(4/6) of dPM patients were women. One complicated with RA, and one was dPM overlaped with systemic sclerosis. All of them had muscle weakness, mild elevation of CK level [611(391,1 451) U/L], and were myositis-specific autoantibodies negative. Except one dPM patients who did not receive immunoregulatory therapy due to chronic obstructive pulmonary disease, the others were administrated with low or medium dose prednisone combined with or without immunosuppressive agents. After a median follow-up of (38±26) months, the muscle strength of dPM patients were improved.Conclusion:dPM is a very rare clinical subtype of IIM. PM is an over-diagnosed entity in clinical practice. Patients with dPM have mild symptoms and good outcome.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective:To identify dermatopathological features of patients with dermatomyositis (DM) and analyze its correlation with cutaneous diseases activity.Methods:The clinical data and skin biopsies of 48 patients were collected. The relevance was analyzed using Spearman's correlation analysis. The two groups were compared using Chi-square test or Fisher's exact test. Multi-factors line regression model was established to analyze the relationship between cutaneous disease activity and dermatopathological features.Results:The most common dermatopathological feature was perivascular inflammation (37 cases, 88%), followed by epidermal atrophy (22 cases, 52%) and melanocyte loss (20 cases, 48%), basal vacuolization (15 cases, 36%). The incidence of basal vacuolization ( χ2=9.110, P=0.022), interface dermatitis ( χ2=11.672, P=0.005) and mucin deposition ( χ2=7.795, P=0.029) were significantly different in patients with myositis specific antibody (MSA) subgroup. The patients with positive tranional intermediary factor-1 (anti-TIF1-γ) antibody had higher incidence of interface dermatitis and basal vacuolization, and patients with melanoma differentiation-associated gene 5 (anti-MDA5) antibody had lower incidence of interface dermatitis. Interface dermatitis was positively associated with epidermal atrophy ( r=0.371, P=0.016) and parakeratosis ( r=0.316, P=0.041). Pigment inco-ntinence was positively associated with basal vacuolization ( r=0.384, P=0.012). Multi-factor line regression showed interface dermatitis was positively related to cutaneous disease area and severity index (CDASI). Conclusion:The dermatopathological features is different in subgroup of patients with DM ( β=10.295, P=0.004). Interface dermatitis is a marker of cutaneous disease activity, and its pathogenesis may be different from that of perivascular inflammation. Keratinocytes may be involved in the pathological process in interface dermatitis.

Objective:To determine the serum levels of chemokine CCL27 and its clinical relevancein patients with dermatomyositis (DM).Methods:The serum CCL27 levels of 58 DM patients, 21 polymyositis (PM) patients, 20 systemic lupus erythematosus (SLE) patients and 31 healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The score of disease activity was measured by two physicians-based on the myositis disease activity assessment tool (MDAAT). Its correlation with serum levels of CCL27 was analyzed. The difference between multiple groups were compared using analysis of variance (ANOVA) and t test, and the relevance was analyzed using Spearman correlation analysis and generalized method of moments (GEE) model. Results:Theserum level of CCL27 in DM patients (178±49) pg/ml was significantly higher than PM (110±40) pg/ml, SLE (141±46) pg/ml and healthy controls (137±38) pg/ml ( F=14.192, P<0.01). Crosssectional analysis showed that the serum CCL27 levelwaspositively correlated with global disease activity ( r=0.301, P=0.022) andskin disease activity ( r=0.493, P<0.01). Patients with V sign had higher serum CCL27 levels (191±52) pg/ml than the patients without (153±33) pg/ml ( t=2.839, P<0.01). Patients with holster sign had higher serum CCL27 levels (196±58) pg/ml than the patients without (168±41) pg/ml ( t=2.176, P=0.034). Follow-up study also found that CCL27l evels were positively correlated with global disease activity ( β=0.031, P=0.042) and skin disease activity ( β=0.032, P<0.01). Conclusion:The serum CCL27 levels are increased in patients with DM and can reflect the skin disease activity. The results of this study suggest that CCL27 may be a marker for cutaneous damage and monitoring of therapeutic effect.

Objective:To investigate the pathological characteristics of skeletal muscle and its association with anti-aminoacyl-tRNA synthetases(ARS) antibodies and clinical features in patients with anti-synthetase syndrome (ASS).Methods:Patients diagnosed as ASS at China-Japan Friendship Hospital from 2008 to 2018 were involved in this study. Immunohistochemistry staining of MHC-Ⅰ, CD3, CD4, CD8 and CD20 molecule were performed in all muscle specimen taken from these patients. According to the muscular pathological characteristics, all patients could be divided into six pathological subgroups: pathologic DM(pDM), pathologic PM (pPM), unspecified myositis(USM), necrotizing myopathies (NAM), only MHC-Ⅰexpression (MHC-Ⅰ) and normal pathology groups. Immunoblotting assay was used to detect anti-ARS antibodies. Statistical analysis was performed using Statistical Product and Service Solutions (SPSS) software. T-test, Mann-Whitney U test and Analysis of Variance (ANOVA) were used for the comparison of measurement data. Chi-square test or Fisher's test were used for categorical data. P<0.05 was considered statistically significant. Results:A total of 77 patients underwent muscle biopsy and anti-ARS antibodies test, with the average age of (50±12) years and disease course of 9(3-24) months. The prevalence of anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ and anti-OJ antibodies in these patients was 47%(36 cases), 29%(22 cases), 12%(9 cases), 13%(10 cases) and 0 respectively. Among all the ASS patients, the most common pathological type was USM(37/77, 48%), followed by pDM(14/77, 18%), the normal pathology(13/77, 17%), NAM(10/77, 13%) and MHC-Ⅰ (3/77, 4%) groups. There were no pPM subtypes in all groups. The frequency of pDM types was significantly different among the anti-ARS antibodies groups( χ2=9.075, P=0.028). The anti-EJ-positive patients had a higher frequency of pDM compared with anti-PL-7-group(40% vs 4%, χ2=6.555, P=0.024). Meanwhile, the CD20 expression in muscle tissue was observed in 30% of anti-EJ-positive patients and 4% of anti-Jo-1-positive ones. There was statistically significant difference in the positive rate of CD20 expression among anti-ARS antibodies groups ( χ2=12.837, P<0.01). Conclusion:The muscle pathological characteristics of ASS are polymorphic and relate to the anti-ARS antibodies. Performing muscle biopsy and distinguishing pathological types are helpful for the diagnosis and stratification of ASS.