Chemical investigation of the stems of Fritillaria unibracteata P.K. Hsiao & K.C. Hsia resulted in the isolation of nine compounds, by means of silica gel column chromatography, and preparative HPLC. Based on spectroscopic and chemical evidence, these compounds were identified as: 27-hydroxychlorogenone (1), sieboldogenin (2), (3β, 25S)-spirost-5-ene-3,17,27-triol (3), laxogenin (4), tigogenone (5), cerevisterol (6), ergosterol peroxide (7), stigmaterol (8), and β-sitosterol (9). Compound 1 was a new compound, and compounds 2-9 were isolated from the stems of Fritillaria unibracteata for the first time. The inhibitory effects of compounds 1−9 on A549 cells were determined using the MTT method. The results show that compound 6 exhibits moderate inhibitory activity with an IC50 value of (14.16 ± 1.11) μmol/L.

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective:To investigate the clinical features and prognostic factors of pediatric patients with acute hyperleukocytic leukemia (AHL).Methods:A retrospective case series study was conducted. The clinical data of 99 pediatric patients diagnosed with AHL who admitted to the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University between May 2015 and November 2020 were retrospectively analyzed. The enrolled children were grouped based on the following factors including gender, age, initial white blood cell count (WBC), initial lactate dehydrogenase (LDH), whether tumor lysis syndrome (TLS) occurred, immunophenotype, fusion gene, whether complete remission (CR) was achieved on the 19th day (D19) after transplantation, and whether CR was achieved on the 46th day (D46) after transplantation. All the patients were treated with the chemotherapy regimen of Shanghai Children's Medical Center - Acute Lymphoblastic Leukemia - 2015 (SCMC-ALL-2015). Flow cytometry was used to monitor the minimal residual disease (MRD); fluorescence in situ hybridization (FISH) was used to screen out the mutant genes. The median follow-up time was 47 months. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used for intergroup comparisons. Multivariate Cox proportional hazard regression model was used to screen out the the prognostic factors.Results:Among 99 AHL patients, there were 65 males and 35 females; the median age was 7.71 (3.32, 11.20) years. At the initial diagnosis, 48 cases had WBC≤100×10 9/L, and 51 cases had WBC>100×10 9/L; 36 cases had LDH ≤ 2 000 U/L, and 63 cases had LDH > 2 000 U/L; 3 cases had TLS, 5 cases had MLL::AF4 positive, 7 cases had BCR::ABL positive, 7 cases had E2APBX1 positive, and 10 cases had TEL::AML1 positive; 28 cases were acute T-cell lymphoblastic leukemia (T-ALL), and 71 cases were acute B-cell lymphoblastic leukemia (B-ALL). At D19, 74 cases achieved bone marrow CR; at D46, 82 cases achieved bone marrow CR; 3-year and 5-year OS rates were 74.5% and 71.3%, respectively. During the follow-up, 14 cases relapsed and 15 died, including 12 dying of relapse, 2 dying of infection and 1 case dying of pulmonary graft-versus-host disease (GVHD). There were statistically significant differences in the 3-year OS rate in patients with different age, initial WBC, initial LDH, immunophenotyping, whether bone marrow CR at D19 was achieved, whether MRD at D19 occurred, whether bone marrow CR at D46 was achieved, whether MRD at D46 occurred, the presence of TLS, MLL::AF4 positive and TEL::AML1 positive (all P < 0.05). Furthermore, multivariate Cox regression analysis showed that LDH(>2 000 U/L), MLL::AF4 positive, T immunophenotyping, relapse, not achieving bone marrow CR at D19, not achieving bone marrow CR at D46, and MRD positive at D46 were independent risk factors influencing 3-year OS rate (all P < 0.05). Conclusions:Pediatric patients with AHL have high tumor burden at early stage, and TLS may cause death. Patients treated with the SCMC-ALL-2015 protocol can achieve favorable therapeutic effects and prognosis. LDH, MLL::AF4, immunophenotyping and relapse are prognostic factors.

In recent years,the incidence of heat-related diseases has been on a steady upward trend,which is closely associated with environmental factors such as climate change and air pollution.Exposure to a hot environment and/or strenuous physical activities can progress to heat stroke(HS),an acute disease that can lead to death.Current research indicates that gut injury occupies the most crucial initiating position in the pathophysiological changes and pathogenesis of HS.Probiotics can reduce the incidence and mortality of HS through maintaining the health of the gut microbiota,regulating the intestinal immune system,and other effects.In addition,the gut microbiota can construct axis systems to interact with multiple organs such as the liver,lungs,and brain,which is of great significance for alleviating the damage to distant organs caused by HS.This paper reviews the regulation of the gut microbiota by probiotics to improve the intestinal heat tolerance ability and barrier function,aiming to provide references for the prevention and treatment of heat stroke in clinical practice.

To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.

The advantages of 3D printing technique in medicine were described.The current status of 3D printing technique was introduced when applied to customized radiotherapy compensation film,printing tumor models and breast cancer surgical navigation molds,individualized postoperative implants and printing models for drug testing and research of new therapies.The problems of 3D printing technique in breast cancer therapy were analyzed,and the future direction of development was envisioned.[Chinese Medical Equipment Journal,2024,45(11):103-108]

Objective:To investigate the involvement of ferroptosis mediated by glutathione peroxidase 4(Gpx4)in acute lung injury in rats with sepsis,as well as the intervention mechanism of curcumin(Cur).Methods:Twenty-four rats were randomly divided into three groups,with 8 rats in each group:Sham group,Sepsis group and Cur group.The rat model of acute lung injury in sepsis was established by cecal ligation and puncture(CLP).The Sham group only underwent laparotomy and closure.Both Sepsis group and Cur group underwent CLP,Cur group was injected with curcumin(200 mg/kg)intraperitoneally 1 hour after modeling,and the administra-tion was repeated 24 hours later.The lung tissues of the rats were sampled 48 hours after surgery,and the wet/dry weight of lung tissue ratio(W/D)of lung tissues in each group was measured.Morphological changes of lung tissues were observed by HE staining.The con-tents of GSH,MDA,and Fe2+and the levels of inflammatory factors including TNF-α,IL-6,and IL-1β in the lung tissues were mea-sured using test kits.Western blot was used to detect the expressions of nuclear factor E2-related factor 2(Nrf2)and the key regulatory protein of ferroptosis Gpx4.Apoptosis of alveolar epithelial cells was detected by TUNEL method.Ultrastructural changes of alveolar epithelial cells were observed by transmission electron microscopy.Results:Compared with the Sham group,lung tissues in the Sepsis group showed an increased W/D(P<0.05),significantly higher levels of inflammatory factors TNF-α,IL-6,and IL-1β and contents of MDA and Fe2+(P<0.05),decreased content of GSH,up-regulated expression of Nrf2,and down-regulated expression of Gpx4(P<0.05),the type Ⅱ alveolar epithelial cells were seen to be edematous,congested,and infiltrated with inflammatory cells via light microscopy,and ferroptosis signs such as mitochondrial crinkling,thickened bilayer membrane density,and reduced or broken cristae were seen via transmission electron microscopy.Compared with Sepsis group,lung tissues in the Cur group showed decreased W/D(P<0.05),lower levels of TNF-α,IL-6 and IL-1β,lower contents of MDA and Fe2+,increased content of GSH,down-regulated expression of Nrf2,and up-regulated expression of Gpx4(P<0.05),the pathological changes of lung tissues were significantly reduced.Conclusion:Curcumin reduces sepsis-induced acute lung injury in rats,and the mechanism is related to inhibiting inflamma-tory response and GPX4-mediated ferroptosis.

Objective To investigate the gray matter volume(GMV)changes and molecular basis underlying antipsychotic-induced weight gain(AIWG).Methods One hundred twenty-nine first-episode schizophrenia patients from October 2019 to December 2021 were enrolled in this study.Patients with≥7%weight gain(weight gain,WG)and patients with<3%weight changes(weight stable,WS)were studied.All patients underwent T1-weighted MRI scanning at baseline and after 8 week treatment.Transcriptome-neuroimaging correlations were used to investigate brain gene profiles from the Allen Human Brain Atlas and GMV changes induced by AIWG.Results Thirty-three patients with WG and 27 with WS completed the GMV measures.Compared with baseline,the WG group showed reduced GMV in right hippocampus,left basal ganglia,and right inferior parietal lobule,etc.and increased GMV in bilateral thalamus(P<0.05).The WS group showed reduced GMV in bilateral orbital gyrus,bilateral inferior frontal gyrus and bilateral hippocampus(P<0.05).These GMV changes in WG group were spatially correlated with expression levels of 354 genes,which were exclusively enriched in Cushing syndrome,neuroinflammation and glutamatergic signaling,and Pnoc+.Conclusion The study has demonstrated increased GMV in thalamus in schizophrenia patients with AIWG which may be associated with Cushing syndrome and Pnoc+.These findings may provide important insights into the molecular mechanisms of AIWG.

Objective:To understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance.Methods:From January 2017 to March 2022,151 471 pregnant women in Women and Children's Hospital of Chongqing Medical University were enrolled in this study,microcolumn gel card test was used for irregular antibody screening,and antibody specificity identification was further performed in some antibody-positive subjects.Results:The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91％(1 375/151 471),0.23％(355/151 471)was detected in the first trimester,0.05％(71/151 471)in the second trimester,and 0.63％(949/151 471)in the third trimester.The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester,and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester.The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11％(689/1 375),which was the highest,the suspicious positive was 18.69％(257/1 375),and the positive was 31.20％(429/1 375).The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group,however,in the third trimester,the proportion of suspicious positive and weakly positive was lower than the first trimester,while,the proportion of positive was higher than the first trimester,and the difference was statistically significant(P＜0.001).Among the irregular antibody screening positive pregnant women,the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy≤1.Among 60 pregnant women who underwent antibody identification,the distributions of the antibodies were as follows:Rh blood group system accounted for 23.33％(14/60),Lewis system 43.33％(26/60),Kidd system 3.33％(2/60),MNS system 16.67％(10/60),P1PK system 1.67％(1/60),autoantibodies 1.67％(1/60),and 4 cases was unable to identify(6.67％,4/60).Among specific antibodies,the anti-Lea was the most common(30.00％),followed by anti-E(16.67％)and anti-M(16.67％).Conclusion:The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds,understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.