ObjectiveTo observe the clinical efficacy and safety of Modified Guomin Decoction （加味过敏煎， MGD） in patients with mild to moderate atopic dermatitis （AD） of the traditional Chinese medicine （TCM） pattern of heart fire and spleen deficiency， and to explore its possible mechanisms. MethodsIn this randomized， double-blind， placebo-controlled study， 72 patients with mild to moderate AD and the TCM pattern of heart fire and spleen deficiency were randomly divided into a treatment group and a control group， with 36 cases in each group. The treatment group received oral MGD granules combined with topical vitamin E emulsion， while the control group received oral placebo granules combined with topical vitamin E treatment. Both groups were treated twice daily for 4 weeks. Clinical efficacy， TCM syndrome scores， Visual Analogue Scale （VAS） for pruritus， Dermatology Life Quality Index （DLQI） scores， Scoring Atopic Dermatitis （SCORAD） and serum biomarkers， including interleukin-33 （IL-33）， interleukin-1β （IL-1β）， immunoglobulin E （IgE）， and tumor necrosis factor-α （TNF-α） were compared before and after treatment. Safety indexes was also assessed. ResultsThe total clinical effective rates were 77.78% （28/36） in the treatment group and 38.89% （14/36） in the control group， with cure rates of 19.44% （7/36） and 2.78% （1/36）， respectively. The treatment group showed significantly better clinical outcomes compared to the control group （P＜0.05）. The treatment group exhibited significant reductions in total TCM syndrome scores， including erythema， edema， papules， scaling， lichenification， pruritus， irritability， insomnia， abdominal distension， and fatigue scores， as well as reductions in VAS， DLQI， SCORAD， and serum IgE and IL-33 levels （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had significantly better improvements in all indicators except for insomnia （P＜0.05）. No adverse events occurred in either group. ConclusionMGD is effective and safe in treating mild to moderate AD patients with heart fire and spleen deficiency pattern. It significantly alleviates pruritus， improves TCM syndromes and quality of life， and enhances clinical efficacy， possibly through modulation of immune responses.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

Ying and wei qi is derived from the essence of water and grain， and is the basic material to maintain the normal life activities of the body. Ying and wei qi has the difference of nature of yin and yang or the clear and the turbid. When the relationship between ying and wei qi is out of order and in reverse disorder， it will lead to the occurrence of various diseases. Based on the analysis of the theory of "ying-wei disorder" in The Inner Canon of Yellow Emperor （《黄帝内经》）， this paper started from the perspective of the exuberance and debilitation， circulation and function of ying qi and wei qi， focused on the theoretical understanding that the change of deficiency and excess （"fall"） and the change of circulation （"move"）， and refined the core mechanism of "ying-wei disorder"， which is the depletion of ying qi and wei qi， stagnation of ying qi and wei qi， and disharmony of ying qi and wei qi， and finally summarized the syndrome identification and treatment method of supporting ying qi and assisting wei qi， promoting ying qi and moving wei qi， regulating ying qi and wei qi， and constructed the syndrome identification and treatment system for ying-wei disorder of malignant tumor in clinic.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Tumor metastasis is closely related to high mortality rate of cancer.It is well known that glutamine plays an important role in the malignant progression of cancer.Notably,as an important carbon and nitrogen donor,glutamine has been found to be closely related to tumor metastasis in recent years.Glutamine is not only involved in regulating the proliferation of tumor cells,but is also closely related to the migration and invasion of tumor cells.Furthermore,various enzymes along with transporters in the metabolism of glutamine are involved in the process of tumor metastasis through different signaling pathways.This review provided a summary of the role of glutamine in tumor metastasis in recent years and proposed therapeutic targets to provide new strategies for the clinical treatment of tumor metastases.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective The aim of the study was to investigate how morphine(Mor)effects mitochondrial dynamics change of H9c2 induced by hypoxia/reoxygenation(H/R).Methods Myocardial H9c2 cells were divided into blank group(without treatment),model group(H/R treatment),control group(5 μmol·L-1 Mor treatment)and experimental group(H/R+5 μmol·L-1 Mor treatment).The content of reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and complex of Ⅰ and Ⅲ activity were detected using ROS,tetramethylrhodamine ethyl ester(TMRE),and mitochondrial complex of Ⅰ and Ⅲ activity detection kits,respectively.The morphology of mitochondria and lysosomes was observed by transmission electron microscope electron microscopy(TEM);Western blot was used to detect the expression of GTPase kinetic protein 1(Drp1),cytochrome c oxidase Ⅳ(COX Ⅳ)and transporters of the outer mitochondrial membrane(TOM20).Results The nuclear membrane was smooth and complete;the mitochondrial size was consistent;the crest arrangement was neat;vacuolization was reduced or even disappeared;the mitochondrial matrix electron density was increased;the number of autophagosomes was decreased in the experimental group.The contents of ROS in blank group,model group,control group and experimental group were 1.03±0.04,1.53±0.10,1.06±0.06 and 1.10±0.11;MMP were 1.00±0.15,0.80±0.16,1.06±0.19 and 1.00±0.19;the activities of complex of Ⅰ were 1.00±0.08,2.28±0.82,1.05±0.26 and 1.13±0.37;the activities of complex of Ⅲ were 1.00±0.09,2.13±0.38,0.83±0.22 and 0.96±0.11;the expression of Drp1 protein were 1.00±0.14,1.27±0.07,0.97±0.21 and 0.93±0.17;the expression of fission protein 1(Fis1)protein were 1.00±0.16,1.33±0.18,1.17±0.25 and 0.99±0.05;the expression of COX Ⅳ protein were 1.00±0.25,0.62±0.08,0.79±0.26 and 0.97±0.16;the expression of TOM20 protein were 1.00±0.13,0.67±0.15,0.75±0.13 and 0.89±0.05.The above indexes of model group were significantly different from those of blank group(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1).The above indexes of experimental group were significantly different from those of model group(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1).Conclusion Morphine may inhibit mitophagy and fission,and alleviated mitochondrial oxidative stress damage by decreasing the activity of respiratory chain complex of Ⅰ and Ⅲ,thus maintaining mitochondrial dynamic homeostasis and alleviating H/R-induced myocardial cell damage.

Objective To investigate the effect of the aqueous extract of Chuan Xiong Rhizoma(CR)on brain metastasis of melanoma B16F10 cells in mice.Methods C57BL/6J mouse models of brain metastasis of melanoma were established by ultrasound-guided intraventricular injection of Luc-labeled B16F10 cells,and brain tumor growth was monitored by in vivo imaging.The mouse models were then randomized for daily gavage of saline or aqueous extract of CR(equivalent crude drug concentration of 1 mg/g).Behavioral tests were used to evaluate the neuroprotective effects of CR in the tumor-bearing mice,and the changes in proteins associated with blood-brain barrier integrity,neuronal cell proliferation and apoptosis,and microglial cell apoptosis and activation were observed using immunofluorescence assay.The efficacy of CR combined with temozolomide(25 mg/kg)against brain metastases of B16F10 cells was observed by in vivo imaging.Results CR-treated mouse models did not show obvious progression of brain metastases and had a reduced rate of body weight loss and lowered protein expressions of ZO-1,claudin-5,occludin,P-gp,TNF-α,AQP4 and PDGFRβ.In the behavioral tests,the CR-treated mice showed prolonged stay on the wooden stick with a shortened time of sticky stick removal.Immunofluorescence assay showed increased proliferation and decreased apoptosis of neuronal cells and microglia in CR-treated mice.CR treatment significantly increased the levels of CD86,CD206,IL-4 and IL-10 and decreased the levels of CD163 and IL-1β in the microenvironment of brain metastases.The mice receiving combined treatments with CR and temozolomide showed significantly lower intensity of fluorescent signals in the brain than those treated with temozolomide alone.Conclusion CR does not promote brain metastasis of melanoma while inducing opening of the blood-brain barrier,and its combined use with TMZ results in enhanced inhibition against brain metastasis of melanoma B16F10 cells in mice.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.