OBJECTIVE To investigate the clinical efficacy and mechanism of Gongliuxiao capsule combined with dienogest （DNG） in the treatment of refractory/recurrent endometriosis （EMT）. METHODS A retrospective analysis was conducted on the clinical data of 94 patients with refractory/recurrent EMT admitted to Qingdao TCM Hospital from January 2022 to January 2025. According to different treatment methods， they were divided into a monotherapy group （47 cases， receiving DNG monotherapy） and a combination group （47 cases， receiving Gongliuxiao capsule combined with DNG）. The cl inical efficacy， symptom and sign scores [Visual Analog Scale （VAS） and Pictorial Blood Loss Assessment Chart （PBAC） scores ] ， vascular endothelial function indicators [serum transforming growth factor-β 1 （TGF-β 1 ）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-2 （MMP-2）， MMP-9， basic fibroblast growth factor （bFGF） ] ， serum pathological factors [carbohydrate antigen 125 （CA125）， CA199， anti-endometrial antibody （EMAb） ] ， and Th1/Th2 drift indicators [interferon-γ （IFN-γ）， interleukin-4 （IL-4） ] were compared between the two groups before and after 6 months of treatment. RESULTS After treatment， the VAS and PBAC scores， serum levels of TGF-β 1 ， VEGF， MMP-2， MMP-9， bFGF， CA125， CA199， EMAb， and IL-4 in both groups were significantly lower than those before treatment， while IFN-γ levels were significantly higher than those before treatment （ P ＜0.05）. Moreover， the magnitude of increase or decrease in the combination group was significantly greater than that in the monotherapy group （ P ＜0.05）. The total effective rate in the combination group was significantly higher than that in the monotherapy group （93.62% vs. 76.60%， P ＜0.05）. CONCLUSIONS The combination of Gongliuxiao capsule and DNG is effective in treating refractory/recurrent EMT， and can effectively improve the degree of dysmenorrhea and abnormal menstrual volume in patients. The mechanism may be related to improving vascular endothelial function， inhibiting the expression of tumor pathological factors， and correcting Th1/Th2 drift.

Objective: To investigate the molecular mechanism of Syk in phagocytosis induced by CD36 antibodies. Methods: In vitro, two CD36 monoclonal antibodies, GZ1 (IgG2a) and GZ4 (IgG1), at different concentrations were co-incubated with platelets from CD36-positive blood donors, and the affinity of the antibodies for platelets was assessed using flow cytometry. CD36 positive platelets from donors were labeled with Red-SE. The GZ1 and GZ4 antibodies were added together with dye-labeled platelets to peripheral blood from blood donors for phagocytosis experiments. The expression of the Spleen Tyrosine Kinase (Syk), P-Syk, P38 MAPK and P-P38 were detected using Western blot(WB). In the in vitro phagocytosis inhibition assay, Fcγ receptor (FcγR) antibodies or Syk inhibitor (R406) were pre-incubated with monocytes prior to performing the phagocytosis experiment. In vivo experiments were performed using female C57BL/6J mice. R406 was administered via intraperitoneal injection, followed by tail vein infusion of GZ1 or GZ4 antibodies. Additionally, a treatment group was set up in which the antibodies were infused first, followed by administration of R406. Changes in platelet counts were analyzed using a blood routine analyzer, and antibody binding to platelets was detected by flow cytometry. Results: GZ1 had higher affinity for CD36positive platelets than GZ4. The phagocytosis rate induced by GZ1 was significantly higher than that of GZ4 [(42.12±2.25)% vs (16.25±6.45)%, P<0.001]. Moreover, GZ1-mediated platelet phagocytosis mainly depends on FcγRⅠ of monocytes, while GZ4-mediated platelet phagocytosis mainly relies on FcγRⅡ of monocytes. WB results showed that the GZ1 group significantly upregulated the expression of Syk and phosphorylated Syk (P-Syk), and induced phosphorylation of the downstream P38 MAPK signaling pathway. Pretreatment of monocytes with R406 inhibited the phagocytosis of antibodyopsonized platelets by monocytes. After injecting GZ1 or GZ4 antibodies into C57BL/6 female mice through the tail vein, GZ1 mAbs had a stronger binding rate to the platelets compared with GZ4 mAbs, leading to a significant decrease in platelet count. After pre-injecting R406 into mice, the platelet count reduction in both the GZ1 and GZ4 groups was alleviated, and the binding rate of antibodies to platelets was also significantly reduced. However, administration of R406 after antibody injection failed to prevent the decrease in platelet counts in mice. Conclusion: This study indicates that Syk plays an important role in the phagocytosis of anti-CD36 opsonized platelets by monocytes/macrophages and is closely associated with the activation of the P38 MAPK signaling pathway.

ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology， animal experiments， and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 （CCK-8） assay was adopted to observe the effects of different volume fractions （5%， 10%， 15%， and 20%） of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells， and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma （5%， 10%， 15%， and 20%） on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-， medium-， and high-dose （4.63， 9.25， 18.5 g·kg^-1） Huangqi Xiayuxue decoction and sorafenib （20 mg·kg^-1） groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention， hematoxylin-eosin （HE） staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay was employed to detect cell apoptosis. Immunohistochemistry （IHC） was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 （PI3K/Akt/FoxO1） signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology， among which tumor protein p53 （TP53）， Akt1， and signal transducer and activator of transcription 3 （STAT3） were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation， as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group， all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells （P<0.01）. The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma （P<0.01）. Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume， promoted tumor cell apoptosis in the high-dose group， up-regulated the protein and mRNA levels of Bax and Caspase-3， down-regulated the protein and mRNA levels of Bcl-2， and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway （P<0.05， P<0.01）. ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.

ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology， animal experiments， and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 （CCK-8） assay was adopted to observe the effects of different volume fractions （5%， 10%， 15%， and 20%） of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells， and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma （5%， 10%， 15%， and 20%） on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-， medium-， and high-dose （4.63， 9.25， 18.5 g·kg^-1） Huangqi Xiayuxue decoction and sorafenib （20 mg·kg^-1） groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention， hematoxylin-eosin （HE） staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay was employed to detect cell apoptosis. Immunohistochemistry （IHC） was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 （PI3K/Akt/FoxO1） signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology， among which tumor protein p53 （TP53）， Akt1， and signal transducer and activator of transcription 3 （STAT3） were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation， as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group， all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells （P<0.01）. The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma （P<0.01）. Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume， promoted tumor cell apoptosis in the high-dose group， up-regulated the protein and mRNA levels of Bax and Caspase-3， down-regulated the protein and mRNA levels of Bcl-2， and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway （P<0.05， P<0.01）. ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.

Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.

Purpose To investigate the clinicopathological features,immunophenotypic profile,differential diag-noses,and prognostic implications of liver metastatic solid pseudopapillary neoplasm(LMSPN).Methods A retro-spective analysis was conducted on the clinicopathological features,immunohistochemical profile,and clinical outcomes of of 15 cases of LMSPN cases,supplemented by a literature review.Results Of the 15 patients,12 were female and 3 were male,with a mean age of 43 years(range 25-67 years).Multiple hepatic lesions were observed in 9 cases,some of which were accompanied by abdominal or omental metastasis.The tumors exhibited a cystic-solid appearence on gross examination,ranging from 0.5 to 15 cm in diameter.Histologically,the tumors showed typical cystic-solid and pseudopapillary areas,with tumor cells arranged around small blood vessels forming characteristic pseudopapillary structures.Tumor cells exhibited relatively uniform morphology,however,some cases presented with tumor necrosis(5/15),cytologic/nuclear atypia(4/15),mitotic figures(5/15),lymphovascular invasion(6/15),perineural inva-sion(3/15),and lymph node metastasis(2/15).Immunohistochemically,tumor cells showed variable expression ofβ-catenin,LEF1,vimentin,CD10,α1-ACT,PR,E-cadherin,NSE,CD56,Syn and Ki67.Notably,the nuclear ex-pression level of Ki67 and PR were significantly associated with prognosis(P＜0.05).β-catenin,LEF1,PR,and Ki67 were predominantly expressed in the nuclei,while markers such as CKpan,CgA,Hep Par-1,Arginase-1,CK7,and CK19 were negative or only weakly expressed.Follow-up data were available for 11 patients(range 10-157 months).Four patients died of widespread hepatic and abdominal metastases,while 7 remained alive.Conclusion The liver is the most most frequent site of distant metastasis for solid pseudopapillary neoplasms of the pancreas.High expression of Ki67 and PR is associated with unfavorable prognosis in LMSPN.

Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.

Objective To evaluate the clinical efficacy of Huanglian Heye Formula(composed of Nelumbinis Folium,Coicis Semen,Atractylodis Rhizoma,Glycyrrhizae Radix et Rhizoma,Coptidis Rhizoma,Crataegi Fructus,and Atractylodis Macrocephalae Rhizoma)combined with insulin aspart in treating obese patients with type 2 diabetes mellitus(T2DM)presenting damp-heat obstructing middle jiao syndrome.Methods A total of 94 obese T2DM patients with damp-heat obstructing middle jiao syndrome were treated at the Endocrinology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from April 2022 to January 2024.The patients were randomly assigned to the control group and the observation group,with 47 patients in each group.The control group was treated with insulin aspart,and the observation group was treated with Huanglian Heye Formula plus insulin aspart,both groups were treated for 12 weeks.Changes in traditional Chinese medicine(TCM)syndrome scores,lipid metabolism parameters[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)],obesity indicators[waist-to-hip ratio(WHR),body mass index(BMI),glucose metabolism markers[glycated hemoglobin(HbA1c),2-hour postprandial glucose(2hPG),fasting plasma glucose(FPG)],and serological indicators(visceral adipose tissue-derived serine protease inhibitor[VASPIN],homeostasis model assessment of[3-cell function(HOMA-β)]were observed before and after treatment.Clinical efficacy and safety were evaluated.Results(1)The observation group demonstrated significantly higher total efficacy[93.62％(44/47)]compared to the control group[78.72％(37/47);the intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P＜0.05).(2)Both groups showed reduced TCM syndrome scores(heaviness in head/body,epigastric fullness,sticky/foul-smelling stools,halitosis,dry/bitter mouth,heartburn/vomiting,yellowish urine,and emotional distress;all P＜0.05),with greater improvements in the observation group(P＜0.01).(3)Lipid profiles of TC,TG and LDL-C were improved in both groups(P＜0.05),with more significant reductions in the observation group(P＜0.01).(4)Obesity indicators(WHR,BMI)decreased in both groups(P＜0.05),showing superior reductions in the observation group(P＜0.05 or P＜0.01).(5)Glucose metabolism markers(HbA1c,2hPG,FPG)were significantly lowered in both groups(P＜0.05),with the observation group achieving better outcomes(P＜0.01).(6)Serological analysis revealed increased VASPIN and HOMA-[3 levels in both groups(P＜0.05),with more pronounced elevations in the observation group(P＜0.01).(7)No severe adverse events occurred.The incidence of adverse reactions was 8.51％(4/47)in the observation group versus 6.38％(3/47)in the control group(P＞0.05).Conclusion Huanglian Heye Formula combined with insulin aspart significantly improves clinical outcomes in obese T2DM patients with damp-heat obstructing middle jiao syndrome by protecting pancreatic[3-cell function,reducing body mass,ameliorating glucose/lipid metabolism,and modulating VASPIN expression,with demonstrated safety.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Purpose To investigate the clinicopathological features,immunophenotypic profile,differential diag-noses,and prognostic implications of liver metastatic solid pseudopapillary neoplasm(LMSPN).Methods A retro-spective analysis was conducted on the clinicopathological features,immunohistochemical profile,and clinical outcomes of of 15 cases of LMSPN cases,supplemented by a literature review.Results Of the 15 patients,12 were female and 3 were male,with a mean age of 43 years(range 25-67 years).Multiple hepatic lesions were observed in 9 cases,some of which were accompanied by abdominal or omental metastasis.The tumors exhibited a cystic-solid appearence on gross examination,ranging from 0.5 to 15 cm in diameter.Histologically,the tumors showed typical cystic-solid and pseudopapillary areas,with tumor cells arranged around small blood vessels forming characteristic pseudopapillary structures.Tumor cells exhibited relatively uniform morphology,however,some cases presented with tumor necrosis(5/15),cytologic/nuclear atypia(4/15),mitotic figures(5/15),lymphovascular invasion(6/15),perineural inva-sion(3/15),and lymph node metastasis(2/15).Immunohistochemically,tumor cells showed variable expression ofβ-catenin,LEF1,vimentin,CD10,α1-ACT,PR,E-cadherin,NSE,CD56,Syn and Ki67.Notably,the nuclear ex-pression level of Ki67 and PR were significantly associated with prognosis(P＜0.05).β-catenin,LEF1,PR,and Ki67 were predominantly expressed in the nuclei,while markers such as CKpan,CgA,Hep Par-1,Arginase-1,CK7,and CK19 were negative or only weakly expressed.Follow-up data were available for 11 patients(range 10-157 months).Four patients died of widespread hepatic and abdominal metastases,while 7 remained alive.Conclusion The liver is the most most frequent site of distant metastasis for solid pseudopapillary neoplasms of the pancreas.High expression of Ki67 and PR is associated with unfavorable prognosis in LMSPN.