OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Tripterygium wilfordii is a traditional Chinese medicinal herb belonging to the genus Tripterygium in the Celastraceae family， which has the effects of clearing heat and detoxifying， dispelling wind and dampness， and invigorating blood circulation to relieve pain， and is used to treat diseases such as rheumatoid arthritis， glomerulonephritis， nephrotic syndrome， lupus erythematosus， scabies， and stubborn tinea. Its chemical composition is diverse. Among them， triptolide（TP） is one of the main active and toxic components of T. wilfordii. It has significant biological activities such as anti-inflammation， anti-tumor， and immunosuppression. However， it causes serious adverse reactions such as liver and kidney function damage and reproductive system disorders. At the same time， TP has poor water solubility and low bioavailability， and the enhancement of bioavailability by increasing the dosage undoubtedly improves the exposure of the drug in non-target organs， leading to the occurrence of adverse reactions， and these largely limit the clinical application of TP. Based on this， this article extracted relevant data from the Web of Science， PubMed， and China National Knowledge Infrastructure（CNKI） databases， summarized the research on the adverse reactions of TP in recent years， and reviewed the progress of toxicity reduction research from the perspectives of structural modification， novel drug delivery systems， and compatibility. Structural modification can precisely alter the chemical structure of TP， reduce the activity of its toxic groups， and retain its biological activity while fundamentally reducing the occurrence of adverse reactions. New drug delivery systems can achieve targeted delivery of TP， increase its concentration in target organs， and reduce its exposure in non-target organs， thereby enhancing therapeutic efficacy and reducing adverse effects. In addition， the combination of TP with Chinese medicine compound， single-flavored Chinese medicine or monomer can reduce the adverse effects of TP and enhance the efficacy to different degrees， which is of clinical value. This paper systematically explains attenuation research from the above three perspectives， aiming to provide a theoretical basis for the full utilization of biological activity and drug development of TP.

Objective: To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis. Methods: Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed. Results: ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group. Conclusion SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.

Type 2 diabetes mellitus （T2DM） is a heterogeneous disease with insulin deficiency and insulin resistance （IR） as the main etiology and is often accompanied by complications. Volatile oil is a volatile oily liquid extracted from natural plants， which has many pharmacological effects such as regulating Qi， relieving pain， inhibiting bacteria， and reducing inflammation. In recent years， there have been numerous reports on the treatment of T2DM by natural plant volatile oil and its effective components， which has become one of the new directions in the treatment of T2DM. With natural plant essential oil and its active components as the starting point， this paper comprehensively analyzed and summarized the material basis， mechanism， and signaling pathways of essential oil in the treatment of T2DM and its complications in China and abroad in recent years， and focused on the inhibitory effect of essential oil and its active components， such as carvacrol， paeonol， and β-caryophylene， on IR to improve T2DM by protecting pancreatic β-cells， inhibiting α-glucosidase activity， regulating the abundance and diversity of intestinal microbiota， and regulating glucose transporter protein type4 （GLUT4）， adenylate 5′-monophosphate-activated protein kinase （AMPK）， phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt） signaling pathways to provide some references for the volatile oil intervention in T2DM and the development of new green antidiabetic drugs.

Chloroquine has played a pivotal role in the treatment of malaria.Recently,with the development of clinical application,they are increasingly recognized for their effectiveness in other as-pects,such as anti-inflammation,immunosuppression,anti-amoebic effects and so on.In the outbreak of the new coronavirus infection,chloroquine and its derivative hydroxychloroquine swiftly included in the treatment of infected patients in many countries.However,several studies have shown these drugs have some detrimental influence,especially in cardiac arrhythmia(prolonged the QT interval and in-creased risk of torsional ventricular tachycardia).Thus,we should pay attention to both their benefi-cial effects and potential adverse manifestation.In order to regulate the use of drugs and guide the clin-ic,this paper reviewed the electrophysiological basis and clinical characteristics of cardiac adverse re-actions of these drugs from the perspective of ion channels.

Chloroquine has played a pivotal role in the treatment of malaria.Recently,with the development of clinical application,they are increasingly recognized for their effectiveness in other as-pects,such as anti-inflammation,immunosuppression,anti-amoebic effects and so on.In the outbreak of the new coronavirus infection,chloroquine and its derivative hydroxychloroquine swiftly included in the treatment of infected patients in many countries.However,several studies have shown these drugs have some detrimental influence,especially in cardiac arrhythmia(prolonged the QT interval and in-creased risk of torsional ventricular tachycardia).Thus,we should pay attention to both their benefi-cial effects and potential adverse manifestation.In order to regulate the use of drugs and guide the clin-ic,this paper reviewed the electrophysiological basis and clinical characteristics of cardiac adverse re-actions of these drugs from the perspective of ion channels.

AIM: To investigate the effect of oxypeucedanin (OPD) on doxorubicin resistance in human breast cancer MCF-7/DOX cells and its possible mechanism. METHODS: MCF-7/DOX cells were cultured in vitro, MTT assay was used to detect the effect of OPD on the survival of MCF-7/DOX cells, and the effect of OPD combined with different concentrations of doxorubicin on the proliferation of MCF-7/DOX cells were investigated. The effect of OPD combined with doxorubicin on the expression of genes including MDR1, MRP1, AGPAT2, CHKA, CEPT1, DGKA, PCYT1A, PLA2G15 in MCF-7/DOX cells was measured by qRT-PCR. The effect of OPD combined with doxorubicin on the protein expression of MDR1, MRP1, CHKA and CCTα in MCF-7/DOX cells was determined by Western blot. RESULTS: The IC

Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

granulocytic sarcoma (GS) is rare in the breast, histologically and immunophenotypically similar to myelogenous leukemia, radiologically lacking specificity, similar to breast cancer or mammary abscess. It should not be misdiagnosed as invasive cancer, especially in the case of frozen diagnosis, leading to excessive surgery. Three cases of GS were collected, specimens were fully drawn, microscopic pathologic examinations and immunohistochemistry (SP method) granulocytic sarcoma of breast were performed. The clinicopathological, immunohistochemical features, diagnosis and prognosis of GS are discussed to improve the awareness of the disease.

【Objective】 To estimate the application value of washed red blood cells (RBC) in perioperative patients with liver cancer. 【Methods】 86 perioperative patients with liver cancer who met the inclusion/exclusion criteria were divided into observation group (n=42) and control group (n=44). In the observation group, 22 patients were transfused with RBC and 20 with washed RBC. Patients without RBC transfusion worked as the controls. The name of disease, tumor stage, tumor size, Hb before and after blood transfusion, transfusion volume and blood components, adverse reaction to blood transfusion, operation time and blood loss during surgery, systemic infection, tumor recurrence and metastasis, and survival time were recorded. Blood transfusion efficacy, survival time, adverse reaction to blood transfusion, tumor recurrence and metastasis among these groups were compared. 【Results】 Among the non-transfusion group, washed RBC group and RBC group, the Hb(g/L)were 93.9±16.5 vs 80.4±24.5 vs 74.7±26.1, operative time (h) 2.8±0.7 vs 4.3±1.6 vs 3.9±2.0, operative blood loss(mL) 291.0±0.3 vs 388.0±165.8 vs 466.3±198.4 respectively before blood transfusion (all P<0.05). There were no significant differences in the efficacy of blood transfusion and survival time among the three groups (P>0.05). There were significant differences in tumor metastasis (50% vs 43%) and recurrence (50% vs 43.1%) between blood transfusion group and non-blood transfusion group (P<0.05). There was no difference in tumor metastasis (50% vs 48%) and recurrence (50% vs 49%) between the washed RBC group and RBC group (P>0.05). The nosocomial infection rate in washed RBC group (36%) was significantly lower that that in RBC group (88.6%) and non-transfusion group (50%) (P<0.05). 【Conclusion】 Blood transfusion caused by hypoxia may increase tumor metastasis and recurrence in perioperative patients with liver cancer. Transfusion of washed RBC can achieve the curative effect and reduce adverse reactions to blood transfusion, but has no significant impact on the survival time.