Steroid-induced avascular necrosis of femoral head（SANFH） is a bone and joint disease caused by prolonged and excessive steroid use. Its typical pathological features involve progressive circulatory disorders in the blood supply system of femoral head， leading to osteocyte apoptosis and bone tissue necrosis. As the disease progresses， it ultimately results in structural collapse and necrotic lesions of the femoral head， severely affecting patients' limb function and quality of life. Glucocorticoids mediate pathological damage through dual mechanisms， on the one hand， they disrupt the dynamic equilibrium between bone formation and resorption by suppressing osteoblast differentiation activity and activating osteoclastogenesis， on the other hand， they induce lipid metabolism disorders， inhibit angiogenesis， and impair endothelial cell function， thereby triggering microcirculatory disorders. Epimedii Folium and its active components exhibit multidimensional regulatory effects in SANFH prevention and treatment. Literature review reveals that it is rich in multiple active ingredients， primarily including total flavonoids of Epimedii Folium， icaritin， icariin， kaempferol， icariside Ⅱ， etc. These compounds exert multiple pharmacological effects（regulating bone metabolic homeostasis， modulating angiogenesis， correcting lipid metabolism disorders， and controlling cellular autophagy processes） through multiple signaling pathways， including Wnt/β-catenin， transforming growth factor（TGF）-β/bone morphogenetic protein（BMP）/Smad， mitogen-activated protein kinase（MAPK）， phosphoinositide 3-kinase/protein kinase B（PI3K/Akt）， osteoprotegerin/receptor activator of nuclear transcription factor-κB ligand/receptor activator of nuclear transcription factor-κB（OPG/RANKL/RANK）， etc. Based on existing research findings， this paper systematically elucidates the intervention mechanisms of active components in Epimedii Folium on key pathological processes of SANFH through the above pathways. It also deeply analyzes their regulatory roles in key nodes of different signaling pathways， aiming to provide valuable references for future clinical treatment and experimental research.

The aetiology of inflammatory bowel disease (IBD) involves genetic, immunological and microbiological factors, and the specific mechanisms of which are not yet fully understood. Intestinal organoids have an important role to play in the study of IBD, particularly with regard to mechanical barrier damage to the intestinal epithelium, intestinal micro-ecological dysregulation and genetic mechanisms. Intestinal organoids can also be used for screening of IBD therapeutics and individualized treatment monitoring in IBD, and are expected to cure IBD by means of repairing the intestinal mucosa or by transplantation. The application of intestinal organoids faces standardization, ethical, legal and technical challenges. However, with the improvement of standardization and technological advancement, it is expected to be combined with technologies such as artificial intelligence to further elucidate the pathogenesis of IBD and promote treatment innovation.

Purpose/Significance The paper systematically reviews relevant research on infectious disease prediction models based on internet data,helps to realize the advancement of infectious disease surveillance,and provides references for the construction of intelli-gent three-dimensional prevention and treatment system of infectious diseases.Method/Process The development history and research direction of infectious disease surveillance and early warning based on internet data collected in the core database of Web of Science and CNKI in the past 20 years are reviewed,major existing problems and challenges are analyzed,and common prediction models and their optimization directions are summarized.Result/Conclusion The study on internet infectious disease surveillance shows the trend of diver-sification of monitoring diseases,refinement and specialization of data sources.Due to the complexity and uncertainty of internet data,most of the existing models are only suitable for short-term or real-time prediction.By constructing a combination model,strengthening multi-source data fusion,improving the selection of keywords and influencing factors,the model can be further optimized and the fitting effect and prediction capacity can be strengthened.

Cervical cancer is the fourth-ranked malignant tumor of female cancer in the world, and it seriously threatens women’s health. The main treatment options for patients with cervical cancer are surgery or concurrent chemoradiotherapy. With the development of medical research, researchers are committed to exploring more effective and specific treatment options in order to increase the treatment options for cervical cancer and improve the treatment effect. Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology is a method in which the Cas9 protein uses guide RNA (gRNA) to target the target gene and achieve precise editing of the target gene. At present, CRISPR/Cas9 technology has become a promising and powerful gene editing tool, a new and effective targeted therapy that has been applied in the treatment of various tumors. The research progress of CRISPR/Cas9 technology in the treatment of cervical cancer is mainly reviewed in terms of action targets, combination therapy strategies, and related drug resistance gene screening in order to provide new strategies for the treatment of cervical cancer.

Objective To investigate the reversal effects of tetramethylpyrazine(TMP) and cyclosporin A(CsA) on multidrug resistance(MDR) of human erythroleukemia cells with gene transfer K562/MDR and to discuss the possible correlative mechanism.Methods K562/MDR cells in culture medium were treated with TMP(50—6 400 mg?L-1) and CsA(0.5—256 mg?L1) respectively.The growth rates of these cells were measured by MTT assay.Non-cytotoxic doses of TMP and CsA were determined.There were 5 growps in the experiment:G1(TMP+ADM+K562/MDR),G2(CsA+ADM+K562/MDR),G3(TMP+CsA+ADM+K562/MDR),negative control(K562/MDR subsitituted by K562/S),control(drugs subsitituted by 1640 culture medium),the inhibitory effects of adriamycin(ADM) used alone or in combination with TMP or/and CsA on the proliferation of K562/S and K562/MDR cells were observed by resisting fold and reversal folds.The effects of TMP and CsA on ADM accumulation in K562/S and K562/MDR cells were analyzed by fluorospectrophotometry.The protein level of P-glycoprotein(P-gp) was detected by flow cytometry(FCM).Results The non-cytotoxic doses of TMP and CsA were 320 and 2.0 mg?L-1,respectively.The resistance of K562/MDR cells to ADM was 19.2 folds of that of K562/S cells.When TMP and CsA were added along with ADM to the K562/MDR culture,the reversal folds were 5.2 and 9.6.When TMP in combination with CsA was added along with ADM to the K562/MDR culture,the reversal folds were 15.6.When various concentrations ADM were added to the K562/MDR culture,TMP and CsA could increase the intracellular accumulation of ADM.The effect of TMP in combination with CsA was more evident.Compared with control,TMP and CsA could inhibit the overexpression of P-gp protein(P

OBJECTIVE: To observe the effects of psoralen plus ultraviolet-A light (PUVA) on K562 cells and the relative mechanism. METHODS: The effects of psoralen, ultraviolet-A light and PUVA on K562 cells were assayed by monotetrazolium test (MTT). DNA content was analyzed by flow cytometry (FCM). The apoptotic rates of K562 cells treated with 40 and 80 microg/ml psoralen for 24 and 48 hours were assayed by Annexin-V-FITC/PI reagent kit on FCM respectively. The ultrastructures of apoptotic cells were observed by a transmission electron microscope (TEM). RESULTS: Either single psoralen therapy or single ultraviolet-A irradiation had inhibiting effect on K562 cells. The inhibiting effect of PUVA on K562 cells was stronger than that of the single psoralen therapy or single ultraviolet-A light irradiation (P<0.05). Apoptotic peak (AP) was detected by FCM. TEM test showed that K562 cells treated with PUVA were smaller, having condensed cell nucleus, assembled chromatin, disintegrated nucleus body and the majority of the cells appeared to be apoptotic conformation. CONCLUSION: Psoralen has inhibiting effect on K562 cells, and the effect of PUVA is more significant. It is suggested that 10 min irradiation and 40 microg/ml terminal concentration of psoralen be probably the best choice for PUVA. The inhibiting effect of PUVA is due to apoptosis.

Objective To study the reversal effect of adriamycin (ADM) resistance in human breast cancer cell line MCF-7/ADM by realgar (REA) combined with ?-elemene (?-ELE), two types of anticancer drugs. Methods The sensitivity to ADM of MCF-7/ADM cells was studied by MTT assay.The intracellular accumulation of ADM in MCF-7/ADM cells was observed by fluorescent-spectrophotometry. Expressions of P-GP protein and Bcl-2 protein were detected by flow cytometry. Results The combined treatment of REA and ?-ELE could significantly enhance the cytotoxic effect of ADM on MCF-7/ADM cells to 4.2 fold as compared with the treatment of REA or ?-ELE respectively (P

OBJECTIVETo investigate the effect of drug resistance by arsenic trioxide (As(2)O(3)) and its possible mechanism in human breast cancer cell line MCF-7/ADM.

METHODSCytotoxicity of As(2)O(3) and the sensibility to adriamycin (ADM) in MCF-7/ADM cell line, a ADM-resistance cell line of human breast cancer, were studied through MTT assay. The concentration of intracellular ADM was detected by spectrofluorometry. With MCF-7/ADM cells treated with As(2)O(3) in combination with ADM, the glutathione-s-transferase (GST) activity was measured by biochemical method. The expression of GST-pi mRNA was assessed by RT-PCR.

RESULTSThe non-cytotoxic dose of As(2)O(3) was 0.2 micro mol/L and the low cytotoxic dose was 0.8 micro mol/L to MCF-7/ADM cell line. 0.2 micro mol/L As(2)O(3) could significantly increase the intracellular accumulation of ADM in MCF-7/ADM cell line (P < 0.05). The medium inhibition concentration (IC(50)) was obviously reduced from 53.74 micro mol/L to 25.0 micro mol/L, with a reversal ratio of 2.1 as compared to its parental cell line. Before and after 0.2 micro mol/L, 0.8 micro mol/L As(2)O(3) were given, GST activities were decreased from 29.68 +/- 0.29 U/ml to 19.29 +/- 2.10 U/m l and 12.66 +/- 2.78 U/ml (P < 0.05). In addition, MCF-7/ADM cell line had overexpression of GST-pi mRNA. A significant down regulation of GST-pi mRNA was observed in MCF-7/ADM cells when As(2)O(3) and ADM (21.55 micro mol/L) were given for 24 hours.

CONCLUSIONAs(2)O(3) is able to enhance the cytotoxicity of ADM and partly reverse the ADM resistance of MCF-7/ADM cell line of human breast cancer, which may be related to the variation of GST-pi enzyme.

Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Breast Neoplasms ; Dose-Response Relationship, Drug ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Gene Expression ; Glutathione S-Transferase pi ; Glutathione Transferase ; genetics ; Humans ; Isoenzymes ; genetics ; Oxides ; pharmacology ; RNA, Messenger ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured

Objective To study the expression of ABC gene family of MCF 7/ADM cells as compared to parental cell line MCF 7/S, and its reversion by realgar of the expressed genes. Methods Expression of ABC family genes was examined by RT PCR, and cell growth by MTT test. Results The expression of ABC gene family was positive in MCF 7/ADM cells compared to MCF 7/S cells; Realgar can down regulate the expression ABC gene family in MCF 7/ADM cells; the IC 50 of ADM to MCF 7/ADM cells was decreased.Conclusion ABC gene family was responsible for the induced resistance of MCF 7/ADM cells to ADM; Realgar is able to reverse partly the multidrug resistance of the human breast cancer cell line MCF 7/ADM. [

Objective One of the major obstacle to the successful treatment of cancer in clinic is the drug-resistance phenotype.In this study,the effect of realgar(REA) on the induction of apoptosis and the reversal of drug resistance were investigated. Methods Human breast cancer line MCF-7 and its adriamycin(ADM) resistant counterpart MCF-7/ADM cells were used in this study.15mg/L REA and 25mg/L REA were selected as non-cytotoxic dose and low-cytotoxic to MCF-7/ADM cells respectively by MTT assay.Then,they were adopted to affect the growth of MCF-7/ADM cells. MTT assay was used to analyze the effect of REA on drug sensitivity to ADM.The cells apoptosis was detected by transmission electron microscope and flow cytornetry.The expressions of anti-apoptosis protein Bcl-2 were detected by flow cytometry.Finally,the intracellular accumulation of ADM in MCF-7/ADM cells was detected by fluorescent-spectrophotometry. Results REA reversed the drug-resistance of ADM in MCF-7/ADM cells with dose-dependent relationship.When 15mg/L REA or 25mg/L REA was added into the culture,the 50% inhibitory concentration(IC_(50)) of ADM in MCF-7/ADM cells was reduced from 30.4mg/L to 13.2mg/L and 10.8mg/L(P