Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

The immune response against infection is a multifaceted process encompassing the activation and migration of diverse immune cells, as well as the clearance of pathogens. The behaviors of immune cells and the identification of pathogens play pivotal roles as indicators for disease diagnosis and prediction. In recent years, the utilization of microfluidic chip technology has gained substantial attention within the areas of biology, pharmacology, and clinical research and diagnosis. This is primarily attributed to the numerous advantages it offers, including miniaturization, enhanced throughput, heightened sensitivity, expedited analysis, and reduced sample consumption. As a result, microfluidic technology has facilitated the development and utilization of immune cell behavioral assays, bacterial growth studies, and drug-screening assays. This paper is to review the application of microfluidic technology in the field of anti-infection immunity research, focusing on the analysis of migratory behavior of innate immune cells, deformation of their nuclei, and rapid identification of pathogenic bacteria and viruses. The primary objective of this review is to advance the application of microfluidic technology in research on both anti-infection immunity and clinical diagnosis.

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin’s action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

OBJECTIVE：To explore th e applicatio n of team situatio nal simulation education and teaching mode in clinical pharmacy teaching. METHODS ：A total of 60 clinical pharmacy interns were selected as the research objects ，and course disease was type 2 diabetes mellitus. Thirty interns were randomly selected as control group ，using traditional teaching mode ；other 30 interns were selected as trial group ，which carried out team situational simulation education and teaching mode. The teaching effects were evaluated by using the satisfaction of interns to the two modes ，the comprehensive score of graduation examination and the self-evaluation of learning effect. RESULTS ：Compared with traditional teaching mode ，team situational simulation education and teaching mode was conducive to stimulate the learning interest of interns ，improve their interpersonal communication ability ， cultivate teamwork spirit ，improve the awareness of humanistic care ，and cultivate the professional attitude of clinical pharmacists （P＜0.05）. Compared with control group ，the comprehensive score of trial group was dominantly increased （P＜0.001），and the scores of professional quality ，humanistic care and communication skills in the trial group were significantly higher than control group（P＜0.01）. In terms of self-evaluation of learning effect ，except for the pathogenesis of type 2 diabetes and the commonly used treatment regimens ，the self-evaluation scores of the other items in trial group were significantly higher than control group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Team situational simulation education and teaching mode is superior to traditional teaching mode for clinical pharmacy teaching.

Objective To investigate the effect of Taurine on the differentiation of neural stem cells(NSCs)in fetal rats with intrauterine growth restriction( IUGR),and to explore the neuroprotective mechanism of Taurine. Methods IUGR fetal rats models were established with low protein diet. NSCs from subventricular zone( SVZ)were isolated and cultured in υitro. The NSCs were divided into 3 groups:normal control group,IUGR group,and IUGR+Taurine group. The cells were examined by adopting immunofluorescence for counting βⅢ-tubulin protein,glial fibril-lary acidic protein(GFAP)and myelin basic protein(MBP)-positive cells. Protein levels of βⅢ-tubulin and GFAP were detected by using Western blot. Results (1)The number of βⅢ-tubulin protein positive cells in normal control group,IUGR group and IUGR+Taurine group were(18. 50 ± 0. 64)%,(15. 61 ± 0. 76)% and(18. 42 ± 0. 82)%, respectively;the number of GFAP positive cells in normal control group,IUGR group and IUGR+Taurine group were (72. 19 ± 0. 82)%,(74. 87 ± 0. 67)% and(71. 68 ± 0. 92)%,respectively;and the differences were statistically sig-nificant(F＝49. 103,44. 643,all P<0. 01). Compared with the normal control group,βⅢ-tubulin protein positive cells in IUGR group decreased significantly(P<0. 01),but GFAP positive cells in IUGR group increased significantly (P<0. 01). Compared with IUGR Group,βⅢ-tubulin protein positive cells in IUGR+Taurine group increased sig-nificantly(P<0. 01),but GFAP positive cells in IUGR+Taurine group decreased significantly(P<0. 01). There was no significant difference between groupⅠand groupⅢ(all P>0. 05).(2)The levels of βⅢ-tubulin protein in nor- mal control group,IUGR group and IUGR+Taurine group were 0. 44 ± 0. 02,0. 33 ± 0. 03 and 0. 42 ± 0. 02,respective-ly;and the levels of GFAP protein in normal control group,IUGR group and IUGR+Taurine group were 1. 13 ± 0. 02, 1. 50 ± 0. 04,1. 21 ± 0. 01,respectively;and the differences were statistically significant(F＝45. 191,234. 525,all P<0. 01). Compared with normal control group,the levels of βⅢ-tubulin protein in IUGR group decreased significantly (P<0. 01),but the levels of GFAP in IUGR group increased significantly(P<0. 01). Compared with IUGR group, the levels of βⅢ-tubulin protein in IUGR+Taurine group increased significantly(P<0. 01),but the levels of GFAP in IUGR+Taurine group decreased significantly(P<0. 01). There was no significant difference between normal control group and IUGR+Taurine group(all P>0. 05). Conclusions Taurine can promote the differentiation of NSCs toward neurons in IUGR fetal rats,and maintain the normal proportion of all differentiated cells.

OBJECTIVE: To investigate the prognostic value of preoperative serum tumor markers combined with peripheral blood routine indexes in colorectal cancer patients. METHODS: From January 2010 to March 2013, clinicopathological data of colorectal cancer patients receiving surgery treatment at the Third Affiliated Hospital of Sun Yat-sen University were collected. INCLUSION CRITERIA: (1) histologically confirmed adenocarcinoma; (2) primary cancer resected; (3) intact clinical data; (4) no signs of clinical infection. Patients with intestinal perforation or obstruction, hematological diseases or other malignant tumors were excluded. Informations were recorded containing sex, age, tumor location, degree of differentiation, tumor size, vascular tumor thrombus, nerve invasion, depth of infiltration, lymph node metastasis, distant metastasis, TNM stage, peripheral serum CEA, CA199, number of neutrophil, monocyte, platelet and lymphocyte. Positive CEA was defined as ≥5 μg/L, CA199 as ≥35 U/L; while NLR (neutrophil-to-lymphocyte ratio), MLR (monocyte-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) greater than their cut-off values were defined as positive. ROC curve was used to determine the cut-off values (with greatest area under curve) of NLR, MLR and PLR. The prognostic values of these indexes were analyzed using Kaplan-Meier regression and log-rank test. COX regression was used to perform risk factor analysis. RESULTS: A total of 312 colorectal cancer patients were enrolled, including 192 males and 120 females with median age of 61 (15-85) years. Till March 11, 2018, during median follow-up period of 65 months(2-96), the follow-up rate was 90.4% with loss of 30 cases and the mortality was 37.2% with 116 death. Univariate analysis found that colorectal cancer patients with positive CEA, CA199, NLR (>2.32), MLR (>0.24) and PLR (>164.1) had poor prognosis (all P<0.01). When combining CEA, CA199 with NLR, MLR, PLR, the survival analysis showed that patients with both negative indexes had the best prognosis, one positive the worse and both positive were the worst (all P<0.01). COX regression revealed that CEA(HR= 1.702,95%CI:1.148-2.522, P<0.01), combination of CA199 and MLR (HR=2.292, 95%CI:1.426-3.683, P<0.01) were independent risk factors for colorectal cancer. CONCLUSION Combination of preoperative serum tumor markers and peripheral blood routine indexes can provide prognostic information for the patients with colorectal cancer.
Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Blood Platelets ; Colorectal Neoplasms ; blood ; diagnosis ; Female ; Humans ; Lymphocytes ; Male ; Middle Aged ; Neoplasm Staging ; Neutrophils ; Prognosis ; Retrospective Studies

Toll-like receptor recognizes the pathogens , activates the innate immunity and plays an important role in infectious diseases.Researchers have focuses on the pathway of Toll-like receptor and developed a series of related drugs to seek new therapy for infectious diseases .This article reviews the research progress on Toll-like receptor related-preparations in prevention and treatment of infectious diseases.

Objective:To investigate the expression levels of PPARα/γin RAW264. 7 cells in the early stages of co-cultivation with Echinococcus granulosus in vitro. Methods:RAW264. 7 cells were co-cultured with E. granulosus and collected at 12,24,36,48, 72 h. The mRNA levels of PPAR-γ,PPAR-α,M1 macrophages-associated cytokines including TNF-α,MCP-1 and IL-1β,and M2 mac-rophages-associated cytokines including Arg-1,TGF-β and Fizz-1 were detected by qRT-PCR. The protein levels of Arg-1 and MR were analyzed by ELISA. Results:The expression levels of PPAR-γ, PPAR-αand the M2 macrophages-associated cytokines including Arg-1,TGF-β,Fizz-1 and MR were significantly increased,especially at 72 h (P<0. 05). M1 macrophages-associated cytokines including TNF-α,MCP-1 and IL-1β were decreased at 72h although increased at first. Conclusion:During the early stages of co-cultivation with Echinococcus granulosus in vitro, the levels of PPAR-γ/α are up-regulated in RAW264. 7 cells, which may drive macrophage polarization and play a role in the immune escape.

Objective:To observe the effect of protoscolex on Th subsets and correlative cytokine in mice spleen cells in vitro.Methods:Co-culture spleen cells from BALB/c mice with protoscolices,then IL-4,IFN-γand TGF-βproduction in cell culture supernatants were analyzed by ELISA.The percentage of Th subsets were detected by Flow Cytometry analysis.Results:Secretion levels of IL-4 and TGF-βwere significantly increased in spleen cells at different time point in co-culture system with protoscolices.Ratios of Th2 and Treg cells were also significantly increased in co-culture system at different time points than the control groups.However,there was no statistical significance for ratio of Th1 cells at different time points.Conclusion:The protoscolex can increase the ratios of Th2 cells and Treg cells from spleen cells.Secretion levels of IL-4 and TGF-βwere also increased in spleen cells co-cultured with protosco-lices.The results suggest that these Th cell subsets play a role in the immune escape of the hydatid disease.