Objective To investigate the effect of Saikosaponin A(SSA)on the differentiation,apoptosis and function of mouse bone marrow derived macrophages(BMDM)-derived M1/M2 macrophages,and to explore its molecular mechanism.Methods BMDM was induced to differentiate into M1/M2 macrophages in vitro,and SSA was added at the same time:CCK-8 assay was used to detect the viability of BMDM and M1/M2 macrophages.The morphology of M1/M2 macrophages was observed by inverted fluorescence microscopy.Flow cytometry(FCM)and ELISA were used to detect the levels of surface markers and cytokines in M1/M2 macrophages.Real-time fluorescent quantitative PCR(qPCR)was used to detect the mRNA levels of IL-6,TNF-α and arginase-1(Arg-1).FCM was used to detect the phagocytosis of peritoneal macrophages to fluorescent microsphere particles.Immunofluorescence(IF)assay and Western blotting were used to detect the molecular mechanism of SSA regulating M1/M2 macrophages.Results No significant effect on viability of M1/M2 macrophages was observed at SSA concentration of 10.0 mg/L,and obvious inhibition was seen at a concentration of 15.0 mg/L(P<0.01).Treatment of 10.0 mg/L SSA induced obvious morphologic changes in M1/M2 macrophages,with M1 macrophages in irregular shape,a few having pseudopods,and some showing unclear boundaries;while some M2 macrophages presenting round or irregular(P<0.001)with unclear boundaries.SSA treatment also resulted in significantly decreased proportion of M1/M2 macrophages after BMDM differentiation(P<0.05),with reduced contents of IL-6 and TNF-α secreted by M1 macrophages and their mRNA levels(P<0.05),but increased secretion of Arg-1 and mRNA levels by M2 macrophages(P<0.05).SSA treatment also inhibited the phagocytosis ability of peritoneal macrophages to fluorescent microsphere particles(P<0.01)in a concentration-dependent manner.SSA decreased the phosphorylation of NF-kappaB(p-NF-κB)(P<0.01)and enhanced the phosphorylation of signal transducer and activator of transcription 6(p-STAT6)in M2 macrophages(P<0.05).Conclusion SSA may affect the differentiation and function of M1/M2 macrophages by regulating NF-κB and STAT6 signaling pathways.

Endometrial cancer is one of the most common malignant tumors in the female reproductive system.Previous studies have shown that the myometrial invasion depth for endometrial cancer affects the treatment choice.MRI is currently the preferred imaging method to assess the myometrial invasion.In recent years,some studies have shown that MRI radiomics has potential value in comprehensively assessing the depth of myometrial invasion in stage I endometrial cancer.This article summarizes the progress of MRI radiomics for myometrial invasion in stage I endometrial cancer.

Endometrial cancer is one of the most common malignant tumors in the female reproductive system.Previous studies have shown that the myometrial invasion depth for endometrial cancer affects the treatment choice.MRI is currently the preferred imaging method to assess the myometrial invasion.In recent years,some studies have shown that MRI radiomics has potential value in comprehensively assessing the depth of myometrial invasion in stage I endometrial cancer.This article summarizes the progress of MRI radiomics for myometrial invasion in stage I endometrial cancer.

Objective To investigate the effect of Angelica polysaccharide(APS)on the differentiation and function of M2 macrophages and underlying molecular mechanism.Methods Mouse bone marrow derived macrophages(BMDM)and M2 macrophages were induced and treated with APS(0,80,160,320 μg/mL);Mouse peritoneal macrophages were isolated and treated with APS(0,160 μg/mL).Flow cytometry(FCM)was used to detect mannose receptor(MR),CD11b,F4/80,CD163,and ARG-1 expression levels,apoptosis,and phagocytic ability of M2 macrophages and peritoneal macrophages.Mice were randomly divided into APS gavage group and control group,APS was intragastrically administered to mice,and macrophage MR expression level in blood and spleen were detected by FCM.Fluorescence microscopy was used to observe the morphology of BMDM-differentiated M2 macrophages.RT-qPCR was employed to detect the mRNA expression levels of MR and ARG-1 in M2 macrophages.Immunofluorescence assay was performed to detect the expression of the proteins related to molecular mechanism of differentiation and function of M2 macrophages.Results Compared with the 0 μg/mL APS group,the MR expression level in the M2 macrophages was decreased with the increase of APS concentration within a certain concentration range(80～320 μg/mL),and the MR expression level in peritoneal macrophages was also decreased in the 160 μg/mL APS treatment group(P＜0.01).The expression level of macrophage MR was also significantly decreased in peripheral blood and spleen in the APS gavage mice than the control group(P＜0.05).Compared with the 0 μg/mL APS group,the expression levels of CD11b,F4/80,and CD163 in the macrophages were increased in the 80～320 μg/mL APS treatment groups(P＜0.01).The morphology of macrophage had changed,from mostly spindle-shaped and pseudopodia to mostly round or irregular,and even a few cells with pseudopodia.APS induced apoptosis in M2 macrophages(P＜0.05).Compared with the 0 μg/mL APS group,M2 macrophages treated with 160 μg/mL APS had an increased ability to phagocytose fluorescent microspheres(P＜0.01),but the expression level of ARG-1 was decreased(P＜0.01).The mRNA expression of MR and ARG-1 in M2 macrophages was decreased(P＜0.05).The mean fluorescence intensity of phosphate acidified-signal transducers and activators of transcription 6(p-STAT6)-positive signals in M2 macrophages was significantly reduced in the 160 μg/mL APS-treated group(P＜0.05).Conclusion APS has bidirectional regulation on the differentiation and function of M2 macrophages,which may be associated with its downregulation of signal transducers and activators of transcription 6(STAT6)signaling pathway.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population of myeloid origin with immunosuppressive function. MDSCs can inhibit the normal immune response of the host to tumor by inhibiting the activity of T cells, natural killer cells, macrophage, B cells, and promoting the proliferation of Treg and other mechanisms. Therefore, MDSCs are potential targets for tumor immunotherapy. However, whether immunotherapy or other treatments, the effectiveness of monotherapy is limited, so immunotherapy combined with other treatments is a breakthrough combination. In recent years, immunotherapy combined with other treatments has shown initial results, with better results than monotherapy. It has become a research hotspot in tumor treatment and a new treatment method in the future. This article summarized the research progress on the effects of immunotherapy combined with chemotherapy, radiotherapy, Chinese herbal extract and Immunotherapy combination on MDSCs, in order to provide theoretical support for the clinical application of immunotherapy based combined tumor treatment measures.

Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-

Objective To investigate the differences in the condylar position of subjects with skeletal class Ⅰ and skeletal class Ⅱ. To provide a basis of diagnosis and treatment. Methods Group A was composed of 50 subjects with skeletal class Ⅰ(27 males and 26 females; age range=18 years to 30 years; mean age=26 years). Group B comprised 50 subjects with skeletal class Ⅱ(24 males and 26 females; age range=18 years to 28 years; mean age=25 years). The condylar position and the shapes of the condyle and the glenoid fossa were linearly measured on the sagittal and coronal sections by cone-beam computed tomography (CBCT). Data were analyzed by SPSS 19.0. Results No statistically significant differences were found in the measurements of the condylar position between the sides of each group on the sagittal plane and the coronal plane (P>0.05). There were significant differences on the anterior space and the posterior space between group A and B (P<0.05). The A/P joint space ratio of group A was larger than that of group B (P<0.05). Conclusion The subjects of skeletal class Ⅰ show an anterior condyle position. The subjects of skeletal class Ⅱ show a posterior condyle position.

OBJECTIVETo investigate the differences in the condylar position of subjects with skeletal class I and skeletal class II. To provide a basis of diagnosis and treatment.

METHODSGroup A was composed of 50 subjects with skeletal class I (27 males and 26 females; age range = 18 years to 30 years; mean age=26 years). Group B comprised 50 subjects with skeletal class II (24 males and 26 females; age range = 18 years to 28 years; mean age=25 years). The condylar position and the shapes of the condyle and the glenoid fossa were linearly measured on the sagittal and coronal sections by cone-beam computed tomography (CBCT). Data were analyzed by SPSS 19.0.

RESULTSNo statistically significant differences were found in the measurements of the condylar position between the sides of each group on the sagittal plane and the coronal plane (P > 0.05). There were significant differences on the anterior space and the posterior space between group A and B (P < 0.05). The A/P joint space ratio of group A was larger than that of group B (P < 0.05).

CONCLUSIONThe subjects of skeletal class I show an anterior condyle position. The subjects of skeletal class II show a posterior condyle position.

Adolescent ; Adult ; Cone-Beam Computed Tomography ; Face ; Female ; Humans ; Male ; Mandibular Condyle ; Temporomandibular Joint ; Young Adult

Aim To investigate the behavioral changes of the pain related neuromodulation and neurotransmission in peripheral and central nervous systems in rats with trigeminal neuralgia (TN)and provide a disease relevant animal model for mecha-nism study of TN.Methods The male SD rats were randomly divided into sham operation group and TN surgical group.The latter group was further divided into model group and gabapentin group (100 mg · kg-1 ). TN was induced by intravenous erythrosine B injection and laser irradiation.The pain behavior of rats was evaluated using mechanical pain threshold measured with Von Frey hairs.Fluorescence quantitative PCR technique was deployed to study the change of Tac1 mRNA expressions in trigeminal ganglia.Utilizing microdialysis technique followed by high performance liquid chromatography fluorescence detection (HPLC-FLD),the extracellular striatum fluid was collected and glutamate(Glu)concentration was determined.Results In the model group,the average mechanical pain threshold in facial ar-ea innervated by the trigeminal nerve remained below 4g after 7 days post surgery.The mechanical threshold of the model group (1.63 ±1.27)g was significantly lower (P<0.01)than the control group (24.17 ±4.49)g on day10 post surgery.In gen-eral,the mechanical withdraw threshold was decreased from the preoperative value of 26g to the postoperative value of (1.60 ± 1.74)g (P<0.01),and maintained stable at (0.71 ±1.24) g during the whole dynamic monitoring period from day7 to day60.The successful rate of this model was 63%.After sur-gery,Tac1 mRNA expression in trigeminal ganglia and extracel-lular Glu levels in striatum were significantly up-regulated (P<0.05 ) in the model group. Animals receiving Gabapentin showed significant improvement in pain symptoms,as well as re-ductions of Tac1 mRNA expression in trigeminal ganglia and ex-tracellular Glu concentration in striatum (P<0.05 ).Conclu-sions The above described photochemically induced TN rat model can partially mimic the clinical TN symptoms and its pathophysiology.Considering its overall high stability,it is very likely that this model could be used in preclinical mechanism study or drug screening of TN.

Objective To investigate the expression of CD26 (dipeptidyl peptidase 4) in the kidney tissues of diabetic rats and the effects of mycophenolate mofetil (MMF) on the renal CD26 expression.Methods Wistar rats were randomly divided into three groups:normal control group (NC group,n=7),diabetic model group (DM group,n=7) and MMF-treated group (MMF group,n=7).Wistar rats were fed with high-sucrose-high-fat diet and injected with streptozotocin into abdominal cavity to induce diabetes.Sixteen weeks later,blood glucose (BG),blood urea nitrogen (BUN),serum creatinine (Scr),renal hypertrophy index (kidney weight]body weight) and 24 hour urinary protein (24Upro) were measured.The number of CD37CD4+ T cells in renal tissues were measured through flow cytometry.The expression of CD26 in kidney was examined by using Western blotting and immunohistochemistry.Results Compared with NC group,BG,BUN,Scr,kidney weight/body weight,24Upro were significantly increased in DM group (P ＜ 0.05).Except BG and kidney weight] body weight,the above-mentioned parameters were lower in MMF group compared with that in DM group (P ＜ 0.05).Intrarenal CD37CD4+ T cells were significantly up-regulated in DM group compared with that in NC group (P ＜ 0.01).CD26 in renal tissue was mainly expressed in T lymphocytes of renal interstitium.CD26 expression in DM group was significantly higher than that in NC group,and also higher than that in MMF group (P ＜ 0.05).In DM group,CD26+ T lymphocytes infiltration of renal interstitium was positively correlated with 24Upro (r2=0.770,P ＜ 0.05).Conclusions CD26 is related with diabetic nephropathy.MMF maybe inhibit T lymphocytes infiltration to reduce the expression of CD26 in renal interstitium,thus protecting the kidney function.