At present,reforming and innovating the public health talent training model are the challenges that the construc-tion of new medical in our country.Medical Immunology is the initial driving force in preventive medicine.Based on the course con-struction of Medical Immunology and centering on the core link of post competency of preventive medicine undergraduates,this study comprehensively reshapes the course system of Medical Immunology from the aspects of theoretical courses,practical courses,experi-mental courses,ideological and political courses and assessment methods,so as to provide reference for improving the teaching quality of preventive healthcare undergraduates.

At present,reforming and innovating the public health talent training model are the challenges that the construc-tion of new medical in our country.Medical Immunology is the initial driving force in preventive medicine.Based on the course con-struction of Medical Immunology and centering on the core link of post competency of preventive medicine undergraduates,this study comprehensively reshapes the course system of Medical Immunology from the aspects of theoretical courses,practical courses,experi-mental courses,ideological and political courses and assessment methods,so as to provide reference for improving the teaching quality of preventive healthcare undergraduates.

Objective:To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies.Methods:A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated.Results:Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction ( P < 0.05). Conclusion:It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

Objective To investigate the effect of human colorectal fibroblast(CCD-18Co)-conditioned medium(CCD18-Co-CM)on biological behaviors of colorectal cancer(CRC)cells and explore the possible molecular mechanisms.Methods Real-time cellular analysis(RTCA),clone formation assay and wound healing assay were used to analyze the changes in proliferation,clone formation,and migration abilities of CRC cell lines HCT116 and Caco-2 treated with CCD18-Co-CM.Western blotting was used to detect the changes in ATK,ERK and STAT3 signaling pathways in the CRC cells activated by CCD18-Co-CM.The effect of CCD18-Co-CM on spheroidization ability of the cells was assessed with sphere-formation assay,and the changes in expressions of CRC stemness markers were detected using RT-PCR.Results CCD-18Co-CM significantly promoted proliferation,colony formation,and migration of HCT116 and Caco-2 cells,enhanced sphere-forming ability and expressions of CRC stemness markers,and increased ERK phosphorylation in the cells.Treatment with SCH772984 effectively inhibited CCD-18Co-CM-induced ERK signaling pathway activation,suppressed the malignant phenotype,and lowered the sphere-forming ability and expression of stemness markers of the two CRC cells.Conclusion Colorectal fibroblasts promote malignant phenotype of CRC cells by activating the ERK signaling pathway.

Objective To investigate the effect of human colorectal fibroblast(CCD-18Co)-conditioned medium(CCD18-Co-CM)on biological behaviors of colorectal cancer(CRC)cells and explore the possible molecular mechanisms.Methods Real-time cellular analysis(RTCA),clone formation assay and wound healing assay were used to analyze the changes in proliferation,clone formation,and migration abilities of CRC cell lines HCT116 and Caco-2 treated with CCD18-Co-CM.Western blotting was used to detect the changes in ATK,ERK and STAT3 signaling pathways in the CRC cells activated by CCD18-Co-CM.The effect of CCD18-Co-CM on spheroidization ability of the cells was assessed with sphere-formation assay,and the changes in expressions of CRC stemness markers were detected using RT-PCR.Results CCD-18Co-CM significantly promoted proliferation,colony formation,and migration of HCT116 and Caco-2 cells,enhanced sphere-forming ability and expressions of CRC stemness markers,and increased ERK phosphorylation in the cells.Treatment with SCH772984 effectively inhibited CCD-18Co-CM-induced ERK signaling pathway activation,suppressed the malignant phenotype,and lowered the sphere-forming ability and expression of stemness markers of the two CRC cells.Conclusion Colorectal fibroblasts promote malignant phenotype of CRC cells by activating the ERK signaling pathway.

Objective To evaluate the efficacy and adverse reactions of BRAF inhibitor vermorafenib on the treat-ment of refractory craniopharyngioma carrying BRAF-V600E mutation.Methods Clinical data of two patients with refractory craniopharyngiomas(CP)were recorded and reviewed.The patients were followed up for 3-5 years.Lit-erature on CPs receiving BRAF or BRAF/MEK therapy was reviewed.Results 1)Papillary CP progressed after multiple operations and radiotherapy in two patients.Further treatments were very difficult.2)The presence of BRAF-V600E mutation in the tumor was confirmed,and vermorafenib was administered for 6.5-7.5 months.Tumor volumes remarkably shrank by 95%-99%.No tumor relapse was observed during the follow-up of 3-5 years after discontinuation of vemurafenib.3)The main adverse reaction was rash,which was dose dependent.4)Litera-ture review showed the volume shrank by 50%-100%in 33/34 tumors during BRAF or BRAF/MEK inhibitor therapy.Conclusions BRAF inhibitor vemurafenib is effective in treating refractory craniopharyngioma carrying BRAF-V600E mutation with endurable side effects,which may bring some changes to the management of CP in future.

AIM:To explore the molecular mechanism by which leukemia inhibitory factor(LIF)enhances the stemness characteristics of colorectal cancer(CRC)cells by regulating the expression of the molecular marker CD44 in cancer stem cells(CSCs).METHODS:The expression of LIF in CRC tissues was analyzed using the TCGA public data-base and RNAscope in situ hybridization method.Stable knockdown of LIF was constructed in CRC cell lines(HCT116 and Caco2 cells)using a lentiviral infection system.The experiment was divided into 4 groups:CRC cells control group,CRC cells plus LIF group,CRC cells knockdown control group,and CRC cells knockdown LIF group.The impact of exog-enous LIF on CRC cells' capacity for spheroidization was assessed through stem cell spheroidization assays.The ability of CRC cells to proliferate and migrate was evaluated using MTT,RTCA,plate cloning,and migration tests following the ad-dition or removal of LIF.The impact of LIF on the expression of the transcription factor ELF3 and CD44 in CRC tumor cells was determined using RT-qPCR,a fully automated protein expression analysis system,and Western blot.RT-qPCR was used to identify changes in CD44 splicing variant expression following LIF knockdown.RESULTS:The results dem-onstrated that the expression level of LIF in CRC tissue was higher than that in neighboring cancer tissue(P<0.01),and that patients with CRC who had high expression of LIF had a shorter disease-free survival time(P<0.05).While LIF knockdown can decrease CRC cells' capability to proliferate and migrate(P<0.05),exogenous LIF can boost CRC cells' sphericity,proliferation,and migration capacity(P<0.05).Exogenous LIF can raise(P<0.05)CD44 expression in CRC tumor cells,however LIF reduction can lower(P<0.01)CD44 expression and lower the transcription level of CD44 splic-ing variants.Exogenous injection of LIF or LIF knockdown can cause a significant change(P<0.05)in the expression lev-el of the transcription factor ELF3.CONCLUSION:LIF improves the stemness characteristics of colorectal cancer cells by upregulating the transcription factor ELF3,which also promotes the development of malignancy by increasing CD44 ex-pression in CRC cells.

Objective:To discussed the regulation role of calcium/calmodulin dependent protein kinase(CaMK4)on γδT cells in the pathogenesis of lupus nephritis.Methods:The proportion of γδT cells in peripheral blood of LN patients and healthy con-trols were compared by flow cytometry.Magnetic bead was used to separation LN patients and healthy controls of gamma delta T cells in peripheral blood.RNA-SEQ analysis were performed in γδT cells of peripheral blood from LN patients and healthy controls.Real-time PCR and western blot were used to verify the expression level of differential gene CaMK4.The expression levels of CD80,CD86 and CD40L on γδT cells treated with CaMK4 inhibitor were detected by flow cytometry.ELISA was used to measure the level of IL-17 secreted by γδT cells after CaMK4 inhibitor treatment.Results:The proportion of γδT cells in the peripheral blood of LN patients was lower than that of healthy control group.A total of 28 differential genes related to LN were screened by RNA-SEQ sequencing,among which CaMK4 had significant by differences at molecular level and protein level.After γδT cells from LN patients were treated with CaMK4 inhibitor,KN-93,the expressions of surface costimulatory molecules CD80,CD86 and CD40L was decreased,and the level of IL-17 also was decreased.Conclusion:CaMK4 regulates γδT cells to participate in the pathogenesis of LN by IL-17 secretion and the expression of costimulatory molecules.Inhibition of CaMK4 may become a new target for the treatment of LN.

Objective:To construct and validate a prediction model for the risk of intermediate cesarean delivery for primiparous women with failed vaginal trial of labor.Methods:Clinical data of 6 128 pregnant women who gave birth in the Affiliated Hospital of Jining Medical College from January 2019 to December 2020 were collected. The puerpera was randomly divided into train set ( n=4 290) and validation set ( n=1 838). The factors influencing the conversion to cesarean section in primiparous women with failed vaginal trial of labor were analyzed with univariate and binary multivariate logistic regression, and a risk prediction model was established based on the influencing factors. The predictive power of the model was assessed by receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness-of-fit test in train set and validation set. Results:Among 6 128 pregnant women 1 042 cases failed in vaginal trial of labor and were transferred to cesarean section. Univariate analysis showed age, occupation, gestational weight gain, days of gestation, body temperature before delivery, fetal heart condition at delivery, fetal abdominal circumference, Bishop score, premature rupture of membranes, gestational illness, mode of induction of labor, labor analgesia, and fetal orientation were significantly associated with converting to cesarean delivery (all P<0.05). The multivariate binary logistic regression analysis showed that the age, gestational weight gain, body temperature, gestational co-morbidities, days of gestation, premature rupture of membranes, amniotic fluid contamination, induction of labor, and abnormal occipital position were independent risk factors for intermediate cesarean delivery ( OR=1.03-8.06, all P<0.05); while height, occupation, Bishop score, and labor analgesia were protective factors for intermediate cesarean delivery ( OR=0.17-0.96, all P<0.05). A risk prediction model was constructed based on the risk factors and protective factors. In train set, the area under the ROC curve(AUC) of the model was 0.902 (95% CI: 0.89-0.92, P<0.001), with the best cutoff value of 0.138, the sensitivity and specificity were 0.837 and 0.825, respectively; and the Hosmer-Lemeshow goodness-of-fit test showed P=0.192. In validation set the AUC of the model was 0.917 (95% CI: 0.90-0.93, P<0.001), and the sensitivity and specificity were 0.826 and 0.851, respectively; the total correct rate of the model was 87.21% (1 603/1 838). Conclusion:The risk prediction model of failed vaginal trial of labor in primiparous women for intermediate cesarean delivery constructed in this study has good clinical prediction efficacy and high correctness rate.

OBJECTIVE: To investigate the mechanism by which conditioned medium of colorectal cancer cells promotes the formation of cancer-associated fibroblasts (CAFs). METHODS: Normal human colorectal fibroblasts (CCD-18Co cells) in logarithmic growth phase were treated with the conditioned media of colorectal cancer HCT116 cells (HCT116-CM) or Caco-2 cells (Caco-2-CM) alone or in combination with 300 nmol/L ERK inhibitor SCH772984. The expression levels of CAFs-related molecular markers were detected in the treated cells with real-time quantitative PCR (RT- qPCR) and immunofluorescence assay, and the changes in cell proliferation, colony formation and migration were assessed with RTCA, colony formation and wound healing assays; Western blotting was performed to detect the activated signaling pathways in the fibroblasts and the changes in CAFs formation after blocking of the signaling pathway. RESULTS: HCT116-CM and Caco-2-CM significantly upregulated mRNA expression levels of CAFs markers (including α-SMA, FAP, FN and TGF-β) in CCD-18Co cells, and strongly promoted fibroblast transformation into CAFs (P < 0.05). The two conditioned media also promoted the proliferation, colony formation and migration of CCD-18Co cells (P < 0.05) and significantly increased the levels of α-SMA protein and ERK phosphorylation in the cells (P < 0.05). The ERK inhibitor SCH772984 obviously inhibited the expression of α-SMA and the transformation of CCD-18Co cells into CAFs induced by the conditioned medium of colorectal cancer cells (P < 0.05). CONCLUSION Colorectal cancer cells may induce the formation of colorectal CAFs by activating the ERK pathway in the fibroblasts.
Humans ; Cancer-Associated Fibroblasts/metabolism* ; Culture Media, Conditioned/pharmacology* ; MAP Kinase Signaling System ; Caco-2 Cells ; Fibroblasts ; Signal Transduction ; Cell Proliferation ; Cell Line, Tumor ; Colorectal Neoplasms/genetics* ; Cell Movement