Inhibitor of DNA binding 1 (ID1) has an aberrantly high expression in multiple cancer tissues, including colon cancer, lung cancer, breast cancer, and so on, which is closely related to cancer aggressiveness and poor clinical outcomes in cancer patients. It has been reported that ID1 maintains colorectal cancer cells (CRCs) stemness traits and contributes to the CRC drug resistance. While, the biological molecular mechanisms have not been fully elucidated. In this research, we found that ID1 upregulates octamer binding transcription factor (OCT4) protein level as well as OCT4 signaling pathway via Western blot, gene set enrichment analysis (GSEA), dual-luciferase reporter assay, and real-time PCR. Through the in vitro sphere formation assay, we found that overexpression of OCT4 reverses the inhibitory effect of knocking down ID1 on CRC sphere formation ability. With the help of JASPAR and GEPIA database, we predicted a novel transcriptional repressor—forkhead box D3 (FOXD3) of OCT4. Finally, by using co-immunoprecipitation (Co-IP), confocal and real-time PCR, we demonstrated that ID1 interacts with FOXD3 to inhibit its transcriptional repression activity and therefore to upregulate OCT4 transcription and OCT4 signaling pathway. In conclusion, this study provides a new theoretical basis for the regulation mechanism of colon cancer stem cells, and the newly found protein-protein interaction of ID1-FOXD3 provides a potential drug target for the therapy of CRC.

Macrophage migration inhibitory factor (MIF) is an enzyme-active pleiotropic cytokine that is expressed in various immune cells and tumor cells. MIF plays diverse roles in inflammation and tumor progression. It acts as a cytokine involved in immune response and inflammatory lesions. Additionally, MIF is closely associated with tumor proliferation, metastasis, and other tumor hallmarks, exerting a multifaceted influence on tumor occurrence and progression. MIF not only functions by being secreted into the extracellular space as a cytokine but can also be localized within the cytoplasm and nucleus, exhibiting diverse biological functions. As MIF in promoting tumor progression becomes increasingly recognized, MIF-based therapeutic strategies have become a hot research topic in oncology. Here, we provide a comprehensive review of MIF with different subcellular localization about their pro-tumoral functions. A better understanding of MIF in tumor biology will bring broader perspectives for the development of novel MIF targeting strategies and give promising direction for future tumor treatments.

To investigate the effect of naringenin on ovariectomy-induced postmenopausal osteoporosis comprehensively and systemically, thirty-two virgin Sprague-Dawley rats about 3-month-old were used and randomly divided into 4 groups: sham control group (Sham), OVX control group (OVX), naringenin treatment group and 17β-estradiol (E2) treatment group. After 12 weeks treatment with different drugs, 24 h urine were collected, organs were weighed and the organ indies were computed. Uterine pathological changes were observed by making paraffin section. Biochemical parameters and bone turnover markers: serum osteocalcin (BGP) and urine deoxypyridinoline (DPD) were analyzed with automatic biochemical analyzer or ELISA assay. Bone mineral density (BMD) and bone mineral content (BMC) were analyzed by DEXA, bone biomechanical properties was measured by three point bending test and the trabecular bone microarchitecture was evaluated by Micro CT. From the results, we can see that: the gaining of weight and the increasing of bone turnover markers such as serum BGP and urinary DPD could be inhibited by naringenin. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture, increase the bone volume, trabecular number and thickness, and decrease the trabecular space. The effects mentioned above were not accompanied with stimulating effects on uterus. Long-term using of naringenin had no obvious influence on other organs and the liver and kidney functions. The study suggests that naringenin had obvious antiosteoporotic effect on ovariectomized rats and it had the potential value for the treatment of postmenopausal osteoporosis.
Amino Acids ; urine ; Animals ; Bone Density ; Disease Models, Animal ; Estradiol ; pharmacology ; Estrogen Antagonists ; pharmacology ; Female ; Flavanones ; pharmacology ; Osteocalcin ; blood ; Osteoporosis ; drug therapy ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Uterus ; pathology

Acute Disease ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Humans ; Infant ; Inpatients ; Insecticides ; poisoning ; Middle Aged ; Organophosphorus Compounds ; Pesticides ; poisoning ; Poisoning ; etiology ; mortality ; therapy ; Risk Factors ; Survival Rate

Based on the analysis of survey results and random interviews on medical students , this paper dis-cussed from the perspective of medical students under the present situation of doctor -patient relationship:satisfied with prescriptions basic medical quality , but there are still a large room to improve;to cure medical ethics appraisal is higher , but still need to strengthen medical ethics education; the parties are still lack of trust in the prescrip-tions;the doctor-patient relationship nervous .And put forward the following countermeasures on how to relieve the strain on the doctor -patient relationship , strengthening medical ethics education , strengthen the study and practice of doctor-patient communication , pay attention to legal consciousness propaganda and training , use media power to improve direction of publit opinion .

OBJECTIVE Study the role of estrogen receptor (ER)in the inhibition of cell viability and differentiation induced by bisphenol A (BPA)in micro mass culture of rat e mbryonic midbrain(MB) cells.METHODS Micro mass cultures of MB were prepared fro m rat e mbryonic midbrain on gestation day 13.MB cells were exposed to BPA (10 -4 ,10 -6 ,10 -8 ,10 -10 ,10 -12 mol·L -1 )for 5 d.Cell viability was assessed by neutral red uptake test.MB differentiation was detected by he matoxylin staining and i mage analysis.In order to observe the role of ER pathway in the toxicity induced by BPA,cell cultures were co-treated with ICI182780 0.1 n mol·L -1 ,ta moxifen 1 n mol·L -1 and BPA 0.1 mmol·L -1 for 5 d, the cell viability and foci differentiation were detected.Moreover,the protein expression levels of ER in normal e mbryonic brain of gestation day 18,testis tissue fro m adult rats and midbrain cells untreated with BPA were investigated by Western blot.The mRNA expression levels of ER in normal e mbryonic brain of gestation day 13 and gestation day 18,ovary and testis tissue fro m adult rats,and midbrain cells un-treated with BPA were investigated by real-ti me PCR.The mRNA expression levels of Notch1 and Hes1 in MB cells treated with BPA 0.1 mmol·L -1 were also detected by real-ti me PCR.RESULTS BPA 0.1 mmol·L -1 could inhibited MB cell viability and foci differentiation.However,this effect could not be reversed by ER antagonist.The protein and mRNA expression levels of ER in e mbryonic brain and MB cells untreated with BPA were found to be extre mly low.In addition,BPA 0.1 mmol·L -1 could inhibited the mRNA expression levels of Notch1 and Hes1 .CONCLUSION BPA could inhibited MB cell viability and foci differentiation.ER pathway might be not involved in this effect.Instead,Notch-Hes pathway might be involved for this effect.

Objective To evaluate the sensitivity and specificity of different HbA1C cutoff points for diabetes diagnosis in high risk outpatients in Harbin.Methods A total of 2 122 high risk outpatients(male 1 032 and female 1 090)for diabetes screening in the Fourth affiliated Hospital of Harbin Medical University from April 2013 to February 2015 were included in this study, with the average age of(49.26±13.00)year. Oral glucose tolerance tests(OGTT)were conducted and HbA1C levels were examined in these patients. The sensitivity and specificity of different HbA1C cutoff points were calculated and a receiver operator characteristic(ROC)curve was then built.Results The average level of HbA1C in these subjects was(6.45±1.72)%. The prevalence of diabetes was 41.85%. The area under ROC curve(AUC)was 0.89 with the optimal cutoff point of HbA1C 6.0% and 0.68 for the highest Yonden index. The sensitivity and specificity of HbA1C 6.0% were 84.01% and 83.67% respectively. The sensitivity and specificity of HbA1C 6.5% were 62.84% and 95.92%, respectively. The AUC of HbA1C≥6.5% was 0.732. Conclusion HbA1C works well as the diagnostic standard for diabetes in high risk outpatients of Harbin city. The cutoff point of HbA1C 6.0% is suitable for screening diabetes in high risk population, and HbA1C 6.5% is appropriate for diabetes diagnosis, with high sensitivity and specificity.

Objective To analyze the characteristics of pain in children with spastic and dyskinetic cerebral palsy,and to explore the influence of pain on the functional independence and rehabilitation. Methods A self-made Pain Questionnaire for Children with Cerebral Palsy was used to conduct a questionnaire survey on 125 children who were diagnosed as spastic and dyskinetic cerebral palsy from January to October,2017,and the returned questionnaires were analyzed.According to the pain questionnaires,the subjects were divided into pain group(n=40)and no pain group(n=85).Then,15 cases of spastic cerebral palsy and 15 cases of dyskinetic cerebral palsy were selected in each group.Both of them received routine rehabilitation.They were assessed with Gross Motor Function Measure-88(GMFM-88),Fine Motor Function Measure(FMFM)and Wee Functional In-dependence Measure(WeeFIM),and the adductor angle,popliteal angle and foot dorsiflexion angle were record-ed before,and four weeks and eight weeks after treatment. Results The pain characteristics of spastic and dyskinetic cerebral palsy were different.Four weeks and eight weeks af-ter treatment,all the indexes improved in both groups(P<0.01).There was no significant difference in all the in-dexes before and four weeks after treatment between two groups (t<1.732, P>0.05), however, all the indexes were significantly better in the no pain group than in the pain group eight weeks after treatment (t>2.119, P<0.05). Conclusion The pain characteristics are different in children with spastic and dyskinetic cerebral palsy.The pain may af-fect their rehabilitation and functional independence.

Objective To investigate the success rate and safety of transcranial electrical stimulation motor evoked potentials (TES-MEP) and somatosensory evoked potential(SEP) in the monitor of the spinal operation.Methods A total of 98 patients with spinal surgery in our hospital from December 2015 to December 2016 were selected and divided into observation group and control group according to the intraoperative monitoring method,49 cases in each group.SEP conbined with TES-MEP were used in the observation group,and SEP monitoring was used in the control group.Intravenous anesthesia was used in all patients to observe and record the amplitude and latency of SEP and TES-MEP.The results of the two groups were compared with those of the postoperative spinal motor and sensory function and the complications.Results The successful detection rate of the observation group and the control group were respectively 100％ and 91.84％,and the difference was statistically significant(P ＜ 0.05).The sensitivity,specificity and Youden index of the spinal cord movement were significantly higher in the observation group than those in the control group,the difference was not significant(P ＞ 0.05).In addition,the sensitivity,specificity and Youden index of the sensory function were higher than those in the control group,and the differences were statistically significant (P ＜ 0.05).There was no significant difference in postoperation complication between the two groups (P ＞ 0.05).Conclusion SEP combined with TES-MEP in monitoring function changes of the spine during spinal surgery on sensitivity and specificity are higher than the SEP monitoring,which can accurately reflect the function of the spine in the operation state,and provide a good reference for surgery.

OBJECTIVETo explore the mechanism of transcription regulation of the liver-selective genes responsible for cell communication.

METHODSTissue-selective Affymetrix probe sets (3919 probes in total) were clustered by functional categories. Liver-selective cell communication (LSCC) genes were selected for further analysis. The 500-bp upstream sequences of all the LSCC genes were extracted for predicting the transcription factor binding sites (TFBS) of known transcription factors (TFs) using 3 programs; literature mining was then performed for these LSCC genes and TFs, and the transcription regulatory network were constructed.

RESULTSThe binding sites of 50 and 72 transcription factors were predicted from the upstream sequences of 23 LSCC genes by two programs respectively. Among them, 18 transcription factors were found in common. The top 10 TFBS sequences were basically consistent to the predicted TFs. Literature mining indicated that LSCC genes and TFs were closely related to such terms as albumin, diabetes, glucose, lipid, metabolism, and JNK, in addition to those associated with hepatic tissue and TFs. These observations suggested that LSCC genes and TFs were involved in the regulation of glucose and lipid metabolism, binding and transport, coagulation signal cascades, inflammatory response, etc. PPP2R1B, which was out of the network, showed a partial functional similarity to DUSP10 in the network.

CONCLUSIONSLSCC genes and the predicted TFs may be involved in the regulation of many important functions of the liver, which are integrated into a sophisticated transcription regulatory network. JUN may be the key target for regulation, and PPP2R1B is presumed to participate in the regulation of JUN.

Binding Sites ; genetics ; Cell Communication ; genetics ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; genetics ; Humans ; Liver ; cytology ; metabolism ; Models, Biological ; Transcription Factors ; genetics ; Transcription, Genetic