Objective To construt and validate a risk prediction model for hepatocellular carcinoma(HCC)in patients with chronic liver disease based on age-male-ALBI-platelets(aMAP)score combined with RAR and PIV.Methods A total of 143 patients with chronic liver disease were divided into the HCC group(32 cases)and the non-HCC group(111 cases)according to whether HCC occurred.General clinical data,aMAP score and peripheral blood indicator level were compared between two groups.Multivariate Logistic regression was used to analyze influencing factors of HCC in inpatients with chronic liver disease.A nomogram risk prediction model was constructed and validated.Results Compared with the non-HCC group,there were higher age,higher proportion of males,higher levels of total bilirubin(TBIL),red blood cell distribution width(RDW),neutrophil count(NEU)and monocyte count(MON),lower levels of albumin(ALB)and lymphocyte count(LYM),higher levels of aMAP score,RDW to ALB(RAR)and pan-immune inflammation value(PIV)in the HCC group(P＜0.05).Multivariate Logistic regression showed that higher levels of aMAP score,RAR and PIV were independent risk factors for HCC in inpatients with chronic liver disease(P＜0.05).The area under receiver operator characteristic(ROC)curve(AUC)of the nomogram risk prediction model constructed based on above factors was 0.823(95%CI:0.747-0.899).The calibration curve showed that the predicted value was basically consistent with the actual observed value,and the Brier score was 0.125.The decision curve showed that the model had a clear positive net benefit.The AUC of internal validation of the prediction model by Bootstrap method was 0.823(95%CI:0.820-0.825),indicating that the model had a good degree of differentiation.Conclusion The nomogram risk prediction model based on aMAP score,RAR and PIV showed a good predictive performance of HCC in patients with chronic liver disease,which could benefits the individualized treatment and follow-up.

Objective To analyze the correlation between ferroptosis and post operative cognitive dysfunction(POCD)in elderly patients with fractures.Methods A total of 120 elderly patients with fracture were divided into the control group and the POCD group according to whether POCD occurred,with 60 cases in each group.Basic data of the two groups were collected.The levels of nerve injury indicators[brain myelin basic protein(MBP),glial fibrillary acidic protein(GFAP)],and fractures markers[glutathione peroxidase 4(GPX4),cyclooxygenase 2(COX2),long-chain acyl-CoA synthase 4(ACSL4)]were detected by enzyme-linked immunosorbent assay at 6 h after surgery.Logistic regression was used to analyze risk factors of POCD in elderly patients with fracture.The correlations between MBP,GFAP and GPX4,COX2 and ACSL4 were analyzed by Pearson correlation analysis.Receiver operating characteristic(ROC)curves were used to analyze predictive values of MBP,GFAP,GPX4,COX2 and ACSL4 levels to POCD.Results The age,proportion of general anesthesia,anesthesia time,intraoperative blood loss and MBP,GFAP,COX2,ACSL4 levels were higher in the POCD group than those in the control group(P＜0.05),while GPX4 was lower than that in the control group(P＜0.05).The levels of MBP and GFAP were negatively correlated with levels of GPX4 in elderly patients with fractures,and positively correlated with levels of COX2 and ACSL4(P＜0.05).Advanced age,general anesthesia,long duration of anesthesia,increased levels of MBP,GFAP,COX2 and ACSL4,and decreased level of GPX4 were independent risk factors for POCD in elderly fracture patients(P＜0.05).The critical values of GPX4,COX2 and ACSL4 for predicting POCD in elderly patients with fractures were GPX4≤23.05 μg/L,COX2≥20.35 μg/L and ACSL4≥237.85 μg/L,and the AUC were 0.869,0.736 and 0.841.The sensitivity was 76.67%,68.33%and 88.33%,and the specificity was 86.67%,78.33%and 75.00%,respectively.The diagnostic efficacy of GFAP,COX2 and ACSL4 was higher than that of MBP and GFAP.Conclusion The incidence of POCD in elderly patients with fracture is associated with ferroptosis,and levels of GPX4,COX2 and ACSL4 have certain predictive value for the incidence of POCD after surgery in elderly patients with fracture.

Objective To investigate the clinical efficacy of stellate ganglion block(SGB)combined with nicergoline in patients with dysphagia after stroke.Methods A total of 104 patients with dysphagia after stroke were randomly divided into the observation group and the control group.The observation group was treated with niergoline and SGB,while the control group received functional electrical stimulation.The total effective rate,swallowing condition,inflammatory factor level and adverse events were compared between the two groups.Results After treatment,the total effective rate was significantly higher in the observation group(92.31%)than that of the control group(73.08%,P＜0.05).The level of interleukin-6(IL-6),the standardized swallowing assessment(SSA)score and the level of tumor necrosis factor alpha(TNF-α)were significantly lower in the observation group than those in the control group(P＜0.05).The Mann swallowing ability assessment scale(MASA)score was significantly higher in the observation group than that of the control group(P＜0.05).There were no significant differences in adverse reactions such as glottis closure and laryngeal spasm between the two groups(P＞0.05).Conclusion The combined treatment of SGB and nicergoline can effectively improve swallowing function in patients with dysphagia after stroke,with good safety,ideal results and high clinical application value.

Nausea and vomiting are the most common adverse reactions of chemotherapy.In recent years,with the progression of palliative and supportive care,the prevention and control rate of chemotherapy induced nausea and vomiting(CINV)have been effectively improved.However,a small number of CINV still cannot be controlled satisfactorily or recurrence after receiving CINV prevention and treatments,which gradually develops into refractory CINV.Refractory CINV is a very difficult problem in the field of supportive care,which seriously affects the quality of life of patients,chemotherapy progress and prognosis.Therefore,Tianjin Anti-Cancer Association Committee of Rehabilitation and Palliative Care and Tianjin Medical Doctor Association Committee of Tumor Multidisciplinary Diagnosis and Treatment(MDT)organized experts to formulate a Tianjin expert consensus on the prevention and treatment of refractory CINV.The concept of refractory CINV,prevention and treatment strategies,specific medication guidance,traditional Chinese medical treatments,nursing and MDT management are summarized.Meanwhile,the corresponding recommendations are also given in order to provide more reference for improving the prevention and treatment of refractory CINV.This consensus only provides academic guidance for refractory CINV,the specific implementation plans need to be determined based on actual clinical conditions.

Objective To explore effects of protein tyrosine phosphatase receptor type R(PTPRR)on malignant biological behavior of glioma cells.Methods UALCAN website was used to analyze the expression of PTPRR in glioma samples from the Cancer Genome Atlas(TCGA)database.The fresh brain glioma tissue samples of 20 patients with glioma and normal brain tissue samples of 20 patients with traumatic cerebral hemorrhage removed during operation were obtained.Human glioma cell line and human astrocyte cell line were cultured.U87 cells were respectively transfected with PTPRR over-expression plasmid pcDNA3.1/PTPRR(pcDNA3.1/PTPRR group)and blank control plasmid pcDNA3.1(pcDNA3.1 group).The expression of PTPRR mRNA in different glioma cell lines and glioma tissue samples were detected by quantitative real-time PCR.Cell activity was detected by CCK-8 assay.Cell proliferation capacity was detected by colony formation assay.Cell migration and invasion ability were detected by transwell assay.Meanwhile,the cell apoptosis experiment was performed.Results The result of UALCAN database analysis indicated that the expression of PTPRR in glioma was lower than that in normal brain tissue,and the expression of PTPRR was lower in high grade gliomas than that of low grade gliomas.The survival time of glioma patients with low/medium PTPRR expression was shorter than that of patients with high PTPRR expression.The result quantitative real-time PCR showed that the expression levels of PTPRR mRNA in different glioma cell lines and glioma tissue were decreased.CCK-8 assay showed that the cell viability at 24 h and 48 h after over-expression of PTPRR was decreased respectively compared with the pcDNA3.1 group.Results of colony formation assay,Transwell migration and invasion assays showed that the number of colony formation,migration and invasion ability of glioma cells after over-expression of PTPRR were lower than the pcDNA3.1 group.The result of apoptosis experiment showed that the apoptosis rate of glioma cells after over-expression of PTPRR was increased compared with that of the pcDNA3.1 group.Conclusion The expression of PTPRR in glioma is lower.PTPRR acted as a tumor suppressor gene inhibits the activity,proliferation,migration and invasion of glioma cells,and promotes glioma cell apoptosis.

Objective To explore the mechanism of excessive mechanical stress regulated ferroptosis induced by Piezo1 channel in mouse chondrocytes.Methods The experiment was performed on mouse ATDC5 chondrocytes.siRNA-Piezo1 interference plasmid and Piezo1 overexpression plasmid were used to transfect chondrocytes,and mechanical stress stimulation was given.The control group,the mechanical stress stimulation group(MS group),the MS+siRNA-Piezo1 group(MS+sh group)and the MS+Piezo1 overexpression group(MS+OV group)were constructed,respectively.The cell viability,Fe2+,ROS levels,the expression of ferroptosis-related proteins SLC7A11 and GPX4,and the expression of Collagen Ⅱ,MMP-13,Aggrecan and p53 proteins were detected in each group.Results Compared with the control group,the cell viability was decreased in the MS group(P＜0.05).Levels of Fe2+,reactive oxygen species(ROS)and malondialdehyde(MDA)were increased(P＜0.05).Levels of reduced glutathione(GSH)and superoxide dismutase(SOD)were decreased(P＜0.05),and the mitochondrial ridge was decreased detected by transmission electron microscopy.Protein levels of SLC7A11,GPX4,Collagen Ⅱ and Aggrecan were decreased(P＜0.05),while protein levels of p53 and MMP-13 were increased(P＜0.05).Compared with the MS group,Fe2+,ROS and MDA levels were decreased in the MS+sh group(P＜0.05),GSH and SOD levels were increased(P＜0.05),and protein levels of SLC7A11,Collagen Ⅱ,GPX4 and Aggrecan were increased(P＜0.05).The protein levels of MMP-13 and p53 were decreased(P＜0.05).Compared with the MS group,cell viability was decreased(P＜0.05),Fe2+,ROS and MDA levels were increased(P＜0.05),GSH and SOD levels were decreased(P＜0.05),and protein levels of SLC7A11,Collagen Ⅱ,GPX4 and Aggrecan were decreased in the MS+OV group(P＜0.05).Levels of MMP-13 and p53 protein were increased(P＜0.05).Conclusion Excessive mechanical stress can induce chondrocyte ferroptosis and promote extracellular matrix degradation via Piezo1 channel protein.

Objective To explore the effects of Magu Xujin capsule on hip fracture healing and stromal cell-derived factor-1/CXC chemokine receptor 4(SDF-1/CXCR4)signaling pathway in elderly hip fracture rats.Methods The hip fracture model of aged rats was established,and successfully modeled rats were randomly separated into the model group,the low-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule+pathway inhibitor group(the high-dose Magu Xujin capsule and AMD3100 group),with 12 rats in each group.An additional 12 healthy rats were selected as the control group.X-ray was used to observe the healing of hip fractures in rats,and Garrett score was performed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of inflammatory factors related to fracture healing,such as tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10).CT scanning analysis was used to determine bone volume fraction(BV/TV)and bone surface area/volume ratio(BS/BV).Immunohistochemistry was applied to detect the expression of fracture healing factor insulin-like growth factor-1(IGF-1)and bone morphogenetic protein-2(BMP-2).Western blot assay was applied to detect the expression of SDF-1/CXCR4 signaling pathway related proteins.Results Garrett score,IL-10 level,BV/TV,BS/BV,the IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the model group than those in the control group,while TNF-α level was higher(P＜0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were higher in the low-dose and high-dose Magu Xujin capsule groups than those in the model group,while TNF-α level was lower(P＜0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the high-dose Magu Xujin capsule+AMD3100 group than those in the high-dose Magu Xujin capsule group,while TNF-α level was higher(P＜0.05).Conclusion Magu Xujin capsule can promote hip fracture healing in aged rats,and its mechanism may be related to the activation of SDF-1/CXCR4 signaling pathway.

Objective To explore effects and action mechanism of Fu Fang Ku Shen Zhu She Ye on adverse reactions of 5-fluorouracil(5-FU)chemotherapy in rats with liver cancer.Methods The rat model of liver cancer was constructed by diethylnitrosamine(DEN).Model rats were divided into the liver cancer group,the chemotherapy group and the chemotherapy+Fu Fang-L/M/H groups.At 24 h after modeling,the chemotherapy group and the chemotherapy+Fu Fang groups were given intraperitoneally injection of 5-FU(100 mg/kg,once/week),and the chemotherapy+Fu Fang-L/M/H groups were given intraperitoneally injection of Fu Fang Ku Shen Zhu She Ye[0.7,1.4 and 2.8 mL/kg,once/d]for 8 weeks.The cardiac function,myocardial injury markers and pathological changes of myocardial tissue were compared between different groups.Serum levels of brain natriuretic peptide(BNP),cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)were detected by enzyme-linked immunosorbent assay.The expression levels of glucose-regulating protein 78(GRP78),activating transcription factor 6(ATF6)and endoplasmic reticulum stress-related protein(CHOP)in myocardial tissue were detected by Western blot assay.Changes of immune function indexes were compared between different groups.Results Compared with the liver cancer group,left ventricular ejection fraction(LVEF)and left ventricular anterior wall thickness in systole(LVAWs)were decreased in the chemotherapy group(P＜0.05),left ventricular end diameter in systole(LVEDs),levels of BNP,cTnI and CK-MB were increased(P＜0.05),levels of tumor necrosis factor α(TNF-α),interleukin(IL)-1β and IL-6 in myocardial tissue,expression levels of GRP78,ATF6 and CHOP were increased(P＜0.05).Levels of CD3+,CD4+,CD4+/CD8+,IgG,IgM and IgA were decreased in the chemotherapy group(P＜0.05).The myocardial tissue was disordered,vacuolated and infiltrated by inflammatory cells.Compared with the chemotherapy group,the above indexes and pathological changes of myocardial tissue were significantly improved in the chemotherapy+Fu Fang-L/M/H groups,and the improvement was more significant in the chemotherapy+Fu Fang-H group.Conclusion Fu Fang Ku Shen Zhu She Ye injection can alleviate cardiotoxic injury induced by 5-FU in rats with liver cancer,which may be related to alleviating endoplasmic reticulum stress.It can also alleviate immunosuppression.

Objective To elucidate the mechanistic role of bone marrow mesenchymal stromal cells(BM-MSCs)in T-cell acute lymphoblastic leukemia(T-ALL),and to find effective therapeutic strategies targeting BM-MSCs.Methods A T-ALL mouse model induced by Notch-1 overexpression was constructed.An in vitro co-culture system was established to investigate the proliferative capacity of T-ALL cells upon co-culturing with leukemia-derived MSCs.RNA sequencing was performed to identify key differentially expressed genes,which were further validated by PCR.BGJ398 was injected into mice to detect tumor growth.Results Co-culturing with T-ALL-derived MSCs resulted in a significant increase in T-ALL cell proliferation.RNA sequencing results revealed that the secretion of fibroblast growth factor 2(FGF2)from T-ALL-derived MSCs was increased,which binds to fibroblast growth factor 2 receptor(FGFR2)on T-ALL cells,activating the PI3K/AKT/mTOR signaling pathway.Blocking the interaction between FGF2 and FGFR2 using BGJ398 inhibited the growth of T-ALL tumors in mice.Conclusion BM-MSCs can promote T-ALL tumor growth through FGF2/FGFR2 pathway,and blocking FGF2/FGFR2 pathway is an effective strategy to overcome BM-MSCS-mediated T-ALL progression.

Objective To investigate the effect and mechanism of nodakenin(Nod)in neuropathic pain(NP).Methods Differential expression genes in the primary somatsensory cortex(S1)of NP data and overlapping genes between the dataset and mitochondrial data were screened and analyzed.Overlapping gene interaction networks were overlapped and core genes were screened.A total of 27 mice were randomly divided into the sham operation group,the model group and the drug administration group(9 mice/group).The chronic compression injury model of sciatic nerve was constructed in the model group and the drug administration group.Nod 10 mg/kg was intraperitoneally injected into the drug administration group for 1 week.Changes of pain behavior and motor ability in mice were detected.HE staining and Nissl staining were used to detect effects of nerve injury and inflammation on brain tissue of S1 region of mice.The expression levels of interleukin-1β,early gene(c-Fos),panthenol-cytochrome c reductase complex III subunit(Uqcrq)and ubiquinone oxidoreductase subunit(Nduf)b5 in S1 brain region were analyzed by Western blot assay.Molecular docking was used to study the target of Nod.PC12 cells were divided into the control group,the IL-1β group(1 μmol/L IL-1β treatment)and the IL-1β+Nod group(1 μmol/L IL-1β+1 μmol/L Nod treatment),and mitochondrial membrane potential was detected in each group.Results In the NP dataset GSE180627,S1 brain region contained 293 differentially expressed genes,and the mitochondrial data contained 1 082 genes.There were 34 overlapping genes,and genes related to oxidative phosphorylation and electron transport chain were enriched.The protein interaction network showed that core genes included electron transport chain related proteins Ndufb5,Uqcrq,Ndufs8,Ndufa7,Ndufa3,Cox6b1 and Mrps33.Compared with the model group,the mechanical foot shrinkage threshold,thermal foot shrinkage reflex latency and rod rotation residence time of mice were increased in the drug administration group,the number of inflammatory infiltrating cells in S1 tissue and the number of Nislet bodies in neurons,expression levels of c-Fos and IL-1β in neurons were decreased,and expression levels of Uqcrq and Ndufb5 were increased(P＜0.05).Molecular docking showed that Nod could bind Uqcrq and Ndufb5.Compared with the IL-1β group,the fluorescence signal of mitochondrial membrane potential was enhanced in the IL-1β+Nod group(P＜0.05).Conclusion Nodakenin can improve pain behavior in mice,and its mechanism involves ameliorating mitochondrial damage in S1.