Research progress on mesenchymal stem cell products and their exosomes in the treatment of inflammatory bowel disease / 中国药科大学学报

@#Abstract: Inflammatory bowel disease (IBD), whose pathogenesis remains elusive, is a group of autoimmune diseases characterized by chronic, progressive, and lifelong inflammation of the digestive tract. The pathogenesis of IBD remains elusive. Although a number of drugs have been developed to treat IBD, their effects are merely anti-inflammatory. In addition, current treatments for IBD are easily susceptible to resistance in clinical practice. Mesenchymal stem cells (MSCs) have been reported to have the ability to migrate to the site of inflammation, with potent immunoregulatory effects, and to rebalance the immune microenvironment and restore the integrity of the epithelial barrier with significant value of application, particularly for patients who are refractory to classic medicines. In this paper, we reviewed the clinical applications, mechanisms and engineerable properties of MSC products and their exosomes to provide some reference for the use of MSCs and their exosomes in the treatment of IBD.

Comparative analysis of domestic Octoparms and imported Celect inferior vena cava filter in interventional treatment of venous thromboembolism / 实用放射学杂志

Objective To compare and analyze the application value of domestic Octoparms and imported Celect inferior vena cava filter(IVCF)in the interventional treatment of venous thromboembolism(VTE).Methods Forty patients with VTE were randomly divided into Octoparms group(experimental group)and Celect group(control group)according to the double-blinded method of the central random system.All the patients underwent filter placement,catheter-directed thrombolysis and filter retrieval.The primary end point was the success of filter placement and retrieval,and the secondary end point included indwelling complications such as the occurrence of pulmonary embolism(PE)and filter tilt and migration.Results Forty patients were enrolled in this study,22 patients and 18 patients were divided into the experimental group and the control group,respectively.Among them,11 cases were identified with right lower extremity deep vein thrombosis,29 cases with left lower extremity deep vein thrombosis,17 cases with PE,and 6 cases with inferior vena cava thrombosis.The success rate of IVCF placement was 100%in all participants.Immediately after filter place-ment,the angle of filter tilt was(3.8±2.3)° in the experimental group and(4.9±2.8)° in the control group(t=1.44,P=0.16).Filter retrieval was successful in 21 cases(21/22,95.5%)of the experimental group and 17 cases(17/18,95.5%)of the control group.There was no significant difference between the two groups(t=0.14,P=0.89).The mean indwelling time of filter was(8.0±2.1)days in the experimental group and(9.7±3.1)days in the control group(t=0.73,P=0.47).The angle of filter tilt was(5.3±3.4)° in the experimental group and(5.7±7.7)° in the control group(t=0.19,P=0.85).There was no significant difference for filter placement and retrieval between the two groups(t=0.48 and 2.00,P=0.06 and 0.64,respectively).There were no complications of filter migration,strut penetration or new PE in both groups.Conclusion The application value of domestic Octoparms and impor-ted Celect IVCF is similar in interventional treatment of VTE.

Clinical application of individualized coil embolization in interventional therapy of renal artery aneurysm / 实用放射学杂志

Objective To explore the clinical application of individualized coil embolization in the interventional treatment of renal artery aneurysm(RAA).Methods Data of 23 patients with RAA treated by individualized coil embolization were analyzed.There were 27 RAAs,in which narrow-necked RAAs were treated with coil embolization and wide-necked RAAs were treated with stent-assisted coil embolization.The efficacy of the two embolization methods were analyzed and the changes of renal function and symptoms were observed.Results A total of 27 RAAs in 23 patients were successfully embolized at one time,including 23 narrow-necked RAAs in 19 cases treated with coil embolization and 4 wide-necked RAAs in 4 patients treated with stent-assisted coil embolization.The embolization effect of 20 cases(86.96%)reached Raymond grade Ⅰ,and 3 cases(13.04%)reached gradeⅡ.Postoperative computed tomography angiography(CTA)showed that all parent arteries were patent,the RAA was not visualized,and there was no renal infarction.There was no statistical difference in creatinine values before operation,1 month,6 months and 1 year after operation(P>0.05).In the 12 patients with hypertension,there were statistically significant differences in blood pressure at 1 year after operation compared with preoperative,1 month,and 6 months after operation(P<0.05).The symptoms of low back pain and hematuria disappeared after operation.Conclusion Individualized coil embolization for RAA is safe,effective and worthy of clinical promotion.

Correlation analysis of preoperative red blood cell distribution width and prognosis of patients undergoing TACE for hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To evaluate the relationship between red blood cell distribution width (RDW) and prognosis of patients with hepatocellular carcinoma (HCC) andergoing transcatheter arterial chemoembolization (TACE).Methods:Clinical data of 212 patients with HCC andergoing TACE for the first time in Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2011 to May 2018 were retrospectively analyzed, including 184 males and 28 females, aged (56.8±11.2) years. Follow-up for survival. X-tile software was used to determine 13.1% as the optimal threshold for preoperative RDW prediction of prognosis, and enrolled patients were divided into a low level group (RDW<13.1%, n=70) and a high level group (RDW≥13.1%, n=142). Aspartate aminotransferase, total bilirubin, albumin, hemoglobin and lipoprotein a, Barcelona clinical liver cancer (BCLC) stage and other indexes were compared between the two groups. Survival analysis was performed by Kaplan-Meier method, survival rate was compared by log-rank test, and the effect of RDW on prognosis was analyzed by Cox regression. Results:The 1-year, 2-year and 3-year cumulative survival rates in RDW high level group were 34.5%, 14.1% and 6.3%, respectively, while those in RDW low level group were 64.3%, 38.6% and 21.4%, respectively, with significant difference ( χ2=23.09, P<0.001). Compared with the low level group, the levels of aspartate aminotransferase and total bilirubin were higher, the levels of albumin, hemoglobin and lipoprotein a were lower, the proportion of portal vein cancer thrombin was higher, and the stage of BCLC was later, with statistical significance (all P<0.05). Cox regression analysis showed that HCC patients with RDW≥13.1%( HR=1.732, 95% CI: 1.223-2.452, P=0.002) had poor survival prognosis after TACE. Conclusion:Preoperative RDW≥13.1% is an independent risk factor for survival after TACE in patients with HCC. RDW has potential predictive value for prognosis of patients with HCC.

Chronic active EB virus infection in a child with the onset of IgA nephropathy / 中华肾脏病杂志

Chronic active Epstein-Barr virus (CAEBV) infection with renal involvement is not common. The paper reported a child of multisystem-compromised CAEBV infection with the onset of IgA nephropathy (IgAN). The child presented with intermittent gross hematuria, and renal biopsy showed focal proliferative IgAN, administered methylprednisolone pulse followed by oral prednisolone treatment. Intermittent increase of blood Epstein-Barr virus (EBV) load and abnormal EBV antibody, pneumonia caused by EBV and Staphylococcus aureus-mixed infection, periappendiceal abscess, and pancytopenia occurred during treatment follow-up. The CAEBV infection was considered. Echocardiography suggested pulmonary hypertension. Head CT presented multiple calcifications in the bilateral basal ganglia. Bone marrow biopsy showed bone marrow EBV-DNA 6.5×10 3 copies per liter. Immunohistochemistry of renal biopsy showed about 50 CD8 + (scattered +) cells per high power field (HPF), about 40 CD4 + (focal +) cells per HPF (local), CD68 + (-), latent membrane protein 1 (-), EBV-encoded small RNA (scattered +) approximately 25 cells per HPF. The lymphocyte subsets infected with EBV showed CD4 + T cells EBV-DNA 3.4×10 4 copies per 1 million cells, CD8 + T cells EBV-DNA 3.3×10 5 copies per 1 million cells, B cells EBV-DNA 1.25×10 4 copies per 1 million cells, NK cells/NK T cells EBV-DNA 2.3×10 4 copies per 1 million cells. The clinical diagnosis was CAEBV infection and EBV-associated IgAN. The patient currently receives oral prednisone treatment, and it is recommended to undergo hematopoietic stem cell transplantation and treatment is under follow up.

Impact of parental efficacy in doctor-patient communication on rehabilitation outcomes for children with autism spectrum disorder / 中国康复理论与实践

ObjectiveTo explore the potential influencing factors and complex pathways affecting rehabilitation effect for children with autism spectrum disorder (ASD) from the perspective of parental efficacy in doctor-patient communication, and to provide evidence for improving the quality of rehabilitation service for children with ASD. MethodsAn anonymous face-to-face questionnaire survey was conducted to collect general demographic information of parents of children with ASD at designated rehabilitation institutions in Gansu province. The data included parental efficacy in doctor-patient communication, parental compliance of treatment and children's rehabilitation outcomes were collected. A structural equation model was used to explore the impact mechanism of parental communication efficacy on the rehabilitation outcomes of children with ASD. ResultsData from 519 parents at 37 rehabilitation institutions across 13 cities/counties in Gansu province were collected. Significant positive correlations were found between parental efficacy in doctor-patient communication, doctor-patient relationships, parental compliance with treatment and rehabilitation outcomes for children with ASD (P < 0.05). Through structural equation model analysis, the standardized direct effect of children with ASD from parents' doctor-patient communication efficacy was 0.151 (P = 0.023). The mediating effect of doctor-patient relationship and parental compliance with treatment were 0.160 (P = 0.001) and 0.111 (P = 0.001), respectively, with a chained mediating effect of 0.035 (P = 0.001). The pathway "parental efficacy in doctor-patient communication → doctor-patient relationship → ASD child's rehabilitation outcome" accounted for the highest proportion of the total mediating effect, at 52.29%. ConclusionParental doctor-patient communication efficacy may positively impact on the rehabilitation outcomes of children with ASD directly, and indirectly through the doctor-patient relationship and parental compliance with treatment. Rehabilitation institutions should focus on fostering parental communication skills and enhancing high-quality and humanized rehabilitation services.

Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Effect of Chaihu Guizhitang on Triple-negative Breast Cancer Cells： Based on HIF-1α/VEGFA Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Chaihu Guizhitang on triple-negative breast cancer （TNBC） cells based on hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor A （VEGFA） signaling pathway. MethodTNBC xenograft model was established and the cells were randomized into model group， capecitabine group （0.2 mg·kg-1）， Chaihu Guizhitang low-dose group， medium-dose group， and high-dose group （10.62， 21.23， 42.46 g·kg-1）， with 10 mice in each group. After 21 days of medication， the content of tumor necrosis factor-α （TNF-α） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The expression of HIF-1α mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction （real-time PCR）. Immunohistochemistry （IHC） was employed to detect the expression of HIF-1α， TNF-α， and VEGFA in tumor tissues， and CD34 staining to examine the angiogenesis in tumor tissues. Microvessel density （MVD） was calculated， and the protein expression of HIF-1α， VEGFA， and epidermal growth factor receptor （EGFR） in tumor tissues was measured by Western blot. ResultCompared with the model group， the rest four groups showed low levels of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， VEGFA， and CD34 in cells， and MVD （P<0.05， P<0.01）， and low protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. Compared with capecitabine group， medium-dose and high-dose Chaihu Guizhitang decreased the level of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， and VEGFA in cells （P<0.01）， CD34 expression， MVD， and protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. ConclusionChaihu Guizhitang may inhibit the angiogenesis in TNBC cells by regulating the expression of HIF-1α/VEGFA signaling pathway， thus exerting anti-tumor effect.

The application of liver shear wave velocity and its correlation with portal vein pressure in evaluating the efficacy of interventional treatment for Budd-Chiari syndrome / 介入放射学杂志

Objective To discuss the application value of liver shear wave velocity(SWV)and its correlation with portal vein pressure in evaluating the efficacy of interventional therapy for Budd-Chiari syndrome(BCS).Methods The clinical data of 40 BCS patients,who were admitted to the Affiliated Hospital of Xuzhou Medical University of China to receive treatment between April 2020 and April 2022,were collected.During interventional procedure,the hepatic venous pressure gradient(HVPG)was determined separately before and after recanalization of the treated vessels,the liver SWV was determined at one day before,2 days,1 month and 3 months after the treatment,and the above indexes were statistically analyzed.Results Successful initial interventional therapy was accomplished in all patients.The preoperative one-day,postoperative 2-day,one-month and 3-month mean liver SWV values were(2.34±0.36)m/s,(1.74±0.36)m/s,(1.62±0.30)m/s,and(1.56±0.28)m/s respectively.The differences in the mean liver SWV between its preoperative value and its postoperative 2-day,one-month and 3-month value were statistically significant(all P＜0.05),and statistically significant difference in the mean liver SWV also existed between postoperative 2-day value and postoperative 3-month value(P＜0.05).The mean HVPG decreased from preoperative(15.19±2.35)mmHg(1 mmHg=0.133 kPa)to postoperative(6.44±1.34)mmHg(P＜0.05).The preoperative one-day liver SWV was positively correlated with preoperative HVPG(r=0.803,P＜0.01).The postoperative 2-day liver SWV also carried a positive correlation with the postoperative HVPG(r=0.844,P＜0.01).The difference value(D-value)between preoperative liver SWV value and postoperative 2-day liver SWV value was(0.59±0.27)m/s,and the D-value between preoperative HVPG value and postoperative HVPG value was(8.75±1.92)mmHg,and a positive correlation existed between the above two D-values(r=0.676,P＜0.01).Conclusion There is a good correlation between liver SWV and HVPG,which can be used to evaluate the postoperative efficacy of BCS patients after receiving interventional therapy.(J Intervent Radiol,2023,32:1178-1183)

The clinical value of preoperative systemic immune-inflammation index in predicting the prognosis of patients with extrahepatic cholangiocarcinoma treated with biliary stenting combined with 125I seeds implantation / 介入放射学杂志

Objective To discuss the clinical value of systemic immune-inflammation index(SII)in predicting the prognosis of patients with extrahepatic cholangiocarcinoma(ECCA)treated with biliary stenting combined with 125I seeds implantation.Methods A total of 128 patients with unresectable ECCA,who received biliary stenting combined with 125I seeds implantation at the Interventional Department of the Affiliated Hospital of Xuzhou Medical University of China between August 2018 and August 2021,were enrolled in this study.The peripheral blood routine testing was performed within 3 days before operation,based on which the SII was calculated.Receiver operating characteristic(ROC)curve was applied to determine the optimal cut-off value of SII,based on which the patients were divided into high-SII group and low-SII group.Cox regression model was used to analyze the independent factors affecting patient prognosis.The Kaplan-Meier curve was plotted to analyze the one-year survival.Results The optimal cut-off value of SII was 1 050,the sensitivity was 66.0％,the specificity was 69.3％,and the area under ROC curve of SII was 0.676.The one-year survival rate of patients with ECCA in the high-SII group was significantly lower than that in the low-SII group(P＜0.05).Univariate Cox regression analysis indicated that vascular invasion,T stage,adjuvant chemotherapy,CA19-9,and preoperative SII were the important factors affecting the prognosis of patients with ECCA.Multivariate Cox regression analysis revealed that T stage,CA19-9,and preoperative SII were the independent risk factors for patient prognosis,while adjuvant chemotherapy was a protective factor.The Kaplan-Meier curves showed that the one-year survival rate in high-SII group was remarkably lower than that in the low-SII group.Conclusion Preoperative SII has an important value in evaluating the prognosis of patients with ECCA who are treated with biliary stenting combined with 125I seed implantation.(J Intervent Radiol,2023,32:1221-1225)

Neglect of preschool children in urban area of Xi an under the background of multi-child policy / 中国学校卫生

Objective@#To understand the situation of neglect of preschool children in the urban area of Xi an under the background of multi child policy, so as to provide a reference for making effective prevention.@*Methods@#In Novmber 2022, according to the multi stage stratified cluster sampling principle, 2 450 parents of children aged 3-6 years were randomly selected from 7 urban areas of Xi an to participate in the questionnaire survey. A questionnaire survey was conducted using the "Neglect Evaluation Norms of 3-6 Years Old (Preschool) Children in Urban Areas of China". SPSS 18.0 software was used for statistical description, Chi square test and variance analysis.@*Results@#The total neglect rate of preschool children in the urban area of Xi an was 29.0% and the total neglect score was (37.58±8.44). There was no statistical difference in the neglect status of children in different grade groups ( χ 2/ F =1.61, 2.98, P >0.05). The neglect score of boys was higher than girls ( t =2.45, P <0.05). There was no statistical difference in the neglect rate and neglect score of boys and girls in other levels ( P >0.05); except for the significant difference in the neglect degree of medical treatment, education and safety ( t =2.01, 2.28, 2.02, P <0.05). The rate and score of neglect in multi-child families were higher than only-child families ( χ 2/ t = 13.68, -4.54, P <0.05). There were significant differences in the rate and degree of neglect of children with different birth order, which were "third and fourth-born>second-born>first-born" ( χ 2/ F = 10.84 , 2.79, P <0.05). The neglect rate and score of "single parent family" were significantly higher than that of "nuclear family" and "three-generation family" ( χ 2/ F =4.78, 2.79, P <0.05).@*Conclusion@#The neglect situation of preschool children in urban area of Xi an is still serious, especially in multi-child families. It should actively explore the risk factors and formulate effective intervention measures.

Mechanism of effect of Zhuang medicine Semiliquidambar cathayen. Sis Chang on depression inflammation based on network pharmacology, molecular docking and animal experiments / 中国药理学通报

Aim To predict the key targets and signaling pathways of Semiliquidambar cathayen. sis Chang (JLBFH) by network pharmacology and molecular docking,etc, then to explore the mechanism of JLBFH' s effect on inflammatory response to depression through reserpine-induced depression rat model. Methods The target of drug and disease was predicted by network pharmacological database, protein interaction network diagram was constructed, biofunctional enrichment and pathways were analyzed, and molecular docking prediction was performed by AGFR software. Based on reserpine-induced depression, the role of JLBFH in depression inflammation was verified by behavior, molecular biology and pathological examination, and so on. Results A total of 13 active ingredients were screened, 11 key targets of JLBFH modulation of depression were selected, and the bioenrichment results were mainly related to cognition, prominent plasticity regulation, etc. The pathways were mainly related to Rapl signaling pathway, Toll-like receptor signaling pathways. The results of validation experiments showed that high and low doses of JLBFH extract significantly shortened the forced swimming immobility time in mice, markedly reduced the retention time in the circle of rats, increased serum levels of 5-HT and DA, decreased serum levels of IL-6, improved inflammatory infiltration in the prefrontal cortex, decreased brain tissue levels of IL-6,IL-1β ,TNF-α mRNA expression,and increased AKT1 mRNA expression in brain tissue. Conclusions The present study reveals that JLBFH can exert antidepressant effects through multi-component, multi-target and multi-pathway, and the experimental validation results show that JLBFH can improve the d¬pression-like symptoms by improving the inflammatory response of depression through TOLL-like signaling pathway.

Clinical Analysis of SET-NUP214 Fusion Gene Positive Patients with Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene.@*METHODS@#The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively.@*RESULTS@#Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive.@*CONCLUSION@#The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.

Emerging roles of Aurora-A kinase in cancer therapy resistance

Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.

Molecular insights into AabZIP1-mediated regulation on artemisinin biosynthesis and drought tolerance in Artemisia annua

Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Efficacy of TIPS in treatment of recurrent portal hypertension after splenectomy and devascularization in patients presenting with upper gastrointestinal bleeding / 中华肝胆外科杂志

Objective:To study the efficacy, feasibility and safety of transjugular intrahepatic portosystemic shunt (TIPS) in treatment of recurrent portal hypertension after splenectomy and devascularization in patients presenting with upper gastrointestinal bleeding.Methods:Cirrhotic patients with recurrent portal hypertension after splenectomy and devascularization and presenting with upper gastrointestinal bleeding from August 2015 to December 2020 were studied. Thirty-nine patients were included in this study. There were 24 males and 15 females, with age of (51.56±9.08) years old. These patients were treated with TIPS by using the Viabahn stent. Intraoperative portal vein pressure, success operative rate, hemostasis rate after surgery, changes in hematological indicators and postoperative efficacy and complication rate were studied.Results:Thirty-eight of 39 patients successfully underwent TIPS shunt and 1 patient failed because of portal vein spongiosis. The success rate was 97.44%(38/39). Thirty-three patients underwent TIPS and variceal vein embolization, while 5 patients were treated with TIPS alone. Thirty-nine Viabahn stents with a diameter of 8 mm were implanted in 38 patients, of which 5 patients had the stent expanded to its nominal diameter of 8 mm. The remaining 33 patients (86.84%) had a shunt with a diameter of 6 mm. The hemostasis rate of postoperative gastrointestinal bleeding was 97.37% (37/38). The portal vein pressure and portal venous pressure gradient decreased from (31.28±6.24), (20.61±5.14) mmHg (1 mmHg=0.133 kPa) to (19.58±4.69), (9.24±3.07) mmHg respectively, the differences were significant (all P<0.001). All patients were followed-up for 3 to 36 months, with a median follow-up of 12 months. The postoperative rebleeding rate was 6.90% (2/29). The incidence of hepatic encephalopathy was 13.79% (4/29), and the incidence of shunt disorder was 13.79% (4/29). Conclusion:TIPS was safe, effective and feasible in treating patients with recurrent portal hypertension after splenectomy and devascularization presenting with upper gastrointestinal bleeding. Most patients obtained good clinical outcomes with a 6 mm diameter shunt.

Analysis of risk factors of Budd-Chiari syndrome associated with hepatocellular carcinoma in patients who underwent endovascular recanalization / 中华肝胆外科杂志

Objective:To study the risk factors of Budd-Chiari syndrome (BCS) associated with hepatocellular carcinoma in patients who underwent endovascular recanalization.Methods:The data of 340 patients with BCS who underwent endovascular recanalization at the Affiliated Hospital of Xuzhou Medical University between January 2015 and June 2021 were retrospectively collected. Using propensity score matching, a total of 57 patients (40 males and 17 females) were enrolled into this study, with the age of (50.4±8.7) years. Patients were divided into the hepatocellular carcinoma group ( n=19) and the control group ( n=38) according to whether occurrence of hepatocellular carcinoma after cardovascular recanalization. Preoperative indicators including gender, age, BCS type, and model for end-stage liver disease (MELD) score, and postoperative indicators including alpha fetoprotein, intrahepatic nodule formation, vascular restenosis, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were compared between the two groups after propensity score matching. Multivariate logistic regression analysis was used to analyze the risk factors of BCS associated with after endovascular recanalization in these patients. Results:There were no significant differences in gender, age, BCS type, MELD score and other preoperative data between the two groups (all P>0.05). The proportions of patients with postoperative alpha fetoprotein>9.0 μg/L, AST>40 U/L, ALT>50 U/L, intrahepatic nodules and vascular restenosis after endovascular treatment in the hepatocellular carcinoma group were significantly higher than those in the control group (all P<0.05). Multivariate analysis showed postoperative alpha fetoprotein >9.0 μg/L ( OR=46.778, 95% CI: 3.310-661.140), AST>40 U/L ( OR=36.307, 95% CI: 1.317-1 001.009), intrahepatic nodule formation ( OR=66.254, 95% CI: 4.225-1 038.974) and vascular restenosis ( OR=16.276, 95% CI: 1.712-154.773) to have an increased risk of being associated with hepatocellular carcinoma in these BCS patients (all P<0.05). Conclusion:Postoperative alpha fetoprotein>9.0 μg/L, AST>40 U/L, intrahepatic nodule formation and vascular restenosis were independent risk factors of BCS associated with hepatocellular carcinoma in patients who underwent endovascular recanalization.

Infection and distribution characteristics of HPV of middle-aged and elderly women from a certain hospital in Guangxi Zhuang Autonomous Region from 2018 to 2020 / 中华预防医学杂志

Objectives: To analyze the type and distribution characteristics of human papillomavirus (HPV) infection along with cervical cytology in middle-aged and elderly women in Guangxi and to provide a basis for the prevention and treatment of cervical cancer in elderly women. Methods: 21 subtypes of HPV and cervical cytology of women over 45-year-old visiting the First Affiliated Hospital of Guangxi Medical University from January 2019 to December 2020 were collected. They were divided into two groups by age, 45-64 years group and over 65 years group. The HPV, HR-HPV, and multiple HPV infection prevalence were analyzed, as well as HPV genotypes, the age distribution of HPV infection rate, and cervical cytology. Results: A total of 6 657 eligible women were included. 6 238 women were in the 45-64 years group, with a HPV prevalence about 20.86% (1 301), while 419 women were in the over 65 years group, with a HPV prevalence about 32.94% (138). The age-associated HPV and HR-HPV prevalence increased with the age, peaking at the age group of 70-74 years (P<0.001). The most prevalent genotype was HPV52, and the infection rate was 5.3% (353), followed by HPV16 and HPV 58, about 4.63% (308) and 3.08% (205) respectively. The majority cytology of HPV-positive middle-aged and elderly women was normal. 8.70% (88) of them were ASC-US, 6.52% (66) for HSIL, 4.55% (46) for LSIL, and 2.96% (30) for ASC-H, and 0.10% (1) for SCC. Compared to middle-aged women, elderly women had a lower negative cytology rate, 69.79% (67) vs. 77.95% (714), but a higher HSIL rate, 13.54% (13) vs. 5.79% (53) (P<0.05). Conclusions: HPV and HR-HPV prevalence of elderly women in a medical center of Guangxi are higher than those of middle-aged women. The most prevalent genotype is HPV16 in elderly women, followed by HPV52 and HPV58.