Resistance to ferroptosis, a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis, is closely related to tumorigenesis and tumor drug resistance; therefore, targeting ferroptosis-related pathways has garnered attention as a potential antitumor therapeutic strategy. However, the molecular mechanisms underlying ferroptosis resistance in tumor cells remain unknown. Zinc-finger estrogen receptor interaction clone 6 (ZER6) consists of two isoforms with distinct N-termini, p52-ZER6 and p71-ZER6. ZER6 is upregulated in tumors and promotes tumorigenic potential; however, whether ZER6 is involved in tumor cell ferroptosis resistance remains unknown. Herein, we identified p52-ZER6 as a novel regulator of tumor cell ferroptosis resistance. p52-ZER6 promotes the transcriptional activity of DAZAP1, an RNA-binding protein. DAZAP1, in turn, enhances the stability of SLC7A11 mRNA by binding to its 3'-UTR region, thereby increasing SLC7A11 expression and cellular glutathione levels. This subsequently reduces lipid peroxide accumulation and enhances tumor cell ferroptosis resistance, eventually promoting tumorigenic potential. These findings reveal a new function of p52-ZER6 in regulating SLC7A11 mRNA stability via DAZAP1, ultimately leading to ferroptosis resistance and tumorigenic potential. Additionally, we also suggest targeting p52-ZER6 as a potential strategy to promote the efficacy of ferroptosis-based antitumor therapies.

Objective:To evaluate neutrophil/lymphocyte ratio(NLR) and the model for end-stage liver disease-sodium(MELD-Na)score in predicting short-term prognosis of patients with HBV-related acute-on-chronic liver failure(HBV-ACLF).Methods:A total of 234 consecutive HBV-ACLF patients(194 males and 40 females, aged 23-85 years)admitted to Hangzhou Xixi Hospital from January 2019 to December 2021 were enrolled. According to the 12-week clinical outcomes, patients were divided into good prognosis group( n=141)and poor prognosis group( n=93). Univariate and multivariate Logistic regression were performed to identify independent risk factors for poor prognosis of HBV-ACLF patients. Receiver operating characteristics(ROC)curve was applied to evaluate the accuracy of risk factors in predicting short-term prognosis of HBV-ACLF patients. Results:The age [(48.7±11.9) vs. (52.5±9.9) years old, t=-2.59, P=0.011], proportion of males [78.0%(110/141) vs. 90.3%(84/93), χ2=5.99, P=0.014], total bilirubin[202.9(141.2, 287.6) vs. 320.0(224.4, 400.0) μmol/L, Z=-5.14, P<0.001], creatinine [71.0(59.0, 78.0) vs. 81.0(64.0, 111.0)μmol/L, Z=-3.98, P<0.001], international normalized ratio[1.66(1.52, 1.86) vs. 1.91(1.66, 2.27), Z=-5.46, P<0.001], leukocyte count[5.16(3.99, 6.95)×10 9/L vs. 6.57(4.83, 8.30)×10 9/L, Z=-4.14, P=0.001], NLR[2.77(2.02, 3.55) vs. 5.48(3.44, 8.53), Z=-8.48, P<0.001], MELD score[22.0(20.0, 24.0) vs. 26.0(24.0, 29.0), Z=-9.22, P<0.001], MELD-Na score[22.8(20.0, 25.6) vs. 29.0(25.0, 36.0), Z=-9.16, P<0.001], liver cirrhosis[77.3%(109/141) vs. 88.2%(82/93), χ2=4.41, P=0.036], hepatorenal syndrome[4/141(2.8%) vs. 12/93(12.9%), χ2=8.91, P=0.003] and the proportion of artificial liver treatment[21/141(14.9%) vs. 24/93(25.8%), χ2=4.30, P=0.038] were significantly elevated in poor prognosis group compared with survival group. Logistic regression analysis showed that NLR( OR=3.76, 95 %CI: 2.10-6.74, P<0.001)and MELD-Na score( OR=2.24, 95 %CI: 1.17-4.29, P=0.015) were independent risk factors for poor short-term prognosis of HBV-ACLF patients. The area under the ROC curve(AUC)of NLR, and MELD-Na for the short-term prognosis of HBV-ACLF patients was 0.792 and 0.822, respectively. The AUC of the combination of NLR with MELD-Na was 0.858, which was significantly higher than that of NLR( Z=-3.04, P=0.001) or MELD-Na score( Z=-2.16, P=0.031)alone. Based on the cut-off value of the combined model, patients were classified into high combined model score (≥0.04) group and low combined model score (<0.04) group, the survival rate of the high group was significantly higher than that of the low group( χ2=67.47, P<0.001). Conclusions:NLR and MELD-Na score are independent risk factors of the short-term prognosis of HBV-ACLF patients. The combination of NLR and MELD-Na score will be beneficial to predict the short-term prognosis of HBV-ACLF patients.

Objective To investigate the clinical value of glycosylated hemoglobin(HbA1c),glycosylated serum protein(GSP),sex hormone binding globulin(SHBG),three acylglycerol(TG),free fatty acid(FFA)in diagnosing gestational diabetes mellitus(GDM).Methods 103 cases of GDM patients and 98 cases of healthy pregnant women from February 2015 to August 2016 were selected as the GDM group and control group.The positive detection rates and levels of HbA1c,GSP,SHBG,TG and FFA were compared between the two groups.Moreover the diagnostic efficiency of various indicators was analyzed.Results The levels of HbA1c, GSP,TG and FFA in the GDM group were significantly higher than those in the control group,while the SH-BG level was significantly lower than that in the control group,the difference was statistically significant(P<0.05);the positive rates of HbA1c,GSP,SHBG,TG and FFA in the GDM group were significantly higher than those in the control group,the difference was statistically significant(P<0.05);the specificity,sensitivity and positive prediction value of HbA1c,GSP,SHBG,TG and FFA for jointly diagnosing GDM were signifi-cantly higher than those of single indicator,the difference was statistically significant(P<0.05).Conclusion Detecting HbA1c,NGSP,SHBG,TG and FFA is more accurate for jointly diagnosing GDM,has an important diagnostic value,and can serve as the assisted diagnostic indicators.

Objective To investigate the status of soil fertility of Good Agricultural Practices ( GAP) base for Spatholobus suberectus Dunn. (SSD) in Pingyuan county of Guangdong province, thus to provide reference for GAP research and the subsequent fertilization for SSD. Methods The deep layer and superficial layer of GAP soil were collected for the physiochemical detection and nutrient assay. Compared with the classification standard of the second national general soil investigation, single base soil fertility index was diagnosed and the comprehensive soil fertility was evaluated with modified Nemoro Index. Results The soil pH value and the contents of exchangeable calcium and magnesium were unbalanced, and the contents of macroelements of nitrogen and phosphonium, microelements, and organic matter were low. Therefore, the measures for improving the base soil fertility should be as follows: ( 1) soil amendments of bentonite, gypsum and slaked lime should be used to adjust the soil pH value; ( 2) each plant should be given 10 kg of slaked organic fertilizer as base fertilizer; ( 3) in the process of nurturing, some special micro-fertilizer solution should be used to treat the cut slips, and 5 kg of urea should be used for every 667 meter square of land; ( 4) besides compound fertilizer, every 667 meter square of land should be fertilized with 15 kg of ammonium dihydrogen phosphate for the supplement of nitrogen and phosphorus, and slaked lime and magnesium carbonate should be used for the supplement of soil moderate-quantity elements after transplantation. Conclusion The comprehensive fertility of Pingyuan GAP base for Spatholobus suberectus Dunn. is at low level, and should be improved in combination with GAP requirements.

Prolyl-4-hydroxylase domain (PHDs) family is one of the most important regulatory factors in hypoxic stress. PHD2 plays a critical role in cells and tissues adaptation to the low oxygen environment. Its hydroxylation activity regulates the stability and transcriptional activity of the hypoxia-inducible factor 1 (HIF-1), which is the key factor in response to hypoxic stress. Subsequently, PHD2 acts as an important factor in oxygen homeostasis. Studies have shown that PHD2, through its regulation on HIF-1, plays an important role in the post-ischemic neovascularization. Furthermore, under hypoxic condition, PHD2 also regulates other pathways that positively regulate angiogenesis factors HIF-1 independently. Moreover, recently, several evidences have also shown that PHD2 also affects tumor growth and metastasis in a tumor microenvironment. Based on these facts, PHD2 have been considered as a potential therapeutic target both in treating ischemic diseases and tumors. Here, we review the molecular regulation mechanism of PHD2 and its physiological and pathological functions. We focus on the role of PHD2 in both therapeutic angiogenesis for ischemic disease and tumor angiogenesis, and the current progress in utilizing PHD2 as a therapeutic target.

Objective To investigate the diversity evolution of hepatitis B virus(HBV) quasispecies during the long-term entecavir therapy and its impact on the virological reponse.Methods Sixty-four chronic hepatitis B patients were received Entecavir therapy for the first time.Serum samples were collected at six different time points during Entecavir therapy (0,4,12,24,36,48weeks,respectively).Twenty-two patients could be detected HBV DNA at week 4,which were divided into two groups according to the therapeutic effect at week 12:complete response group (ll cases) and partial response group (11 cases).The sequence of HBV RT region was amplified by polymerase chain reaction(PCR) and cloned into T-vector for these serum samples at baseline and week 4.Twenty to thirty clones per sample were selected,sequenced and analyzed.Results Despite comparable at baseline,the diversity change of HBV quasispecies in complete responders were statistically higher than those of partial reponders in week 4 (P ＜ 0.05).Conclusion The HBV quasispecies changed during the primary stage of Entecavir treament.And the heterogeneity of HBV quasispecies during the first 4 weeks was significant association with the long term therapeutic outcome of Entecavir.

Objective To investigate the mutation patterns of hepatitis B virus in chronic hepatitis B patients with rtA181 mutations.Methods Forty-five chronic hepatitis or cirrhosis patients undergoing nucleos(t)ide analogues treatment were found HBV rtA181 locus mutation.Their serum HBV DNA levels were detected,HBV P gene was amplified and PCR products were sequenced to analyze genotype as well as mutation patterns.The information of medication history,salvage regimen and efficacy were collected.Results Three mutation forms of HBV rtA181 were found in 45 cases which were rtA181T 66.67％ (30/ 45),rtA181V 31.11％ (14/45) and rtA181S 2.22％ (1/45) respectively.The rate of HBV genotype C was higher than that of genotype B in rtA181T carriers (P ＜ 0.05).Thirteen kinds of patterns involved rtA181 of HBV mutations were found.Multi-site rtA181 mutations occurred 57.78％ (26/45).rtA181 combined with rt236 occurred 40.00％ joint (18/45),rtA181 combined with rtM204 mutation occurred 22.2％ (10/45),and the patients with multi-site rtA181 mutations seemed have higher viral load distribution,but the difference was not statistically significant (P ＞ 0.05).Nor the rtA181 mutation form either the HBV genotype correlated with multi-site rtA181 mutation (P ＞ 0.05); Most of patients (97.78％,44/45) with rtA181 mutation had lamivudine and (or) adefovir treatment history,the other one only had telbivudine antiviral treatment previously.Some kinds of subsequent salvage antiviral treatment strategy obtained 2 lg HBV DNA decrease in a month,such as plusing or switching to entecavir,lamivudine & adefovir,and telbivudine & adefovir.Long follow-up study indicated plusing (or) switching to entecavir can achieve significant sustained response of the salvage treatment to rtA181 mutation.Conclusions HBV rtA181 mutation patterns varied,correlated with long-term lamivudine,adefovir or telbivudine monotherapy or sequential treatment.The subsequent salvage therapy should be focused on plusing or switching to entecavir.

The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.
Animals ; Brain Neoplasms ; genetics ; pathology ; Breast Neoplasms ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics ; Multifactorial Inheritance ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Proteins ; genetics ; Neoplasm Staging ; Neoplasms ; genetics ; Transcription, Genetic ; Transcriptome ; Tumor Suppressor Proteins ; genetics