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.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

Objective To investigate the relationship between the expression of matrix metalloproteinase(MMP)-2,MMP-9,MMP-13 and disease activity in pemphigus patients.Methods A total of 60 pemphigus patients treated in the dermatology department of the hospital from January 2021 to January 2023 were select-ed as the study group,and another 60 healthy volunteers who underwent physical examination in the same pe-riod were recruited as the control group.The levels of MMP-2,MMP-9 and MMP-13 in serum and the expres-sion of MMP-2,MMP-9 and MMP-13 in peripheral blood mononuclear cells were compared between the two groups,and the relationship between the expression of MMP-2,MMP-9 and MMP-13 in peripheral blood mononuclear cells of patients with pemphigus was analyzed.Pemphigus patients were divided into acute phase group(n=22),chronic phase group(n=23)and stable phase group(n=15)according to their disease activi-ty.The expression of MMP-2,MMP-9 and MMP-13 in peripheral blood mononuclear cells of the three groups were compared,as well as the correlation between the three indexes and disease activity.Receiver operating characteristic(ROC)curve was plotted for analysis.Results The levels of MMP-2,MMP-9 and MMP-13 in serum and the expression of MMP-2,MMP-9 and MMP-13 in peripheral blood mononuclear cells in the study group were higher than those in the control group,with statistical significance(P＜0.05).The expression of MMP-2,MMP-9 and MMP-13 in peripheral blood mononuclear cells in severe patients were higher than those in moderate and mild patients,and the difference was statistically significant(P＜0.05).The expression of MMP-2,MMP-9 and MMP-13 and disease activity scores of mononuclear cells in acute attack group were higher than those in chronic attack group,and the differences were statistically significant(P＜0.05).The ex-pression of MMP-2,MMP-9 and MMP-13 in peripheral blood mononuclear cells were positively correlated with disease activity(rMMP-2=0.545,rMMP-9=0.592,rMMP-13=0.580,P＜0.05).ROC curve analysis showed that compared with the single diagnostic efficacy of MMP-2,MMP-9 and MMP-13 expression in peripheral blood mononuclear cells,the three combined diagnostic efficacy was better.Conclusion The expression of MMP-2,MMP-9 and MMP-13 in peripheral blood mononuclear cells of pemphigus patients is related to the disease activity,and these three indicators can be used as reference indicators for the diagnosis of pemphigus disease activity.

Abstract: Objective　To understand the epidemiological characteristics of the migratory bird population with hypertension in Hainan and to provide a basis for the health management of the migratory bird population. Methods　One hundred and eighty migratory birds with hypertension who had lived in in the Mangrove Bay community of Chengmai, Hainan for 3 months or more were selected as the study population. Demographic data, including gender, age, ethnicity, occupation, medication use, family history of hypertension, hometown living environment, Hainan living environment (presence of water area and greenbelt around the residence, type of water area and greenbelt), smoking and alcohol consumption, and height and weight were collected by questionnaire and physical examination to investigate the epidemiological characteristics of the study subjects, and unconditional dichotomous logistic regression analysis was used to identify factors affecting the reduction of blood pressure among the hypertensive migratory bird population before and after taking medication in Hainan. Results　A total of 180 study subjects were included, including 77 (42.8%) males and 103 (57.2%) females, with 78 (43.3%) subjects aged ≤65. The hypertension levels were: 87 (48.3%) had normal high blood pressure, 56 (31.1%) had grade 1 hypertension and 37 (20.6%) had grade 2 hypertension. The higher the blood pressure classification, the lower the percentage of migratory individuals whose blood pressure dropped during their stay in Hainan. Age, hypertension classification, dietary habits, living environment, body mass index (BMI), and alcohol consumption were associated with a decrease in blood pressure during Hainan among the study participants who took hypertension medication regularly. Salty diet (OR=2.778, 95%CI:1.070-7.213, P=0.036) and alcohol consumption (OR=2.686, 95%CI:1.042-6.925, P=0.041) were unfavorable factors for lower diastolic blood pressure before taking medication; overweight (OR=3.487, 95%CI:1.306-9.310, P=0.013) was an unfavorable factor in the reduction of diastolic blood pressure after taking medication. Conclusion　The blood pressure reduction is more significant in migratory individuals in migratory individuals under 65 years old, with a light diet, no alcohol consumption and normal BMI. Environmental factors, age, dietary habits and lifestyle are the main causes of blood pressure, which can provide a reference basis for the health management of the migratory birds with hypertension in Hainan.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective:To investigate the efficacy of Yanghe Pingchuan Decoction in the treatment of chronic obstructive pulmonary disease (COPD) with syndrome of kidney deficiency and phlegm in the acute exacerbation stage.Methods:A total of 86 patients meeting the standard with acute exacerbation of COPD who were admitted to Haikou Hospital of TCM from May 2019 to July 2021 were selected and divided into an observation group and a control group by random number table method, with 43 cases in each group. The patients in the control group were treated with conventional Western medicine, and the patients in the experimental group were treated with Yanghe Pingchuan Decoction on the basis of the treatment in the control group. Both groups took 14 days of treatment. Scoring of TCM symptom of both groups before and after treatment was conducted. The serum levels of CRP, TNF-α and IL-6 were detected by ELISA, and the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) and the percentage of FEV1 to predicted value (FEV1%) were detected by automatic pulmonary function tester. Clinical efficacy was evaluated.Results:The observed total effective rate was 90.70% (39/43) in the observation group, which was significantly higher than 72.09% (31/43) in the control group, with statistical significance ( χ2=4.91, P<0.05). After treatment, the symptom scores of cough and expectoration, wheezing, shortness of breath, poor appetite, sweating and cold limbs in the observation group were significantly lower than those in the control group ( t values were 10.21, 11.30, 15.77, 13.87, 8.73, respectively, all Ps<0.01); the levels of CRP and TNF-α，IL-6 in the observation group were significantly lower than those in the control group ( t values were 22.43, 18.21, 20.90, respectively, all Ps<0.01); the levels of FEV1/FVC (62.58±5.23 vs. 58.47±11.61, t=2.12), FEV1 (63.79±1.47 vs. 60.17±10.94, t=2.15) in the observation group were significantly higher than those in the control group ( P<0.05). Conclusion:Yanghe Pingchuan Decoction can effectively improve the pulmonary function of patients with acute exacerbation of COPD, relieve clinical symptoms, reduce the levels of serum CRP, TNF-α and IL-6, and improve the efficacy.

Objective:To explore the effect of estrogen-related receptor α (ERRα) on lipopolysaccharide (LPS)-induced vascular endothelial cell apoptosis and tight junction protein degradation.Methods:RPMVECs transfected with shERRα were cultured in vitro and divided into four groups: Normal control group (Ctr group); shERRα knockdown group (shERRα group); normal cells + LPS treated group (LPS group): The cells in the six-well plates were cultured in serum-free medium for 12 h, and then treated with 20 μg/mL LPS for 12 h; and shERRα+LPS group: ERRα knockdown cells were treated as the LPS group. ROS fluorescence kit was used to detect the intracellular ROS levels . Apoptosis ratio was detected by TUNEL staining, AnnexinV-FITC and PI. Cell membrane ZO-1 expression was detected by cellular immunofluorescence, and the levels of apoptosis-related proteins Bcl-2, Bax, Smac, Cytochrome c, and tight junction protein ZO-1, as well as the expression of Occludin, JAM-A and E-Ca at molecular level were detected by Western blot.Results:Compared with the Ctr group and the shERRα group, the ROS level, apoptosis rate (TUNEL test: 16.44 ± 2.55; and flow cytometry test: 23.56 ± 2.22), the expression of pro-apoptotic proteins Bax, Smac and Cytochrome c were increased in the LPS group, while the expression of anti-apoptotic proteins Bcl-2 and tight junction protein were decreased. In the LPS group. Cellular immunofluorescence results showed that the ZO-1 was degraded in the cell membrane and the network structure was broken. Compared with the LPS group, inhibition of ERRα in the shERRα+LPS group increased cell damage.Conclusions:ERRα can negatively regulate the apoptosis and affect the function of pulmonary microvascular endothelial cells, thereby regulating sepsis-induced acute lung injury.

Objective:To compare the clinical outcomes and safety of haploidentical donor (HID)and HLA-matched sibling donor(MSD)hematopoietic stem cell transplantation(HSCT)for severe aplastic anemia(SAA).Methods:From January 1, 2012 to December 31, 2019, retrospective review of clinical data was performed for 75 SAA patients undergoing HSCT at Department of Hematology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.Based upon donor sources, they were divided into two groups of MSD(49 cases)and HID (26 cases). And two groups were compared with regards to hematopoietic recovery, graft-versus-host disease(GVHD)infection and overall survival(OS).Results:Time of platelet and neutrophil engraftment of two groups was comparable(11 d vs.11 d, P=0.84; 11 d vs.12 d, P=0.08). Compared with HID group, MSD group had a lower incidence of acute GVHD(46.2% vs.18.4%, P=0.01)with a comparable incidence of grade Ⅱ-Ⅳ acute GVHD(26.9% vs.14.3%, P=0.24), grade Ⅲ-Ⅳ acute GVHD(15.4% vs.4.1%, P=0.09)and chronic GVHD(23.9% vs.23.1 %, P=0.71). A reactivation of CMV occurred in 27(55.1%)MSD and 22(84.6%)HID recipients( P=0.01). And the incidence of EB viremia was 69.4% and 61.5% respectively.After a median follow-up period of 54.0 and 18.5 months, the estimated 3-year OS rate of MSD and HID groups were 94.0% and 88.0% respectively ( P=0.35). Conclusions:HID HSCT is an effective and relatively safe option for SAA patients, especially for those in urgent need of treatment without MSD or refractory/relapse to immunosuppressive therapy.

Objective:To explore the early application effect of the bedside sitting respiratory training in patients with respiratory failure and noninvasive positive pressure ventilation of the acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods:A total of 102 patients with respiratory failure and noninvasive positive pressure ventilation of the AECOPD treated in Shanghai Public Health Clinical Center from June 2018 to December 2019 were selected and divided into the control group and the research group by random digits table method with 51 cases in each group. The control group was given the conventional treatment and nursing measures; and the research group was given the bedside sitting respiratory training. Pulmonary functional and blood -gas analysis parameters, clinical outcome of patients, etc. before and after the intervention between the two groups were compared. Results:After the intervention, the forced expiratory volume in one second (FEV 1), forced vital capacity(FVC), FEV 1/FVC were (1.79±0.22) L, (3.09±0.28) L, (62.16±5.94)% in the research group, and (1.43±0.18) L, (2.66±0.23) L, (53.48±5.31)% in the control group, the differences were statistically significant(t values were 8.36, 8.00, 7.19, P<0.01). Arterial partial pressure of carbon dioxide (PaCO 2) and arterial partial pressure of oxygen (PaO 2) in blood gas analysis were (51.14±3.79) mmHg(1 mmHg=0.133 kPa), (71.07±5.49) mmHg in the research group, and (57.52±3.86) mmHg, (65.62±5.27) mmHg in the control group, the differences were statistically significant ( t values were -7.78, 4.72, P<0.01). The non-invasive positive pressure ventilation time, hospital stays were (7.41±1.76) d, (11.27±2.41) d in the research group, and (9.79±2.11) d, (15.46±3.12) d in the control group, the differences were statistically significant ( t values were -5.71, -6.70, P<0.01). The incidence of adverse events was 3 cases in the research group, 1 case in the control group, the difference was no statistically significant ( P>0.05). Conclusions:The application of the bedside sitting respiratory training in patients with respiratory failure and noninvasive positive pressure ventilation of the AECOPD can effectively improve the pulmonary physiological function, shorten the noninvasive positive pressure ventilation time and hospitalization time, which has clinical application value.

Objective:To investigate the association between oxygen saturation (SpO 2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods:The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2<94% was defined as abnormal). Results:The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P<0.001). After adjusting for confounding factors, compared to participants with normal SpO 2, participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2group, respectively; HR (95% CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion:Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.