The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:To investigate the effect of 4-octyl itaconate(4-OI)on transforming growth factor-β1(TGF-β1)-induced lung fibroblast-to-myofibroblast differentiation and related mechanisms.Methods:TGF-β1 was employed to induce the differentiation of the human embryonic lung fibroblast cell line MRC-5, and the effect of 4-OI on lung fibroblast-to-myofibroblast differentiation was examined.Cytotoxicity of 4-OI on MRC-5 cells was detected by the CCK-8 assay.Western blot was used to detect the protein levels of α-smooth muscle actin(α-SMA), collagen 1α1(COL1A1), fibronectin(FN), phosphorylated and total Smad2/3, and nuclear facor-E2 related factor 2(Nrf2).Real-time fluorescence quantitative PCR was used to detect the mRNA expression of α-SMA, COL1A1 and FN.Reactive oxygen species(ROS)levels were assessed by fluorescence microscopy and flow cytometry.Intracellular glutathione(GSH)concentrations were measured by spectrophotometry.Results:Pretreatment with 4-OI was able to inhibit TGF-β1-induced protein overexpression of α-SMA, COL1A1 and FN( F=122.8, 51.5, 27.2, all P<0.05), and increased mRNA levels( F=29.83, 51.62, 94.82, all P<0.01).In addition, 4-OI inhibited TGF-β1-mediated phosphorylation of Smad2/3 proteins in a dose-dependent manner( F=21.80, 36.69, P<0.01 for both).Pretreatment with 4-OI also reversed increased ROS levels( P<0.01)induced by TGF-β1 and enhanced GSH concentrations via disinhibition of TGF-β1( P<0.05).The inhibitory effect of TGF-β1 on Nrf2 expression was alleviated and Nrf2 nuclear translocation was uplifted by 4-OI pretreatment( P<0.05).After silencing Nrf2, 4-OI was unable to inhibit the increased protein expression of COL1A1 induced by TGF-β1, but was still able to inhibit the increased expression of α-SMA and FN protein induced by TGF-β1( P<0.05). Conclusions:4-OI could inhibit lung fibroblast-to-myofibroblast differentiation partially via Nrf 2 activation.

Objective To investigate the effects of glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) on glioma growth and macrophage infiltration. Methods Initially, the expression of GPIHBP1 in glioma samples and macrophage infiltration were analyzed using TCGA database, and these bioinformatics results were validated in clinical tissue samples. A stable glioma cell line overexpressing GPIHBP1 was then established to further explore the effects of GPIHBP1 overexpression on glioma cell proliferation, apoptosis, migration, and invasion. Finally, the impact of GPIHBP1 overexpression on tumor growth and macrophage infiltration was verified through xenograft experiments. Results TCGA database analysis revealed that GPIHBP1 expression was higher in low-grade gliomas compared to normal tissues, while it was lower in high-grade gliomas. Additionally, the expression level of GPIHBP1 in low-grade gliomas was higher than in high-grade gliomas, which was confirmed by immunohistochemistry (IHC). Western blot analysis confirmed the successful construction of the GPIHBP1-overexpressing glioma cell line. CCK-8, flow cytometry, scratch and Transwell assays demonstrated that the proliferation, migration and invasion capabilities of the stable cell line were reduced compared to the control group. Xenograft experiments further showed that the tumor growth and macrophage infiltration were decreased in the stable cell line. Conclusion The differential expression of GPIHBP1 in different grades of gliomas may be associated with tumor progression. Overexpression of GPIHBP1 can inhibit glioma growth, possibly by influencing the tumor microenvironment and promoting the polarization of macrophages towards the antitumor M1 phenotype, thereby inhibiting glioma growth.

Objective:To compare the efficacy and safety of bi-level positive airway pressure (BiPAP) ventilation and heated humidified high flow nasal cannula (HHHFNC) ventilation as initial respiratory support for premature infants with respiratory distress syndrome (RDS).Methods:From January 2019 to June 2021, premature infants [gestational age (GA) 28~35 weeks)] with grade Ⅰ to Ⅲ RDS admitted to Suining County People's Hospital were prospectively enrolled. The infants were randomly assigned into BiPAP group and HHHFNC group. The clinical characteristics, ventilation efficacy and complications were analyzed.Results:A total of 33 infants were in BiPAP group and 32 in HHHFNC group. No significant differences existed between the two groups in the following items: the frequency of apnea within 24 h of ventilation, FiO 2 and PaCO 2 at 24 h, the use of pulmonary surfactant (PS), the incidence of non-invasive ventilation failure within 72 h, non-invasive ventilation duration and the age achieving total enteral nutrition. HHHFNC group had lower score in premature infants pain profile (PIPP) than BiPAP group at 24 h of non-invasive ventilation [4 (3, 6) vs. 8 (6, 11), P<0.001]. No significant differences existed in nasal injury, pneumothorax, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia and mortality rate between the two groups ( P>0.05). Conclusions:As the initial treatment for premature infants with grade Ⅰ to Ⅲ RDS, BiPAP and HHHFNC has similar rates of non-invasive ventilation failure within 72 h,non-invasive ventilation duration and adverse events. HHHFNC may ease the pain of the infants.

Objective:To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy.Methods:The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors.Results:From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) ( β=-0.370, P<0.001), per capita health expenditure ( β=-0.116, P=0.021), number of beds per thousand population ( β=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP ( β=-0.310, P=0.002) and standard management rate of hypertension ( β=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP ( β=-0.481, P<0.001), per capita health expenditure ( β=-0.184, P=0.001), number of beds per thousand population ( β=-0.288, P=0.001) and standard management rate of hypertension ( β=-0.336, P=0.029). Conclusions:A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

Leucine rich glioma inactivated 1 (LGI1) is a protein which is identified as the target involving in autoimmune encephalitis. Seizures and cognitive declines are two main symptoms of LGI1-antibody encephalitis. However, autonomic dysfunction symptoms are not prominent as seizures and cognitive defection and are easily overlooked by physicians. We reported a case with LGI1-antibody encephalitis whose onset symptoms were autonomic dysfunction including sweating, orthostatic hypotension. The features of this case was described in detail and the related literatures were reviewed in order to enhance the knowledge of the disease.

Objective:To evaluate the effect of comprehensive intervention combined with clinical preventive services and lifestyle adjustment on high-risk populations of cardiovascular disease.Methods:In 2015, 4 towns (streets) in Tongxiang City, of Zhejiang Province including Heshan Town, Longxiang Street, Wutong Street, and Fengming Street, were selected by using the typical sampling. The towns (streets) were allocated to the intervention group (Heshan Town and Longxiang Street) and the control group (Wutong Street and Fengming Street) by using the cluster random sampling. In each town (street), hypertension patients aged 50 to 74 years old who were taking community medicine management and with a 10-year cardiovascular disease risk ≥10% were recruited as subjects. There were 1 823 subjects in the intervention group and 1 883 in the control group. The intervention group was given a 1-year comprehensive intervention combining clinical preventive services and lifestyle adjustment, while the control group received routine chronic disease management. After the intervention, the final questionnaire investigation was conducted and health physical examination data were obtained. The death, acute coronary heart disease events and stroke incidence were the primary outcomes, and cardiovascular disease-related knowledge and behavior, clinical preventive services utilization, physical changes, blood fat index and 10-year cardiovascular disease risk were the secondary outcomes. The difference-in-difference model was used to evaluate the effects of interventions.Results:The age of subjects in the intervention and control group was (68.76±3.75) and (67.90±4.56) years old, respectively. After 1-year intervention, the incidence of mortality, acute coronary events and stroke in intervention group was 1.65% (30 cases), 0.27% (5 cases) and 2.69% (49 cases), respectively, which showed no statistical difference compared to the control group [1.33% (25 cases), 0.32% (6 cases) and 2.07% (39 cases)]. After adjusting for the age, gender, education, marital status, self-assessed family income level and situation of taking antihypertensive drugs, the difference-in-difference model showed that the body mass index and diastolic blood pressure in the intervention group decreased by 0.33 kg/m 2 and 1.49 mmHg (1 mmHg=0.133 kPa). Compared with the control group, daily vegetable consumption proportion, the awareness rates of aspirin, stains, salt intake, and oil intake increased by 4.76%, 26.22%, 29.56%, 10.80%, and 15.17%, respectively ( P<0.05). Conclusion:After the 1-year comprehensive intervention, there was no significant change in primary outcomes among high-risk populations of cardiovascular disease. In secondary outcomes, body mass index and diastolic blood pressure declined and cardiovascular disease-related knowledge awareness increased.

Objective:To evaluate the effect of comprehensive intervention combined with clinical preventive services and lifestyle adjustment on high-risk populations of cardiovascular disease.Methods:In 2015, 4 towns (streets) in Tongxiang City, of Zhejiang Province including Heshan Town, Longxiang Street, Wutong Street, and Fengming Street, were selected by using the typical sampling. The towns (streets) were allocated to the intervention group (Heshan Town and Longxiang Street) and the control group (Wutong Street and Fengming Street) by using the cluster random sampling. In each town (street), hypertension patients aged 50 to 74 years old who were taking community medicine management and with a 10-year cardiovascular disease risk ≥10% were recruited as subjects. There were 1 823 subjects in the intervention group and 1 883 in the control group. The intervention group was given a 1-year comprehensive intervention combining clinical preventive services and lifestyle adjustment, while the control group received routine chronic disease management. After the intervention, the final questionnaire investigation was conducted and health physical examination data were obtained. The death, acute coronary heart disease events and stroke incidence were the primary outcomes, and cardiovascular disease-related knowledge and behavior, clinical preventive services utilization, physical changes, blood fat index and 10-year cardiovascular disease risk were the secondary outcomes. The difference-in-difference model was used to evaluate the effects of interventions.Results:The age of subjects in the intervention and control group was (68.76±3.75) and (67.90±4.56) years old, respectively. After 1-year intervention, the incidence of mortality, acute coronary events and stroke in intervention group was 1.65% (30 cases), 0.27% (5 cases) and 2.69% (49 cases), respectively, which showed no statistical difference compared to the control group [1.33% (25 cases), 0.32% (6 cases) and 2.07% (39 cases)]. After adjusting for the age, gender, education, marital status, self-assessed family income level and situation of taking antihypertensive drugs, the difference-in-difference model showed that the body mass index and diastolic blood pressure in the intervention group decreased by 0.33 kg/m 2 and 1.49 mmHg (1 mmHg=0.133 kPa). Compared with the control group, daily vegetable consumption proportion, the awareness rates of aspirin, stains, salt intake, and oil intake increased by 4.76%, 26.22%, 29.56%, 10.80%, and 15.17%, respectively ( P<0.05). Conclusion:After the 1-year comprehensive intervention, there was no significant change in primary outcomes among high-risk populations of cardiovascular disease. In secondary outcomes, body mass index and diastolic blood pressure declined and cardiovascular disease-related knowledge awareness increased.