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.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective To analyze the risk factors of ultrasound-guided percutaneous transluminal angioplasty(PTA)for treating thrombotic occlusion of autogenous arteriovenous fistula(AVF).Methods A total of 144 patients with thrombotic occlusion of autologous AVF were retrospectively enrolled and divided into success group(n=114)and failure group(n=30)according to the success of treatment or not.Clinical data and ultrasonic parameters of AVF were compared between groups.A multivariate logistic regression model was constructed to analyze the risk factors of PTA for treating thrombotic occlusion of autologous AVF,and the results were visualized by nomogram.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the predictive efficacy of this model.Results Patients'age,use years of AVF,degree of vascular calcification,the mean Young modulus(Emean),the maximum Young modulus(Emax)and the minimum Young modulus(Emin)were all higher,while the number of venous outflow tracts of AVF was less in failure group than those in success group(all P＜0.05).Moderate to severe calcification of vascular,high Emean of thrombus and 1 venous outflow tract of in AVF were all independent risk factors of ultrasound-guided PTA for treating thrombotic occlusion of autologous AVF(all P＜0.05),and AUC of the obtained model for predicting failure of treatment was 0.969.Conclusion Moderate to severe calcification of vascular,high Emean of thrombus and 1 venous outflow tract of AVF were all independent risk factors of ultrasound-guided PTA for treating thrombotic occlusion of autologous AVF.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective To analyze the risk factors of ultrasound-guided percutaneous transluminal angioplasty(PTA)for treating thrombotic occlusion of autogenous arteriovenous fistula(AVF).Methods A total of 144 patients with thrombotic occlusion of autologous AVF were retrospectively enrolled and divided into success group(n=114)and failure group(n=30)according to the success of treatment or not.Clinical data and ultrasonic parameters of AVF were compared between groups.A multivariate logistic regression model was constructed to analyze the risk factors of PTA for treating thrombotic occlusion of autologous AVF,and the results were visualized by nomogram.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the predictive efficacy of this model.Results Patients'age,use years of AVF,degree of vascular calcification,the mean Young modulus(Emean),the maximum Young modulus(Emax)and the minimum Young modulus(Emin)were all higher,while the number of venous outflow tracts of AVF was less in failure group than those in success group(all P＜0.05).Moderate to severe calcification of vascular,high Emean of thrombus and 1 venous outflow tract of in AVF were all independent risk factors of ultrasound-guided PTA for treating thrombotic occlusion of autologous AVF(all P＜0.05),and AUC of the obtained model for predicting failure of treatment was 0.969.Conclusion Moderate to severe calcification of vascular,high Emean of thrombus and 1 venous outflow tract of AVF were all independent risk factors of ultrasound-guided PTA for treating thrombotic occlusion of autologous AVF.

Over the past decade, research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment (TME). Lipids, diverse biomolecules, not only constitute biological membranes but also function as signaling molecules and energy sources. Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation. Moreover, lipids secreted into the TME influence tumor-resident immune cells (TRICs), thereby aiding tumor survival against chemotherapy and immunotherapy. This review aims to highlight recent advancements in understanding lipid metabolism in both tumor cells and TRICs, with a particular emphasis on exogenous lipid uptake and endogenous lipid de novo synthesis. Targeting lipid metabolism for intervention in anticancer therapies offers a promising therapeutic avenue for cancer treatment. Nano-drug delivery systems (NDDSs) have emerged as a means to maximize anti-tumor effects by rewiring tumor metabolism. This review provides a comprehensive overview of recent literature on the development of NDDSs targeting tumor lipid metabolism, particularly in the context of tumor immunotherapy. It covers four key aspects: reprogramming lipid uptake, reprogramming lipolysis, reshaping fatty acid oxidation (FAO), and reshuffling lipid composition on the cell membrane. The review concludes with a discussion of future prospects and challenges in this burgeoning field of research.

Objective:To investigate the correlation between time within the glucose target range(TIR) and hyperuricemia(HUA) in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 215 patients with T2DM in the First Affiliated Hospital of Bengbu Medical College from June 2021 to May 2022 were selected and divided into HUA group and non-HUA group according to serum uric acid level. The clinical characteristics and biochemical indicators of the patients were collected. The association of 72 h glucose monitoring system(FGMS) related indicators TIR, mean blood glucose fluctuation range(MAGE), blood glucose variability(CV), blood glucose standard deviation(SDBG), and mean blood glucose(MBG) with serum uric acid level was analyzed. The influencing factors of T2DM combined with HUA were analyzed with binary logistic regression, and receiver operating characteristic(ROC) curve was drawn to evaluate their predictive values.Results:TIR of HUA group was significantly decreased compared with non-HUA group, while HbA 1C, MAGE, CV, SDBG, and MBG were increased( P<0.001). Spearman correlation analysis showed that serum uric acid levels were negatively correlated with TIR, but positively correlated with MAGE, CV, SDBG, and MBG( P<0.001). After dichotomous logistic regression analysis, TIR was found to be an independent protective factor for T2DM with HUA. The ROC curve results showed that the area under the curve(AUC) of TIR for predicting HUA in T2DM was 0.856(95% CI 0.803-0.909, P<0.001), with the best cut-off value being 64.5%, the sensitivity being 76.8%, and the specificity being 90.3%. Conclusion:TIR in patients with T2DM combined with HUA was significantly decreased. TIR is an independent protective factor for T2DM combined with HUA, and TIR shows a certain predictive value for T2DM combined with HUA.

Objective:To summarize the survival rate, complications, and outcomes of 32 periviable extremely preterm infants (PEPIs) born at ≤23 gestational weeks.Methods:This was a retrospective observational study involving PEPIs born at the Shenzhen Maternity & Child Healthcare Hospital from January 1, 2015, to December 31, 2021. Clinical data of all subjects were collected and analyzed. The survival rates of PEPIs born from 2015 to 2019 and 2020 to 2021 were compared. Chi-square (or Fisher's exact) test was used for statistical analysis. Results:(1) During the study period, 32 PEPIs were admitted, accounting for 0.024% (32/132 534) of all newborns born in the same hospital during the study period. The median gestational age of the 32 PEPIs was 23 weeks (21 +4-23 +6 weeks), and the birth weight was 480 g (350-720 g). (2) The survival rate of PEPIs born between 2020 and 2021 was 10/19, which appears to be a trend higher than that between 2015 and 2019 (3/13, χ2=2.79, P=0.095), while the rate of withdrawal of treatment was 8/13 and 3/19, respectively, with a statistically significant difference ( χ2=7.16, P=0.007). (3) Thirteen of the 32 PEPIs survived on discharge, including four born at 22 weeks and nine at 23 weeks. The birth weights of these surviving infants were 300-<400 g in one case, 400-<500 g in five cases, 500-<600 g in four cases, 600-<700 g in one case, and ≥700 g in two cases. (4) The most common complication was moderate and severe bronchopulmonary dysplasia (10/13), followed by retinopathy of prematurity requiring surgical intervention (5/13), patent ductus arteriosus requiring ligation (4/13), late-onset sepsis (2/13), necrotizing enterocolitis (stage Ⅱa or above) (2/13) and grade Ⅲ-Ⅳ intraventricular hemorrhage or periventricular leukomalacia (2/13). The median duration of follow-up was ten months (6-69 months), and motor retardation occurred in three infants. Conclusions:The overall survival rate of PEPIs in our hospital is relatively high, with a lower incidence of complications during hospitalization and relatively better outcome. However, further studies are required for the long-term prognosis in this group of infants.