MicroRNAs (miRs) are involved in lymphoma progression by regulating tumor cell interaction with microenvironment. MiR155 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological effect on tumor microenvironment needs to be futher investigated. MiR155 was detected by quantitative real-time PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR155 on lymphoma progression and tumor microenvironment was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model. Serum miR155 was significantly elevated, correlated with tumor miR155 expression, and indicated poor disease outcome in DLBCL. MiR155 overexpression was associated with decreased peripheral blood CD8+T cells and inhibition of T-cell receptor signaling. Of note, EBV-positive patients showed higher serum miR155 than EBV-negative patients. In co-culture systems of B-lymphoma cells with immune cells, miR155 induced Fas-mediated apoptosis of CD8+T cells, which could be targeted by anti-PD-1 and anti-PD-L1 antibodies. Moreover, miR155 enhanced lymphoma cell PD-L1 expression, recruited CD8+T cells by PD-1/PD-L1 interaction and inhibited CD8+T cell function via dephosphorylating AKT and ERK. MiR155-induced AKT/ERK inactivation was more obvious in CD8+T cells co-cultured with EBV-infected B-lymphoma cells. In vivo in a murine xenograft model established with subcutaneous injection of A20 cells, PD-L1 blockade particularly retarded miR155-overexpressing tumor growth, consistent with maintenance of CD8+T cells and their function. As a oncogenic biomarker of B-cell lymphoma, serum miR155 was related to lymphoma progression through modulating PD-1/PD-L1-mediated interaction with CD8+T cells of tumor microenvironment, indicating the sensitivity of B-cell lymphoma to PD-L1 blockade. Also CD8+T cells could be a therapeutic mediator of immune checkpoint inhibitors in treating EBV-associated lymphoid malignancies.

Hyperuricemia (HUA) is very common in chronic kidney disease (CKD). HUA is associated with an increased risk of cardiovascular events and accelerates the progression of CKD. Our study aimed to explore the relationship between baseline serum uric acid levels and renal histopathological features. One thousand seventy patients receiving renal biopsy in our center were involved in our study. The baseline characteristics at the time of the kidney biopsy were collected from Renal Treatment System (RTS) database, including age, gender, serum uric acid (UA), glomerular filtration rate (eGFR), serum creatinine (Cr), urea, albumin (Alb), 24 h urine protein quantitation (24 h-u-pro) and blood pressure (BP). Pathological morphological changes were evaluated by two pathologists independently. Statistical analysis was done using SPSS 21.0. Among 1070 patients, 429 had IgA nephropathy (IgAN), 641 had non-IgAN. The incidence of HUA was 38.8% (n = 415), 43.8% (n = 188), and 43.2% (n = 277) in all patients, patients with IgAN and non-IgAN patients, respectively. Serum uric acid was correlated with eGFR (r = − 0.418, p < 0.001), Cr (r = 0.391, p < 0.001), urea (r = 0.410, p < 0.001), 24-u-pro (r = 0.077, p = 0.022), systolic blood pressure (SBP) (r = 0.175, p < 0.001) and diastolic blood pressure (DBP) (r = 0.109, p = 0.001). Multivariate logistic regression analysis showed that after adjustment for Cr, age and blood pressure, HUA was a risk factor for segmental glomerulosclerosis (OR = 1.800, 95% CI:1.309–2.477) and tubular atrophy/interstitial fibrosis (OR = 1.802, 95% CI:1.005–3.232). HUA increased the area under curve (AUC) in diagnosis of segmental glomerulosclerosis. Hyperuricemia is prevalent in CKD. The serum uric acid level correlates not only with clinical renal injury indexes, but also with renal pathology. Hyperuricemia is an independent risk factor for segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis.

Background: Burkitt leukemia/lymphoma is a major subtype of aggressive B-cell lymphoma. Biological targeted therapies on this disease need to be further investigated and may help to improve the clinical outcome of the patients. Methods: This study examined the anti-tumor activity of the histone deacetylases (HDAC) inhibitor valproic acid (VPA) combined with the mammalian target of rapamycin (MTOR) inhibitor temsirolimus in Burkitt leukemia/lymphoma cell lines, as well as in primary tumor cells and a murine xenograft model. Results: Co-treatment of VPA and temsirolimus synergistically inhibited the tumor cell growth and triggered the autophagic cell death, with a significant inhibition of MTOR signaling and MYC oncoprotein. Functioned as a class I HDAC inhibitor, VPA potentiated the effect of temsirolimus on autophagy through inhibiting HDAC1. Molecular silencing of HDAC1 using small interfering RNA (siRNA) attenuated VPA-mediated regulation of CDKN1A, CDKN1B and LC3-I/II, regression of tumor cell growth and induction of autophagy. Meanwhile, VPA counteracted temsirolimus-induced AKT activation via HDAC3 inhibition. HDAC3 siRNA abrogated the ability of VPA to modulate AKT phosphorylation, to suppress tumor cell growth and to induce autophagy. Strong antitumor effect was also observed on primary tumor cells while sparing normal hematopoiesis ex vivo. In a murine xenograft model established with subcutaneous injection of Namalwa cells, dual treatment efficiently blocked tumor growth, inhibited MYC and induced in situ autophagy. Conclusions: These findings confirmed the synergistic effect of the HDAC and MTOR inhibitors on Burkitt leukemia/lymphoma, and provided an insight into clinical application of targeting autophagy in treating MYC-associated lymphoid malignancies.

Early prediction of acute kidney injury (AKI) may provide a crucial opportunity for AKI prevention. To date, no prediction model targeting AKI among general hospitalized patients in developing countries has been published. Here we show a simple, real-time, interpretable AKI prediction model for general hospitalized patients developed from a large tertiary hospital in China, which has been validated across five independent, geographically distinct, different tiered hospitals. The model containing 20 readily available variables demonstrates consistent, high levels of predictive discrimination in validation cohort, with AUCs for serum creatinine-based AKI and severe AKI within 48 h ranging from 0.74–0.85 and 0.83–0.90 for transported models and from 0.81–0.90 and 0.88–0.95 for refitted models, respectively. With optimal probability cutoffs, the refitted model could predict AKI at a median of 72 (24–198) hours in advance in internal validation, and 54–90 h in advance in external validation. Broad application of the model in the future may provide an effective, convenient and cost-effective approach for AKI prevention.

The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.3.4.4b viruses, which have been shown to infect a range of mammalian species, including most recently being detected in dairy cattle. Ferrets were immunized with mRNA vaccines encoding either hemagglutinin alone or hemagglutinin and neuraminidase, derived from a 2.3.4.4b prototype vaccine virus recommended by the World Health Organization. Kinetics of the immune responses, as well as protection against a lethal challenge dose of A(H5N1) virus, were assessed. Two doses of mRNA vaccination elicited robust neutralizing antibody titers against a 2022 avian isolate and a 2024 human isolate. Further, mRNA vaccination conferred protection from lethal challenge, whereas all unvaccinated ferrets succumbed to infection. It also reduced viral titers in the upper and lower respiratory tracts of infected ferrets. These results underscore the effectiveness of mRNA vaccines against HPAI A(H5N1), showcasing their potential as a vaccine platform for future influenza pandemics.