Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders and a primary cause of pain and disability among the elderly population. Research on the relationship between metalloproteins (MPs) and OA is limited, and causality remains unclear. Our objective is to utilize Mendelian randomization (MR) to explore the possible causal relationship between MPs and OA. The data on MPs were derived from a Genome-Wide Association Study (GWAS) analysis involving 3301 samples. The GWAS data for OA were obtained from an analysis involving 462,933 European individuals. In this study, a variety of two-sample Mendelian randomization methods (two-sample MR) to evaluate the causal effect of MPs on OA, including inverse variance weighted method (IVW), MR-Egger method, weighted median method (WM), simple mode, weight mode, and Wald ratio. The primary MR analysis using the IVW method reveals a significant negative correlation between Metallothionein-1F (MT-1F), zinc finger protein 134 (ZNF134), calcium/calmodulin-dependent protein kinase type 1D (CAMK1D), and EF-hand calcium-binding domain-containing protein 14 (EFCAB14) with the occurrence of osteoarthritis (OA) (p value < 0.05). However, no causal relationship was observed in the opposite direction between these MPs and OA. Notably, even in combined models accounting for confounding factors, the negative association between these four MPs and OA remained significant. Sensitivity analysis demonstrated no evidence of horizontal pleiotropy or heterogeneity, and leave-one-out analysis confirmed the robustness of the results. In this study, we have established a conspicuous association between four distinct MPs and OA. This discovery augments our understanding of potential avenues for the diagnosis and treatment of this condition. Key Points • The MR method was employed to assess the relationship between MPs and OA. • A total of four types of MPs have demonstrated inhibitory effects on the occurrence of OA.

GLIM criteria for definition of malnutrition in peritoneal dialysis: a new aspect of nutritional assessment.

Background: The aim of our study was to evaluate the effectiveness of Global Leadership Initiative on Malnutrition (GLIM) criteria in assessing malnutrition within the peritoneal dialysis (PD) population.Methods: We conducted a retrospective analysis involving 1057 PD patients across multiple institutions, characterized by an age of 56.1 ± 14.4 years, 464 (43.9%) female, and a median follow-up of 45 (25, 68) months. Malnutrition was diagnosed according to GLIM criteria. The endpoint event was overall mortality. The survival rate and hazard ratio (HR) of death between malnutrition and well-nourished were analyzed in all patients and various subgroups. Receiver operator characteristic curve and integrated discrimination improvement (IDI) were used to distinguish the efficacy of the nutritional tools prediction model.Results: According to the GLIM criteria, the prevalence of malnutrition among the study population was 34.9%. The adjusted HR of overall mortality was 2.91 (2.39 - 3.54, p < 0.001) for malnutrition versus well-nourished. In sensitivity analyses, the HR remained robust except the cardiovascular disease subgroup. The area under the curve of GLIM predicting 5-year mortality was 0.65 (0.62-0.68, p < 0.001). As a complex model for forecast the long-term mortality, the performance of adjusted factors combined with GLIM was poorer than combined malnutrition inflammation score (MIS) (IDI >0, p < 0.001), but fitter than combined geriatric nutritional risk index (GNRI) (IDI <0, p < 0.001).Conclusions: The GLIM criteria provide a viable tool for nutritional assessment in patients with PD, and malnutrition defined according to the GLIM can predict prognosis with an acceptable performance.

Pull-through technique through antegrade radial artery puncture without sheath insertion in balloon-assisted radiocephalic arteriovenous fistulas maturation.

PURPOSE: The aim of this study was to investigate the effectiveness and safety of the pull-through technique through antegrade radial artery puncture without sheath insertion in balloon-assisted radiocephalic AVF maturation. METHODS: We retrospective studied a total of 62 patients with immature radiocephalic AVF, who received balloon-assisted maturation in our hospital. 15 patients received pull-through technique through radial artery without sheath insertion and 47 patients received treatment through a regular venous approach. RESULTS: The success rate of pull-through technique group and control group was 86.7% (13 out of 15), 89.1% (41 out of 46) respectively. There was no significant difference between two groups (P > 0.05). In our study, there were 2 patients in the pull-through technique group and 3 patients in the control group, which had hematoma in the vein puncture site (P = 0.59). There were also no differences in the primary patency rate between two groups at 6 months and 12 months (76.9% vs 70.7%, 38.4% vs 41.5%, respectively, P > 0.05). CONCLUSION: The pull-through technique through antegrade radial artery without sheath insertion in promoting radiocephalic AVF maturation is effective and safe.

Association between sarcopenia and new-onset chronic kidney disease among middle-aged and elder adults: findings from the China Health and Retirement Longitudinal Study.

BACKGROUND: Sarcopenia is a senile syndrome of age-related muscle loss. It is thought to affect the development of chronic kidney disease and has a serious impact on the quality of life of the elder adults. Little is known about the association between sarcopenia and new-onset chronic kidney disease in middle-aged and elder adults. Using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a longitudinal analysis to investigate the association between sarcopenia status and new-onset chronic kidney disease in middle-aged and elder adults in China. METHODS: The study population consisted of 3676 participants aged 45 or older selected from 2011 CHARLS database who had no history of chronic kidney disease at the baseline and completed the follow-up in 2015. A multivariate cox regression model was employed to examine the association between sarcopenia and the incidence of new-onset chronic kidney disease. RESULTS: Followed up for 4 years, a total of 873 (22.5%) new cases of chronic kidney disease occurred. Among them, participants diagnosed with sarcopenia (HR1.45; 95% CI 1.15-1.83) were more likely to develop new-onset chronic kidney disease than those without sarcopenia. Similarly, patients with sarcopenia were more likely to develop new-onset chronic kidney disease than those with possible sarcopenia (HR 1.27; 95%CI 1.00-1.60). Subgroup analysis revealed that elder adults aged between 60 and 75 years old (HR 1.666; 95%CI 1.20-22.28), with hypertension (HR 1.57; 95%CI 1.02-2.40), people with sarcopenia had a significantly higher risk of developing new-onset chronic kidney disease than those without sarcopenia (all P < 0.05). CONCLUSION: Middle-aged and elder adults diagnosed with sarcopenia have a higher risk of developing new-onset chronic kidney disease.

NEDD4 lactylation promotes APAP induced liver injury through Caspase11 dependent non-canonical pyroptosis.

Caspase-11 detection of intracellular lipopolysaccharide mediates non-canonical pyroptosis, which could result in inflammatory damage and organ lesions in various diseases such as sepsis. Our research found that lactate from the microenvironment of acetaminophen-induced acute liver injury increased Caspase-11 levels, enhanced gasdermin D activation and accelerated macrophage pyroptosis, which lead to exacerbation of liver injury. Further experiments unveiled that lactate inhibits Caspase-11 ubiquitination by reducing its binding to NEDD4, a negative regulator of Caspase-11. We also identified that lactates regulated NEDD4 K33 lactylation, which inhibits protein interactions between Caspase-11 and NEDD4. Moreover, restraining lactylation reduces non-canonical pyroptosis in macrophages and ameliorates liver injury. Our work links lactate to the exquisite regulation of the non-canonical inflammasome, and provides a basis for targeting lactylation signaling to combat Caspase-11-mediated non-canonical pyroptosis and acetaminophen-induced liver injury.

Pleural effusion portends a poor prognosis in patients on continuous ambulatory peritoneal dialysis.

AIMS: Pleural effusion is not an infrequent complication in patients undergoing continuous ambulatory peritoneal dialysis. However, there is not adequate data to evaluate pleural effusion and prognosis in clinical practice. In this study, we validated this potential association by a multicenter cohort. METHODS: We screened 1,162 patients who met the inclusion criteria with PD. According to the existence of pleural effusion on stable dialysis (4-8 weeks after dialysis initiation), the participants were divided into pleural effusion and non-pleural effusion groups. The hazard ratios (HRs) of all-cause and cause-specific death were estimated with adjustment for demographic characteristics and multiple potential clinical confounders. Subgroup analysis and propensity score matching (PSM) were used to further verify the robustness of the correlation between hydrothorax and prognosis. RESULTS: Pleural effusion was found in 8.9% (104/1162) of PD individuals. After adjusting for the confounding factors, patients with pleural effusion had significantly increased HRs for all-cause death was 3.06 (2.36-3.96) and cardiovascular death was 3.78 (2.67-5.35) compared to those without pleural effusion. However, it was not associated with infectious and other causes of death. After PSM, the HR of all-cause mortality was 3.56 (2.28-5.56). The association trends were consistent in the subgroup sensitivity analysis. CONCLUSION: Pleural effusion is not rare in PD, and is significantly associated with overall and cardiovascular mortality, which is independent of underlying diseases and clinically relevant indicators.

Convergent relationships between flower economics and hydraulic traits across aquatic and terrestrial herbaceous plants.

Maintaining open flowers is critical for successful pollination and depends on long-term water and carbon balance. Yet the relationship between how flower hydraulic traits are coordinated in different habitats is poorly understood. Here, we hypothesize that the coordination and trade-offs between floral hydraulics and economics traits are independent of environmental conditions. To test this hypothesis, we investigated a total of 27 flower economics and hydraulic traits in six aquatic and six terrestrial herbaceous species grown in a tropical botanical garden. We found that although there were a few significant differences, most flower hydraulics and economics traits did not differ significantly between aquatic and terrestrial herbaceous plants. Both flower mass per area and floral longevity were significantly positively correlated with the time required for drying full-hydrated flowers to 70% relative water content. Flower dry matter content was strongly and positively related to drought tolerance of the flowers as indicated by flower water potential at the turgor loss point. In addition, there was a trade-off between hydraulic efficiency and the construction cost of a flower across species. Our results show that flowers of aquatic and terrestrial plants follow the same economics spectrum pattern. These results suggest a convergent flower economics design across terrestrial and aquatic plants, providing new insights into the mechanisms by which floral organs adapt to aquatic and terrestrial habitats.

Intermolecular Carbophosphination of Alkynes with Phosphole Oxides via Ni-Al Bimetal-Catalyzed C-P Bond Activation.

Intermolecular carbophosphination reaction of alkynes or alkenes with unreactive C-P bonds remains an elusive challenge. Herein, we used a Ni-Al bimetallic catalyst to realize an intermolecular carbophosphination reaction of alkynes with 5-membered phosphole oxides, providing a series of 7-membered phosphepines in up to 94 % yield.

Visit-to-visit HbA1c variability is associated with poor prognosis in peritoneal dialysis patients with type 2 diabetes mellitus.

BACKGROUND: The prognosis of diabetic peritoneal dialysis patients is poor. HbA1c serves as a crucial indicator for monitoring blood glucose control in patients with diabetes. Nevertheless, the relationship between visit-to-visit HbA1c variability and prognosis in peritoneal dialysis with diabetes remains unclear. METHODS: All participants were categorized into 3 groups based on the HbA1c variability score (HVS), which is the frequency of 0.5% (5.5 mmol/mol) alter in visit-to-visit HbA1c values. Then, the hazard ratio to HVS with all-cause mortality was analyzed using the Cox hazard model, followed by the Fine-Gray competing risk model for major adverse cardiovascular events. Subgroup and sensitivity analysis were conducted to ascertain the robustness of the findings. RESULTS: Eight hundred twenty patients with type 2 diabetes were finally enrolled in this study from 2,855 participants with a mean age of 56.9 ± 14.6 years and a median follow-up time of 44 months [IQR: 27-70], death occurred in 496 (60.2%) individuals. Compared with the lowest category (HVS < 1/3) after being adjusted by potential confounding factors, the hazard ratio for all-cause mortality was 4.59 (3.74-5.64) and the sub-distribution hazard ratio for major adverse cardiovascular events was 1.91 (1.46-2.51) of the highest category (HVS ≥ 2/3). Subgroup interaction and sensitivity analysis, including the adjustment for variables such as time-weighted average HbA1c, HbA1c measurement times and expansion, confirmed the reliability of the results. CONCLUSION: The HVS is related to the risk of poor prognosis in peritoneal dialysis with type 2 diabetes mellitus, independently of clinical multiple variables, and is a novel indicator with clinical guidance.

Discovery of novel cGAS inhibitors based on natural flavonoids.

Cyclic GMP-AMP synthase (cGAS) plays an important role in the inflammatory response. It has been reported that aberrant activation of cGAS is associated with a variety of immune-mediated inflammatory disorders. The development of small molecule inhibitors of cGAS has been considered as a promising therapeutic strategy for the diseases. Flavonoids, a typical class of natural products, are known for their anti-inflammatory activities. Although cGAS is closely associated with inflammation, the potential effects of natural flavonoid compounds on cGAS have been rarely studied. Therefore, we screened an in-house natural flavonoid library by pyrophosphatase (PPiase) coupling assay and identified novel cGAS inhibitors baicalein and baicalin. Subsequently, crystal structures of the two natural flavonoids in complex with human cGAS were determined, which provide mechanistic insight into the anti-inflammatory activities of baicalein and baicalin at the molecular level. After that, a virtual screening based on the crystal structures of baicalein and baicalin in complex with human cGAS was performed. As a result, compound C20 was identified to inhibit both human and mouse cGAS with IC50 values of 2.28 and 1.44 µM, respectively, and its detailed interactions with human cGAS were further revealed by the X-ray crystal structure determination. These results demonstrate the potential of natural products used as hits in drug discovery and provide valuable hints for further development of cGAS inhibitors.

The hemoglobin, albumin, lymphocyte, and platelet (HALP) is a potent indicator for the prognosis in hemodialysis patients.

The hemoglobin, albumin, lymphocyte, and platelet (HALP) values were marked as a original index of general nutritional and inflammatory conditions. The purpose of this investigation was to evaluate the potential relationship between HALP and prognosis in hemodialysis (HD) patients. Patients with maintenance HD from multiple dialysis centers in China were retrospectively analyzed. The primary poor outcome were cardiovascular disease (CVD) and all-cause death. The computational equation of HALP values as the follows: hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/ platelets (/L). All participants were divided into Tertile 1, Tertile 2, and Tertile 3 according to the tertiles of baseline HALP values. The Kaplan-Meier curve and the Cox regression was done to figure out the relationship about HALP and adverse outcomes. The restricted cubic splines further identified the possible associations. The time-dependent receiver operating characteristic curve and C-index were implemented for evaluate the predictive values of the HALP composite model. There were 4796 patients incorporate into ultimate study. Compared with patients in Tertile 1, patients in Tertile 3 had an lower risk of all-cause mortality [hazard ratios = 0.66, 95% confidence intervals: 0.49-0.86, P = .007] and CVD mortality [sub-distribution hazard ratio = 0.51, 95% confidence intervals: 0.34-0.80, P = .005]. The composite model with the supplement of HALP outperformed the traditional factor model in the time-dependent receiver operating characteristic curve. High HALP values at baseline are related to a diminished risk of CVD death and all-cause death in HD patients. HALP is a novel and potent index for the prognosis of HD patients.

Catalyst-Controlled Nickel-Catalyzed Intramolecular endo-Selective C-H Cyclization of Benzimidazoles with Alkenes.

Compared with the widely explored exo-selective C-H cyclization, transition metal-catalyzed endo-selective C-H cyclization of benzimidazoles with alkenes has been a formidable challenge. Previous efforts mainly rely on substrate-controlled methods, rendering the product complexity restricted. Herein we report a catalyst-controlled method to facilitate endo-cyclization, in which a bulky N-heterocyclic carbene ligand and tBuOK base-enabled Ni-Al bimetallic catalyst prove critical to the endo selectivity.

Pan-immune-inflammation value is associated with poor prognosis in patients undergoing peritoneal dialysis.

BACKGROUND: Immune-inflammatory biomarkers (IIBs) have been shown to be correlated with prognosis in patients undergoing peritoneal dialysis (PD). In this study, we aimed to evaluate the relationship between a novel comprehensive biomarker, the pan-immune-inflammation value (PIV), and the prognosis of patients undergoing PD. METHODS: We retrospectively analyzed data from a multicenter, large-sample PD database. PIV was calculated as (neutrophil count × platelet count × monocyte count)/lymphocyte count. The prognostic endpoints in this study were all-cause death all-cause, cardiovascular disease (CVD) and infection-related death. The Kaplan-Meier method, a Cox proportional hazards regression, Fine-Gray competing risk model, smooth curve, and subgroup analysis were used to analyze the independent relationship between PIV and the prognosis of patients undergoing PD. RESULTS: A total of 2796 cases of PD were included, and the study population was divided into Tertiles 1, 2, and 3, according to the tertiles of baseline PIVs. After adjusting for multiple model factors, patients in the Tertile 3 group had a significantly higher risk of all-cause death, CVD death and infection-related death compared with patients with PIV in the Tertile 1 group. Interaction tests showed no positive correlations for subgroup parameters. Regarding all-cause death, compared with the lowest tertile, the multivariable-adjusted hazard ratios (95% confidence intervals) of the highest and middle tertiles were 1.55 (1.25-1.94) and 1.77 (1.43-2.19), respectively; PIV (log2 processing) was associated with 17% excess of mortality in the continuous model. CONCLUSIONS: A high PIV at baseline was significantly associated with an increased risk of deaths due to all-causes, CVD and infection in patients undergoing PD.

Circ_0005925 Promotes Granulosa Cell Growth by Targeting MiR-324-3p to Upregulate MAP2K6 in Polycystic Ovary Syndrome.

Circular RNA has been reported to be involved in the development of polycystic ovary syndrome (PCOS), but the role of circ_0005925 in the progression of PCOS is unclear. The expression levels of circ_0005925, microRNA (miR)-324-3p, and MAPK kinase 6 (MAP2K6) were examined by quantitative real-time PCR. Cell proliferation and apoptosis were determined using cell counting kit 8 assay, EdU assay, colony formation assay, and flow cytometry. Western blot analysis was used to detect the protein expression of apoptosis markers and MAP2K6. RNA interaction was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_0005925 was upregulated in GCs from PCOS patients, as well as in KGN and SVOG cells. Circ_0005925 knockdown repressed GCs proliferation and promoted apoptosis. MiR-324-3p was downregulated in PCOS patients, and it was sponged by circ_0005925. The regulation of circ_0005925 knockdown on GCs growth was abolished by miR-324-3p inhibitor. MAP2K6 was targeted by miR-324-3p, and its expression was positively regulated by circ_0005925. MiR-324-3p inhibited GCs proliferation and increased apoptosis by targeting MAP2K6. Collectively, our findings suggested that circ_0005925 promoted GCs growth through miR-324-3p/MAP2K6, which provided a promising therapeutic target for PCOS.

ZFP36L1 Promotes Gastric Cancer Progression via Regulating JNK and p38 MAPK Signaling Pathways.

BACKGROUND: The RNA-binding protein Zinc Finger Protein 36 like 1(ZFP36L1) plays an important role in regulating the AU-rich elements (AREs) in the 3' untranslated region (3' UTR) of mRNAs, indicating a potential link between its expression and cancers. However, the role and mechanism of ZFP36L1 in gastric cancer (GC) are unclear. OBJECTIVES: This study aimed to explore the role and mechanism of ZFP36L1 in gastric cancer. MATERIALS AND METHODS: GC tissue samples and matched normal gastric tissues were collected, and the ZFP36L1 expression in these samples was evaluated by immunohistochemistry analysis. GC cells with different differentiation were selected for in vitro experiments. The ZFP36L1 expression in GC cells was examined by quantitative real-time polymerase chain reaction (qRTPCR) and Western blot analysis. The viability and invasiveness of GC cells were assayed by 5- Ethynyl-2-deoxyuridine (EdU) and Transwell assays, respectively. Western blot assay was used to detect the expression of epithelial-to-mesenchymal transition (EMT) related proteins and proteins of the c-Jun N-terminal kinase (JNK) and p38 Mitogen-Activated Protein Kinase (MAPK) signaling pathways. RESULTS: ZFP36L1 is overexpressed in GC tissues. Patients with high ZFP36L1 expression have a poor prognosis. Moreover, ZFP36L1 is overexpressed in the cell lines with a high degree of malignancy. ZFP36L1 increases cell proliferation, invasion, and migration in vitro. Furthermore, ZFP36L1 induces EMT. The JNK inhibitor and p38 inhibitor alone or in combination affect the biological function of GC cells. Furthermore, ZFP36L1 promotes GC progression by inhibiting JNK and p38 MAPK signaling pathways. CONCLUSION: RNA-binding protein ZFP36L1 exerts a role in the occurrence of gastric cancer by the regulation of the JNK and p38 MAPK signaling pathways. The combination of inhibitors of the JNK and p38 MAPK signaling pathways could be a novel treatment strategy for gastric cancer.

Identification of hepatocellular carcinoma subtypes based on PcG-related genes and biological relevance with cancer cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is an extensive heterogeneous disease where epigenetic factors contribute to its pathogenesis. Polycomb group (PcG) proteins are a group of subunits constituting various macro-molecular machines to regulate the epigenetic landscape, which contributes to cancer phenotype and has the potential to develop a molecular classification of HCC. RESULTS: Here, based on multi-omics data analysis of DNA methylation, mRNA expression, and copy number of PcG-related genes, we established an epigenetic classification system of HCC, which divides the HCC patients into two subgroups with significantly different outcomes. Comparing these two epigenetic subgroups, we identified different metabolic features, which were related to epigenetic regulation of polycomb-repressive complex 1/2 (PRC1/2). Furthermore, we experimentally proved that inhibition of PcG complexes enhanced the lipid metabolism and reduced the capacity of HCC cells against glucose shortage. In addition, we validated the low chemotherapy sensitivity of HCC in Group A and found inhibition of PRC1/2 promoted HCC cells' sensitivity to oxaliplatin in vitro and in vivo. Finally, we found that aberrant upregulation of CBX2 in Group A and upregulation of CBX2 were associated with poor prognosis in HCC patients. Furthermore, we found that manipulation of CBX2 affected the levels of H3K27me3 and H2AK119ub. CONTRIBUTIONS: Our study provided a novel molecular classification system based on PcG-related genes data and experimentally validated the biological features of HCC in two subgroups. Our founding supported the polycomb complex targeting strategy to inhibit HCC progression where CBX2 could be a feasible therapeutic target.

Targeting Tumor Physical Microenvironment for Improved Radiotherapy.

Radiotherapy has led to important clinical advances; existing cancer radiotherapy resistance is one remaining major challenge. Recently, biophysical cues in the tumor microenvironment (TME) have been regarded as the new hallmarks of cancer, playing pivotal roles in various cancer behaviors and treatment responses, including radiotherapy resistance. With recent advances in micro/nanotechnologies and functional biomaterials, radiotherapy exerts great influence on biophysical cues in TME, which, in turn, significantly affect the response to radiotherapy. Besides, various strategies have emerged that target biophysical cues in TME, to potentially enhance radiotherapy efficacy. Therefore, this paper reviews the four biophysical cues (i.e., extracellular matrix (ECM) microarchitecture, ECM stiffness, interstitial fluid pressure, and solid stress) that may play important roles in radiotherapy resistance, their possible mechanisms for inducing it, and their change after radiotherapy. The emerging therapeutic strategies targeting the biophysical microenvironment, to explore the mechanism of radiotherapy resistance and develop effective strategies to revert it for improved treatment efficacy are further summarized.

Enantioselective Nickel-Catalyzed C(sp3 )-H Activation of Formamides.

Enantioselective Ni-catalyzed C(sp3 )-H bond activation remains an elusive challenge. Herein, we used phosphine oxide-ligated Ni-Al bimetallic catalyst to realize enantioselective Ni-catalyzed aliphatic C(sp3 )-H activation of formamides, providing a series of chiral N-containing heterocycles in 40-95 % yield and 70-95 % ee.

[ZFP36L1 inhibits proliferation, invasion and migration of human breast cancer cells by inducing epithelial-mesenchymal transition through STAT3/p-STAT3 signaling pathway].

Objective To explore the role and mechanism of zinc finger protein 36 like 1 (ZFP36L1) in breast cancer. Methods Sixty breast cancer patients were enrolled in the study. Immunohistochemistry was performed to evaluate the ZFP36L1 expression. Clinicopathological parameters were observed. MCF-7 cells were transfected with overexpressed ZFP36L1 plasmid. The viability of MCF-7 cells was assayed by the 5-ethynyl-2-deoxyuridine (EdU) and MTS assay. The invasion of MCF-7 cells was assessed by TranswellTM assay. Western blot analysis was used to detect the expression of ß-catenin, vimentin, E-cadherin, signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3). Results ZFP36L1-low expression has been found to be associated with poor prognosis in patients with breast cancer. Moreover, ZFP36L1 overexpression inhibited cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) in vitro. Accordingly, the expression of STAT3 and p-STAT3 increased significantly. Conclusion ZFP36L1, as a cancer suppressor gene, inhibits cell proliferation, invasion, and migration through EMT and STAT3 signaling pathway.

Clinical Value of Prognostic Nutritional Index and Neutrophil-to-Lymphocyte Ratio in Prediction of the Development of Sepsis-Induced Kidney Injury.

Background: Sepsis-related acute kidney injury (S-AKI) is a frequent complication of hospitalized patients and is linked to increased morbidity and mortality. Early prediction and detection remain conducive to optimizing treatment strategies and limiting further insults. This study was aimed at evaluating the potential predictive value of the combined prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) to predict the risk of AKI in septic patients. Methods: In this retrospective study, 1238 adult patients with sepsis who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to June 2021 were enrolled. Patients were divided into two groups: the non-AKI group (n = 731) and the S-AKI group (n = 507). Univariate and multivariate logistic regression analyses were performed to screen the independent predictive factors of S-AKI. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of PNI and NLR. Results: Multivariate logistic regression analysis indicated that age, chronic liver disease, cardiovascular disease, respiratory rate (RR), white blood cells (WBC), blood urea nitrogen (BUN), creatinine (CRE), international normalized ratio (INR), neutrophil-to-lymphocyte ratio (NLR), and prognostic nutrition index (PNI) were independent prognostic factors of S-AKI. In the three models, the adjusted OR of PNI for S-AKI was 0.802 (0.776-0.829), 0.801 (0.775-0.829), and 0.717 (0.666-0.772), while that of NLR was 1.094 (1.078-1.111), 1.097 (1.080-1.114), and 1.044 (1.016-1.072), respectively. In addition, the area under the ROC curve of the PNI plus NLR group was significantly greater than that of the CRE plus BUN group (0.801, 95% CI: 0.775-0.827 vs. 0.750, 95% CI: 0.722-0.778, respectively; P < 0.001). Conclusions: PNI and NLR have been identified as readily available and independent predictors in septic patients with S-AKI. PNI, in combination with NLR, is of vital significance for early warning and efficient intervention of S-AKI and is superior to combined BUN and CRE.