Sulindac (K-80003) with nab-paclitaxel and gemcitabine overcomes drug-resistant pancreatic cancer.

The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance's core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.

Ocean wave energy harvesting with high energy density and self-powered monitoring system.

Constructing a ocean Internet of Things requires an essential ocean environment monitoring system. However, the widely distributed existing ocean monitoring sensors make it impractical to provide power and transmit monitored information through cables. Therefore, ocean environment monitoring systems particularly need a continuous power supply and wireless transmission capability for monitoring information. Consequently, a high-strength, environmentally multi-compatible, floatable metamaterial energy harvesting device has been designed through integrated dynamic matching optimization of materials, structures, and signal transmission. The self-powered monitoring system breaks through the limitations of cables and batteries in the ultra-low-frequency wave environment (1 to 2 Hz), enabling real-time monitoring of various ocean parameters and wirelessly transmitting the data to the cloud for post-processing. Compared with solar and wind energy in the ocean environment, the energy harvesting device based on the defective state characteristics of metamaterials achieves a high-energy density (99 W/m3). For the first time, a stable power supply for the monitoring system has been realized in various weather conditions (24 h).

Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits.

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

Nonlocal Acoustic Moiré Hyperbolic Metasurfaces.

The discovery of the topological transition in twisted bilayer (tBL) materials has attracted considerable attention in nano-optics. In the analogue of acoustics, however, no such topological transition has been found due to the inherent nondirectional scalar property of acoustic pressure. In this work, by using a theory-based nonlocal anisotropic design, the in-plane acoustic pressure is transformed into a spatially distributed vector field using twisted multilayer metasurfaces. So-called "acoustic magic angle"-related acoustic phenomena occur, such as nonlocal polariton hybridization and the topological Lifshitz transition. The dispersion becomes flat at the acoustic magic angle, enabling polarized excitations to propagate in a single direction. Moreover, the acoustic topological transition (from hyperbolic to elliptic dispersion) is experimentally observed for the first time as the twist angle continuously changes. This unique characteristic facilitates low-loss tunable polariton hybridization at the subwavelength scale. A twisted trilayer acoustic metasurface is also experimentally demonstrated, and more possibilities for manipulating acoustic waves are found. These discoveries not only enrich the concepts of moiré physics and topological acoustics but also provide a complete framework of theory and methodologies for explaining the phenomena that are observed.

Specific expression profile of follicular fluid-derived exosomal microRNAs in patients with diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR) is defined as a reduction in ovarian reserve and oocyte quality. The pathophysiology of DOR has not been completely explained as of yet. Scholars have uncovered a large number of exosomes that have been detected in follicular fluid, and exosomal miRNAs have been proven to play a critical role in controlling ovarian disorders and follicle formation. We focused on the expression profile of follicular fluid-derived exosomal microRNAs (miRNAs) and attempted to understand if their role is connected to the pathomechanism of DOR. METHODS: The follicular fluid-derived differentially expressed exosomal miRNAs (DEmiRs) between patients with DOR and those with normal ovarian function were investigated using the next-generation sequencing (NGS) method. The main metabolic and signaling pathways of DEmiRs were identified using the KEGG pathway database, disease ontology (DO) analysis, and gene ontology (GO) analysis. In the end, a Protein-Protein Interaction (PPI) network was built to search for exosomal miRNAs and their target genes that were potentially strongly connected with DOR. RESULTS: In comparison to normal controls, 52 DEmiRs were discovered in follicular fluid-derived exosomes of DOR patients, of which 19 were up-regulated and 33 were down-regulated (|log2(fold change) |>2, P < 0.05). GO, DO analysis, and the KEGG pathway database revealed that many of these DEmiRs have broad biological roles that are connected to ovarian function and disorders. The top ten DEmiRs in terms of expression were then chosen for miRNA-mRNA interaction analysis. Totally, 8 experimentally supported miRNAs (hsa-miR-1246, hsa-miR-483-3p, hsa-miR-122-5p, hsa-miR-130b-3p, hsa-miR-342-3p, hsa-miR-625-3p, hsa-miR-675-3p, and hsa-miR-134-5p) and 126 target genes were filtrated by utilizing Cytoscape software. The module analysis findings of the PPI network showed that the main module cluster with a score > 6.0 (MCODE score = 15) had six hub genes, including IGFR, VEGFA, KRAS, ERBB2, RHOA, and PTEN (MCODE score = 11.472). CONCLUSION: Our data suggested a special expression profile of follicular fluid-derived exosomal miRNAs in patients with DOR, which was probably correlated to ovarian dysfunction and follicle formation. These results may give a unique insight into a better understanding of the molecular process in the pathogenesis of DOR or other ovarian diseases.

Optical bistability in a heterodimer composed of a quantum dot and a metallic nanoshell.

We theoretically explore the conditions for generating optical bistability (OB) in a heterodimer comprised of a semiconductor quantum dot (SQD) and a metallic nanoshell (MNS). The MNS is made of a metallic nanosphere as a core and a dielectric material as a shell. For the specific hybrid system considered, the bistable effect appears only if the frequency of the pump field is equal to (or slightly less than) the exciton frequency for a proper shell thickness. Bistability phase diagrams, when plotted, show that the dipole-induced bistable region can be greatly broadened by changing the shell thickness of the MNS in a strong exciton-plasmon coupling regime. In particular, we demonstrate that the multipole polarization not only narrows the bistable zone but also enlarges the corresponding thresholds for a given intermediate scaled pumping intensity. On the other hand, when the SQD couples strongly with the MNS, the multipole polarization can also significantly broaden the bistable region and induce a great suppression of the FWM (four-wave mixing) signal for a fixed shell thickness. These interesting findings offer a fresh understanding of the bistability conditions in an SQD/MNS heterodimer, and may be useful in the fabrication of high-performance and low-threshold optical bistable nanodevices.

Two new dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.

Two undescribed dammarane triterpenoid saponins, cypaliurusides O and P (1 and 2), were isolated from the ethanol extracts of the leaves of Cyclocarya paliurus. Bioactivity assay results showed that compound 1 has potential cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 14.55 ± 0.55 to 22.75 ± 1.54 µM. Compound 1 showed better antitumor activity against HepG2 cells with IC50 of 14.55 ± 0.55 µM. In addition, compound 2 showed no obvious antitumor activity.

The functional specificity of ERECTA-family receptors in Arabidopsis stomatal development is ensured by molecular chaperones in the endoplasmic reticulum.

Stomata are epidermal pores that control gas exchange between plants and the atmosphere. In Arabidopsis, the ERECTA family (ERECTAf) receptors, including ERECTA, ERECTA-LIKE 1 (ERL1) and ERL2, redundantly play pivotal roles in enforcing the 'one-cell-spacing' rule. Accumulating evidence has demonstrated that the functional specificities of receptors are likely associated with their differential subcellular dynamics. The endoplasmic reticulum (ER)-resident chaperone complex SDF2-ERdj3B-BiP functions in many aspects of plant development. We employed pharmacological treatments combined with cell biological and biochemical approaches to demonstrate that the abundance of ERECTA was reduced in the erdj3b-1 mutant, but the localization and dynamics of ERECTA were not noticeably affected. By contrast, the erdj3b mutation caused the retention of ERL1/ERL2 in the ER. Furthermore, we found that the function of SDF2-ERdj3B-BiP is implicated with the distinct roles of ERECTAf receptors. Our findings establish that the ERECTAf receptor-mediated signaling in stomatal development is ensured by the activities of the ER quality control system, which preferentially maintains the protein abundance of ERECTA and proper subcellular dynamics of ERL1/ERL2, prior to the receptors reaching their destination - the plasma membrane - to execute their functions.

Arabidopsis ERdj3B coordinates with ERECTA-family receptor kinases to regulate ovule development and the heat stress response.

The endoplasmic reticulum-localized DnaJ family 3B (ERdj3B), is a component of the stromal cell-derived factor 2 (SDF2)-ERdj3B-binding immunoglobulin protein (BiP) chaperone complex, which functions in protein folding, translocation, and quality control. We found that ERdj3B mutations affected integument development in the Ler ecotype but not in the Col-0 ecotype of Arabidopsis (Arabidopsis thaliana). Map-based cloning identified the ERECTA (ER) gene as a natural modifier of ERdj3B. The double mutation of ERdj3B and ER caused a major defect in the inner integument under heat stress. Additional mutation of the ER paralog ERECTA-LIKE 1 (ERL1) or ERL2 to the erdj3b er double mutant exacerbated the defective integument phenotype. The double mutation of ER and SDF2, the other component of the SDF2-ERdj3B-BiP complex, resulted in similar defects in the inner integument. Furthermore, both the protein abundance and plasma membrane partitioning of ER, ERL1, and ERL2 were markedly reduced in erdj3b plants, indicating that the SDF2-ERdj3B-BiP chaperone complex might control the translocation of ERECTA-family proteins from the endoplasmic reticulum to the plasma membrane. Our results suggest that the SDF2-ERdj3B-BiP complex functions in ovule development and the heat stress response in coordination with ERECTA-family receptor kinases.

3D printed collagen/silk fibroin scaffolds carrying the secretome of human umbilical mesenchymal stem cells ameliorated neurological dysfunction after spinal cord injury in rats.

Although implantation of biomaterials carrying mesenchymal stem cells (MSCs) is considered as a promising strategy for ameliorating neural function after spinal cord injury (SCI), there are still some challenges including poor cell survival rate, tumorigenicity and ethics concerns. The performance of the secretome derived from MSCs was more stable, and its clinical transformation was more operable. Cytokine antibody array demonstrated that the secretome of MSCs contained 79 proteins among the 174 proteins analyzed. Three-dimensional (3D) printed collagen/silk fibroin scaffolds carrying MSCs secretome improved hindlimb locomotor function according to the Basso-Beattie-Bresnahan scores, the inclined-grid climbing test and electrophysiological analysis. Parallel with locomotor function recovery, 3D printed collagen/silk fibroin scaffolds carrying MSCs secretome could further facilitate nerve fiber regeneration, enhance remyelination and accelerate the establishment of synaptic connections at the injury site compared to 3D printed collagen/silk fibroin scaffolds alone group according to magnetic resonance imaging, diffusion tensor imaging, hematoxylin and eosin staining, Bielschowsky's silver staining, immunofluorescence staining and transmission electron microscopy. These results indicated the implantation of 3D printed collagen/silk fibroin scaffolds carrying MSCs secretome might be a potential treatment for SCI.

Ultra-strong optical four-wave mixing signal induced by strong exciton-phonon and exciton-plasmon couplings.

We propose a scheme to generate ultra-strong four-wave mixing (FWM) signal based on a suspended monolayer graphene nanoribbon nanomechanical resonator (NR) coupled to an Au nanoparticle (NP). It is shown that, the FWM spectrum can switch among two-peaked, three-peaked, four-peaked or five-peaked via the modulation of exciton-phonon and exciton-plasmon couplings. This is mainly attributed to the vibrational properties of NR related to the exciton-phonon coupling, and the energy-level splitting of the localized exciton correlated to three classes of resonances consisting of three-photon resonance, Rayleigh Resonance, and AC-Stark atomic resonance. Especially, in a dual-strong coupling regime, the gains for these peaks can be as high as nine orders of magnitude (∼ 109) around the lower bistable threshold due to a combined effect of two couplings. Our findings not only offer an efficient way to measure the vibrational frequency of NR and the exciton-phonon coupling strength but also provide a possibility to fabricate high-performance optoelectronic nanodevices.

Genome-wide association study reveals the genetic architecture of root hair length in maize.

BACKGROUND: Root hair, a special type of tubular-shaped cell, outgrows from root epidermal cell and plays important roles in the acquisition of nutrients and water, as well as interactions with biotic and abiotic stress. Although many genes involved in root hair development have been identified, genetic basis of natural variation in root hair growth has never been explored. RESULTS: Here, we utilized a maize association panel including 281 inbred lines with tropical, subtropical, and temperate origins to decipher the phenotypic diversity and genetic basis of root hair length. We demonstrated significant associations of root hair length with many metabolic pathways and other agronomic traits. Combining root hair phenotypes with 1.25 million single nucleotide polymorphisms (SNPs) via genome-wide association study (GWAS) revealed several candidate genes implicated in cellular signaling, polar growth, disease resistance and various metabolic pathways. CONCLUSIONS: These results illustrate the genetic basis of root hair length in maize, offering a list of candidate genes predictably contributing to root hair growth, which are invaluable resource for the future functional investigation.

The Mildew Resistance Locus O 4 Interacts with CaM/CML and Is Involved in Root Gravity Response.

The plant-specific mildew resistance locus O (MLO) proteins, which contain seven transmembrane domains and a conserved calmodulin-binding domain, play important roles in many plant developmental processes. However, their mechanisms that regulate plant development remain unclear. Here, we report the functional characterization of the MLO4 protein in Arabidopsis roots. The MLO4 was identified as interacting with CML12 in a screening for the interaction between the proteins from Arabidopsis MLO and calmodulin/calmodulin-like (CaM/CML) families using yeast two hybrid (Y2H) assays. Then, the interaction between MLO4 and CML12 was further verified by Luciferase Complementation Imaging (LCI) and Bimolecular Fluorescence Complementation (BiFC) assays. Genetic analysis showed that the mlo4, cml12, and mlo4 cml12 mutants displayed similar defects in root gravity response. These results imply that the MLO4 might play an important role in root gravity response through interaction with CML12. Moreover, our results also demonstrated that the interaction between the MLO and CaM/CML families might be conservative.

[A Cross-sectional Study of Osteoporosis and Cardiovascular Calcification in Patients with Chronic Kidney Disease at Different CKD Stages].

OBJECTIVE: To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. METHODS: A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and ß-crosslaps (ß-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. RESULTS: Compared with control group, levels of serum P, iPTH, BALP, PINP and ß-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). CONCLUSION: The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.

Efficacy of short-term moderate or high-dose statin therapy for the prevention of contrast-induced nephropathy in high-risk patients with chronic kidney disease: systematic review and meta-analysis.

Although previous studies have indicated that statin therapy can effectively prevent the development of CIN, this observation remains controversial, especially in high-risk patients. A meta-analysis was performed to evaluate the efficacy of statin pretreatment for preventing the development of CIN in patients with chronic kidney disease (CKD) and to determine its effectiveness in various subgroups. We searched the online databases PubMed, EMBASE, and the Cochrane Library. RCTs that involved the comparison of the short-term moderate or high-dose statin pretreatment with placebo for CIN prevention in CKD patients undergoing angiography were included. The primary outcome was CIN prevalence. Seven RCTs comprising 4256 participants were investigated in this analysis. The risk of developing CIN in patients pretreated with statins was significantly lower than that in patients pretreated with placebo (RR=0.57, 95%CI=0.43-0.76, p=0.000). The SCr values of the statin group, when analyzed 48h after angiography were lower than those of the placebo group ((SMD=-0.15, 95% CI=-0.27 to -0.04, p=0.011). In the subgroup analysis, statin pretreatment could decrease the risk of CIN in CKD patients with DM (RR=0.54, 95% CI=0.39-0.76, p=0.000), but not in CKD patients without DM (RR=0.84, 95% CI=0.44-1.60, p=0.606). The efficacy of atorvastatin for preventing CIN was consistent with that observed with the use of rosuvastatin. The risk ratios (RR) were 0.51 (95% CI=0.32-0.81, p=0.004) and 0.60 (95% CI=0.41-0.88, p=0.009), respectively. Our study demonstrated that statin pretreatment could prevent the development of CIN in CKD patients. However, subgroup analysis demonstrated that statin pretreatment, despite being effective in preventing CIN in patients with CKD and DM, was not helpful for CKD patients without DM. Rosuvastatin and atorvastatin exhibited similar preventive effects with respect to CIN.

Protein complex formation in methionine chain-elongation and leucine biosynthesis.

During the past two decades, glucosinolate (GLS) metabolic pathways have been under extensive studies because of the importance of the specialized metabolites in plant defense against herbivores and pathogens. The studies have led to a nearly complete characterization of biosynthetic genes in the reference plant Arabidopsis thaliana. Before methionine incorporation into the core structure of aliphatic GLS, it undergoes chain-elongation through an iterative three-step process recruited from leucine biosynthesis. Although enzymes catalyzing each step of the reaction have been characterized, the regulatory mode is largely unknown. In this study, using three independent approaches, yeast two-hybrid (Y2H), coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC), we uncovered the presence of protein complexes consisting of isopropylmalate isomerase (IPMI) and isopropylmalate dehydrogenase (IPMDH). In addition, simultaneous decreases in both IPMI and IPMDH activities in a leuc:ipmdh1 double mutants resulted in aggregated changes of GLS profiles compared to either leuc or ipmdh1 single mutants. Although the biological importance of the formation of IPMI and IPMDH protein complexes has not been documented in any organisms, these complexes may represent a new regulatory mechanism of substrate channeling in GLS and/or leucine biosynthesis. Since genes encoding the two enzymes are widely distributed in eukaryotic and prokaryotic genomes, such complexes may have universal significance in the regulation of leucine biosynthesis.

The Arabidopsis AGC kinases NDR2/4/5 interact with MOB1A/1B and play important roles in pollen development and germination.

Pollen formation and pollen tube growth are essential for the delivery of male gametes into the female embryo sac for double fertilization. Little is known about the mechanisms that regulate the late developmental process of pollen formation and pollen germination. In this study, we characterized a group of Arabidopsis AGC kinase proteins, NDR2/4/5, involved in pollen development and pollen germination. The NDR2/4/5 genes are mainly expressed in pollen grains at the late developmental stages and in pollen tubes. They function redundantly in pollen formation and pollen germination. At the tricellular stages, the ndr2 ndr4 ndr5 mutant pollen grains exhibit an abnormal accumulation of callose, precocious germination and burst in anthers, leading to a drastic reduction in fertilization and a reduced seed set. NDR2/4/5 proteins can interact with another group of proteins (MOB1A/1B) homologous to the MOB proteins from the Hippo signaling pathway in yeast and animals. The Arabidopsis mob1a mob1b mutant pollen grains also have a phenotype similar to that of ndr2 ndr4 ndr5 pollen grains. These results provide new evidence demonstrating that the Hippo signaling components are conserved in plants and play important roles in sexual plant reproduction.

Efficacy of short-term moderate or high-dose statin therapy for the prevention of contrast-induced nephropathy in high-risk patients with chronic kidney disease: systematic review and meta-analysis

Although previous studies have indicated that statin therapy can effectively prevent the development of CIN, this observation remains controversial, especially in high-risk patients. A meta-analysis was performed to evaluate the efficacy of statin pretreatment for preventing the development of CIN in patients with chronic kidney disease (CKD) and to determine its effectiveness in various subgroups. We searched the online databases PubMed, EMBASE, and the Cochrane Library. RCTs that involved the comparison of the short-term moderate or high-dose statin pretreatment with placebo for CIN prevention in CKD patients undergoing angiography were included. The primary outcome was CIN prevalence. Seven RCTs comprising 4256 participants were investigated in this analysis. The risk of developing CIN in patients pretreated with statins was significantly lower than that in patients pretreated with placebo (RR=0.57, 95%CI=0.43-0.76, p=0.000). The SCr values of the statin group, when analyzed 48h after angiography were lower than those of the placebo group ((SMD=-0.15, 95% CI=-0.27 to -0.04, p=0.011). In the subgroup analysis, statin pretreatment could decrease the risk of CIN in CKD patients with DM (RR=0.54, 95% CI=0.39-0.76, p=0.000), but not in CKD patients without DM (RR=0.84, 95% CI=0.44-1.60, p=0.606). The efficacy of atorvastatin for preventing CIN was consistent with that observed with the use of rosuvastatin. The risk ratios (RR) were 0.51 (95% CI=0.32-0.81, p=0.004) and 0.60 (95% CI=0.41-0.88, p=0.009), respectively. Our study demonstrated that statin pretreatment could prevent the development of CIN in CKD patients. However, subgroup analysis demonstrated that statin pretreatment, despite being effective in preventing CIN in patients with CKD and DM, was not helpful for CKD patients without DM. Rosuvastatin and atorvastatin exhibited similar preventive effects with respect to CIN.