Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.

Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4.

Ferroptosis holds great potential as a therapeutic approach for gastric cancer (GC), a prevalent and deadly malignant tumor associated with high rates of incidence and mortality. Myricetin, well-known for its multifaceted biomedical attributes, particularly its anticancer properties, has yet to be thoroughly investigated regarding its involvement in ferroptosis. The aim of this research was to elucidate the impact of myricetin on ferroptosis in GC progression. The present study observed that myricetin could trigger ferroptosis in GC cells by enhancing malondialdehyde production and Fe2+ accumulation while suppressing glutathione levels. Mechanistically, myricetin directly interacted with NADPH oxidase 4 (NOX4), influencing its stability by inhibiting its ubiquitin degradation. Moreover, myricetin regulated the inhibition of ferroptosis induced by Helicobacter pylori cytotoxin-associated gene A (CagA) through the NOX4/NRF2/GPX4 pathway. In vivo experiments demonstrated that myricetin treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice. It was accompanied by increased NOX4 expression in tumor tissue and suppression of the NRF2/GPX4 antioxidant pathway. Therefore, this research underscores myricetin as a novel inducer of ferroptosis in GC cells through its interaction with NOX4. It is a promising candidate for GC treatment.

Uncovering lupus nephritis-specific genes and the potential of TNFRSF17-targeted immunotherapy: a high-throughput sequencing study.

Introduction: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets. Methods: We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry. Results: Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the 'regulation of biological quality' GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells. Discussion: Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN.

A Novel Signature Based on m6A Regulator-Mediated Genes Along Glycolytic Pathway Predicts Prognosis and Immunotherapy Responses of Gastric Cancer Patients.

N6-methyladenosine (m6A) modification is involved in many aspects of gastric cancer (GC). Moreover, m6A and glycolysis-related genes (GRGs) play important roles in immunotherapeutic and prognostic implication of GC. However, GRGs involved in m6A regulation have never been analyzed comprehensively in GC. Herein, the study aims to identify and validate a novel signature based on m6A-related GRGs in GC patients. Therefore, a m6A-related GRGs signature is established, which can predict the survival of patients with GC and remain an independent prognostic factor in multivariate analyses. Clinical significance of the model is well validated in internal cohort and independent validation cohort. In addition, the expression levels of risk model-related GRGs in clinical samples are validated. Consistent with the database results, all model genes are up-regulated in expression except DCN. After regrouping the patients based on this risk model, the study can effectively distinguish between them in respect to immune-cell infiltration microenvironment and immunotherapeutic response. Additionally, candidate drugs targeting risk model-related GRGs are confirmed. Finally, a nomogram combining risk scores and clinical parameters is created, and calibration plots show that the nomogram can accurately predict survival. This risk model can serve as a reliable assessment tool for predicting prognosis and immunotherapeutic responses in GC patients.

In situ biosynthesized polyphosphate nanoparticles/reduced graphene oxide composite electrode for highly sensitive detection of heavy metal ions.

The development of an effective sensing platform is critical for the electrochemical detection of heavy metal ions (HMIs) in water. In this study, we fabricated a newly designed sensor through the in situ assembly of reduced graphene oxide (rGO) and polyphosphate nanoparticles (polyP NPs) on a carbon cloth electrode via microorganism-mediated green biochemical processes. The characterization results revealed that the rGO produced via microbial reduction had a three-dimensional porous structure, serving as an exceptional scaffold for hosting polyP NPs, and the polyP NPs were evenly distributed on the rGO network. In terms of detecting HMIs, the numerous functional groups of polyP NPs play a major role in the coordination with the cations. This electrochemical sensor, based on polyP NPs/rGO, enabled the individual and simultaneous determination of lead ion (Pb2+) and copper ion (Cu2+) with detection limits of 1.6 nM and 0.9 nM, respectively. Additionally, the electrode exhibited outstanding selectivity for the target analytes in the presence of multiple interfering metal ions. The fabricated sensor was successfully used to determine Pb2+/Cu2+ in water samples with satisfactory recovery rates ranging from 92.16% to 104.89%. This study establishes a facile, cost-effective, and environmentally friendly microbial approach for the synthesis of electrode materials and the detection of environmental pollutants.

The emerging roles of N6-methyladenosine RNA modifications in thyroid cancer.

Thyroid cancer (TC) is the most predominant malignancy of the endocrine system, with steadily growing occurrence and morbidity worldwide. Although diagnostic and therapeutic methods have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of TC remain enigmatic. The N6-methyladenosine(m6A) RNA modification is designed to impact RNA metabolism and further gene regulation. This process is intricately regulated by a variety of regulators, such as methylases and demethylases. Aberrant m6A regulators expression is related to the occurrence and development of TC and play an important role in drug resistance. This review comprehensively analyzes the effect of m6A methylation on TC progression and the potential clinical value of m6A regulators as prognostic markers and therapeutic targets in this disease.

Effect of Cold Rolling Reduction Rate on the Microstructure and Properties of Q&P Steel with a Ferrite-Pearlite Initial Structure.

Quenching and partitioning (Q&P) steel has garnered attention as a promising third-generation automotive steel. While the conventional production (CP) method for Q&P steel involves a significant cumulative cold rolling reduction rate (CRRR) of 60-70%, the thin slab casting and rolling (TSCR) process has emerged as a potential alternative to reduce or eliminate the need for cold rolling, characterized with a streamline production chain, high-energy efficiency, mitigated CO2 emission and economical cost. However, the effect of the CRRR on the microstructure and properties of Q&P steel with an initial ferrite-pearlite microstructure has been overlooked, preventing the extensive application of TSCR in producing Q&P steel. In this work, investigations involving different degrees of CRRRs reveal a direct relationship between increased reduction and decreased yield strength and plasticity. Notably, changes in the microstructure were observed, including reduced size and proportion of martensite blocks, increased ferrite proportion and decreased retained austenite content. The decrease in yield strength was primarily attributed to the increased proportion of the softer ferrite phase, while the reduction in plasticity was primarily linked to the decrease in retained austenite content. This study provides valuable insights for optimizing the TSCR process of Q&P steel, facilitating its wider adoption in the automotive sector.

Tespa1 deficiency reduces the antitumour immune response by decreasing CD8+T cell activity in a mouse Lewis lung cancer model.

Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a key molecule in T-cell development and has been linked to immune diseases. However, its role in antitumour CD8+T cell immunity remains unclear. Here, we demonstrated that Tespa1 plays an important role in antitumour CD8+T cell immunity. First, compared with wild-type (WT) mice, Lewis lung cancer cells grew faster in Tespa1 knockout (Tespa1-/-) mice, with reduced apoptosis, and decreased CD8+T cells in peripheral blood and tumor tissues. Second, the proportion of CD8+T and Th1 cells in the splenocytes of Tespa1-/- mice was lower than that in WT mice. Third, Tespa1-/- CD8+ tumor-infiltrating lymphocytes (TILs) showed weakened proliferation, invasion, cytotoxicity, and protein expression of IL-2 signalling pathway components compared to WT CD8+TILs. Furthermore, PD-1 expression in CD8+TILs was higher in Tespa1-/- than in WT mice. Lastly, CD8+TILs in WT mice improved the antitumour ability of Tespa1-/- mice. In conclusion, these findings suggest that Tespa1 plays a critical role in the tumor immune system by regulating CD8+T cells.

Exosomal miR-let-7c-5p is involved in the cognitive function of type 2 diabetes mellitus patients by interleukin 10: A cross-sectional study.

BACKGROUND: Interleukin (IL)-10 plays a notable role in the inflammatory-associated mild cognitive impairment (MCI). We aimed to investigate whether IL-10 and its upstream factors exert an impact on MCI in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 117 T2DM patients were recruited and divided into Control group and MCI group based on the presence or absence of MCI. Clinical parameters were collected. The Montreal Cognitive Assessment (MoCA) was conducted for global cognitive function. Digit Span Test (DST), Verbal Fluency Test (VFT), and Trail Making Test-B (TMTB) were used to evaluate the executive functions of the diabetic patients. Trail Making Test-A (TMTA) was performed to examine the information processing speed function. Patients' scene memory was examined by Logical Memory Test (LMT). After the baseline data were compared, correlation and regression analyses were performed to explore the relationship among IL-10, miR-let-7c-5p and cognitive function. RESULTS: Compared to 80 patients in the control group, 37 patients in the MCI group exhibited lower IL-10 in plasma and higher miR-let-7c-5p levels in exosomes from plasma. The IL-10 level was negatively associated with MoCA. Likewise, miR-let-7c-5p levels were negatively correlated with IL-10 levels and MoCA. Elevated miR-let-7c-5p levels and decreased IL-10 levels are risk factors for MCI in T2DM patients. Increased miR-let-7c-5p and downregulated IL-10 may influence VFT and TMTB, respectively, associated with executive function. CONCLUSIONS: We demonstrated that IL-10 is correlated to the executive function of T2DM patients. Decreased IL-10 may result from the regulation of miR-let-7c-5p in exosomes.

Micrometer-precision absolute distance measurement with a repetition-rate-locked soliton microcomb.

The soliton microcomb has sparked interest in high-precision distance measurement, owing to its ultrahigh repetition rate and chip-integrated scale. We report absolute distance measurements based on synthetic wavelength interferometry with a soliton microcomb. We stabilized the repetition rate of 48.98 GHz through injection locking, with fluctuations below 0.25 Hz. Distance measurements up to 64 mm were demonstrated, presenting residuals below 2.7 µm compared with a referenced laser interferometer. Long-term distance measurements were made at two fixed positions of approximately 0.2 m and 1.4 m, resulting in a minimum Allan deviation as low as 56.2 nm at an average time of 0.05 s. The dynamic demonstration illustrated that the proposed system could track round-trip motion of 3 mm at speeds up to 100 mm/s. The proposed distance measurement system is, to our knowledge, the first microcomb-based synthetic wavelength interferometer and achieves a ranging precision of tens of nanometers, with potential applications in the fields of satellite formation flying, high-end manufacturing, and micro-nano processing.

Hierarchical porous loofah-like carbon with sulfhydryl functionality for electrochemical detection of trace mercury in water.

Mercury is a common contaminant found in natural waters, which is highly toxic to human health. Thus, the facile and reliable monitoring of mercury in waters is of great significance. In this study, we fabricated a novel loofah-like hierarchical porous carbon with sulfhydryl functionality (S-LHC), and applied it as an ultrasensitive sensor for the electrochemical detection of mercury in water. The S-LHC was prepared through the direct pyrolysis of a triazole-rich metal-organic framework (MOF), followed by chemical modification using thioglycolic acid. The highly conductive N-doped carbon framework of S-LHC facilitated the electron transfer in mercury electrochemical sensing. Meanwhile, the open hierarchical pore structure and abundant sulfhydryl groups allowed the fast diffusion and effective enrichment of mercury ions. Consequently, the S-LHC sensor exhibited an exceptionally high sensitivity for mercury ions, with the mercury detection limit (0.36 nM) orders of magnitude lower than the regulated values in drinking water (typically 10∼30 nM). The constructed sensor also afforded good anti-interference ability and excellent stability for long-term detection of mercury in a variety of complex real water samples. The present study provides not only a facile method for mercury detection, but also a new idea for the construction of highly sensitive electrochemical sensors.

A erythrocyte-platelet hybrid membrane coated biomimetic nanosystem based on ginsenosides and PFH combined with ultrasound for targeted delivery in thrombus therapy.

Thrombus is one of the culprits for global health problems. However, most current antithrombotic drugs are limited by restricted targeting ability and a high risk of systemic bleeding. A hybrid cell membrane-coated biomimetic nanosystem (PM/RM@PLGA@P/R) was constructed in this paper to fulfil the targeted delivery of ginsenoside (Rg1) and perfluorohexane (PFH). Poly lactic-co-glycolic acid (PLGA) is used as carriers to coat Rg1 and PFH. Thanks to the camouflage of erythrocyte membrane (RM) and platelet membrane (PM), the nanosystem in question possesses remarkable features including immune escape and self-targeting. Therefore, a compact nano-core with PLGA@P/R was formed, with a hybrid membrane covering the surface of the core, forming a "core-shell" structure. With its "core-shell" structure, this nanoparticle fancifully combines the advantages of both PFH (the low-intensity focused ultrasound (LIFU)-responsive phase-change thrombolysis) and Rg1(the antioxidant, anti-inflammatory and anticoagulant abilities). Meanwhile, PM/RM@PLGA@P/R nanoparticles exhibits superior in-vitro performance in terms of ROS scavenging, anticoagulant activity and immune escape compared with those without cell membranes (PLGA@P/R). Furthermore, in the animal experiment in which the tail vein thrombosis model was established by injecting k-carrageenan, the combined treatment of LIFU and PM/RM@PLGA@P/R showed a satisfactory antithrombotic efficiency (88.20 %) and a relatively higher biological safety level. This strategy provides new insights into the development of more effective and safer targeted biomimetic nanomedicines for antithrombotic treatments, possessing potential application in synergistic therapy field.

Exploring choices of early nutritional support for patients with sepsis based on changes in intestinal microecology.

BACKGROUND: Sepsis exacerbates intestinal microecological disorders leading to poor prognosis. Proper modalities of nutritional support can improve nutrition, immunity, and intestinal microecology. AIM: To identify the optimal modality of early nutritional support for patients with sepsis from the perspective of intestinal microecology. METHODS: Thirty patients with sepsis admitted to the intensive care unit of the General Hospital of Ningxia Medical University, China, between 2019 and 2021 with indications for nutritional support, were randomly assigned to one of three different modalities of nutritional support for a total of 5 d: Total enteral nutrition (TEN group), total parenteral nutrition (TPN group), and supplemental parenteral nutrition (SPN group). Blood and stool specimens were collected before and after nutritional support, and changes in gut microbiota, short-chain fatty acids (SCFAs), and immune and nutritional indicators were detected and compared among the three groups. RESULTS: In comparison with before nutritional support, the three groups after nutritional support presented: (1) Differences in the gut bacteria (Enterococcus increased in the TEN group, Campylobacter decreased in the TPN group, and Dialister decreased in the SPN group; all P < 0.05); (2) different trends in SCFAs (the TEN group showed improvement except for Caproic acid, the TPN group showed improvement only for acetic and propionic acid, and the SPN group showed a decreasing trend); (3) significant improvement of the nutritional and immunological indicators in the TEN and SPN groups, while only immunoglobulin G improved in the TPN group (all P < 0.05); and (4) a significant correlation was found between the gut bacteria, SCFAs, and nutritional and immunological indicators (all P < 0.05). CONCLUSION: TEN is recommended as the preferred mode of early nutritional support in sepsis based on clinical nutritional and immunological indicators, as well as changes in intestinal microecology.

Consumption in Non-Pastoral Regions Drove Three-Quarters of Forage-Livestock Conflicts in China.

Forage-livestock conflict (FLC) is a major anthropogenic cause of rangeland degradation. It poses tremendous threats to the environment owing to its adverse impacts on carbon sequestration, water supply and regulation, and biodiversity conservation. Existing policy interventions focus on the in situ FLCs induced by local production activities but overlook the role of consumption activities in driving FLCs. Here, we investigate the spatiotemporal variations in China's FLCs and the domestic final consumers at the county level by combining remote sensing data and multi-regional input-output model. Results show that during 2005-2015, China's pastoralism induced an average of 82 million tons of FLCs per year. Domestic final demand was responsible for 85-93% of the FLCs in China. There was spatiotemporal heterogeneity in domestic consumption driving China's FLCs. In particular, the final demand of non-pastoral regions was responsible for around three-quarters (74-79%) of the total FLCs throughout the decade. The rangeland-based livestock raising, agricultural and sideline product processing, and catering sectors are important demand-side drivers. These findings can support targeted demand-side strategies and interregional cooperation to reduce China's FLCs, thus mitigating rangeland degradation.

Amino-Functionalized Hierarchical Porous Carbon Derived from Zeolitic Imidazolate Frameworks for Ultrasensitive Electrochemical Sensing of Heavy Metals in Water.

Electrochemical sensing provides a feasible avenue to monitor heavy metal ions (HMIs) in water, whereas the construction of highly sensitive and selective sensors remains challenging. Herein, we fabricated a novel amino-functionalized hierarchical porous carbon by the template-engaged method using ZIF-8 as the precursor and polystyrene sphere as the template, followed by carbonization and controllable chemical grafting of amino groups for efficient electrochemical detection of HMIs in water. The amino-functionalized hierarchical porous carbon features an ultrathin carbon framework with a high graphitization degree, excellent conductivity, unique macro-, meso-, and microporous architecture, and rich amino groups. As a result, the sensor exhibits prominent electrochemical performance with significantly low limits of detection for individual HMIs (i.e., 0.93 nM for Pb2+, 2.9 nM for Cu2+, and 1.2 nM for Hg2+) and simultaneous detection of HMIs (i.e., 0.62 nM for Pb2+, 1.8 nM for Cu2+, and 0.85 nM for Hg2+), which are superior to most reported sensors in the literature. Moreover, the sensor displays excellent anti-interference ability, repeatability, and stability for HMI detection in actual water samples.

High throughput sequencing revealed enhanced cell cycle signaling in SLE patients.

The multi-system involvement and high heterogeneity of systemic lupus erythematosus (SLE) pose great challenges to its diagnosis and treatment. The purpose of the current study is to identify genes and pathways involved in the pathogenesis of SLE. High throughput sequencing was performed on the PBMCs from SLE patients. We conducted differential gene analysis, gene ontology (GO) analysis, kyoto encyclopedia of genes and genomes (KEGG) analysis, and quantitative real-time PCR (qRT-PCR) verification. Protein-protein interaction (PPI) analysis, alternative splicing analysis, and disease correlation analysis were conducted on some key pathogenic genes as well. Furthermore, si-CDC6 was used for transfection and cell proliferation was monitored using a cell counting kit-8 (CCK-8) assay. We identified 2495 differential genes (1494 upregulated and 1001 downregulated) in SLE patients compared with healthy controls. The significantly upregulated genes were enriched in the biological process-related GO terms of the cell cycle, response to stress, and chromosome organization. KEGG enrichment analysis revealed 7 significantly upregulated pathways including SLE, alcoholism, viral carcinogenesis, cell cycle, proteasome, malaria, and transcriptional misregulation in cancer. We successfully verified some differential genes on the SLE pathway and the cell cycle pathway. CDC6, a key gene in the cell cycle pathway, had remarkably higher MXE alternative splicing events in SLE patients than that in controls, which may explain its significant upregulation in SLE patients. We found that CDC6 participates in the pathogenesis of many proliferation-related diseases and its levels are positively correlated with the severity of SLE. Knockdown of CDC6 suppressed the proliferation of Hela cells and PBMCs from SLE patients in vitro. We identified SLE-related genes and their alternative splicing events. The cell cycle pathway and the cell cycle-related biological processes are over-activated in SLE patients. We revealed a higher incidence of MXE events of CDC6, which may lead to its high expression in SLE patients. Upregulated cell cycle signaling and CDC6 may be related to the hyperproliferation and pathogenesis of SLE.

Agile offset frequency locking for single-frequency fiber lasers.

Single frequency fiber lasers (SFFLs) have seen increasing applications in state-of-the-art quantum technologies, which usually require precise and stable offset frequency locking (OFL). However, limited by the piezoelectric transducer bandwidth in SFFLs and the loop bandwidth of the OFL, the large-gap jumping between two locked offset frequencies will take an undesirable amount of time. In order to diminish that consuming time, we developed an agile offset frequency locking system based on a hybrid loop of a feed-forward path and a feedback path. In accordance with the experimental demonstration, we characterized the performances of the offset frequency locking system, as frequency-locking stability with an Allan deviation of 3.2 × 10-14 at 1 s averaging time and jumping agility with a duration of 0.6 ms at 1.3 GHz frequency gap, which is a factor of 60 faster than that without the feed-forward path. This mechanism can find direct applications in existing quantum metrology experiments with SFFLs where high-speed frequency jumping or sweeping is needed.

SB431542 alleviates lupus nephritis by regulating B cells and inhibiting the TLR9/TGFß1/PDGFB signaling.

Lupus nephritis (LN) is the most common cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Currently, immunosuppressive treatments for LN are suboptimal and can induce significant side effects. SB431542 is a selective and potent inhibitor of the TGFß/Activin/NODAL pathway. Here, we study the effects of SB431542 treatment on LN and discuss the potential mechanisms. SB431542 ameliorated clinical outcomes with a consequent histological improvement in NZB/W mice. A comparative transcriptional profiling analysis revealed 586 differentially expressed genes (247 downregulated genes) in the SB431542 group compared to the control group. We found that the downregulated genes were mainly enriched in the biological processes of B cell activation, B cell proliferation, B cell differentiation, and B cell receptor signaling. Kyoto encyclopedia of genes and genomes pathway analysis revealed that the hematopoietic cell linage pathway was significantly downregulated in the SB431542 group. In addition, we observed that SB431542 reduced the splenic or renal levels of CD20 and the serum levels of anti-dsDNA antibody (IgG) in NZB/W mice. Furthermore, qRT-PCR and immunohistochemistry confirmed that SB431542 inhibits the production of TLR9, TGFß1, and PDGFB. Thus, due to its immunomodulatory activities, SB431542 could be considered for clinical therapy development for LN.

[Clinical characteristics and risk factors of early septic patients complicated with bloodstream infection].

OBJECTIVE: To analyze the clinical characteristics, risk factors and prognosis of early septic patients with bloodstream infection (BSI) in department of critical care medicine of Ningxia Medical University General Hospital. METHODS: Patients with sepsis admitted to department of critical care medicine of Ningxia Medical University General Hospital from November 1, 2019 to August 31, 2021 were included in a prospective observational study. Blood samples were collected for culture within 24 hours of sepsis diagnosis. General information, laboratory test indicators and blood culture results within 24 hours of sepsis diagnosis were recorded. Patients were followed up and prognostic indicators [mechanical ventilation time, length of intensive care unit (ICU) stay, and 28-day survival] were observed. According to blood culture results, patients were divided into BSI group and non-BSI group. Univariate and multivariate Logistic regression analysis were performed on the general clinical characteristics of patients in the two groups to screen the risk factors of early BSI in septic patients. Receiver operator characteristic curve (ROC) was drawn to evaluate the predictive value of risk factors for early BSI in septic patients. RESULTS: A total of 202 septic patients were included in this study, with 62 patients in BSI group and 140 patients in non-BSI group. The majority of patients in the BSI group were associated with abdominal infection (61.3%), and the majority of patients in the non-BSI group were associated with pulmonary infection (49.3%). A total of 76 strains were isolated from septic patients in BSI group, and the most common pathogens were Escherichia coli (26 strains, 34.2%), Klebsiella pneumoniae (11 strains, 14.4%), Enterococcus (7 strains, 9.2%), Bacteroides fragilis (6 strains, 7.9%) and Staphylococcus aureus (6 strains, 7.9%). There were no significant differences in mechanical ventilation time, the length of ICU stay and 28-day mortality between the BSI group and the non-BSI group. The difference of variables was statistically significant between two group according to Univariate analysis, which included body temperature, acute physiology and chronic health score II (APACHE II), use of antibiotics before admission to ICU, abdominal infection, hypersensitivity C-reactive protein (hs-CRP), serum creatinine (SCr), total bilirubin (TBil), platelet count (PLT), blood lactic acid (Lac) and hypercalcitonin (PCT). Multivariate analysis showed that low PLT [odds ratio (OR) = 1.004, P = 0.019], high Lac (OR = 1.314, P = 0.002), high body temperature (OR = 1.482, P = 0.027), concomitant abdominal infection (OR = 2.354, P = 0.040), no use of antibiotics before admission to ICU (OR = 2.260, P = 0.049) were independent risk factors for early BSI in septic patients. The area under ROC curve (AUC) of PLT, Lac, body temperature, abdominal infection and no use of antibiotics before admission to ICU for predicting early BSI in septic patients were 0.711, 0.686, 0.594, 0.592 and 0.590, respectively. Youden index was used to calculate the optimal cut-off values, which was PLT 122.50×109/L, Lac 2.95 mmol/L, body temperature 39.45 centigrade, respectively. The highest level of AUC was 0.754, the PI guidance group was expected to achieve PI the sensitivity was 75.8%, and the specificity was 68.8%, which were observed when the 5 items were combined. CONCLUSIONS: Early septic patients with BSI are more serious than those without BSI. Low PLT, high Lac, high temperature, concomitant abdominal infection and no use of antibiotics before admission to ICU are independent risk factors for early BSI in septic patients, and the combination of these five factors has good predictive value.