NMDAR antagonists suppress tumor progression by regulating tumor-associated macrophages.

Neurotransmitter receptors are increasingly recognized to play important roles in anti-tumor immunity. The expression of the ion channel N-methyl-D-aspartate receptor (NMDAR) on macrophages was reported, but the role of NMDAR on macrophages in the tumor microenvironment (TME) remains unknown. Here, we show that the activation of NMDAR triggered calcium influx and reactive oxygen species production, which fueled immunosuppressive activities in tumor-associated macrophages (TAMs) in the hepatocellular sarcoma and fibrosarcoma tumor settings. NMDAR antagonists, MK-801, memantine, and magnesium, effectively suppressed these processes in TAMs. Single-cell RNA sequencing analysis revealed that blocking NMDAR functionally and metabolically altered TAM phenotypes, such that they could better promote T cell- and Natural killer (NK) cell-mediated anti-tumor immunity. Treatment with NMDAR antagonists in combination with anti-PD-1 antibody led to the elimination of the majority of established preclinical liver tumors. Thus, our study uncovered an unknown role for NMDAR in regulating macrophages in the TME of hepatocellular sarcoma and provided a rationale for targeting NMDAR for tumor immunotherapy.

USP11 regulates proliferation and apoptosis of human spermatogonial stem cells via HOXC5-mediated canonical WNT/ß-catenin signaling pathway.

Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate fate determinations of human SSCs and male infertility. In this study, we explored the expression, function, and mechanism of USP11 in controlling the proliferation and apoptosis of human SSCs as well as the association between its abnormality and azoospermia. We found that USP11 was predominantly expressed in human SSCs as shown by database analysis and immunohistochemistry. USP11 silencing led to decreases in proliferation and DNA synthesis and an enhancement in apoptosis of human SSCs. RNA-sequencing identified HOXC5 as a target of USP11 in human SSCs. Double immunofluorescence, Co-immunoprecipitation (Co-IP), and molecular docking demonstrated an interaction between USP11 and HOXC5 in human SSCs. HOXC5 knockdown suppressed the growth of human SSCs and increased apoptosis via the classical WNT/ß-catenin pathway. In contrast, HOXC5 overexpression reversed the effect of proliferation and apoptosis induced by USP11 silencing. Significantly, lower levels of USP11 expression were observed in the testicular tissues of patients with spermatogenic disorders. Collectively, these results implicate that USP11 regulates the fate decisions of human SSCs through the HOXC5/WNT/ß-catenin pathway. This study thus provides novel insights into understanding molecular mechanisms underlying human spermatogenesis and the etiology of azoospermia and it offers new targets for gene therapy of male infertility.

Human defensin-inspired discovery of peptidomimetic antibiotics.

SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial targets, the lead compound is efficacious in vitro and in vivo against bacteria with highly inducible antibiotic resistance, promising a useful therapeutic agent for the treatment of infections caused by antibiotic-resistant bacteria.

Glioma stem cell-derived exosomes induce the transformation of astrocytes via the miR-3065-5p/DLG2 signaling axis.

Tumor-associated astrocytes (TAAs) in the glioblastoma microenvironment play an important role in tumor development and malignant progression initiated by glioma stem cells (GSCs). In the current study, normal human astrocytes (NHAs) were cultured and continuously treated with GSC-derived exosomes (GSC-EXOs) induction to explore the mechanism by which GSCs affect astrocyte remodeling. This study revealed that GSC-EXOs can induce the transformation of NHAs into TAAs, with relatively swollen cell bodies and multiple extended processes. In addition, high proliferation, elevated resistance to temozolomide (TMZ), and increased expression of TAA-related markers (TGF-ß, CD44, and tenascin-C) were observed in the TAAs. Furthermore, GSC-derived exosomal miR-3065-5p could be delivered to NHAs, and miR-3065-5p levels increased significantly in TAAs, as verified by miRNA expression profile sequencing and Reverse transcription polymerase chain reaction. Overexpression of miR-3065-5p also enhanced NHA proliferation, elevated resistance to TMZ, and increased the expression levels of TAA-related markers. In addition, both GSC-EXO-induced and miR-3065-5p-overexpressing NHAs promoted tumorigenesis of GSCs in vivo. Discs Large Homolog 2 (DLG2, downregulated in glioblastoma) is a direct downstream target of miR-3065-5p in TAAs, and DLG2 overexpression could partially reverse the transformation of NHAs into TAAs. Collectively, these data demonstrate that GSC-EXOs induce the transformation of NHAs into TAAs via the miR-3065-5p/DLG2 signaling axis and that TAAs can further promote the tumorigenesis of GSCs. Thus, precisely blocking the interactions between astrocytes and GSCs via exosomes may be a novel strategy to inhibit glioblastoma development, but more in-depth mechanistic studies are still needed.

Long noncoding RNA XIST inhibition promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-145a-5p that targets SIRT1 in late-onset hypogonadism.

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 µM H2O2 for 8 h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.

AdipoRon Ameliorates Synaptic Dysfunction and Inhibits tau Hyperphosphorylation through the AdipoR/AMPK/mTOR Pathway in T2DM Mice.

There is growing evidence showing that adiponectin (APN) can improve Alzheimer's disease(AD)-like pathological changes by improving insulin resistance. However, the role of AdipoRon (an Adiponectin receptor agonist) on synaptic plasticity and cognitive dysfunction in the early stages of type 2 diabetes mellitus(T2DM) remains unknown. In this study, we investigated the neuroprotective effect and the molecular mechanism underlying the effect of AdipoRon in T2DM mice. We found that AdipoRon significantly restored the cognitive deficits in T2DM mice, including shorter escape latency, more crossing times, increased distances, and percentage of time in the target quadrant. In addition, AdipoRon treatment up-regulated synaptic proteins (PSD95, SYN, GAP43, and SYP), increased the number of hippocampal synapses and attenuated synaptic damage, including the length, the number and the density of dendritic spines in CA1 and DG regions. Furthermore, AdipoRon attenuated Tau phosphorylation at multiple AD-related sites (p-tau 205, p-tau 396, p-tau 404) by promoting AdipoR expression and activating the AMPK/mTOR pathway. Our data suggests that AdipoRon exerts neuroprotective effects on the T2DM mice, which may be mediated by the activation of the AdipoR/AMPK/mTOR signaling pathway.

Predictors of mortality and poor outcome for patients with severe infectious encephalitis in the intensive care unit: a cross-sectional study.

BACKGROUND: There are few thorough studies assessing predictors of severe encephalitis, despite the poor prognosis and high mortality associated with severe encephalitis. The study aims to evaluate the clinical predictors of mortality and poor outcomes at hospital discharge in patients with severe infectious encephalitis in intensive care units. METHOD: In two Chinese hospitals, a retrospective cohort study comprising 209 patients in intensive care units suffering from severe infectious encephalitis was carried out. Univariate and multivariate logistic regression analyses were used to identify the factors predicting mortality in all patients and poor outcomes in all survivors with severe infectious encephalitis. RESULTS: In our cohort of 209 patients with severe encephalitis, 22 patients died, yielding a mortality rate of 10.5%. Cerebrospinal fluid pressure ≥ 400mmH2O (OR = 7.43), abnormal imaging (OR = 3.51), abnormal electroencephalogram (OR = 7.14), and number of rescues (OR = 1.12) were significantly associated with an increased risk of mortality in severe infectious encephalitis patients. Among the 187 survivors, 122 (65.2%) had favorable outcomes, defined as the modified Rankine Scale (mRS) score (0 ~ 3), and 65(34.8%) had poor outcomes (mRS scores 4 ~ 5). Age (OR = 1.02), number of rescues (OR = 1.43), and tubercular infection (OR = 10.77) were independent factors associated with poor outcomes at discharge in all survivors with severe infectious encephalitis. CONCLUSIONS: Multiple clinical, radiologic, and electrophysiological variables are independent predictive indicators for mortality and poor outcomes in patients with severe encephalitis in intensive care units. Identifying these outcome predictors early in patients with severe encephalitis may enable the implementation of appropriate medical treatment and help reduce mortality rates.

Computer-aided designing of a novel multi­epitope DNA vaccine against severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins--nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.

Effect of sodium bicarbonate Ringer's solution on lung injury in rats with traumatic hemorrhagic shock.

This study aimed to explore the impact of different pH values of resuscitation fluid on traumatic hemorrhagic shock (THS), focusing on their effects on glycocalyx and inflammation. A rat model of THS was induced by hemorrhage from a left femur fracture, while an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced HULEC-5a cell model was considered as an in vitro THS model. The lung tissue pathology and glycocalyx structure were assessed through hematoxylin-eosin (H&E) staining and transmission electron microscope examination. The levels of glycocalyx-related factors and inflammation-related factors were determined by enzyme-linked immunosorbent assay (ELISA). The expression of glycocalyx-related proteins, cell junction-related proteins, and proteins involved in the PI3K/Akt/NF-κB signaling pathway was analyzed by western blot. The results showed that both sodium bicarbonate Ringer's solution (BRS) and lactate Ringer's solution (LRS) were effective in restoring mean arterial pressure and heart rate in THS rats. However, LRS has a stronger impact on promoting inflammation and damaging the glycocalyx compared with BRS. In OGD/R-induced HULEC-5a cells, a pH of 7.4 and 6.5 increased inflammation and disrupted the glycocalyx, while a pH of 8.1 had no significant effect on inflammation or glycocalyx. Furthermore, the PI3K/Akt/NF-κB signaling pathway was activated by fluid resuscitation and different pH values. However, the activating effect of BRS and pH 8.1 on the PI3K/Akt/NF-κB signaling pathway was milder compared with LRS and pH6.5. In conclusion, an alkaline recovery environment was more beneficial for the treatment of THS.

Embryological characteristics and clinical outcomes of oocytes with different degrees of abnormal zona pellucida during assisted reproductive treatment.

Abnormalities in the zona pellucida (ZP) adversely affect oocyte maturation, embryo development and pregnancy outcomes. However, the assessment of severity is challenging. To evaluate the effects of different degrees of ZP abnormalities on embryo development and clinical outcomes, in total, 590 retrieval cycles were scored and divided into four categories (control, mild, moderate and severe) based on three parameters: perivitelline space, percentage of immature oocytes and percentage of oocytes with abnormal morphology. As the severity of abnormal ZP increased, both the number of retrieved oocytes and mature oocytes decreased. The fertilization rate did not differ significantly among groups. The rates of embryo cleavage and day-3 high-quality embryos in the mild group and the moderate group did not vary significantly between the two groups but were significantly higher than those in the severe group. The blastulation rates of the abnormal ZP groups were similar; however, they were lower than those of the control group. Moreover, the cycle cancellation rate of the severe abnormal ZP group was as high as 66.20%, which was significantly higher than that of the other three groups. Although the rates of cumulative clinical pregnancy and live births were lower than those in the control group, they were comparable among the abnormal ZP groups. There were no differences in the neonatal outcomes of the different groups. Together, ZP abnormalities show various degrees of severity, and in all patients regardless of the degree of ZP abnormalities who achieve available embryos, there will be an opportunity to eventually give birth.

Unravelling the interplay of local structure and valence transitions in Ce-doped CaYAlO4 luminescent materials.

Cerium has been widely used as a dopant in luminescent materials due to its unique electronic configurations. It is generally anticipated that the luminescence properties of rare-earth-doped materials are closely related to the local environment of activators, especially for Ce3+ . In addition, it is convenient to modulate its emission wavelength by adjusting the composition and structure. In this study, we systematically analyzed the microstructure of the Ce-doped CaYAlO4 system at atomic resolution. The quantitive results indicated that the structure distortion greatly influenced the valence state of the Ce dopant, which is critical to its luminescence efficiency. In addition, valence variations also exist from surface to inner structure due to the big distortion area around the surface. Our results unravel the interplay of local structure and valence transitions in Ce-doped aluminate phosphors, which has the potential to be applied in other luminescent materials.

Mixed-Dimensional Nanoparticle-Nanowire Channels for Flexible Optoelectronic Artificial Synapse with Enhanced Photoelectric Response and Asymmetric Bidirectional Plasticity.

A mixed-dimensional dual-channel synaptic transistor composed of inorganic nanoparticles and organic nanowires was fabricated to expand the photoelectric gain range. The device can actualize the sensitization features of the nociceptor and shows improved responsiveness to visible light. Under electrical pulses with different polarities, the apparatus exhibits reconfigurable asymmetric bidirectional plasticity. Moreover, the devices demonstrate good operational tolerance and mechanical stability, retaining more than 60% of their maximum responsiveness after 100 consecutive/bidirectional and 1000 flex/flat operations. The improved photoelectric response of the device endows a high image recognition accuracy of greater than 80%. Asymmetric bidirectional plasticity is used as punishment/reward in a psychological experiment to emulate the improvement of learning motivation and enables real-time forward and backward deflection (+7 and -25°) of artificial muscle. The mixed-dimensional optoelectronic artificial synapses with switchable behavior and electron/hole transport type have important prospects for neuromorphic processing and artificial somatosensory nerves.

Study of Molecular Dimer Morphology Based on Organic Spin Centers: Nitronyl Nitroxide Radicals.

In this work, in order to investigate the short-range interactions between molecules, the spin-magnetic unit nitronyl nitroxide (NN) was introduced to synthesize self-assembly single radical molecules with hydrogen bond donors and acceptors. The structures and magnetic properties were extensively investigated and characterized by UV-Vis absorption spectroscopy, electron paramagnetic resonance (EPR), and superconducting quantum interference devices (SQUIDs). Interestingly, it was observed that the single molecules can form two different dimers (ring-closed dimer and "L"-type dimer) in different solvents, due to hydrogen bonding, when using EPR to track the molecular spin interactions. Both dimers exhibit ferromagnetic properties (for ring-closed dimer, J/kB = 0.18 K and ΔES-T = 0.0071 kcal/mol; for "L"-type dimer, the values were J/kB = 9.26 K and ΔES-T = 0.037 kcal/mol). In addition, the morphologies of the fibers formed by the two dimers were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM).

miR-140 and miR-200 regulate the migratory heterogeneity of location-specific Schwann cell population.

Schwann cells are functional cells in nerve regeneration and are commonly used as seed cells in tissue engineering. Enhanced Schwann cell migration capacity improves recovery effects, and thus, the identification of Schwann cells with greater migration ability is of great importance. In the present study, we examined the biological activities of Schwann cells collected from rat sciatic nerves (SN) and dorsal root ganglia (DRG). Observations from transwell migration assay and wound healing assay demonstrate that DRG Schwann cells migrate at a faster speed as compared with SN Schwann cells. Sequencing and bioinformatics suggest that differentially expressed genes between SN and DRG Schwann cells are associated with cell motility and migration. miR-140 and miR-200, two microRNAs (miRNAs) that are highly expressed in SN Schwann cells negatively influence Schwann cell migration and thus may be key regulators of Schwann cell phenotype. Igsf10, Plxna2, and Lcp1 are screened as candidate downstream targets of miR-140 and miR-200 based on bioinformatic analysis and their expression correlation with miRNAs. Our comparative analysis displays the unique characteristics of Schwann cells in different anatomical localizations and demonstrates that DRG Schwann cells are suitable seed cells for tissue engineering and regenerative medicine.

Schistosome infection promotes osteoclast-mediated bone loss.

Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4+ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.

ApoM suppresses kidney renal clear cell carcinoma growth and metastasis via the Hippo-YAP signaling pathway.

Renal cell carcinoma is one of the most common malignancies worldwide, and kidney renal clear cell carcinoma (KIRC) is the most common histopathological type of renal cell carcinoma. However, the mechanism of KIRC progression remains poorly understood. Apolipoprotein M (ApoM) is a plasma apolipoprotein and a member of the lipid transport protein superfamily. Lipid metabolism is essential for tumor progression, and its related proteins can be used as therapeutic targets for tumors. ApoM influences the development of several cancers, but its relationship with KIRC remains unclear. In this study, we aimed to investigate the biological function of ApoM in KIRC and to reveal its potential molecular mechanisms. We found that ApoM expression was significantly reduced in KIRC and was strongly correlated with patient prognosis. ApoM overexpression significantly inhibited KIRC cell proliferation in vitro, suppressed the epithelial mesenchymal transition (EMT) of KIRC cells, and decreased their metastatic capacity. Additionally, the growth of KIRC cells was inhibited by ApoM overexpression in vivo. In addition, we found that overexpression of ApoM in KIRC attenuated Hippo-YAP protein expression and YAP stability and thus inhibited KIRC growth and progression. Therefore, ApoM may be a potential target for the treatment of KIRC.

CRISPR Cas12a-enabled biosensors coupled with commercial pregnancy test strips for the visible point-of-care testing of SARS-CoV-2.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the development of nucleic acid diagnosis technology. Several platforms with isothermal amplification methods have achieved sensitive and specific detection of SARS-CoV-2. However, they still suffer from complicated operations, delicate instruments, and unintuitive signal output modes. Here, a system consisting of CRISPR Cas12a-based biosensors and commercial pregnancy test strips (CRISPR-PTS) was established for the point-of-care testing of SARS-CoV-2. The target viral nucleic acids were finally reflected on the test strips through four steps, namely sample pretreatment, RT-RAA amplification, CRISPR Cas12a reaction, and separation-free hCG detection. This CRISPR-PTS assay possessed an outstanding sensitivity of as low as 1 copy per µL for SARS-CoV-2 detection and showed an excellent specificity in distinguishing the SARS-CoV-2 pseudovirus as well as other SARS-like viral clinical samples. In addition, the CRISPR-PTS assay performed well in practical applications, with 96.3% agreement versus RT-qPCR in spiked samples. With the advantages of low reagent cost, simple operation procedure, and visible signal output, CRISPR-PTS assay was expected to provide a strong supplement in the prevention and early diagnosis of infectious diseases in resource-limited situations.

Maternal BPAF exposure impaired synaptic development and caused behavior abnormality in offspring.

Bisphenol A (BPA) has been widely restricted, leading to a significant increase in the production of bisphenol AF (BPAF), one of the most common bisphenol analogs use as a substitute for BPA. However, there is limit evidence on the neurotoxicity of BPAF, especially the potential effects of maternal exposed to BPAF on offspring. A maternal BPAF exposure model was used to evaluate its effects on long-term neurobehaviors in offspring. We found that maternal BPAF exposure resulted in immune disorders, characterized by abnormal CD4+T cell subsets, and their offspring exhibited anxiety- and depression-like behaviors, as well as impairments in learning-memory, sociability and social novelty. Further, brain bulk RNA-sequencing (RNA-seq) and hippocampus single-nucleus RNA-sequencing (snRNA-seq) of offspring showed that differentially expressed genes (DEGs) were enriched in pathways related to synaptic and neurodevelopment. Synaptic ultra-structure of offspring was damaged after maternal BPAF exposure. In conclusion, maternal BPAF exposure induced behavior abnormality in adult offspring, together with synaptic and neurodevelopment defects, which might be related to maternal immune dysfunction. Our results provide a comprehensive insight into the neurotoxicity mechanism of maternal BPAF exposure during gestation. Given the increasing and ubiquitous exposure to BPAF, especially during sensitive periods of growth and development, the safety of BPAF requires urgent attention.

Five New C21 -Steroidal Sapogenins from the Acid Hydrolysate of Cynanchum otophyllum Roots.

Five new C21 -steroidal sapogenins (1-5) named cynotogenins J-N, were isolated from the acid hydrolysate of Cynanchum otophyllum roots. Their structures were established by extensive spectroscopic analysis (UV, IR, HR-ESI-MS, and NMR). Most notably, compounds 1-3 harboring a rare 5ß,6ß-epoxy group in the C21 -steroidal skeleton of Cynanchum plants. All compounds were evaluated for their cytotoxicities against multiple cancer cell lines, in which compounds 5 showed weak cytotoxicity against HepG2 cancer cells with IC50 values of 44.90 µM.

Prognostic value of APTT combined with fibrinogen and creatinine in predicting 28-Day mortality in patients with septic shock caused by acute enteric perforation.

BACKGROUND: Septic shock is one of the leading causes of mortality in intensive care units. This retrospective study was carried out to evaluate the association of clinical available factors with 28-day mortality. PATIENTS AND METHOD: In this observational study, patients with perioperative septic shocks secondary to intra-abdominal infection caused by enteric perforation were included. A total of 328 sepsis patients were admitted to the surgical intensive care units from January 2012 to December 2016. A total of 138 patients met the enrolment criteria and were included in the study. The data of demographic, clinical and laboratory were all recorded. RESULT: All these 138 patients received abdominal surgery prior to surgical intensive care units caused by acute enteric perforation. These patients were all met the diagnostic criteria of septic shock according to Sepsis-3. Statistical analysis showed that lactic acid, blood platelet, fibrinogen, creatinine and activated partial thromboplastin time were found to be associated with 28-day mortality. A combination of serum activated partial thromboplastin time combined with fibrinogen and creatinine could predict in-hospital 28-day mortality. The area under the curve of serum activated partial thromboplastin time combined with fibrinogen and creatinine is 0.875 (0.806-0.944). CONCLUSION: In conclusion, this pilot study demonstrated that these factors can predict the prognosis of septic shock caused by enteric perforation. In order to reduce the mortality, surgeons and intensive care units physician may consider these data in perioperative period.