Metabolome and Transcriptome Association Analysis Reveals Mechanism of Synthesis of Nutrient Composition in Quinoa (Chenopodium quinoa Willd.) Seeds.

Quinoa (Chenopodium quinoa Willd.) seeds are rich in nutrition, superior to other grains, and have a high market value. However, the biosynthesis mechanisms of protein, starch, and lipid in quinoa grain are still unclear. The objective of this study was to ascertain the nutritional constituents of white, yellow, red, and black quinoa seeds and to employ a multi-omics approach to analyze the synthesis mechanisms of these nutrients. The findings are intended to furnish a theoretical foundation and technical support for the biological breeding of quinoa in China. In this study, the nutritional analysis of white, yellow, red, and black quinoa seeds from the same area showed that the nutritional contents of the quinoa seeds were significantly different, and the protein content increased with the deepening of color. The protein content of black quinoa was the highest (16.1 g/100 g) and the lipid content was the lowest (2.7 g/100 g), among which, linoleic acid was the main fatty acid. A combined transcriptome and metabolome analysis exhibited that differentially expressed genes were enriched in "linoleic acid metabolism", "unsaturated fatty acid biosynthesis", and "amino acid biosynthesis". We mainly identified seven genes involved in starch synthesis (LOC110716805, LOC110722789, LOC110738785, LOC110720405, LOC110730081, LOC110692055, and LOC110732328); five genes involved in lipid synthesis (LOC110701563, LOC110699636, LOC110709273, LOC110715590, and LOC110728838); and nine genes involved in protein synthesis (LOC110710842, LOC110720003, LOC110687170, LOC110716004, LOC110702086, LOC110724454 LOC110724577, LOC110704171, and LOC110686607). The data presented in this study based on nutrient, transcriptome, and metabolome analyses contribute to an enhanced understanding of the genetic regulation of seed quality traits in quinoa, and provide candidate genes for further genetic improvements to improve the nutritional value of quinoa seeds.

Exploring the molecular mechanism of sepsis-associated encephalopathy by integrated analysis of multiple datasets.

BACKGROUND: We aim to deal with the Hub-genes and signalling pathways connected with Sepsis-associated encephalopathy (SAE). METHODS: The raw datasets were acquired from the Gene Expression Omnibus (GEO) database (GSE198861 and GSE167610). R software filtered the differentially expressed genes (DEGs) for hub genes exploited for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Hub genes were identified from the intersection of DEGs via protein-protein interaction (PPI) network. And the single-cell dataset (GSE101901) was used to authenticate where the hub genes express in hippocampus cells. Cell-cell interaction analysis and Gene Set Variation Analysis (GSVA) analysis of the whole transcriptome validated the interactions between hippocampal cells. RESULTS: A total of 161 DEGs were revealed in GSE198861 and GSE167610 datasets. Biological function analysis showed that the DEGs were primarily involved in the phagosome pathway and significantly enriched. The PPI network extracted 10 Hub genes. The M2 Macrophage cell decreased significantly during the acute period, and the hub gene may play a role in this biological process. The hippocampal variation pathway was associated with the MAPK signaling pathway. CONCLUSION: Hub genes (Pecam1, Cdh5, Fcgr, C1qa, Vwf, Vegfa, C1qb, C1qc, Fcgr4 and Fcgr2b) may paticipate in the biological process of SAE.

A Retrospective Study of the Effect of Spinopelvic Parameters on Fatty Infiltration in Paraspinal Muscles in Patients With Lumbar Spondylolisthesis.

OBJECTIVE: The effect on fat infiltration (FI) of paraspinal muscles in degenerative lumbar spinal diseases has been demonstrated except for spinopelvic parameters. The present study is to identify the effect of spinopelvic parameters on FI of paraspinal muscle (PSM) and psoas major muscle (PMM) in patients with degenerative lumbar spondylolisthesis. METHODS: A single-center, retrospective cross-sectional study of 160 patients with degenerative lumbar spondylolisthesis (DLS) and lumbar stenosis (LSS) who had lateral full-spine x-ray and lumbar spine magnetic resonance imaging was conducted. PSM and PMM FIs were defined as the ratio of fat to its muscle cross-sectional area. The FIs were compared among patients with different pelvic tilt (PT) and pelvic incidence (PI), respectively. RESULTS: The PSM FI correlated significantly with pelvic parameters in DLS patients, but not in LSS patients. The PSM FI in pelvic retroversion (PT > 25°) was 0.54 ± 0.13, which was significantly higher in DLS patients than in normal pelvis (0.41 ± 0.14) and pelvic anteversion (PT < 5°) (0.34 ± 0.12). The PSM FI of DLS patients with large PI ( > 60°) was 0.50 ± 0.13, which was higher than those with small ( < 45°) and normal PI (0.37 ± 0.11 and 0.36 ± 0.13). However, the PSM FI of LSS patients didn't change significantly with PT or PI. Moreover, the PMM FI was about 0.10-0.15, which was significantly lower than the PSM FI, and changed with PT and PI in a similar way of PSM FI with much less in magnitude. CONCLUSION: FI of the PSMs increased with greater pelvic retroversion or larger pelvic incidence in DLS patients, but not in LSS patients.

Antifungal and anti-biofilm activities of patchouli alcohol against Candida albicans.

The opportunistic fungal pathogen Candida albicans could cause severe clinical outcomes which could be exacerbated by the scarcity of antifungals. The capacity of C. albicans to form biofilms on medical devices that are hard to eradicate, further deepen the need to develop antifungal agents. In this study, we, for the first time, showed that patchouli alcohol (PA) can inhibit the growth of multiple C. albicans strains, as well as four other Candida species, with MICs of 64 µg/mL and MFCs from 64 to 128 µg/mL. The biofilm formation and development, adhesion, yeast-to-hyphal transition and extracellular polysaccharide of C. albicans can be inhibited by PA in a concentration-dependent manner. Confocal microscopy analyses of cells treated with PA showed that PA can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. In C. elegans, PA did not influence the survival below 64 µg/mL. In this study PA demonstrated antifungal and antibiofilm activity against C. albicans and our results showed the potential of developing PA to fight Candida infections.

Polyphyllin I, a strong antifungal compound against Candida albicans.

This study was performed to explore the antifungal and antibiofilm effects of polyphyllin I (PPI) on Candida albicans. Microdilution assay was performed to determine the minimal inhibitory concentrations (MIC) of PPI against Candida species. Adhesion assay, hyphal growth assay, biofilm formation, and development were used to test the impacts of PPI on C. albicans virulence factors. Propidium iodide staining was performed to test whether the permeability of cell membrane was influenced by PPI. PPI showed significant antifungal activities against several Candida species, with MIC below or equal to 6.25 µM. PPI also inhibited the adhesion to polystyrene surfaces, hyphal growth, and biofilm formation. PPI significantly increased the permeability of C. albicans cell membrane. In sum, PPI can suppress the planktonic growth and biofilm of C. albicans and its mechanism involves the increased permeability of cell membrane.

Dehydrocostus lactone inhibits Candida albicans growth and biofilm formation.

Candida albicans infections are threatening public health but there are only several antifungal drugs available. This study was to assess the effects of dehydrocostus lactone (DL) on the Candida albicans growth and biofilms Microdilution assays revealed that DL inhibits a panel of standard Candida species, including C. albicans, as well as 9 C. albicans clinical isolates. The morphological transition of C. albicans in RPMI-1640 medium and the adhesion to polystyrene surfaces can also be decreased by DL treatment, as evidenced by microscopic, metabolic activity and colony forming unit (CFU) counting assays. The XTT assay and microscopy inspection demonstrated that DL can inhibit the biofilms of C. albicans. Confocal microscopy following propidium iodide (PI) staining and DCFH-DA staining after DL treatment revealed that DL can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. N-acetyl-cysteine could mitigate the inhibitory effects of DL on growth, morphological transition and biofilm formation, further confirming that ROS production induced by DL contributes to its antifungal and antibiofilm effects. This study showed that DL demonstrated antifungal and antibiofilm activity against C. albicans. The antifungal mechanisms may involve membrane damage and ROS overproduction. This study shows the potential of DL to fight Candida infections.

Application background and mechanism of short-chain fatty acids in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a frequent brain dysfunction found in sepsis patients, manifesting as delirium, cognitive impairment, and abnormal behaviors. The gut microbiome and short-chain fatty acids (SCFAs) are particularly associated with neuroinflammation in patients with SAE, thus noticeably attracting scholars' attention. The association of brain function with the gut-microbiota-brain axis was frequently reported. Although the occurrence, development, and therapeutic strategies of SAE have been extensively studied, SAE remains a critical factor in determining the long-term prognosis of sepsis and is typically associated with high mortality. This review concentrated on the interaction of SCFAs with microglia in the central nervous system and discussed the anti-inflammatory and immunomodulatory effects of SCFAs by binding to free fatty acid receptors or acting as histone deacetylase inhibitors. Finally, the prospects of dietary intervention using SCFAs as dietary nutrients in improving the prognosis of SAE were reviewed.

Emergency treatment of airway obstruction caused by a laryngeal neuroendocrine tumor: A case report.

RATIONALE: Laryngeal obstruction is a life-threatening adverse event that requires urgent and appropriate management, particularly in patients with coexisting cardiopulmonary and brain comorbidities. However, laryngeal obstruction caused by laryngeal neuroendocrine tumors has rarely been reported. PATIENT CONCERNS: Neuroendocrine tumors can cause pathological changes in the neuro-humoral system, and asphyxia caused by airway obstruction has a more adverse effect on patients with neuroendocrine tumors. DIAGNOSES: We report the case of a 64-year-old man with clinical manifestations of dyspnea. Preoperative and intraoperative pathological examination indicated that the patient was diagnosed with life-threatening airway obstruction caused by a laryngeal neuroendocrine tumor, pneumonia, and scoliosis. INTERVENTIONS: The patient underwent laryngeal tumor resection under general anesthesia. He was recovered well and was generally good without the necessity of undergoing radiotherapy and chemotherapy at the 6-months follow-up. OUTCOMES: This case report has provided an emergency treatment strategy associated with awake intubation. We concluded that flexible establishment of an artificial airway, skilled anesthesia and surgical manipulation, and necessary postoperative intensive care are extremely important for improving the prognosis of patients with severely difficult airway. It is noteworthy that the timely adjust for endotracheal intubation strategy according to the patient's response is needed. It is important for the long-term prognosis of patients to avoid the establishment of a traumatic artificial airway and the occurrence of adverse complications. LESSONS: 1. Introduction; 2. Case presentation; 3. Discussion; 4. Conclusion.

Review of Neurofilaments as Biomarkers in Sepsis-Associated Encephalopathy.

Sepsis is a common and fatal disease, especially in critically ill patients. Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction with acute altered consciousness, permanent cognitive impairment, and even coma, accompanied by sepsis, without direct central nervous system infection. When managing SAE, early identification and quantification of axonal damage facilitate faster and more accurate diagnosis and prognosis. Although no specific markers for SAE have been identified, several biomarkers have been proposed. Neurofilament light chain (NFL) is a highly expressed cytoskeletal component of neurofilament (NF) proteins that can be found in blood and cerebrospinal fluid (CSF) after exposure to axonal injury. NFs can be used as diagnostic and prognostic biomarkers for sepsis-related brain injury. Phosphorylation of NFs contributes to the maturation and stabilization of cytoskeletal structures, especially axons, and facilitates axonal transport, including mitochondrial transport and energy transport. The stability of NF proteins can be assessed by monitoring the expression of NF genes. Furthermore, phosphorylation levels of NFs can be monitored to determine mitochondrial axonal transport associated with cellular energy metabolism at distal axons to assess progression during SAE treatment. This paper provides new insights into the biological characteristics, detection techniques, and scientific achievements of NFs, and discusses the underlying mechanisms and future research directions of NFs in SAE.

Disc degeneration contributes to the denser bone in the subendplate but not in the vertebral body in patients with lumbar spinal stenosis or disc herniation.

BACKGROUND CONTEXT: It is commonly believed that decreased bone quality would lead to endplate degeneration and arthritic changes in the facet joints, and thus accelerated disc degeneration (DD). However, some more detailed studies of vertebral bone structure have found that bone mineral density (BMD) in the vertebral body is increased rather than decreased in moderate or greater disc degeneration. The relationship between BMD and DD still needs further study. MRI-based vertebral bone quality scores have been shown to be effective in reflecting BMD, rendering a new way to evaluate the changes of vertebral body bone with DD using MRI alone. PURPOSE: To evaluate MRI-based vertebral bone quality and Pfirrmann grades in patients with lumbar spinal stenosis or disc herniation, and to identify if DD is associated with denser bone around the endplate. STUDY DESIGN/SETTING: A single-center, retrospective cohort study. PATIENT SAMPLE: A total of 130 patients with lumbar disc herniation and lumbar spinal stenosis from January 2019 to November 2020 who had a complete dual-energy X-ray absorptiometry scan and noncontrast lumbosacral spine MRI data. OUTCOME MEASURES: The vertebral bone quality score (VBQ) and sub-endplate bone quality score (EBQ) was calculated as a ratio of the signal intensity of the vertebral bodies and sub-endplate regions to the signal intensity of the cerebrospinal fluid at L3 on the mid-sagittal T1-weighted MRI images, respectively. The Pfirrmann grades of the lumbar discs were assessed as well. METHODS: The age, gender, body mass index, and T-score of the lumbar spine of the patients were collected. The degeneration grades of the lumbar discs were evaluated according to the Pfirrmann classification. VBQ and EBQ were measured through T1-weighted lumbar MRI. The VBQ and EBQ scores were compared between cranial and caudal sides. The correlation between MRI-based bone quality and DD was calculated. A linear regression model was used to examine the association between DD and adjacent EBQ and VBQ. RESULTS: This study included 569 lumbar segments from 130 inpatients. Cranial and caudal EBQ decreased with the increase of the Pfirrmann grade. The discs with Pfirrmann grade 5 had significantly lower caudal EBQ than the discs with Pfirrmann grades 2, 3, and 4. In the osteoporosis patients, the Pfirrmann grades negatively correlated both with the cranial EBQ and caudal EBQ. Pfirrmann grade greater than 4 was an independent contributor to the cranial EBQ, whereas greater than 3 was an independent contributor to the caudal EBQ. CONCLUSIONS: Disc degeneration grades correlated with the EBQ but not with the VBQ. In patients with lumbar spinal stenosis or disc herniation, DD contributes to the denser bone in the sub-endplate, but not in the whole vertebral body.

Development and evaluation of a predictive nomogram for survival in heat stroke patients: a retrospective cohort study.

BACKGROUND: This study aimed to establish an effective nomogram to predict the survival of heat stroke (HS) based on risk factors. METHODS: This was a retrospective, observational multicenter cohort study. We analyzed patients diagnosed with HS, who were treated between May 1 and September 30, 2018 at 15 tertiary hospitals from 11 cities in Northern China. RESULTS: Among the 175 patients, 32 patients (18.29%) died before hospital discharge. After the univariate analysis, mechanical ventilation, initial mean arterial pressure <70 mmHg, maximum heart rate, lab results on day 1 (white blood cell count, alanine aminotransferase, creatinine), and Glasgow admission prediction score were included in multivariate analysis. Multivariate Cox regression showed that invasive ventilation, initial mean arterial pressure <70 mmHg (1 mmHg=0.133 kPa), and Glasgow admission prediction score were independent risk factors for HS. The nomogram was established for predicting 7-d and 14-d survival in the training cohort. The nomogram exhibited a concordance index (C-index) of 0.880 (95% confidence interval [95% CI] 0.831-0.930) by bootstrapping validation (B=1,000). Furthermore, the nomogram performed better when predicting 14-d survival, compared to 7-d survival. The prognostic index cut-off value was set at 2.085, according to the operating characteristic curve for overall survival prediction. The model showed good calibration ability in the internal and external validation datasets. CONCLUSION: A novel nomogram, integrated with prognostic factors, was proposed; it was highly predictive of the survival in HS patients.

MRI-based vertebral bone quality score effectively reflects bone quality in patients with osteoporotic vertebral compressive fractures.

OBJECTIVE: The present study is aimed to validate the ability of the vertebral bone quality (VBQ) score to evaluate bone quality in patients with osteoporotic vertebral compression fractures (OVCF) and to compare it with the ability of T-score by DXA. In addition, the sensitivity of VBQ score with cerebrospinal fluid (CSF) of L2 and L3 segments as baseline is evaluated. METHODS: 196 inpatients were collected and assigned into OVCF and Non-OVCF groups, respectively. For each patient, the VBQ score was calculated by the signal intensity of the L1-L4 vertebral bodies and CSF at L3 or L2 level from T1-weighted MRIs, while T-score from DXA was also obtained. The VBQ and T-score was compared between OVCF and non-OVCF groups, and among age groups. The OVCF ORs by VBQ score and T-score were calculated using logistic regression. RESULTS: OVCF group was significantly different to the non-OVCF group in the T-score (- 2.9 vs. - 0.7) and VBQ score (4.0 vs. 3.5). VBQ score and T-score in patient aged 60-79 years old could indicate the bone quality, but only T-score in patients aged 50-59 years old. OVCF are associated with both higher VBQ score and lower T-score. The VBQ scores calculated by L2 CSF and L3 CSF were similar. CONCLUSIONS: The VBQ score is an effective indicator of bone quality in OVCF patients and comparable to T-score, particularly in people over 60 years old. The VBQ score is not sensitive to CSF of different segments as a baseline.

Anterior Transarticular Crossing Screw Placement for Atlantoaxial Instability in Children: Computed Tomography-Based Study.

OBJECTIVE: The feasibility of anterior transarticular crossing screw (ATCS) fixation for atlantoaxial instability was confirmed in adults. However, atlantoaxial instability is more common in children. Therefore this study was aimed to ascertain the pediatric morphometric characteristics of ATCS in C1-2. METHODS: Morphometric analysis was conducted on computed tomography scan in 87 pediatric patients who were divided into groups based on ages (1-6 years, 7-10 years, and 11-16 years). Measurements were taken in sagittal and axial planes of computed tomography imaging to determine the range of screw lateral angles, incline angles, and screw lengths. RESULTS: The overall screw lengths were relatively longer in males than females. For those aged 1-6 years, the screw lengths were 25.5-32.8 mm in males and 24.2-31.3 mm in females, respectively. The screw lengths showed no difference in the 7- to 10-year group between sexes, while the incline angle was larger in females than males. And the screw lengths were 33.5-43.2 mm in males and 31.2-40.4 mm in females in the 11- to 16-year group. The screw lengths were increased with age, yet the lateral angles were decreased. We also found that the epiphyseal closure of odontoid reached 93.6% when the age was older than 7 years old. Therefore ATCS was recommended for children older than 7 years. CONCLUSIONS: The overall screw lengths and lateral angles of ATCS were larger in male children than those in females, but the incline angles were larger in females. ATCS is feasible in children, particularly those aged 7 years or older.

Dynamic and Hybrid Configurations for Extracorporeal Membrane Oxygenation: An Analysis of the Chinese Extracorporeal Life Support Registry.

Dynamic or hybrid configurations for extracorporeal membrane oxygenation (ECMO) are needed when patient physiology or clinical conditions change. Dynamic configurations included configurations converting from veno-arterial (V-A) ECMO or veno-venous (V-V) ECMO to other forms. Hybrid configurations included venous-arteriovenous (V-AV) and venovenous-arterial (VV-A) ECMO. This study retrospectively analyzed a total of 3,814 ECMO cases (3,102 adult cases) reported to the Chinese Society of Extracorporeal Life Support from January 1, 2017 to December 31, 2019. Eight-three adult patients had dynamic or hybrid ECMO configurations, whose primary diagnoses included cardiogenic shock (33.7%), cardiac arrest (6.0%), acute respiratory failure (39.8%), septic shock (9.6%), multiple trauma (3.6%), pulmonary hypertension (3.6%), and others (3.6%). Configuration changes occurred in 37 patients with the initial configuration of VA (20 to VV, 13 to V-AV, and 4 to VV-A) and 27 with the initial configuration of VV (7 to VA, and 20 to V-AV). A total of 46 (55.4%) patients received hybrid configurations of V-AV and 10 (12.0%) received VV-A. Patients with the initial configuration of VV who converted to other configurations had higher in-hospital mortality (74.1%) than other initial configurations (VA 45.9%, V-AV 76.9%, VV-A 66.7%, P = 0.021). We concluded that dynamic or hybrid ECMO configurations were used in various underlying diseases, in which V-AV was most commonly used. Patients receiving VV ECMO for respiratory support initially, who then converted to other configurations for both respiratory and circulatory support, had significantly worst outcomes among the groups studied. The initial configuration should be selected carefully after thorough assessment of patient condition.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Shock in China 2018 (SIC-study): a cross-sectional survey.

BACKGROUND: Shock is a critical illness that seriously threatens the lives of patients. This study explains the epidemiology of shock, mortality of shock, and identify factors that related to hospital death. METHODS: This is a multi-centre cross-sectional survey, which included 1,064 tertiary hospitals in 31 provinces, municipalities, and autonomous regions across China mainland. Totally 289,428 patients who diagnosed with shock based on the ICD-10 abstracted from the Hospital Quality Monitoring System (HQMS) in 2018, a national database administrated by National Health Commission of the PRC. RESULTS: Patients diagnosed with shock were screened and classified according to the type of shock. Regression analysis was used to identify factors that related to death. A total of 79,668,156 medical records were included in HQMS in 2018, from which a total of 289,428 records with shock were identified. Hypovolemic shock occurred in 128,436 cases (44.38%), septic shock occurred in 121,543 cases (41.99%), cardiogenic shock occurred in 44,597 cases (15.41), and obstructive shock occurred in 3,168 cases (1.09%). Of these, 8,147 cases (2.81%) had mixed shock, which means had two or more types of shock. For all the shock cases, the top three frequent concomitant diseases recorded were circulatory system diseases (55.22%), digestive system diseases (53.64%), and respiratory system diseases (53.31%). Of the four types of shock, cases with cardiogenic shock had the highest in-hospital mortality (31.6%), followed by those with obstructive shock (25.2%), septic shock (22.9%), and hypovolemic shock (15.5%). Interestingly, the combination of shock and malignant tumors is one of the major factors that related to hospital deaths. CONCLUSIONS: Shock is a serious disease with a high fatality rate and huge clinical costs. According to this epidemiological survey of shock in China 2018, we should clarify the factors related to the hospital death in shock cases.

Gut-liver crosstalk in sepsis-induced liver injury.

Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury.

Mitochondria in Sepsis-Induced AKI.

AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%-80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.

Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice.

NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?

Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit. As the most common treatment of septic AKI, it is believed that continuous renal replacement therapy (CRRT) can not only maintain the water balance and excrete the metabolic products but also regulate the inflammation and promote kidney recovery. CRRT can remove the inflammatory cytokines to regulate the metabolic adaption in kidney and restore the kidney recovery to protect the kidney in septic AKI. Second, CRRT can provide extra energy supply in septic AKI to improve the kidney energy balance in septic AKI. Third, the anticoagulant used in CRRT also regulates the inflammation in septic AKI. CRRT is not only a treatment to deal with the water balance and metabolic products, but also a method to regulate the inflammation in septic AKI.