Joint modeling and multiple comparisons with the best of data from a SMART with survival outcomes.

A dynamic treatment regimen (DTR) is a sequence of decision rules that can alter treatments or doses based on outcomes from prior treatment. In the case of two lines of treatment, a DTR specifies first-line treatment, and second-line treatment for responders and treatment for non-responders to the first-line treatment. A sequential, multiple assignment, randomized trial (SMART) is one such type of trial that has been designed to assess DTRs. The primary goal of our project is to identify the treatments, covariates, and their interactions result in the best overall survival rate. Many previously proposed methods to analyze data with survival outcomes from a SMART use inverse probability weighting and provide non-parametric estimation of survival rates, but no other information. Other methods have been proposed to identify and estimate the optimal DTR, but inference issues were seldom addressed. We apply a joint modeling approach to provide unbiased survival estimates as a mechanism to quantify baseline and time-varying covariate effects, treatment effects, and their interactions within regimens. The issue of multiple comparisons at specific time points is addressed using multiple comparisons with the best method.

HSP90.2 modulates 2Q2-mediated wheat resistance against powdery mildew.

Wheat (Triticum aestivum L.) is a critical food crop feeding the world, but pathogens threaten its production. Wheat Heat Shock Protein 90.2 (HSP90.2) is a pathogen-inducible molecular chaperone folding nascent preproteins. Here, we used wheat HSP90.2 to isolate clients regulated at the posttranslational level. Tetraploid wheat hsp90.2 knockout mutant was susceptible to powdery mildew, while the HSP90.2 overexpression line was resistant, suggesting that HSP90.2 was essential for wheat resistance against powdery mildew. We next isolated 1500 clients of HSP90.2, which contained a wide variety of clients with different biological classifications. We utilized 2Q2, a nucleotide-binding leucine repeat-rich protein, as a model to investigate the potential of HSP90.2 interactome in fungal resistance. The transgenic line co-suppressing 2Q2 was more susceptible to powdery mildew, suggesting 2Q2 as a novel Pm-resistant gene. The 2Q2 protein resided in chloroplasts, and HSP90.2 played a critical role in the accumulation of 2Q2 in thylakoids. Our data provided over 1500 HSP90.2 clients with a potential regulation at the protein folding process and contributed a nontypical approach to isolate pathogenesis-related proteins.

DKK1 promotes NUAK1 transcriptional expression through the activation Akt in hepatocellular carcinoma.

NUAK1 is a serine/threonine kinase that has been shown to be associated with poor prognosis in several cancers. Although NUAK1 is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC), the actual role of NUAK1 and the mechanism of its overexpression in HCC has yet to be reported. In the present study, we found that NUAK1 expression was significantly increased in human HCC tumor tissues. Overexpression of NUAK1 dramatically enhanced HCC cells proliferation and migration in vitro. Stable induction of NUAK1 expression promoted tumor growth and tumor metastases to the lungs in the subcutaneous xenograft models and intravenous metastasis models. At the cellular level, enforced expression of Dickkopf-1 (DKK1) activated the Akt signaling pathway, thereby promoting the mRNA and protein expression of NUAK1 in HCC cells. By contrast, depletion of DKK1 was found to attenuate the mRNA and protein expression of NUAK1. In the subcutaneous xenograft models, stable induction of DKK1 expression not only accelerated tumor growth but also increased p-Akt and NUAK1 expression; whereas knockdown of DKK1 inhibited tumor growth, p-Akt and NUAK1 expression. Furthermore, immunohistochemical analysis of 20 HCC clinical samples showed that the expression level of NUAK1 was positively correlated with DKK1 and p-Akt. Taken together, we provide the first evidence that DKK1 promotes NUAK1 transcriptional expression via the activation Akt in HCC.

Self-Appraisal of Clinical Competence in Echocardiography of Chinese Intensivists Post Basic Echocardiography Training.

Objectives To learn the echocardiography skills of intensivists after receiving a basic critical care echocardiography training course, and investigate factors that may influence their performance. Methods We completed a web-based questionnaire that assessed the skills in ultrasound scanning techniques of intensivists who took a training course on basic critical care echocardiography held in 2019 and 2020. Mann-Whitney test was used to analyze the factors which might affect their performance on image acquisition, recognizing clinical syndrome, and measuring the diameter of inferior vena cava, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral.Results We enrolled 554 physicians from 412 intensive care units across China. Among them, 185 (33.4%) reported that they had 10%-30% chance of being misled by critical care echocardiography when making therapeutic decision, and 34 (6.1%) reported that the chance was greater than 30%. Intensivists who performed echocardiography under the guidance of a mentor and finished ultrasound scanning more than 10 times per week reported significant higher scores in image acquisition, clinical syndrome recognition, and quantitative measurement of inferior vena cava diameter, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral than those without mentor and performing echocardiography 10 times or less per week respectively (all P < 0.05).Conclusion The skills in diagnostic medical echocardiography of Chinese intensivists after a basic echocardiographic training course remain low, and further quality assurance training program is clearly warranted.

Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma.

BACKGROUND: Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. METHODS: Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, ß-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. RESULTS: Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent ß-catenin stabilization and nuclear translocation. Nuclear ß-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. CONCLUSIONS: This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract.

Comparative genomic analysis of ABC transporter genes in Tenebrio molitor and four other tenebrionid beetles (Coleoptera: Tenebrionidea).

ATP-binding cassette (ABC) transporters, one of the largest transmembrane protein families, transport a diverse number of substate across membranes. Details of their diverse physiological functions have not been established. Here, we identified 87 ABC transporter genes in the genomes of Tenebrio molitor along with those from Asbolus verrucosus (104), Hycleus cichorii (65), and Hycleus phaleratus (80). Combining these genes (336 in total) with genes reported in Tribolium castaneum (73), we analyzed the phylogeny of ABC transporter genes in all five Tenebrionids. They are assigned into eight subfamilies (ABCA-H). In comparison to other species, the ABCC subfamily in this group of beetles appears expanded. The expression profiles of the T. molitor genes at different life stages and in various tissues were also investigated using transcriptomic analysis. Most of them display developmental specific expression patterns, suggesting to us their possible roles in development. Most of them are highly expressed in detoxification-related tissues including gut and Malpighian tubule, from which we infer their roles in insecticide resistance. We detected specific or abundant expressions of many ABC transporter genes in various tissues such as salivary gland, ovary, testis, and antenna. This new information helps generate new hypotheses on their biological significance within tissues.

Identification and expression profiling of serine protease-related genes in Tenebrio molitor.

In insects, serine proteases and serine protease homologs (SPs/SPHs) are involved in a variety of physiological processes including digestion, development, and immunity. Here, we identified 112 SP and 88 SPH genes in the genome of the yellow mealworm, Tenebrio molitor. Based on the features of domain structure, they were divided into "S" group containing single Tryp-SPc or Tryp-SPHc domain, "C" group containing 1-4 CLIP domain (CLIPA-D) and "M" group containing the CBD, CUB, EGF, Fz, Gd, LDLa, PAN, SEA, SR, Sushi, and TSP domains, and have 115, 48, and 37 gene members, respectively. According to the active sites in the catalytic triad, the putative trypsin, chymotrypsin, or elastase-like enzyme specificity of the identified SPs/SPHs were predicted. Phylogenetic and genomic location analyses revealed that gene duplication exists in the large amount of SPs/SPHs. Gene expression profiling using RNA-seq data along with real time reverse transcription-polymerase chain reaction analysis showed that most SP/SPH genes display life stage specific expression patterns, indicating their important roles in development. Many SP/SPH genes are specifically or highly expressed in the gut, salivary gland, fat body, hemocyte, ovary, and testis, suggesting that they participate in digestion, immunity, and reproduction. The findings lay the foundation for further functional characterization of SPs/SPHs in T. molitor.

The Wnt gene family in Tenebrio molitor and other coleopterans.

The Wnt gene family is involved in a wide range of developmental processes. Despite its significance, the evolution and function of Wnt genes remain largely unclear. Here, an exhaustive survey of Wnt genes was conducted in Tenebrio molitor and 17 other beetle genomes. A total of 146 Wnt genes were identified, creating a comprehensive coleopteran Wnt gene catalog. Comparative genomics indicates that dynamic evolutionary patterns of Wnt gene loss and duplication occurred in Coleoptera, leading to the diverse Wnt gene repertoire in various beetles. A striking loss of particular Wnt gene subfamilies occurs in Coleoptera. Remarkably, Wnt gene duplication was discovered for the first time in insects. Further analysis of Wnt gene expression in T. molitor indicates that each Wnt gene, including the duplicated ones, has a unique spatial or temporal expression pattern. The current study provides valuable insight into the evolution and functional validation of Wnt genes in Coleoptera.

Effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of GDM.

To investigate the effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of gestational diabetes mellitus. 3966 pregnant women were enrolled in this study. Multivariate logistic regression analysis was conducted to estimate the relative risk between pre-pregnancy BMI, gestational weight gain, and adverse pregnancy outcome. Pre-pregnancy BMI was found to be a risk factor for preeclampsia (OR = 1.159), gestational diabetes mellitus (OR = 1.191), gestational hypertension (OR = 1.221), and macrosomia (OR = 1.165). Gestational weight gain was a risk factor for preeclampsia (OR = 1.783), placental abruption (OR = 2.209), and macrosomia (OR = 1.506). Total weight gain during pregnancy cannot be used as a predictor of GDM. Pre-pregnancy BMI is a risk factor for gestational diabetes mellitus complicated with preeclampsia, preterm delivery, gestational hypertension, and macrosomia. Impact statementWhat is already known on this subject? Obesity during pregnancy includes pre-pregnancy obesity and excessive weight gain during pregnancy. Obese pregnant women have a higher risk of pregnancy complications.What do the results of this study add? We focus on the effects of pre-pregnancy BMI on pregnancy outcomes, classified by Asian criteria. Our findings suggest for the first time that excessive weight gain during pregnancy is a risk factor for placental abruption and we specifically point out that total weight gain during pregnancy cannot be used as a predictor of GDM.What are the implications of these findings for clinical practice and/or further research? This study is helpful to monitor the risk of adverse pregnancy outcomes in the Asian population and suggest the risk of pregnancy complications, such as gestational diabetes mellitus and placental abruption.

HGF/c-MET pathway contributes to cisplatin-mediated PD-L1 expression in hepatocellular carcinoma.

Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8+ T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.

Genome sequence of a novel member of the order Picornavirales from the endoparasitoid wasp Diversinervus elegans.

Here, we report a novel RNA virus from an encyrtid endoparasitoid wasp (Diversinervus elegans). This virus has a genome of 8845 nucleotides in length with a poly(A) tail. It contains one open reading frame (ORF) encoding a single polyprotein that shares the most significant similarity to the polyproteins of dicistroviruses. Phylogenetic analysis suggested that this virus belongs to the family Dicistroviridae from the order Picornavirales, but its genomic organization is distinct from that of the other known dicistroviruses, which have two ORFs. Consequently, we propose that this virus is a member of a new species in the order Picornavirales, and have named it "Diversinervus elegans virus" (DEV).

A Case of AB Para-Bombay Phenotype with Weak A Antigen Expression.

BACKGROUND: The Para-Bombay phenotype is characterized by H antigen partially or totally deficient on red blood cells and the presence of ABH substances in body fluids. METHODS: A patient with discrepant results in forward and reverse ABO phenotyping was further investigated by serological and molecular methods. RESULTS: Ortho gel and tube results showed weak A antigen expression and weak antibody reacting with A and B cells. Absorption-elution assay detected B antigen, and saliva test confirmed substances H were present. The patient was confirmed as A102B101 and Le(a+b+) phenotype. CONCLUSIONS: These findings suggest that the case is AB Para-Bombay Phenotype (secretor).

Homozygous FUT1 Mutations Causing a Para-Bombay Phenotype: a Pedigree Investigation Report.

BACKGROUND: Para-Bombay phenotype is rare in ABO blood group. We describe FUT1 mutations in a Chinese woman with the para-Bombay phenotype, including her familial inheritance. METHODS: ABO grouping, H antigen detection, absorptionelution test, salivary antigen substance detection, deter-mination of titer of ABH antibody, ABO genotyping, gene sequencing (FUT1,2), blood transfusion compatibility test, and pedigree investigation were performed. RESULTS: The patient was confirmed as group A1 para-Bombay phenotype (Amh) in her family's investigation, revealing her FUT1 gene had c.658C>T (p.Arg220Cys) homozygous mutation and FUT2 gene had c.357C>T homozygous mutation. The patient was provided an appropriate transfusion solution. CONCLUSIONS: A combination of using classical serological methods, gene sequencing methods and pedigree investigation methods can effectively analyze the genetic inheritance of patients with para-Bombay phenotype, increasing their choices of blood transfusion.

Comparative Performance of Four Nucleic Acid Amplification Tests for SARS-CoV-2 Virus.

BACKGROUND: COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was discovered in 2019 and spread around the world in a short time. SARS-CoV-2 nucleic acid amplification tests (NAATs) have been rapidly developed and quickly applied to clinical testing of COVID-19. Aim of this study was to evaluate the performance of four NAAT assays. METHODS: Limit of detection (LOD), precision, accuracy, analytical specificity and analytical interference studies on four NAATs (Daan, Sansure, Hybribio, and Bioperfectus) were performed according to Clinical Laboratory Standards Institute protocols and guidelines. The four NAATs were compared using 46 clinical samples. RESULTS: The LOD of the N gene for Daan, Sansure, and Hybribio was 500 copies/mL, and that for Bioperfectus was 1,000 copies/mL. The LOD of the ORF1ab gene for Daan, Bioperfectus, and Hybribio was 3,000 copies/mL, and that for Sansure was 2,000 copies/mL. A good precision was shown at the concentration above 20% of the LOD for all four NAATs, with all individual coefficients of variation below 3.6%. Satisfactory results were also observed in the accuracy, analytical specificity, and analytical interference tests. The results of the comparison test showed that Daan, Sansure, and Hybribio NAATs could detect the samples with a specificity of 100% (30/30) and a sensitivity of 100% (16/16), whereas Bioperfectus NAAT detected the samples with a specificity of 100% (30/30) and a sensitivity of 81.25% (13/16). However, no significant difference in sensitivity was found between Bioperfectus NAAT and the three other NAATs (p > 0.05). CONCLUSIONS: The four SARS-CoV-2 NAATs showed comparable performance, with the LOD of the N gene lower than the LOD of the ORF1ab gene.

Lung ultrasound score based on the BLUE-plus protocol is associated with the outcomes and oxygenation indices of intensive care unit patients.

PURPOSE: The primary objective was to demonstrate the relationship between lung ultrasound (LUS) manifestations and the outcomes of intensive care unit (ICU) patients. The secondary objective was to determine the characteristics of LUS manifestations in different subgroups of ICU patients. METHODS: This prospective multi-center cohort study was conducted in 17 ICUs. A total of 1702 patients admitted between August 31, 2017 and February 16, 2019 were included. LUS was performed according to the bedside lung ultrasound in emergency (BLUE)-plus protocol, and LUS scores were calculated. Data on the outcomes and oxygenation indices were analyzed and compared between different primary indication groups. RESULTS: The LUS scores were significantly higher for non-survivors than for survivors and were significantly different between the oxygenation index groups, with higher scores in the lower oxygenation index groups. The LUS score was an independent risk factor for the 28-day mortality. The area under the receiver operating characteristic curve was 0.663 for prediction of the 28-day mortality and 0.748 for prediction of an oxygenation index ≤100. CONCLUSIONS: The LUS score based on the BLUE-plus protocol was an independent risk factor for the 28-day mortality and was important for the prediction of an oxygenation index ≤100. An early LUS score within 24 hours of ICU admission helps predicting the outcome of ICU patients.

Effect of Focused Cardiac Ultrasound in Combination with Lung Ultrasound on Critically Ill Patients: A Multicenter Observational Study in China.

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8% vs. 49.0%, χ 2=0.003, P=0.956). In the multivariable analysis, admission for respiratory failure was an independent variable associated with treatment change, with an odds ratio (OR) of 2.357 [95% confidence interval (CI): 1.284-4.326, P=0.006]; the timing of examination was not associated with treatment change (OR=0.725, 95%CI: 0.407-1.291, P=0.275). Conclusions FCU in combination with LU, whether performed during the early phase or later phase, had a significant impact on the treatment of critically ill patients. Patients with respiratory failure were more likely to experience treatment change after the ultrasound examination.

Duplication of toll-like receptor 22 in teleost fishes.

The TLRs of teleost fishes have distinct features and are highly diverse, but the duplication characteristics and expression patterns of the tlr22 gene remain unclear. Here, we identified paralogous tlr22 genes in 13 teleost fishes by screening available fish genomic resources and using molecular cloning. We then conducted comprehensive bioinformatics analyses and investigated spatiotemporal differences in the expression patterns of the tlr22 genes in G. eckloni. The results indicated that more than three paralogous tlr22 genes were possessed by some teleost fishes. Of these, tlr22c is specific to some subfamilies of the Cyprinidae (e.g., Barbinae, Cyprininae, Schizothoracinae, and Leuciscinae). Phylogenetic and syntenic analyses showed that the paralogous tlr22 genes originated from two single-gene duplication events. Molecular clock calculations dated the two gene duplication events at 49.5 and 39.3 MYA, which is before the common carp-specific genome duplication event and well after the fish-specific genome duplication. Gene duplication of tlr22 was followed by gene loss or pseudogene events in certain lineages. Spatiotemporal expression differences between the three duplicated tlr22 genes from G. eckloni suggested that these genes diverged functionally after gene duplication.

A Pre-Analytical Performance Evaluation for Measurement of Serum Creatinine in a Multicenter Clinical Trial Study.

BACKGROUND: Our multicenter clinical trial study for stage 4 chronic kidney disease (CKD) populations was conducted at 21 centers in China during the period 2011 to 2016. The CKD definition is based on glomerular filtration rate (GFR) values which can be estimated by creatinine-based predictive formulas. The validity and reliability of GFR estimation is thus largely dependent on the accurate and precise serum creatinine (SCr) measurements. As an integral part of this multicenter study, it is important to ensure the precision, accuracy, and center-to-center comparability of the SCr results. METHODS: Prior to initiating the study, we unified the measurement method of SCr determination as an enzymatic method and standardized the procedure in all of the laboratories. Then, the analytical performance of each analyzer at each laboratory was evaluated, including precision, accuracy, and comparability. RESULTS: All within-run and total CVs of the low and high level internal quality control (IQC) were comprised between 0.2% and 4.1% (< 1/3 CLIA'88). Total error of the IQC fall within the maximum 12% at all centers. The analytical bias against the Standard Reference material 967a target was less than ± 0.5% at Central Laboratory, indicating good accuracy. Correlation between the analyzers and the reference method were very high (r > 0.99). Passing-Bablok regression showed no significant deviation from linearity (p > 0.05). Bland-Altman analysis also showed good agreement (≥ 95% of results fell within the 95% limits of agreement). CONCLUSIONS: Performance evaluation helped in addressing preanalytical variations in measurement and gave op-timal quality assurance of laboratory measurement in the context of a multicenter clinical trial study.

Molecular characterization and expression changes of cytoglobin genes in response to hypoxia in a Tibetan schizothoracine fish, Schizopygopsis pylzovi.

Schizopygopsis pylzovi, an endemic fish of the subfamily Schizothoracinae, is comparatively well adapted to dissolved oxygen fluctuations in the aqueous environments of the Qinghai-Tibetan Plateau. Here, we cloned the complete cDNA of cytoglobin 1 and 2 (Cygb1 and Cygb2) from S. pylzovi and then investigated transcriptional changes of both genes in the selected tissues in response to hypoxia. Both the two genes had the standard exon-intron structure of vertebrate Mb genes but lacked an exon at downstream of the H helix (HC11.2) as seen in mammals. We applied severe hypoxia (4 h at PO2 = 3.6% saturation) and moderate hypoxia (72 h at PO2 = 36.0% saturation) to adult S. pylzovi. Under severe hypoxia, the Cygb1 mRNA levels decreased significantly in the liver, kidney, and brain, but increased significantly in the heart, while the Cygb2 mRNA levels downregulated significantly in the muscle and liver. But, the transcriptional activity of Cygb1 in muscle and that of Cygb2 in the kidney, brain, and heart remained almost unchanged. Under moderate hypoxia, the transcriptional activities of both genes in muscle and brain were turned down quickly after onset hypoxia, while in the liver, kidney, and heart, the transcriptional activities of both genes showed a short-term upregulation in different time periods of hypoxia exposure. Our data suggest that both the Cygb1 and Cygb2 in S. pylzovi are hypoxia-induced genes, and the responses of the transcription regulation of Cygb1 and Cygb2 genes to hypoxia are tissue specific and also depend on the hypoxia regime, which are different from that of other fish species.

[Correlation Between the Severity of Lung Ultrasound Score in Non-gravity Dependent Areas and Poor Prognosis of Patients with Shock and on Mechanical Ventilation].

OBJECTIVE: To explore whether ultrasound abnormalities in the non-gravity dependent areas (area 1-2) of the lungs are associated with poor prognosis in patients with shock and on mechanical ventilation. METHODS: We retrospectively analyzed the data of lung ultrasound from 181 patients with shock from Apr. 2016 to Nov. 2017. The patients were divided into the survival group and the non-survival group according to the 28 d outcome. Single factor and multivariate Cox regression were used to analyze the relationship between lung ultrasound score of the overall and each area and the 28 d mortality.Kaplan-Meier curve was used to analyze the relationship between the severity of ultrasound lesions in area 1-2 and the prognosis at 28 d. RESULTS: 169 patients were included.There were 106 males (62.7%) and 63 females (37.3%).There were 90 patients in the survivel group and 79 patients in the non-survival group.Single factor Cox regression analysis found that adjusting the age, acute physiology and chronic health evaluation (APACHE) Ⅱ score, lactate level, urine output per hour, application of vasoactive agent, oxygenation index, lungs ultrasound score of area 1-6, area 1-2 and area 3-4 were associated with 28 d mortality. Multivariate Cox regression revealed that lung ultrasound score of area 1-2 was the independent risk factor of 28 d mortality, as well as APACHE Ⅱ score and lactate level. The Kaplan-Meier curve found that the more severe the lesion in area 1-2, the lower the survival rate at 28 d. CONCLUSION: Lung ultrasound score of area 1-2 in patients with shock and on mechanical ventilation may be a predictor of poor prognosis at 28 d.