Healthcare services efficiency and its intrinsic drivers in China: based on the three-stage super-efficiency SBM model.

BACKGROUND: The purpose of this study is to examine the development of healthcare services efficiency in China since the reform of the healthcare system. By examining the development environment of healthcare services in China and examining the driving factors affecting the efficiency of healthcare services, we provide a reference for the future high-quality development of healthcare services in China. METHODS: A three-stage super-efficient slack-based measure (SBM) model with undesirable outputs was used to measure the efficiency of healthcae services in 31 Chinese provinces from 2009 to 2021, and a global Malmquist-Luenberger (GML) index was used to assess their spatiotemporal evolution characteristics and internal influencing mechanisms of healthcare services efficiency. RESULTS: The empirical results showed that the efficiency of China's healthcare services changed significantly from 2009-2014 and then remained stable. During the study period, the efficiency of healthcare services in the eastern region was higher than the national level, while it was lower in the western region. The results of the analysis of environmental factors indicated that an increase in population density reduced the redundancy of healthcare input resources and that economic development as well as an increase in government subsidies, contributed to an increase in the redundancy of healthcare input resources. The main contribution to the growth of healthcare sercices efficiency in China came from the technological innovation effect, and the growth was most significant in the western region. CONCLUSION: From 2009 to 2021, the efficiency of national healthcare services generally showed a slow upward trend, and the efficiency of healthcare services varied widely among regions. Under the existing environmental constraints, relevant departments in each region should strengthen technological innovation in healthcare services, completely focus on the regional catch-up effect, and promote the balanced development of regional health.

Machine Learning Approaches-Driven for Mortality Prediction for Patients Undergoing Craniotomy in ICU.

OBJECTIVES: We aimed to predict the mortality of patients with craniotomy in ICU by using predictive models to extract the high-risk factors leading to the death of patients from a retrospective a study. METHODS: Five machine-learning (ML) algorithms were applied for training on mortality predictive models with the data from a surgical intensive care unit (ICU) database of the Fujian Provincial Hospital in China. The accuracy, precision, recall, f1 score and the area under the receiver operator characteristic curve (AUC) were used to evaluate the performance of different models, and the calibration of the model was evaluated by brier score. RESULTS: We demonstrated that eXtreme Gradient Boosting (XGBoost) was more suitable for the task, demonstrating a AUC of 0.84. We analyzed the feature importance with the Local Interpretable Model-agnostic Explanations (LIME) analysis and further identified the high-risk factors of mortality in ICU through this study. CONCLUSIONS: This study established the mortality predictive model of patients who had undergone craniotomy in ICU. Identification of the factors that had great influence on mortality has the potential to provide auxiliary decision support for clinical medical staff on their practices.

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.

Mst1 deletion reduces septic cardiomyopathy via activating Parkin-related mitophagy.

Cardiomyocyte function and viability are highly modulated by mammalian Ste20-like kinase 1 (Mst1)-Hippo pathway and mitochondria. Mitophagy, a kind of mitochondrial autophagy, is a protective program to attenuate mitochondrial damage. However, the relationship between Mst1 and mitophagy in septic cardiomyopathy has not been explored. In the present study, Mst1 knockout mice were used in a lipopolysaccharide (LPS)-induced septic cardiomyopathy model. Mitophagy activity was measured via immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay. Pathway blocker and small interfering RNA were used to perform the loss-of-function assay. The results demonstrated that Mst1 was rapidly increased in response to LPS stress. Knockout of Mst1 attenuated LPS-mediated inflammation damage, reduced cardiomyocyte death, and improved cardiac function. At the molecular levels, LPS treatment activated mitochondrial damage, such as mitochondrial respiratory dysfunction, mitochondrial potential reduction, mitochondrial ATP depletion, and caspase family activation. Interestingly, in response to mitochondrial damage, Mst1 deletion activated mitophagy which attenuated LPS-mediated mitochondrial damage. However, inhibition of mitophagy via inhibiting parkin mitophagy abolished the protective influences of Mst1 deletion on mitochondrial homeostasis and cardiomyocyte viability. Overall, our results demonstrated that septic cardiomyopathy is linked to Mst1 upregulation which is followed by a drop in the protective mitophagy.

Reconstruction of tricarboxylic acid cycle in Corynebacterium glutamicum with a genome-scale metabolic network model for trans-4-hydroxyproline production.

trans-4-Hydroxy- l-proline (Hyp) is an abundant component of mammalian collagen and functions as a chiral synthon for the syntheses of anti-inflammatory drugs in the pharmaceutical industry. Proline 4-hydroxylase (P4H) can catalyze the conversion of l-proline to Hyp; however, it is still challenging for the fermentative production of Hyp from glucose using P4H due to the low yield and productivity. Here, we report the metabolic engineering of Corynebacterium glutamicum for the fermentative production of Hyp by reconstructing tricarboxylic acid (TCA) cycle together with heterologously expressing the p4h gene from Dactylosporangium sp. strain RH1. In silico model-based simulation showed that α-ketoglutarate was redirected from the TCA cycle toward Hyp synthetic pathway driven by P4H when the carbon flux from succinyl-CoA to succinate descended to zero. The interruption of the TCA cycle by the deletion of sucCD-encoding the succinyl-CoA synthetase (SUCOAS) led to a 60% increase in Hyp production and had no obvious impact on the growth rate. Fine-tuning of plasmid-borne ProB* and P4H abundances led to a significant increase in the yield of Hyp on glucose. The final engineered Hyp-7 strain produced up to 21.72 g/L Hyp with a yield of 0.27 mol/mol (Hyp/glucose) and a volumetric productivity of 0.36 g·L -1 ·hr -1 in the shake flask fermentation. To our knowledge, this is the highest yield and productivity achieved by microbial fermentation in a glucose-minimal medium for Hyp production. This strategy provides new insights into engineering C. glutamicum by flux coupling for the fermentative production of Hyp and related products.

Resveratrol Protects the Myocardium in Sepsis by Activating the Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway and Inhibiting the Nuclear Factor-κB (NF-κB) Signaling Pathway.

BACKGROUND Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. However, the molecular mechanism of sepsis-induced myocardial dysfunction has not yet been thoroughly studied. Resveratrol has been an important research topic due its organ-protection function, but the specific mechanism is unclear. The purpose of this study was to explore the mechanism of organ injury in sepsis and to investigate the molecular mechanism of resveratrol in myocardial protection in sepsis. MATERIAL AND METHODS A classical Sprague-Dawley rat model of sepsis peritonitis was constructed for further experiments. The PI3K inhibitor LY294002 and resveratrol were used to intervene in a rat model of cardiomyopathy. HE staining was used to observe pathological changes. Cardiomyocyte apoptosis was detected by TUNEL assay. Western blot analysis was used to detect the level of maker proteins. RESULTS The PI3K inhibitors could promote cardiac abnormalities and apoptosis, but resveratrol showed the opposite effect. The upregulation function of the PI3K inhibitor on the expression of NF-kappaB, IL-6, IL-1ß, and TLR4 in LPS rats was not obvious, but the expression of TNF-a in LPS+LY294002 rats was increased by 22.85% compared with that in LPS rats (P<0.05). Compared with the LPS group, the expression of NF-kappaB, TNF-alpha, IL-6, IL-1ß, and TLR4 in the LPS+resveratrol group was decreased. The expression of p-PI3K, p-AKT, and p-mTOR in LPS+LY294002 was reduced. The expression p-PI3K, p-AKT, and p-mTOR in the myocardium of the LPS+resveratrol group was increased. CONCLUSIONS Resveratrol can protect the myocardium in sepsis by activating the PI3K/AKT/mTOR signaling pathway and inhibiting the NF-kappaB signaling pathway and related inflammatory factors.

A RecET-assisted CRISPR-Cas9 genome editing in Corynebacterium glutamicum.

BACKGROUND: Extensive modification of genome is an efficient manner to regulate the metabolic network for producing target metabolites or non-native products using Corynebacterium glutamicum as a cell factory. Genome editing approaches by means of homologous recombination and counter-selection markers are laborious and time consuming due to multiple round manipulations and low editing efficiencies. The current two-plasmid-based CRISPR-Cas9 editing methods generate false positives due to the potential instability of Cas9 on the plasmid, and require a high transformation efficiency for co-occurrence of two plasmids transformation. RESULTS: Here, we developed a RecET-assisted CRISPR-Cas9 genome editing method using a chromosome-borne Cas9-RecET and a single plasmid harboring sgRNA and repair templates. The inducible expression of chromosomal RecET promoted the frequencies of homologous recombination, and increased the efficiency for gene deletion. Due to the high transformation efficiency of a single plasmid, this method enabled 10- and 20-kb region deletion, 2.5-, 5.7- and 7.5-kb expression cassette insertion and precise site-specific mutation, suggesting a versatility of this method. Deletion of argR and farR regulators as well as site-directed mutation of argB and pgi genes generated the mutant capable of accumulating L-arginine, indicating the stability of chromosome-borne Cas9 for iterative genome editing. Using this method, the model-predicted target genes were modified to redirect metabolic flux towards 1,2-propanediol biosynthetic pathway. The final engineered strain produced 6.75 ± 0.46 g/L of 1,2-propanediol that is the highest titer reported in C. glutamicum. Furthermore, this method is available for Corynebacterium pekinense 1.563, suggesting its universal applicability in other Corynebacterium species. CONCLUSIONS: The RecET-assisted CRISPR-Cas9 genome editing method will facilitate engineering of metabolic networks for the synthesis of interested bio-based products from renewable biomass using Corynebacterium species as cell factories.

Native promoters of Corynebacterium glutamicum and its application in L-lysine production.

OBJECTIVE: To identify useful native promoters of Corynebacterium glutamicum for fine-tuning of gene expression in metabolic engineering. RESULTS: Sixteen native promoters of C. glutamicum were characterized. These promoters covered a strength range of 31-fold with small increments and exhibited relatively stable activity during the whole growth phase using ß-galactosidase as the reporter. The mRNA level and enzymatic activity of the lacZ reporter gene exhibited high correlation (R 2 = 0.96) under the control of these promoters. Sequence analysis found that strong promoters had high similarity of the -10 hexamer to the consensus sequence and preference of the AT-rich UP element upstream the -35 region. To test the utility of the promoter library, the characterized native promoters were applied to modulate the sucCD-encoded succinyl-CoA synthetase expression for L-lysine overproduction. CONCLUSIONS: The native promoters with various strengths realize the efficient and precise regulation of gene expression in metabolic engineering of C. glutamicum.

A novel pyruvate kinase and its application in lactic acid production under oxygen deprivation in Corynebacterium glutamicum.

BACKGROUND: Pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyks are highly conserved in most bacteria and lower eukaryotes. Corynebacterium glutamicum is an industrial workhorse for the production of various amino acids and organic acids. Although C. glutamicum was assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 was annotated as a pyruvate kinase with an unknown role. RESULTS: Here, we identified that NCgl2809 was a novel pyruvate kinase (pyk2) in C. glutamicum. Complementation of the WTΔpyk1Δpyk2 strain with the pyk2 gene restored its growth on D-ribose, which demonstrated that Pyk2 could substitute for Pyk1 in vivo. Pyk2 was co-dependent on Mn2+ and K+ and had a higher affinity for ADP than phosphoenolpyruvate (PEP). The catalytic activity of Pyk2 was allosterically regulated by fructose 1,6-bisphosphate (FBP) activation and ATP inhibition. Furthermore, pyk2 and ldhA, which encodes L-lactate dehydrogenase, were co-transcribed as a bicistronic mRNA under aerobic conditions and pyk2 deficiency had a slight effect on the intracellular activity of Pyk. However, the mRNA level of pyk2 in the wild-type strain under oxygen deprivation was 14.24-fold higher than that under aerobic conditions. Under oxygen deprivation, pyk1 or pyk2 deficiency decreased the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increased the production of lactic acid as the activity of Pyk increased. Fed-batch fermentation of the pyk2-overexpressing WTΔpyk1 strain produced 60.27 ± 1.40 g/L of lactic acid, which was a 47% increase compared to the parent strain under oxygen deprivation. CONCLUSIONS: Pyk2 functioned as a pyruvate kinase and contributed to the increased level of Pyk activity under oxygen deprivation.

YjeH Is a Novel Exporter of l-Methionine and Branched-Chain Amino Acids in Escherichia coli.

Amino acid efflux transport systems have important physiological functions and play vital roles in the fermentative production of amino acids. However, no methionine exporter has yet been identified in Escherichia coli. In this study, we identified a novel amino acid exporter, YjeH, in E. coli. The yjeH overexpression strain exhibited high tolerance to the structural analogues of l-methionine and branched-chain amino acids, decreased intracellular amino acid levels, and enhanced export rates in the presence of a Met-Met, Leu-Leu, Ile-Ile, or Val-Val dipeptide, suggesting that YjeH functions as an exporter of l-methionine and the three branched-chain amino acids. The export of the four amino acids in the yjeH overexpression strain was competitively inhibited in relation to each other. The expression of yjeH was strongly induced by increasing cytoplasmic concentrations of substrate amino acids. Green fluorescent protein (GFP)-tagged YjeH was visualized by total internal reflection fluorescence microscopy to confirm the plasma membrane localization of YjeH. Phylogenetic analysis of transporters indicated that YjeH belongs to the amino acid efflux family of the amino acid/polyamine/organocation (APC) superfamily. Structural modeling revealed that YjeH has the typical "5 + 5" transmembrane α-helical segment (TMS) inverted-repeat fold of APC superfamily transporters, and its binding sites are strictly conserved. The enhanced capacity of l-methionine export by the overexpression of yjeH in an l-methionine-producing strain resulted in a 70% improvement in titer. This study supplements the transporter classification and provides a substantial basis for the application of the methionine exporter in metabolic engineering.

Corrigendum: Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis.

[This corrects the article DOI: 10.3389/fimmu.2023.1247131.].

Characterization and molecular mechanism of AroP as an aromatic amino acid and histidine transporter in Corynebacterium glutamicum.

Corynebacterium glutamicum is equipped with abundant membrane transporters to adapt to a changing environment. Many amino acid transporters have been identified in C. glutamicum, but histidine uptake has not been investigated in detail. Here, we identified the aromatic amino acid transporter encoded by aroP as a histidine transporter in C. glutamicum by a combination of the growth and histidine uptake features. Characterization of histidine uptake showed that AroP has a moderate affinity for histidine, with a Km value of 11.40 ± 2.03 µM, and histidine uptake by AroP is competitively inhibited by the aromatic amino acids. Among the four substrates, AroP exhibits a stronger preference for tryptophan than for tyrosine, phenylalanine, and histidine. Homology structure modeling and molecular docking were performed to predict the substrate binding modes and conformational changes during substrate transport. These results suggested that tryptophan is best accommodated in the binding pocket due to shape compatibility, strong hydrophobic interactions, and the lowest binding energy, which is consistent with the observed substrate preference of AroP. Furthermore, the missense mutations of the putative substrate binding sites verified that Ser24, Ala28, and Gly29 play crucial roles in substrate binding and are highly conserved in the Gram-positive bacteria. Finally, the expression of aroP is not significantly affected by extracellular histidine or aromatic amino acids, indicating that the physiological role of AroP may be correlated with the increased fitness of C. glutamicum to assimilate extracellular amino acid for avoiding the high energy cost of amino acid biosynthesis.

Sepsis-associated encephalopathy: From pathophysiology to clinical management.

Sepsis-associated encephalopathy, which presents as delirium and coma, is a significant complication of sepsis characterized by acute brain dysfunction. The presence of inflammatory pathological changes in the brain of sepsis patients and animal models has been recognized since the 1920 s, initially attributed to the entry of microbial toxins into the brain. In the early 2000 s, attention shifted towards the impact of oxidative stress, the cholinergic system, and cytokines on brain function following sepsis onset. More recently, sepsis-associated encephalopathy has been defined as a diffuse brain dysfunction not directly caused by pathogenic infection of the brain. Currently, there is no evidence-based standard for diagnosing sepsis-associated encephalopathy, and clinical management is primarily focused on symptomatic and supportive measures. This review aims to explore the pathophysiology of sepsis-associated encephalopathy and establish the connection between pathophysiological mechanisms and clinical characteristics. We hope that this work will spark the interest of researchers from various fields and contribute to the advancement of sepsis-associated encephalopathy research.

Ubenimex suppresses glycolysis mediated by CD13/Hedgehog signaling to enhance the effect of cisplatin in liver cancer.

Background: Liver cancer ranks third in fatalities among all cancer-related deaths. As a traditional chemotherapy drug, the application of cis-Diamminedichloroplatinum (II) (cisplatin, CDDP) for the treatment of liver cancer is greatly limited by its side effects and high drug resistance. Therefore, we are in urgent need of a more effective and less toxic CDDP therapeutic regimen. Our research aimed to clarify the possible mechanism of ubenimex in enhancing the effect of CDDP on liver cancer. Methods: The underlying mechanism was determined using Cell Counting Kit-8 (CCK-8) assay, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), transwell assay, wound healing assay and western blot assay. Results: The data indicated that ubenimex suppressed the expression levels of glycolysis-related proteins by decreasing the expression levels of cluster of differentiation 13 (CD13), while overexpression of CD13 could restore the activity of glycolysis. The glycolysis inhibitor 2-deoxy-D-glucose enhanced the antiproliferative effect of ubenimex and CDDP. In addition, the inhibition of the activity levels of the Hedgehog (Hh) pathway members was accompanied by a decrease in CD13 expression, which was reversed following CD13 overexpression. Moreover, ubenimex inhibited the production of lactic acid and adenosine triphosphate (ATP), as well as the expression of key proteins involved in glycolysis, which was similar to the effects caused by the Hh inhibitor cyclopamine. However, the effects of ubenimex were mediated by targeting CD13, while cyclopamine exhibited no effects on CD13, suggesting that Hh signaling occurred in the downstream of CD13. The inhibition of glycolysis by cyclopamine was reduced following CD13 overexpression, which further indicated that ubenimex targeted the CD13/Hh pathway to inhibit glycolysis. Finally, wound healing and transwell assays and cell proliferation and apoptosis analysis demonstrated that ubenimex inhibited glycolysis by alleviating the CD13/Hh pathway, which in turn enhanced the effects of CDDP on inhibiting the progression of liver cancer. Conclusions: Ubenimex inhibits glycolysis by targeting the CD13/Hh pathway, thus playing an anti-tumor role together with CDDP. This study demonstrated the adjuvant effect of ubenimex from the perspective of Hh signal-dependent glycolysis regulation.

Optimization of central venous pressure during the perioperative period is associated with improved prognosis of high-risk operation patients.

Background: While central venous pressure (CVP) measurement is used to guide fluid management for high-risk surgical patients during the perioperative period, its relationship to patient prognosis is unknown. Methods: This single-center, retrospective observational study enrolled patients undergoing high-risk surgery from February 1, 2014 to November 31, 2020, who were admitted to the surgical intensive care unit (ICU) directly after surgery. Patients were divided into the following three groups according to the first CVP measurement (CVP1) after admission to the ICU: low, CVP1 <8 mmHg; moderate, 8 mmHg≤ CVP1 ≤ 12 mmHg; and high, CVP1 >12 mmHg. Perioperative fluid balance, 28-day mortality, length of stay in the ICU, and hospitalization and surgical complications were compared across groups. Results: Of the 775 high-risk surgical patients enrolled in the study, 228 were included in the analysis. Median (interquartile range) positive fluid balance during surgery was lowest in the low CVP1 group and highest in the high CVP1 group (low CVP1: 770 [410, 1205] mL; moderate CVP1: 1070 [685, 1500] mL; high CVP1: 1570 [1008, 2000] mL; all P <0.001). The volume of positive fluid balance during the perioperative period was correlated with CVP1 (r=0.336, P <0.001). The partial arterial pressure of oxygen(PaO2)/fraction of inspired oxygen(FiO2) ratio was significantly lower in the high CVP1 group than in the low and moderate CVP1 groups (low CVP1: 400.0 [299.5, 443.3] mmHg; moderate CVP1: 362.5 [330.0, 434.9] mmHg; high CVP1: 335.3 [254.0, 363.5] mmHg; all P <0.001). The incidence of postoperative acute kidney injury (AKI) was lowest in the moderate CVP1 group (low CVP1: 9.2%; moderate CVP1: 2.7%; high CVP1: 16.0%; P=0.007). The proportion of patients receiving renal replacement therapy was highest in the high CVP1 group (low CVP1: 1.5%; moderate CVP1: 0.9%; high CVP1: 10.0%; P=0.014). Logistic regression analysis showed that intraoperative hypotension and CVP1 >12 mmHg were risk factors for AKI within 72 h after surgery (adjusted odds ratio[aOR]=3.875, 95% confidence interval[CI]: 1.378-10.900, P=0.010 and aOR=1.147, 95%CI: 1.006-1.309, P=0.041). Conclusions: CVP that is either too high or too low increases the incidence of postoperative AKI. Sequential fluid therapy based on CVP after patients are transferred to the ICU post-surgery does not reduce the risk of organ dysfunction caused by an excessive amount of intraoperative fluid. However, CVP can be used as a safety limit indicator for perioperative fluid management in high-risk surgical patients.

Measuring the efficiency of public hospitals: A multistage data envelopment analysis in Fujian Province, China.

Objective: The present study aimed to evaluate the operational efficiency of public hospitals in Fujian Province and the factors responsible for the inefficiency of these hospitals and provide relevant suggestions for health policymakers in allocating service resources. Method: In the first stage of the research, the variables affecting the efficiency of hospitals were extracted by qualitative and quantitative methods, including literature optimization, gray related analysis and gray clustering evaluation. In the second stage, the data envelopment analysis (DEA) method was used to evaluate the operational efficiency of 49 hospitals of different levels and types selected by sampling in 2020. Finally, a Tobit regression model with introduced institutional factors and background factors was established to study the main influencing factors of hospital inefficiency. Results: In the first stage, 10 input variables and 10 output variables necessary from the mangers' point of view were identified to test efficiency. In the second stage, the average comprehensive TE, PTE, and SE of 49 sample hospitals was 0.802, 0.888, and 0.902, respectively. 22.45% of these hospitals met the effective criteria, i.e., the overall effective rate was 22.45%. The low SE value of the hospital was the main reason hindering the improvement of the comprehensive efficiency value. The overall effective rate of secondary public hospitals (30.77%) was higher than that of tertiary public hospitals (19.44%), and the overall effective rate of public specialized hospitals (30%) was higher than that of general public hospitals (18.92%). Based on the third stage results, the bed occupancy rate (BOR) and the proportion of beds (POB) were major factors affecting the operation efficiency of grade III hospitals (p < 0.01). However, the operating efficiency of grade II hospitals was significantly affected by POB and regional per capita GDP(GDPPC) (p < 0.05). Moreover, the impact of BOR and GDPPC was positive, and POB was negatively correlated with hospital operation efficiency. Conclusions: The study results indicated that the overall operation efficiency of public hospitals in Fujian Province is low. This study revealed that intervention should be strengthened from a policy and management perspective to improve the operation efficiency of public hospitals.

The magnitude, but not the duration of elevated central venous pressure is associated with mortality in sepsis patients: An analysis of the MIMIC-IV database.

BACKGROUND: It is unclear whether the magnitude and duration of elevated central venous pressure (ECVP) greater than ten mmHg has the same impact on mortality in sepsis patients. METHODS: Critically ill patients with sepsis were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The duration and the magnitude of ECVP were calculated. Normalized ECVP load was defined as the ECVP load (the sum of ECVP value times its duration) divided by the total duration of ECVP. The primary endpoint was 28-day mortality. Kaplan-Meier survival analysis was used to compare survival between patients with high or low normalized ECVP load. RESULTS: A total of 1071 sepsis patients were included. Higher normalized ECVP load was associated with higher mortality rate; in contrast, the duration of ECVP was not associated with mortality. A linear relationship between normalized ECVP load and mortality was identified. Patients with higher normalized ECVP load had less urine output and more positive fluid balance. CONCLUSION: The magnitude, but not the duration of ECVP, is associated with mortality in sepsis patients. ECVP should be considered as a valuable and easily accessible safety parameter during fluid resuscitation.

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis.

Background: The poor prognosis of sepsis warrants the investigation of biomarkers for predicting the outcome. Several studies have indicated that PANoptosis exerts a critical role in tumor initiation and development. Nevertheless, the role of PANoptosis in sepsis has not been fully elucidated. Methods: We obtained Sepsis samples and scRNA-seq data from the GEO database. PANoptosis-related genes were subjected to consensus clustering and functional enrichment analysis, followed by identification of differentially expressed genes and calculation of the PANoptosis score. A PANoptosis-based prognostic model was developed. In vitro experiments were performed to verify distinct PANoptosis-related genes. An external scRNA-seq dataset was used to verify cellular localization. Results: Unsupervised clustering analysis using 16 PANoptosis-related genes identified three subtypes of sepsis. Kaplan-Meier analysis showed significant differences in patient survival among the subtypes, with different immune infiltration levels. Differential analysis of the subtypes identified 48 DEGs. Boruta algorithm PCA analysis identified 16 DEGs as PANoptosis-related signature genes. We developed PANscore based on these signature genes, which can distinguish different PANoptosis and clinical characteristics and may serve as a potential biomarker. Single-cell sequencing analysis identified six cell types, with high PANscore clustering relatively in B cells, and low PANscore in CD16+ and CD14+ monocytes and Megakaryocyte progenitors. ZBP1, XAF1, IFI44L, SOCS1, and PARP14 were relatively higher in cells with high PANscore. Conclusion: We developed a machine learning based Boruta algorithm for profiling PANoptosis related subgroups with in predicting survival and clinical features in the sepsis.

Chinese experts' consensus on the application of intensive care big data.

The development of intensive care medicine is inseparable from the diversified monitoring data. Intensive care medicine has been closely integrated with data since its birth. Critical care research requires an integrative approach that embraces the complexity of critical illness and the computational technology and algorithms that can make it possible. Considering the need of standardization of application of big data in intensive care, Intensive Care Medicine Branch of China Health Information and Health Care Big Data Society, Standard Committee has convened expert group, secretary group and the external audit expert group to formulate Chinese Experts' Consensus on the Application of Intensive Care Big Data (2022). This consensus makes 29 recommendations on the following five parts: Concept of intensive care big data, Important scientific issues, Standards and principles of database, Methodology in solving big data problems, Clinical application and safety consideration of intensive care big data. The consensus group believes this consensus is the starting step of application big data in the field of intensive care. More explorations and big data based retrospective research should be carried out in order to enhance safety and reliability of big data based models of critical care field.