Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective To investigate the correlation between the expression of circulating exosome miR-485-3p and STYX with the risk of premature coronary heart disease.Methods A total of 50 inpatients with early onset coronary heart disease diagnosed by coronary angiography or CT angiography (CTA) in Af-filiated Puyang Municipal People's Hospital of Xinxiang Medical College from August to December 2023 were selected as the study group and 50 patients with excluded coronary artery disease by examination during the same period were included in the control group.The general clinical data of the two groups were collected,the plasma exosome miR-485-3p and STYX levels were detected.The degree of coronary arterial lesions in the pa-tients of the study group was evaluated by the Gensini score.The Spearman correlation analysis was used to analyze the relationship between plasma exosome miR-485-3p and STYX with LDL and Gensini score.The re-ceiver operating characteristic (ROC) curve was used to analyze the diagnostic value of plasma exosome miR-485-3p and STYX in the diagnosis of premature coronary heart disease.The multivariate logistic regression was used to determine the independent risk factors for premature coronary heart disease.Results Compared with the control group,the family history of coronary heart disease,smoking history,LDL and plasma exo-some miR-485-3p level in the study group were increased,the plasma STYX level was decreased and the differences were statistically significant (P<0.05);the Spearman correlation analysis showed that miR-485-3p was positively correlated with LDL (r=0.546) and Gensini score (r=0.485),and negatively correlated with STYX (r=-0.576).STYX was negatively correlated with LDL (r=-0.389) and Gensini score (r=-0.531).The ROC curve showed that the area under the curve of miR-485-3p,STYX and their combination in the diagnosis of premature coronary heart disease was 0.821 (95％CI:0.736-0.906),0.850 (95％CI:0.772-0.927) and 0.899 (95％CI:0.837-0.960) respectively.Conclusion The expression of circulating exosome miR-485-3p in premature coronary heart disease is up-regulated and the expression of STYX is down-regulated,the both are closely related to the degree of coronary artery lesion,which could be used as the po-tential biomarkers for the diagnosis of premature coronary heart disease.

Objective:To evaluate the prognostic values of parameters from hypothermic machine perfusion (HMP) after static cold storage (SCS) on short-term outcomes of kidney transplantation.Method:From February 2023 to October 2023, the authors retrospectively reviewed the clinical and HMP data of recipients undergoing adult deceased donor kidney transplantation at Xuanwu Hospital, Capital Medical University. HMP resistance and renal arterial anatomical variants were utilized for subgroup analysis. The primary endpoints were delayed graft function (DGF) and whether or not creatine level normalized. The secondary endpoints were the lowest creatine level within 1 month post-kidney transplantation, reduction extent of creatinine level, duration for creatine level to decline to the lowest and duration for creatinine normalization. Single and multiple variable analyses were utilized for examining the correlation between HMP parameters and short-term postoperative outcomes.Result:A total of 157 recipients were included for analysis. Mean serum creatinine level was (870.0±283.9) μmol/L and mean trough creatinine level within 1 month postoperatively (118.5±63.5) μmol/L. Sixteen recipients (10.2%) had delayed graft function (DGF) and creatinine failed to normalize in 10 receipients (6.4%). Average time for creatinine to decline to the lowest level within 1 month was (14.5±7.6) d (3~30 d) and average time for creatinine to normalize (6.4±5.8) d (1~30 d). Multiple variable regression analysis revealed that terminal resistant index was independently correlated with multiple events, including DGF ( P<0.01), whether or not creatinine level normalized within 1 month ( P=0.001), reduction extent of creatinine level ( P<0.01) and duration for creatinine normalization ( P=0.024) . Conclusion:Parameters of HMP after SCS are capable of predicting the short-term outcomes of kidney transplantation. Terminal resistant index is an independent risk factor for several prognostic events.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

OBJECTIVE: To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites. METHODS: A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities. CONCLUSIONS Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Sepsis/metabolism* ; Inflammation

Objectve:To study the effect of gabexate mesylate (GM) on acute lung injury (ALI) in septic rats based on metabonomics.Methods:Fifty-seven SD rats were randomly(random number) divided into three groups: sham operation group (SC group), cecal ligation puncture induced septic ALI group (CLP group), and intraperitoneal administration of GM at 1 h after CLP (CLP-GM group). Twenty-four h after the experiment, the survival of rats in the SC, CLP and CLP-GM groups was observed, the lung tissue was collected for HE staining to observe the pathological changes, and the plasma was collected for metabonomics detection to analyze the characteristics of metabolites.Results:Compared with the SC group, the infiltration of inflammatory cells in the lung tissue of rats in the CLP groupincreased significantly, and the metabolic profile of plasma changed significantly. However, the pathological and metabonomic characteristics of the CLP-GM group showed that the above changes were reversed after the application of GM. Twelve major differential metabolites were found in plasma. The metabolic pathways involved in the disorder included biosynthesis of phenylalanine, tyrosine and tryptophan, phenylalanine metabolism and sphingolipid metabolism.Conclusions:GM may improve septic ALI by regulating amino acid metabolism, sphingolipid metabolism and other metabolic pathways.

Objective:To investigate the changes of intestinal microecology in the early stage of sepsis rat model by 16S rDNA sequencing.Methods:Sixty male Sprague-Dawley (SD) rats were randomly divided into cecal ligation and puncture (CLP) group and sham operation group (Sham group), with 30 rats in each group. In the CLP group, sepsis rat model was reproduced by CLP method; the rats in the Sham group only underwent laparotomy without CLP. At 24 hours after the operation, the intestinal feces and serum samples of 8 rats in each group were collected. The survival rate of the rest rats was observed until the 7th day. The level of serum tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Intestinal feces were sequenced by 16S rDNA sequencing technology. The operational taxonomic unit (OTU) data obtained after sequence comparison and clustering was used for α diversity and β diversity analysis, principal coordinate analysis and linear discriminant analysis effect size analysis (LEfSe) to observe the changes of intestinal microecology in early sepsis rats and excavate the marker flora.Results:At 24 hours after the reproduction of the model, the rats in the CLP group showed shortness of breath, scattered hair and other manifestations, and the level of serum TNF-α increased significantly as compared with that in the Sham group (ng/L: 43.95±9.05 vs. 11.08±3.27, P < 0.01). On the 7th day after modeling, the cumulative survival rate of the Sham group was 100%, while that of the CLP group was 31.82%. Diversity analysis showed that there was no significant difference in α diversity parameter between the Sham group and the CLP group (number of species: 520.00±52.15 vs. 492.25±86.61, Chao1 richness estimator: 707.25±65.69 vs. 668.93±96.50, Shannon index: 5.74±0.42 vs. 5.79±0.91, Simpson index: 0.93±0.03 vs. 0.94±0.05, all P > 0.05). However, the β diversity analysis showed that the difference between groups was greater than that within groups whether weighted according to OTU or not (abundance weighted matrix: R = 0.23, P = 0.04; abundance unweighted matrix: R = 0.32, P = 0.01). At the phylum level, the abundance of Proteobacteria and Candidatus_sacchari in the CLP group increased significantly as compared with the Sham group [18.100% (15.271%, 26.665%) vs. 6.974% (2.854%, 9.764%), 0.125% (0.027%, 0.159%)% vs. 0.018% (0.008%, 0.021%), both P < 0.05]. At the genus level, the abundance of opportunistic pathogen including Helicobacter, Ruthenium, Streptococcus, Clostridium ⅩⅧ in the CLP group was significantly higher than that in the Sham group [5.090% (1.812%, 6.598%) vs. 0.083% (0.034%, 0.198%), 0.244% (0.116%, 0.330%) vs. 0.016% (0.008%, 0.029%), 0.006% (0.003%, 0.010%) vs. 0.001% (0%, 0.003%), 0.094% (0.035%, 0.430%) vs. 0.007% (0.003%, 0.030%), all P < 0.05], and the abundance of probiotics such as Alloprevotella and Romboustia was significantly lower than that in the Sham group [7.345% (3.662%, 11.546%) vs. 22.504% (14.403%, 26.928%), 0.113% (0.047%, 0.196%) vs. 1.229% (0.809%, 2.29%), both P < 0.01]. LEfSe analysis showed that the probiotics belonging to Firmicutes were significantly enriched in the Sham group, and Romboustia was the most significantly enriched species. Opportunistic pathogens such as Helicobacter, Streptococcus and Clostridium ⅩⅧ were significantly enriched in the CLP group, Helicobacter_NGSU_ 2015 was the most significantly enriched species. Conclusion:In the early stage of sepsis, the intestinal microbiota structure of rats is significantly changed, which mainly shows that the abundance of Alloprevotella and other probiotics is significantly reduced, while that of Helicobacter and other opportunistic pathogens is significantly increased.

Objective:To explore the relationship between the changes in the lipid profiles and the intensity of inflammatory response and disease severity in patients with sepsis, in order to find a biomarker that can quickly evaluate the condition and prognosis of sepsis.Methods:A retrospective analysis was performed on 449 patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from October 2019 to May 2021, and 355 patients without sepsis hospitalized in the same period served as the control. The general demographic data, blood lipid and other clinical indicators within 24 hours after admission were collected and compared between the two groups. Bivariate correlation study was used to analyze the relationship between blood lipid levels and inflammation indicators and severity of illness in patients with sepsis. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each blood lipid component on the 28-day mortality of patients with sepsis. According to the results of ROC curve analysis, the blood lipids were divided into two groups with different levels, and the Kaplan-Meier survival curve was used to compare the cumulative survival rates of the two groups without end-point event (the 28-day mortality was the end-point event).Results:Compared with non-septic patients, the levels of plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in patients with sepsis [TC (mmol/L): 2.93±1.33 vs. 4.01±1.14, HDL-C (mmol/L): 0.78±0.47 vs. 1.16±0.40, LDL-C (mmol/L): 1.53±1.00 vs. 2.71±0.98, all P < 0.05]. In patients with sepsis, plasma cholesterol levels were correlated with the degree of inflammation and severity of the disease to varying degrees, but the HDL-C had the strongest correlation with interleukin-6 (IL-6; r = -0.551, P = 0.000), procalcitonin (PCT, r = -0.598, P = 0.000), sequential organ failure assessment (SOFA; r = -0.285, P = 0.000). The ROC curve analysis showed that among all blood lipid components, HDL-C had the highest predictive value for 28-day mortality of sepsis patients, and the area under the ROC curve (AUC) was 0.718, when the best cut-off value was 0.69 mmol/L, the sensitivity and specificity were 67.3% and 65.2% respectively, and the positive predictive value and negative predictive value were 60.6% and 71.5% respectively. According to Kaplan-Meier survival curve analysis, the mortality of sepsis patients with HDL-C ≤ 0.69 mmol/L was significantly higher than the patients with HDL-C > 0.69 mmol/L, and the difference was statistically significant ( P < 0.000 1). In addition, the 28-day mortality [59.73% (135/226) vs. 28.70% (64/223)], the incidence of multiple organ dysfunction [41.15% (93/226) vs. 31.84% (71/223)], the probability of requiring mechanical ventilation and vasoactive drugs [mechanical ventilation: 56.64% (128/226) vs. 46.18% (103/223); vasoactive drugs: 54.42% (123/226) vs. 38.57% (86/223)], the positive rate of microbial culture [45.58% (103/226) vs. 35.43% (79/223)], and the probability of drug-resistant bacteria [19.91% (45/226) vs. 10.31% (23/223)] in the low HDL-C group of sepsis patients were all higher than the high HDL-C group, the differences were statistically significant (all P < 0.05). Conclusions:Plasma cholesterol levels, especially the HDL-C levels, can well reflect the intensity of inflammation and the severity of the disease in patients with sepsis. And the HDL-C levels can be used as a good biomarker for predicting the short-term prognosis of sepsis.

Objective:Investigate the prognostic value of high density lipoprotein (HDL) level in patients with streptococcal bloodstream infection.Methods:A total of 698 patients with streptococcal bloodstream infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were enrolled. Serum lipid and other clinical data of patients with positive blood culture within 48 h were recorded. The patients were followed up by telephone from January to March in 2020, and the end-point events were recorded, which were all-cause death 60 days after the diagnosis of streptococcal bloodstream infection. The patients were divided into two groups according to the levels of HDL: low HDL group (HDL ≤0.84 mmol/L) and high HDL group (HDL > 0.84 mmol/L). Univariate and multivariate Cox regression analysis were used to analyze the 60-day prognostic factors of patients with streptococcus bloodstream infection. The receiver operating characteristic (ROC) curve was used to explore predictive value of HDL level for 60-day prognosis of patients. Kaplan-Meier survival curve was used to compare the cumulative survival of patients with different HDL levels.Results:(1) A total of 491 patients were enrolled according to the inclusion criteria, and 461 patients were followed up successfully, with a follow-up rate of 93.89%. There were 373 survival patients and 88 death patients at 60 days, with a 60-day mortality rate of 19.09% (88/461). (2) There were significant differences in age, total cholesterol (TC), HDL, low density lipoprotein (LDL), platelets, albumin, fibrinogen, triglyceride (TG), creatinine, alanine aminotransferase, aspartate aminotransferase, white blood cell, PCT, total bilirubin, direct bilirubin, and respiratory failure and shock between the survival group and death group. (3) Multivariate Cox regression analysis showed that HDL ( RR=1.922, 95% CI: 1.186-3.117, P=0.008), aspartate aminotransferase ( RR=1.953, 95% CI: 1.233-3.094, P=0.004), shock ( RR=15.196, 95% CI: 6.953-33.211, P< 0.001), and respiratory failure ( RR=9.509, 95% CI: 4.232-21.367, P < 0.001) were independent risk factors for 60-day mortality of patients with streptococcal bloodstream infection. (4) The ROC curve analysis showed that HDL alone had a certain value in predicting the 60-day prognosis of patients with streptococcal bloodstream infection. The area under ROC curve (AUC) was 0.602, and the AUC of the combined predictive value of HDL, aspartate aminotransferase, shock and respiratory failure was 0.960, with a sensitivity of 92% and a specificity of 92%. (5) Kaplan-Meier survival curve analysis showed that the cumulative survival rate of patients without endpoint event in the HDL > 0.84 mmol/L group was higher than that in the HDL ≤ 0.84 mmol/L group, but without statistically significant difference (Log-Rank test: χ20.843, P<0.358). Conclusions:Patients with low HDL level of streptococcal bloodstream infection have an increased risk of 60-day death. HDL is an independent risk factor for 60-day death in patients with streptococcal bloodstream infection, and can be used as an indicator to evaluate the prognosis of patients with streptococcal bloodstream infection.