Single-Cell RNA Sequencing Pro-angiogenic Macrophage Profiles Reveal Novel Prognostic Biomarkers and Therapeutic Targets for Osteosarcoma.

Osteosarcoma (OS) is a malignant bone tumor that most commonly occurs in children and adolescents. OS patients have a poor prognosis, and 5-year survival rates have rarely improved significantly over the past few decades. OS prognosis may be related to the infiltration of tumor-associated macrophages (TAMs). However, the role of proangiogenic macrophages, a subtype of TAMs, in OS prognosis has not been reported. In this study, seven subtypes of TAMs were identified from single-cell RNA sequencing (scRNA-seq) data that we propose defining as proangiogenic TAMs (Angio-TAMs), interferon-primed TAMs (IFN-TAMs), inflammatory cytokine-enriched TAMs (Inflam-TAMs), immune regulatory TAMs (Reg-TAMs), lipid-associated TAMs (LA-TAMs), and resident-tissue macrophages like TAMs (RTM-TAMs) (containing two subcellular types). In the survival analysis of each macrophage subtype, it was found that patients with Angio-TAMs had the most significant difference in survival. Eight genes associated with Angio-TAMs were obtained by differential expression analysis, and these genes were built into a prognostic model using the LASSO algorithm. Clinical OS case samples were categorized into high-risk and low-risk subgroups using median risk scores. In comparison to the low-risk subgroup, the survival time of the high-risk subgroup was much shorter. Additional studies on immune cell infiltration and immune checkpoint molecule expression in the two risk subgroups were carried out. In immunotherapy response prediction, the Angio-TAM-associated gene risk signature was found to be negatively correlated with immune checkpoint responses. In addition, the associated enriched GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were mainly involved in the malignant progression of tumors. As suggested by these findings, the Angio-TAM gene risk signature may be an underlying prognostic biomarker and novel therapeutic target for OS patients.Kindly check and confirm whether the ESM file is correctly identifiedWe have checked this file and confirmed that it can be correctly identified.

A Novel Defined Necroptosis-Related Genes Prognostic Signature for Predicting Prognosis and Treatment of Osteosarcoma.

Osteosarcoma (OS) is a frequent primary malignant bone tumor, with a poor prognosis. Necroptosis is strongly correlated with OS and may be an influential target for treating OS. This study's objective was to establish a necroptosis-related gene (NRG) prognostic signature that could predict OS prognosis and guide OS treatment. First, we identified 20 NRGs associated with OS survival based on the TARGET database. We then derived a 7 NRG prognostic signature. Our findings revealed that the 7 NRG prognostic signature performed well in predicting the survival of OS patients. We next analyzed differences in immunological status and immune cell infiltration. In addition, we examined the relationship between chemo/immunotherapeutic response and the 7-NRG prognostic signature. In addition, to probe the mechanisms underlying the NRG prognostic signature, we performed functional enrichment assays including GO and KEGG. Finally, CHMP4C was selected for functional experiments. Silencing CHMP4C prevented OS cells from proliferating, migrating, and invading. This 7-NRG prognostic signature seems to be an excellent predictor that can provide a fresh direction for OS treatment.

Efficacy and safety of Cook staged Extubation Set in patients with difficult airway: a systematic review and meta-analysis.

BACKGROUND: Cook Stage extubation is a tool developed by Cook Medical for patients with difficult airways. Multiple clinical studies demonstrated the effectiveness and safety of Cook Stage extubation Set (CSES). Currently, no systematic review evidence has been published in this field. Therefore, this study aimed to review the clinical success rate, safety, and tolerability of CSES in patients with difficult airways. METHOD: The inclusion criteria were based on the population, intervention, comparator, outcomes, and study designs. An electronic search was conducted, and the following databases were used: PubMed, EMBASE, Cochrane Library, and Web of Science. Search keywords included difficult airway and CSES. The primary outcome was the CSES clinical success rate.The Joanna Briggs Institute Critical Appraisal tools for Case Series were used to assess the risk of bias in the included studies. R studio, version 4.2.2. was used to perform the statistical analysis. The Cochrane Q and I2 statistics were used to test the heterogeneity among all studies. Details of the included case reports were summarized in the systematic review part. RESULTS: Five studies were eligible for meta-analysis, and 7 case reports were included for systematic review. The pooled overall CSES clinical success rate was 93% (95% CI: 85%, 97%). The CSES intolerable and complication incidence rates were 9% (95% CI: 5%, 18%) and 5% (95% CI: 2%, 12%), respectively. CSES clinical success rate was influenced by the study center and study design. The success rate of CSES was higher in multicenter and prospective design studies. Seven case reports have documented the successful operation of CSES intubation in obese, tall, oncologist, and pediatric patients. DISCUSSION: This meta-analysis suggested that CSES have achieved a high clinical success rate in adult and pediatric patients with different physical conditions and types of surgery. The results of all original studies and meta-analysis confirmed a remarkably high tolerance rate and low overall complication rate. However, regardless of the tools chosen, a personalized, safe intubation strategy and a highly qualified anesthesiologist should be considered as the fundamental guarantee of a high clinical success rate. Future studies should also focus on the success rate of reintubation using CSES in patients with airway difficulties.

Identification of a novel MYC target gene set signature for predicting the prognosis of osteosarcoma patients.

Osteosarcoma is a primary malignant tumor found mainly in teenagers and young adults. Patients have very little long-term survival. MYC controls tumor initiation and progression by regulating the expression of its target genes; thus, constructing a risk signature of osteosarcoma MYC target gene set will benefit the evaluation of both treatment and prognosis. In this paper, we used GEO data to download the ChIP-seq data of MYC to obtain the MYC target gene. Then, a risk signature consisting of 10 MYC target genes was developed using Cox regression analysis. The signature indicates that patients in the high-risk group performed poorly. After that, we verified it in the GSE21257 dataset. In addition, the difference in tumor immune function among the low- and high-risk populations was compared by single sample gene enrichment analysis. Immunotherapy and prediction of response to the anticancer drug have shown that the risk signature of the MYC target gene set was positively correlated with immune checkpoint response and drug sensitivity. Functional analysis has demonstrated that these genes are enriched in malignant tumors. Finally, STX10 was selected for functional experimentation. STX10 silence has limited osteosarcoma cell migration, invasion, and proliferation. Therefore, these findings indicated that the MYC target gene set risk signature could be used as a potential therapeutic target and prognostic indicator in patients with osteosarcoma.

Risk factors for acute kidney injury after intracranial hemorrhage.

OBJECTIVE: This study investigated the risk factors for acute kidney injury (AKI) occurrence in patients with spontaneous intracerebral hemorrhage. METHODS: The clinical data of patients with spontaneous intracerebral hemorrhage who were hospitalized in the Department of Intensive Care Medicine of Mingguang People's Hospital from January 2016 to August 2020 were retrospectively analyzed. The patients were divided into AKI group and non-AKI group according to whether the patient had secondary AKI, and the clinical data of the two groups were compared. Logistic regression analysis was used to screen out the risk factors for secondary AKI in patients with spontaneous intracerebral hemorrhage. RESULTS: Three hundred thirty-seven patients were included in this study, whereby 186 males (55.2%) and 151 females (44.8%). A total of 65 patients developed AKI, of whom 44 patients were (67.69%) in stage 1, 12 patients (18.46%) in stage 2, and 9 patients (13.85%) in stage 3. Univariate logistic regression analysis showed that Acute Physiology, Age and Chronic Health Evaluation (APACHE II score), diabetes, chronic kidney disease, fasting blood glucose level and amount of mannitol used were risk factors for AKI in patients with intracerebral hemorrhage. Multivariate logistic regression analysis showed APACHE II score (OR: 1.846, 95% CI: 1.319 to 2.585, p < 0.001), diabetes (OR: 3.609, 95% CI: 1.596 to 8.163, p=0.002) and amount of mannitol use (OR: 3.495, 95% CI: 1.910~3.395, p < 0.001) are the independent risk factors for AKI after intracranial hemorrhage. CONCLUSION: In summary, APACHE II score, diabetes, and total mannitol use are independent risk factors for AKI in patients with spontaneous intracerebral hemorrhage. It is necessary to monitor renal function frequently in patients with high APACHE II scores and control the amount of mannitol administrated in the prevention of AKI after intracranial hemorrhage. The intervention of the above factors is expected to reduce the risk of secondary AKI.

[Design and application of Checklist for quality control in intensive care unit].

OBJECTIVE: To design a Checklist for quality control in intensive care unit and observe the effect of clinical application. METHODS: By consulting guidelines and literature, such as Critical care medicine professional medical quality control index (2015 edition), the quality control Checklist of intensive care unit was designed. It included four parts: quality control data collection, medical record quality verification, special diagnosis and treatment, and hospital infection prevention and control supervision. Every month, a doctor with a senior professional title served as the quality control director, and was responsible for the quality control of the department's medical care, including collecting data of the past 24 hours during the morning handover, discussing and registering special diagnosis and treatment behaviors that would be performed on the day, and coordinating with the nursing team leader, controlling the quality of the whole department throughout the day, such as supervising each medical staff if they had unreasonable behaviors, checking the running and discharge medical records, and inspecting the status of the staff on duty. The data in 2018, 2019 (Checklist implemented) and 2017 (Checklist not implemented) were retrospectively analyzed, including the status of admitted patients, department management information, length of intensive care unit (ICU) stay, and the incidence of three-tube infection [ventilator-associated pneumonia (VAP), catheter-related bloodstream infection (CRBSI), catheter-associated urinary tract infection (CAUTI)], and standardized mortality, etc. RESULTS: From 2017 to 2019, the number of patients admitted was 373, 446, and 480, with annual growth of 19.57% and 7.62% in 2018 and 2019, respectively, and an increase of 28.69% in 2019 compared with 2017. There was no statistically significant difference in the average age and acute physiology and chronic health evaluation II (APACHE II) of patients in the three years. Compared with 2017, the length of ICU stay of patients in 2018 and 2019 were significantly shortened (days: 8.99±6.12, 9.14±7.02 vs. 10.20±7.21), and the incidence of VAP, CRBSI and CAUTI were significantly reduced [VAP (cases/1 000 ventilation days): 12.97±3.60, 9.62±3.14 vs. 17.48±4.89, CRBSI (cases/1 000 catheter days): 3.75±2.19, 3.87±1.87 vs. 6.19±3.13, CAUTI (cases/1 000 catheter days): 3.29±2.18, 3.28±1.87 vs. 5.61±3.18]. The standardized mortality were also significantly reduced [(77.27±7.24)%, (70.61±7.49)% vs. (84.41±9.05)%], the number of non-compliance with hospital infection prevention per month decreased significantly (person times: 54.00±6.30, 41.08±10.76 vs. 72.08±19.68), and the number of special diagnosis and treatment per month increased significantly (person times: 1 056.67±235.27, 1 361.75±278.48 vs. 722.25±145.96), the rate of etiology submission before antimicrobial treatment [(93.21±3.68)%, (96.59±2.49)% vs. (87.86±5.28)%] and deep vein thrombosis (DVT) prevention rate [(91.13±6.36)%, (96.23±2.99)% vs. (85.58±7.68)%] were significantly improved, and all the differences were statistically significant (all P < 0.05). All medical records in the three years were Grade A, but the average scores in 2018 and 2019 were higher than those in 2017 (96.82±2.84, 96.73±2.94 vs. 93.70±3.33, both P < 0.01). Compared with 2018, the incidence of VAP, the rate of etiology submission before antimicrobial treatment, the DVT prevention rate, and the standardized mortality rate in 2019 were further improved, and the number of non-compliance with hospital infection prevention per month decreased and the number of special diagnosis and treatment per month increased, and the differences were statistically significant (all P < 0.05). CONCLUSIONS: The application of quality control Checklist in intensive care unit can build an effective quality control system, reduce the incidence of three-tube infection, standardized mortality and length of ICU stay, improve the quality control awareness and execution of medical staff, and promote the improvement of medical quality.

[Clinical efficacy of restrictive fluid management in patients with severe traumatic brain injury].

OBJECTIVE: To investigate the effects of restrictive fluid management in patients with severe traumatic brain injury (sTBI). METHODS: Between January, 2019 and June, 2020, we randomly assigned 51 postoperative patients (stay in the ICU of no less than 7 days) with sTBI into treatment group (n=25) with restrictive fluid management and the control group (n=26) with conventional fluid management. The data of optic nerve sheath diameter (ONSD), middle cerebral artery pulsatility index (MAC- PI), neuron-specific enolase (NSE) level, inferior vena cava (IVC) diameter, Glascow Coma Scale (GCS) score, mean arterial blood pressure, heart rate, and fluid balance of the patients were collected at ICU admission and at 1, 3 and 7 days after ICU admission, and the duration of mechanical ventilation, ICU stay, and 28-day mortality were recorded. RESULTS: The cumulative fluid balance of the two groups were positive on day 1 and negative on days 3 and 7 after ICU admission; at the same time points, the patients in the treatment group had significantly greater negative fluid balance than those in the control group (P < 0.05). In both of the groups, the ONSD and MCA-PI values were significantly higher on day 1 than the baseline (P < 0.05), reached the peak levels on day 3, and decreased on day 7; at the same time point, these values were significantly lower in the treatment group than in the control group (P < 0.05). No significant difference was found in NSE level on day 1 between the two groups (P>0.05); on day 3, NSE level reached the peak level and was significantly higher in the control group (P < 0.05); on day 7, NSE level was lowered the level of day 1 in the treatment group but remained higher than day 1 level in the control group. The 28-day mortality rate did not differ significantly between the two groups (16.00% vs 23.08%, P>0.05); the duration of mechanical ventilation, length of ICU stay, and the number of tracheotomy were all significantly shorter or lower in the treatment group than in the control group (P < 0.05). CONCLUSIONS: Restrictive fluid management can reduce cerebral edema and improve the prognosis but does not affect the 28-day mortality of patients with sTBI.

Use of polymyxin B in patients with renal impairment: A retrospective examination of 5 cases.

In order to provide an idea dose of polymyxin B in Chinese patients with renal impairment, the present study collected the clinical data of all patients with renal impairment who received polymyxin B therapy in the intensive care unit (ICU) of The First Affiliated Hospital of Bengbu Medical College (Bengbu, China). The clinical data of six patients treated in the ICU between February 2018 and May 2019 were retrospectively analyzed. All patients had renal impairment and were treated with polymyxin B combination therapy. The patients in the current study received polymyxin B and carbapenem, or polymyxin, carbapenem, cefoperazon and sulbactam, or polymyxin B, carbapenems and aminoglycoside treatment. One patient discontinued treatment. The other five patients received polymyxin B at a dosage of 50 mg every 12 h (100 mg/day) through an intravenous drip. During treatment, four of the five patients had deteriorating renal function to varying degrees, and continuous renal replacement therapy (CRRT) was initiated. Polymyxin B was discontinued in all patients when the infection was controlled. After treatment, four of five patients showed improvement in renal function, and had normal kidney function at the 1-month follow-up evaluation, whereas one patient had chronic renal disease. During hospitalization, one patient experienced neurotoxicity, showing decreased limb muscle strength and cognitive impairment, which might have been caused by polymyxin B, according to the Naranjo adverse drug reactions probability scale (also known as the Naranjo algorithm) score. The present report demonstrated that the administration of 100 mg daily dosage of polymyxin B to the five patients weighing between 50 and 75 kg, could control pulmonary infection during the course of treatment of Chinese patients with renal impairment, however, further research is needed to verify this result. Risk factors for nephrotoxicity and neurotoxicity need to be fully assessed before initiating polymyxin B therapy in patients with renal impairment.

[Correlation analysis of microRNA-126 expression in peripheral blood lymphocytes with apoptosis and prognosis in patients with sepsis].

OBJECTIVE: To analyze the relationship between the expression of microRNA-126 (miR-126) in peripheral blood lymphocytes with apoptosis and prognosis in patients with sepsis, and to explore its potential regulatory mechanism. METHODS: Thirty patients with general infection and 20 patients with sepsis admitted to the department of intensive care unit (ICU) of the First Affiliated Hospital of Bengbu Medical College from January to December 2019 were enrolled. Peripheral blood was taken to separate lymphocytes, and the expressions of miR-126 and caspase-3 were detected by reverse transcription-polymerase chain reaction (RT-PCR). At the same time, the liver and kidney function and other laboratory indexes were measured, and the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores were calculated. The 28-day prognosis was observed. Pearson method was used to analyze the correlation between miR-126 and caspase-3, APACHE II score. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of miR-126 on prognosis; at the same time, according to the best cut-off value of miR-126 in predicting prognosis, the patients were divided into two groups, and the 28-day Kaplan-Meier survival curve was drawn. RESULTS: The expression of miR-126 in peripheral blood lymphocytes of patients with sepsis was lower than that of patients with general infection [miR-126 mRNA (2-ΔΔCt): 1.239±0.134 vs. 1.599±0.110, P < 0.01], while the expression of caspase-3 and APACHE II score were significantly increased [caspase-3 mRNA (2-ΔΔCt): 1.172±0.132 vs. 0.901±0.143, APACHE II: 19.75±3.74 vs. 12.63±3.94, both P < 0.01]. Pearson correlation analysis showed that the expression of miR-126 was negatively correlated with the expression of caspase-3 (r = -0.678, P < 0.001) and APACHE II score (r = -0.581, P < 0.001). ROC curve analysis showed that the area under the ROC curve (AUC) for predicting the prognosis by miR-126 expression in peripheral blood lymphocytes was 0.823 (P < 0.001). When the best cut-off value was 1.395, the sensitivity was 75.0%, the specificity was 71.4%, the positive predictive value was 81.1%, the negative predictive value was 63.6%, the positive likelihood ratio was 2.622, and the negative likelihood ratio 0.350. In addition, the patients were divided into high miR-126 group (miR-126 > 1.395, n = 31) and low miR-126 group (miR-126 ≤ 1.395, n = 19) according to the best cut-off value of miR-126. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate of high miR-126 group was higher than that of low miR-126 group (Log-Rank: χ2 = 11.702, P = 0.001). CONCLUSIONS: miR-126 in peripheral blood lymphocytes of patients with sepsis may affect immune status by promoting apoptosis of lymphocytes, and its expression level can reflect the severity and prognosis of sepsis.

[Changing laws of rest energy expenditure in critically ill patients and the intervention effect for nutritional support: a prospective study].

OBJECTIVE: To investigate the changing laws of rest energy expenditure (REE) in intensive care unit (ICU) patients and the intervention effect for nutritional support. METHODS: A prospective randomized control trial was conducted. Fifty-eight critically ill patients who were expected to be able to receive sustained enteral and (or) parenteral nutrition for more than 7 days admitted to ICU of the First Affiliated Hospital of Bengbu Medical College from December 2016 to June 2017 were enrolled. The patients were divided into REE group (n = 29) and HBREE group (n = 29) according to the random number table. On the 1st to 7th day after ICU admission, the indirect calorimetry and the Harris-Benedict (HB) formula were used to obtain the REE and HBREE values, and nutritional support was given according to REE and HBREE values respectively. The data of hemoglobin (Hb), albumin (Alb), prealbumin (PA), C-reactive protein (CRP), oxygenation index (OI) on 1st, 3rd, 5th, 7th and discharged day, and insulin dosage, vasopressor time, mechanical ventilation time, the length of ICU stay, and 28-day mortality were collected. RESULTS: (1) At the beginning, the REE level was high, and then decreased gradually with the extension of hospitalization, and the decline was obvious on the 2nd to 3rd day (kJ/d: 7 088.38±559.41, 6 751.34±558.72 vs. 7 553.44±645.55, both P < 0.05), and was stable from the 5th day, the changing laws showed high at first, then the low, the first rapid decline, then the slow decline, and then reached the steady, there was a 2-day plateau in the middle. During the first 2 days, the REE value was significantly higher than the HBREE value (kJ/d: 7 553.44±645.55 vs. 6 759.21±668.14, 7 088.38±559.41 vs. 6 759.21±668.14, both P < 0.01); on the 3rd, 4th day, the REE value was almost the same as the HBREE value (kJ/d: 6 751.34±558.72 vs. 6 759.21±668.14, 6 568.03±760.19 vs. 6 759.21±668.14, both P > 0.05). After that, the REE value was significantly lower than the HBREE value (kJ/d: 6 089.55±560.70 vs. 6 759.21±668.14, 5 992.55±501.82 vs. 6 759.21±668.14, 5 860.84±577.59 vs. 6 759.21±668.14, all P < 0.01). (2) After the initiation of nutritional support, Hb in the REE group (the first 3 days) and HBREE group (the first 7 days) all increased slowly in the early stage. It increased obviously on the 5th day in the REE group. Compared with the REE group, Hb increased more slowly in the HBREE group, however, there was no difference between the two groups at the time of discharge (g/L: 113.75±17.28 vs. 110.86±15.35, P > 0.05). PA and OI all enhanced significantly on the 3rd day since the nutritional support was initiated, but the daily increase of the REE group was significantly higher than that of the HBREE group [3rd day, PA (mg/L): 110.38±27.65 vs. 96.28±18.06, OI (mmHg, 1 mmHg = 0.133 kPa): 259.29±49.36 vs. 231.74±28.02, both P < 0.05]. The Alb and CRP in the REE group began to improve on the 3rd day, while the index in the HBREE group was delayed on the 5th day, overall, at the time of discharge, the PA, CRP and OI were lower in the HBREE group than in the REE group [PA (mg/L): 252.28±56.94 vs. 295.86±57.26, CRP (mg/L): 73.14±17.63 vs. 56.52±14.91, OI (mmHg): 353.59±70.36 vs. 417.52±71.58, all P < 0.01]. (3) The vasopressor was used in both groups for less than 3 days, but the REE group was shorter (days: 2.26±0.82 vs. 2.95±1.22, P < 0.05), the insulin dosage in the HBREE group was much more than that in the REE group (U: 101.97±21.05 vs. 84.59±22.21, P < 0.01); compared with the REE group, the time of mechanical ventilation and the length of ICU stay in the HBREE group were longer (hours: 113.07±25.96 vs. 93.41±27.25, days: 10.41±3.11 vs. 8.45±2.44, both P < 0.01). There was no significant difference in the 28-day mortality between the REE group and HBREE group (17.24% vs. 24.14%, P > 0.05). CONCLUSIONS: Indirect calorimetry can more accurately grasp the changing laws of REE in critically ill patients. Nutritional support with REE value can make relevant nutritional indicators as good as possible, and reduce insulin dosage, shorten vasopressor use time, the length of ICU stay and mechanical ventilation time, but does not change the 28-day mortality.

[Changing laws of serum high mobility group box 1 protein in septic rats and the intervention effect of xuebijing].

OBJECTIVE: To investigate the changing laws of serum high mobility group box 1 protein (HMGB1) in septic rats and intervention effect of Xuebijing on it. METHODS: Lipopolysaccharide (LPS) (5 mg/kg BW) was intravenously injected into the tail vein of healthy male Wistar rats to prepare the sepsis rat model. In Experiment 1: 50 Wistar rats were randomly divided into three groups, i.e., the normal group (A, n=10); the LPS model group (B, n=10), the LPS +Xuebijing treatment group (C, n=30). Rats in the C group were further divided into three subgroups, i.e., 2 h before LPS injection (group C1), 2 h after LPS injection (group C2), and 8 h after LPS injection (group C3), 10 in each group. Blood samples were collected from the caudal vein to detect serum HMGB1 levels by Western blot at 4, 12, 24, 48, and 72 h after LPS injection. Experiment 2: 30 Wistar rats were equally divided into the LPS model group (D) and the LPS + Xuebijing treatment group (E), 15 in each group. They were treated as rats in the B group and the C1 group respectively. Five rats were sacrificed at 12, 24, and 48 h after LPS injection in the two groups. Blood as well as the tissue samples were harvested to measure such indices as ALT, AST, Cr, and BUN, as well as pathological changes of liver, lung, and kidney. RESULTS: (1) Compared with the A group, serum HMGB1 levels were higher at various time points in the B group (P < 0.05). Compared with the B group, serum HMGB1 levels at 12,24,48, and 72 h decreased in the C1, C2, and C3 groups. Besides, the decrease was more obvious at 24 h and 48 h.The decrement in the C3 group was less than that in the C1 and C2 groups (P < 0.05). (2) In the D group, ALT, AST, Cr, and BUN were significantly higher than those in the A group and reached the peak at 24 h (P < 0.05). Compared with the E group, AST, Cr, and BUN at 24 and 48 h, and ALT at each time point decreased significantly in the E group (P < 0.05). (3)The results of pathological section of liver, lung, and kidney showed local congestion and hemorrhage, cell edema/necrosis/degeneration, infiltration of inflammatory cells, damage of characteristic structures and so on; particularly serious lesion occurred at 24 and 48 h in the D group. The microscopic lesion was obviously alleviated in the E group than in the D group at corresponding time points. CONCLUSIONS: The serum HMGB1 levels increased in septic rats, with late occurrence of peak value and longer duration of the high value. HMGB1 played an important role in excessive inflammatory response and multiple organ dysfunction. Xuebijing could reduce the serum levels of HMGB1, improve biochemical parameters, and attenuate severe inflammatory response of liver, lung, and kidney tissues in septic rats. Besides, the earlier use, the better effect obtained.