Molecular Mechanism of SOX18 in Lipopolysaccharide-Induced Injury of Human Umbilical Vein Endothelial Cells.

Endothelial dysfunction is associated with the progression of sepsis. This study sought to probe the molecular route of sex-determining region on the Y chromosome-box transcription factor 18 (SOX18) in sepsis-associated endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish the sepsis cell model. Cell viability, lactate dehydrogenase (LDH) release, oxidative stress (reactive oxygen species/malondialdehyde/superoxide dismutase), and inflammation (interleukin-1ß/tumor necrosis factor-α/interleukin-6) were evaluated by cell counting kit-8 assay and relevant assay kits. The expression levels of SOX18, microRNA (miR)-204-5p, and cadherin-2 (CDH2) in cells were determined by real-time quantitative polymerase chain reaction and Western blot assay. The interaction of SOX18, miR-204-5p, and CDH2 was analyzed by chromatin immunoprecipitation and dual-luciferase assay. LPS induced HUVECs injury and downregulation of SOX18. SOX18 overexpression increased cell viability, while decreased LDH activity, oxidative stress, and inflammation. SOX18 bound to the miR-204-5p promoter to promote miR-204-5p expression, and further repressed CDH2 expression. miR-204-5p knockdown and CDH2 overexpression abrogated the protective role of SOX18 in HUVECs injury. Overall, SOX18 alleviated LPS-induced injury of HUVECs by promoting miR-204-5p and repressing CDH2, suggesting it as a potential target for sepsis treatment.

The risk factors for deep venous thrombosis in critically ill older adult patients: a subgroup analysis of a prospective, multicenter, observational study.

BACKGROUND: Older adult patients mainly suffer from multiple comorbidities and are at a higher risk of deep venous thrombosis (DVT) during their stay in the intensive care unit (ICU) than younger adult patients. This study aimed to analyze the risk factors for DVT in critically ill older adult patients. METHODS: This was a subgroup analysis of a prospective, multicenter, observational study of patients who were admitted to the ICU of 54 hospitals in Zhejiang Province from September 2019 to January 2020 (ChiCTR1900024956). Patients aged > 60 years old on ICU admission were included. The primary outcome was DVT during the ICU stay. The secondary outcomes were the 28- and 60-day survival rates, duration of stay in ICU, length of hospitalization, pulmonary embolism, incidence of bleeding events, and 60-day coagulopathy. RESULTS: A total of 650 patients were finally included. DVT occurred in 44 (2.3%) patients. The multivariable logistic regression analysis showed that age (≥75 vs 60-74 years old, odds ratio (OR) = 2.091, 95% confidence interval (CI): 1.308-2.846, P = 0.001), the use of analgesic/sedative/muscarinic drugs (OR = 2.451, 95%CI: 1.814-7.385, P = 0.011), D-dimer level (OR = 1.937, 95%CI: 1.511-3.063, P = 0.006), high Caprini risk score (OR = 2.862, 95%CI: 1.321-2.318, P = 0.039), basic prophylaxis (OR = 0.111, 95%CI: 0.029-0.430, P = 0.001), and physical prophylaxis (OR = 0.322, 95%CI: 0.109-0.954, P = 0.041) were independently associated with DVT. There were no significant differences in 28- and 60-day survival rates, duration of stay in ICU, total length of hospitalization, 60-day pulmonary embolism, and coagulation dysfunction between the two groups, while the DVT group had a higher incidence of bleeding events (2.6% vs. 8.9%, P < 0.001). CONCLUSION: In critically ill older adult patients, basic prophylaxis and physical prophylaxis were found as independent protective factors for DVT. Age (≥75 years old), the use of analgesic/sedative/muscarinic drugs, D-dimer level, and high Caprini risk score were noted as independent risk factors for DVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024956).URL: http://www.chictr.org.cn/listbycreater.aspx .

Severity of acute gastrointestinal injury grade is a predictor of all-cause mortality in critically ill patients: a multicenter, prospective, observational study.

BACKGROUND: In 2012, the European Society of Intensive Care Medicine proposed a definition for acute gastrointestinal injury (AGI) based on current medical evidence and expert opinion. The aim of the present study was to evaluate the feasibility of using the current AGI grading system and to investigate the association between AGI severity grades with clinical outcome in critically ill patients. METHODS: Adult patients at 14 general intensive care units (ICUs) with an expected ICU stay ≥24 h were prospectively studied. The AGI grade was assessed daily on the basis of gastrointestinal (GI) symptoms, intra-abdominal pressures, and feeding intolerance (FI) in the first week of admission to the ICU. RESULTS: Among the 550 patients enrolled, 456 patients (82.9%) received mechanical ventilation, and 470 patients were identified for AGI. The distribution of the global AGI grade was 24.5% with grade I, 49.4% with grade II, 20.6% with grade III, and 5.5% with grade IV. AGI grading was positively correlated with 28- and 60-day mortality (P < 0.0001). Univariate Cox regression analysis showed that age, sepsis, diabetes mellitus, coronary artery disease, the use of vasoactive drugs, serum creatinine and lactate levels, mechanical ventilation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the global AGI grade were significantly (P ≤ 0.02) associated with 60-day mortality. In a multivariate analysis including these variables, diabetes mellitus (HR 1.43, 95% CI 1.03-1.87; P = 0.05), the use of vasoactive drugs (HR 1.56, 95% CI 1.12-2.11; P = 0.01), serum lactate (HR 1.15, 95% CI 1.06-1.24; P = 0.03), global AGI grade (HR 1.65, 95% CI 1.28-2.12; P = 0.008), and APACHE II score (HR 1.04, 95% CI 1.02-1.06; P < 0.001) were independently associated with 60-day mortality. In a subgroup analysis of 402 patients with 7-day survival, in addition to clinical predictors and the AGI grade on the first day of ICU stay, FI within the first week of ICU stay had an independent and incremental prognostic value for 60-day mortality (χ2 = 41.9 vs. 52.2, P = 0.007). CONCLUSIONS: The AGI grading scheme is useful for identifying the severity of GI dysfunction and could be used as a predictor of impaired outcomes. In addition, these results support the hypothesis that persistent FI within the first week of ICU stay is an independent determinant for mortality. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR-OCS-13003824 . Registered on 29 September 2013.

Risk factors for early onset of catheter-related bloodstream infection in an intensive care unit in China: a retrospective study.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is a life-threatening condition encountered in patients with long-term central venous catheter (CVC) indwelling. The objective was to investigate the clinical characteristics, treatment, and prognosis of CRBSI in the intensive care unit (ICU) in a Chinese center, as well as the risk factors for early CRBSI. MATERIAL AND METHODS: A total of 73 CRBSI patients were retrospectively studied in relation to patients' clinical and epidemiological data, microbiological culture, and treatment. Patients were treated at the Taizhou Hospital of Integrated Traditional Chinese and Western Medicine in Zhejiang (Zhejiang Wenlin, China) between January 2010 and December 2012. RESULTS: In this Chinese center, the most common pathogens were Gram-positive cocci, followed by Gram-negative bacilli and fungi. A high prevalence of antibiotic-resistant pathogens was detected, and a higher percentage of non-Candida albicans spp. was observed. Multivariate analysis showed that an acute physiology and chronic health evaluation II (APACHE II) score >20 and >3 types of underlying diseases were independent factors associated with CRBSI occurring within 14 days of CVC indwelling. Untimely CVC removal and/or inappropriate use of antibiotics led to significantly longer time to defervescence and time to negative conversion of blood culture (all P<0.05). CONCLUSIONS: In this Chinese center, Gram-positive bacteria are predominantly detected in CRBSI. APACHE II score >20 and the presence of >3 types of diseases were associated with earlier CRBSI onset. Timely removal of CVC and appropriate use of antibiotics resulted in improved outcomes.

Shenfu injection alleviates intestine epithelial damage in septic rats.

BACKGROUND: Shenfu injection (SFI) promotes tissue microcirculation and oxygen metabolism. We aimed to assess its effects on intestinal epithelial damage in septic rats. METHODS: Fifty Sprague-Dawley rats were randomly divided into sham operation (Sham), sepsis (cecal ligation and puncture [CLP]), and SFI (low-dose, middle-dose, high-dose) groups (n = 10). For Sham animals, the abdominal cavity was opened and closed. For other groups, severe sepsis was induced by CLP. After surgery, saline (Sham and CLP rats) and SFI (treatment groups) were administered intraperitoneally. Samples were collected 12 hours after injection. Serum tumor necrosis factor α, diamineoxidase, and d-lactate levels and ileal mucosal damage and ultrastructural change, as well as protein and messenger RNA expression of tight junction markers, including Claudin-3 and zonula occludens protein-1 in ileal mucosa's epithelial cells, were assessed. All animal experiments were carried out under aseptic conditions. RESULTS: Compared with Sham animals, serum tumor necrosis factor α, DAO, and d-lactic acid levels in CLP animals were significantly higher; the ileal mucosal damage was more severe; and the expression levels of tight junction markers were significantly decreased. These indexes were significantly improved in SFI groups, in a concentration-dependent manner, compared with CLP rats. Sham animals displayed orderly arranged ileal mucosal villi, continuous tight junctions between epithelial cells, intact organelles, and microvilli. Compared with CLP animals (with obvious damage in these structures), an overt improvement was observed in SFI groups, especially in the high-dose SFI group, with tight junctions clearly visible between epithelial cells. CONCLUSIONS: Shenfu injection significantly alleviates intestinal epithelial damage in septic rats, in a dose-dependent manner.

Effect of Shenfu injection on intestinal mucosal barrier in a rat model of sepsis.

PURPOSE: The effects of Shenfu injection on protecting the intestinal mucosal barrier were investigated in rats with sepsis. METHODS: Severe sepsis was established by cecal ligation and puncture (CLP) in 30 healthy Sprague-Dawley rats. Twelve rats that received sham surgery received 10 mL/kg of normal saline. Rats with CLP were randomized to receive 10 mL/kg of normal saline (n = 12) and 5 mL/kg Shenfu (n = 12), and 10 received 10 mL/kg Shenfu injection (n = 12) by tail intravenous injection. Rats were killed after 8 hours. Serum levels of tumor necrosis factor α and interleukin-10, and ileal malondialdehyde and superoxide dismutase activity were measured by enzyme-linked immunosorbent assay. Ileum tissue structures and pathological score were observed by microscopy. Ileal mucosal epithelial cell apoptosis index was calculated by TUNEL assay. Ileal proapoptotic protein Bax, antiapoptotic protein Bcl-2, and tight junction transmembrane protein occludin were measured by immunohistochemistry and immunoblot. RESULTS: The level of tumor necrosis factor α, the ileal malondialdehyde level, ileum pathological score, apoptosis index of ileal mucosal epithelial cells, and Bax protein level were significantly higher, and serum level of interleukin-10, the ileal superoxide dismutase activity, Bcl-2 protein level, Bcl-2/Bax ratio, and occludin protein level were significantly lower in the CLP group than in the sham group (P < .01 or P < .05). Both low- and high-dose Shenfu significantly ameliorated these changes (P < .01 or P < .05), but high-dose injection achieved more significant improvements than did the low-dose injection (P < .01 or P < .05). CONCLUSIONS: Shenfu injection might ameliorate the mucosal barrier function in a model of sepsis in rats in a dose-dependent manner.

[Effect of electro-acupuncture at zusanli (ST36) on the expression of ghrelin and HMGB1 in the small intestine of sepsis rats].

OBJECTIVE: To explore the expression of Ghrelin and high mobility group protein B1 (HMGB1) in the serum and the intestinal tissue of sepsis model rats, and to evaluate the effect of electro-acupuncture (EA) at Zusanli (ST36) on the expression of HMGB1 and Ghrelin. METHODS: Forty-eight male Wistar rats were randomly divided into four groups, i.e., the sham-operation (sham), the cecal ligation and puncture group (CLP), the CLP + EA at Zusanli (ST36) group (EA), and the CLP + Ghrelin receptor blocking agent + EA group (GHSRA), 12 in each group. A sepsis rat model was prepared by CLP. The incision of the abdominal wall was immediately sutured along the ventral midline for rats in the Sham group. In the EA group EA at Zusanli (ST36) was performed 20 min after CLP surgery with the constant voltage (2 - 100 Hz, 2 mA) for 30 min. In the GHSRA group, Ghrelin receptor blocking agent, [D-Arg1, D-Phe5, D-Trp79, Leu11]-substance P (700 nmol/kg), was administered through intravenous injection immediately after CLP, and 20 min later, EA at Zusanli (ST36) was performed in the same way as for rats in the EA group. Blood samples were withdrawn 12 h after CLP. The serum levels of Ghrelin and HMGB1 were detected using ELISA. Ghrelin expressions and the number of Ghrelin immunopositive cell in the jejunum were determined by immunohistochemistry. HMGB1 contents of the jejunum tissue were detected by Western blotting. RESULTS: Compared with the Sham group, the number of serum immunopositive cells and the expression of HMGB1 in the jejunum tissue significantly increased and levels of Ghrelin and the expression rate of immunopositive cells significantly decreased in the CLP group (P < 0.05). Compared with the CLP group, the number of serum immunopositive cells and the expression of HMGB1 in the jejunum tissue significantly decreased, but levels of Ghrelin and the expression rate of immunopositive cells significantly increased in the EA group (P < 0.05). Compared with the EA group, the number of serum immunopositive cells and the expression of HMGB1 in the jejunum tissue significantly increased in the GHSRA group (P < 0.05), but there was no statistical difference in levels of Ghrelin between the two groups (P > 0.05). The serum level of HMGB1 was negatively correlated with Ghrelin in the Sham group, the CLP group, and the EA group (r = -0. 528, P < 0.01). CONCLUSIONS: EA at Zusanli (ST36) could inhibit the expression of HMGB1 in the jejunum of septic rats, and promote the expression of Ghrelin. The expression of HMGB1 was inhibited by Ghrelin receptor blocking agent, which suggested that the anti-inflammation of EA at Zusanli (ST36) might be associated with Ghrelin.

Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI). METHODS: This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia. RESULTS: The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group. CONCLUSION: Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).

[Protective effect of forsythiaside A on acute lung injury in septic rats].

OBJECTIVE: To observe the protective effect of forsythiaside A on acute lung injury (ALI) in septic rats. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into normal control group, sham operation group, sepsis model group, and forsythiaside A intervention group, with 10 rats in each group. The rats in the normal control group did not receive any intervention; the rats in the sham operation group only underwent abdominal surgery; and those in the model group and forsythiaside A intervention group received cecal ligation and puncture (CLP) to establish the sepsis rat model. The rats in the forsythiaside A intervention group were given 75 mL/kg of forsythiaside A within 0.5 hour after operation, and repeated after 6 hours. The rats in the sham operation group and model group were given the same amount of normal saline at the same time points. The lung tissues were collected for pathological examination 12 hours after operation. The lung homogenate was prepared, and enzyme-linked immunosorbent assay (ELISA) was used to detect tumor necrosis factor-α (TNF-α), interleukins (IL-1ß, IL-6). The activity of superoxide dismutase (SOD) was detected by xanthine oxidase method, and the content of malonaldehyde (MDA) was detected by colorimetry. The expression of nuclear factor-κB p65 (NF-κB p65) was detected by Western blotting. RESULTS: There was no significant pathological change of lung tissue in both normal control group and sham operation group, and there was no significant difference in each parameter between the two groups. The rats in the model group had interstitial infiltration of inflammatory cells, alveolar structure destruction, alveolar septum thicken, extensive alveolar hemorrhage, telangiectasia; the levels of TNF-α, IL-1ß, IL-6, MDA and NF-κB p65 protein expression in lung tissue were significantly higher than those in the normal control group and sham operation group [TNF-α (ng/L): 132.81±16.15 vs. 45.08±5.98, 46.10±6.72, IL-1ß (ng/L): 137.32±15.22 vs. 51.03±7.89, 50.92±8.13; IL-6 (ng/L): 138.39±14.28 vs. 51.68±7.03, 52.48±7.36; MDA (kU/g): 1.79±0.13 vs. 0.96±0.05, 0.97±0.05; NF-κB p65 protein (NF-κB p65/GAPDH): 2.82±0.23 vs. 1.76±0.12, 1.82±0.13; all P < 0.05], the activity of SOD decreased significantly (kU/g: 45.90±5.46 vs. 92.11±10.13, 93.36±10.56, both P < 0.05). The changes in lung histopathology in the forsythiaside A intervention group were obviously improved as compared with the model group, which showed less inflammatory cell infiltration, less alveolar septum thickening, less bleeding and more intact structures; the levels of TNF-α, IL-1ß, IL-6, MDA and the expression of NF-κB p65 protein in lung tissue were significantly lower than those in the model group [TNF-α (ng/L): 72.48±9.78 vs. 132.81±16.15, IL-1ß (ng/L): 83.85±12.46 vs. 137.32±15.22, IL-6 (ng/L): 81.88±11.89 vs. 138.39±14.28, MDA (kU/L): 1.29±0.09 vs. 1.79±0.13, NF-κB p65 protein (NF-κB p65/GAPDH): 2.29±0.19 vs. 2.82±0.23, all P < 0.05], SOD activity increased significantly (kU/g: 66.03±7.98 vs. 45.90±5.46, P < 0.05). CONCLUSIONS: Forsythiaside A can effectively alleviate ALI in septic rats. The mechanism may be related to down-regulate the expression of NF-κB p65 and reduce the level of inflammatory factors and free radicals in lung tissue, thereby against acute lung injury in septic rats.

Impact of partial pressure of oxygen trajectories on the incidence of acute kidney injury in patients undergoing cardiopulmonary bypass.

BACKGROUND: To investigate the impact of the dynamic oxygenation status on the incidence of acute kidney injury (AKI) in patients undergoing cardiopulmonary bypass. METHODS: This retrospective study was performed using data extracted from the Medical Information Mart for Intensive Care III database. A group-based trajectory approach was used to identify partial pressure of oxygen (PaO2) trajectories using dynamic change in PaO2 within 48 hours after intensive care unit admission. RESULTS: In total, 5,824 patients were included. Four PaO2 trajectories were identified: Trajectory 1 (Traj-1), hyperoxia and rapid decrease; Trajectory 2 (Traj-2), hyperoxia and rapid decrease similar to that of Traj-1; Trajectory 3 (Traj-3), normoxemia and rapid increase in PaO2; and Trajectory 4 (Traj-4), hyperoxia and gradual decrease. Compared with the Traj-1 group, the Traj-3 group had a significantly lower initial Sequential Organ Failure Assessment score, similar vasopressor use rate, and a higher fraction of inspired oxygen. However, the risk of developing AKI was significantly higher in the Traj-3 [adjusted odds ratio (OR): 1.7, 95% confidence interval (CI): 1.1-2.7] and Traj-4 groups (OR: 1.9, 95% CI: 1.4-2.5) than in the Traj-1 group. CONCLUSIONS: Patients with persistent hyperoxia had a higher incidence of AKI than those with transient hyperoxia. Further studies are required to determine potential underlying mechanisms.

Enteral nutrition modulation with n-3 PUFAs directs microbiome and lipid metabolism in mice.

Nutritional support using exclusive enteral nutrition (EEN) has been studied as primary therapy for the management of liver diseases, Crohn's disease, and cancers. EEN can also increase the number of beneficial microbiotas in the gut, improve bile acid and lipid metabolism, and decrease the number of harmful dietary micro-particles, possibly by influencing disease occurrence and increasing immunity. This study investigated the effects of EEN-n-3 polyunsaturated fatty acids (3PUFAs) (EEN-3PUFAs) on the gut microbiome, intestinal barrier, and lipid or bile acid metabolism in mice. Metagenomic sequencing technology was used to analyze the effects of EEN-3PUFAs on the composition of gut microbiome signatures. The contents of short-chain fatty acids (SCFAs) and bile acids in the feces and liver of the mice were assayed by gas chromatography and ultra-high-pressure liquid chromatography/high-resolution tandem mass spectrometry, respectively. The levels of lipopolysaccharide (LPS) and D-lactic acid in the blood were used to assess intestinal permeability. The results indicated that EEN-3PUFAs could improve the composition of gut microbiome signatures and increase the abundance of Barnesiella and Lactobacillus (genus), Porphyromonadaceae, and Bacteroidia (species), and Bacteroidetes (phylum) after EEN-3PUFAs initiation. In addition, EEN-3PUFAs induced the formation of SCFAs (mainly including acetic acid, propionic acid, and butyric acid) and increased the intestinal wall compared to the control group. In conclusion, EEN-3PUFAs modulate the alterations in gut microbiome signatures, enhanced intestinal barrier, and regulated the fatty acid composition and lipid metabolism shifts and the putative mechanisms underlying these effects.

Magnolol protects against acute gastrointestinal injury in sepsis by down-regulating regulated on activation, normal T-cell expressed and secreted.

BACKGROUND: Sepsis is a major medical challenge. Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects, but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear. AIM: To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms. METHODS: Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue in animal studies. The histopathological changes of the ileal mucosa in different groups were observed under a microscope. Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced decrease in permeability. Immunofluorescence and Western blot assays were used to detect the levels of RANTES, inhibitor of nuclear factor kappa-B kinase ß (IKKß), phosphorylated IKKß (p-IKKß), inhibitor of nuclear factor kappa-B kinase α (IκBα), p65, and p-p65 proteins in different groups in vitro. RESULTS: In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol, magnolol inhibited the expression of proinflammatory cytokines, IL-1ß, IL-6, and TNF-α in a dose-dependent manner. In addition, magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats. Moreover, in vitro studies suggested that magnolol inhibited the increase of p65 nucleation, thereby markedly downregulating the production of the phosphorylated form of IKKß in LPS-treated Caco2 cells. Specifically, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells. CONCLUSION: Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways, thereby suppressing IL-1ß, IL-6, and TNF-α expression to alleviate the mucosal barrier dysfunction in sepsis.

[Electroacupuncture in the treatment of acute gastrointestinal injury in patients with severe traumatic brain injury: a prospective randomized controlled trial].

OBJECTIVE: To evaluate the therapeutic effect of electroacupuncture on acute gastrointestinal injury (AGI) in patients with severe traumatic brain injury (sTBI). METHODS: A prospective randomized controlled trial was conducted. 126 consecutively hospitalized patients with AGI after sTBI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2018 to December 2019 were enrolled. The patients were divided into observation group and control group by random number table. All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days, including the treatments of primary diseases, indwelling nasogastric tube to extract gastric contents every 6 hours to determine gastric residual volume (GRV). When vital signs were basically stable, enteral nutrition (EN) was implemented and EN feeding amount and speed were adjusted according to GRV. On the basis of conventional western medicine treatment, the observation group was treated with electroacupuncture at Zusanli, Tianshu, Shangjuxu, Xiajuxu and Zhongwan, once in the morning and once in the evening, 30 minutes each time. The gastrointestinal function parameters including intra-abdominal pressure (IAP), serum diamine oxidase (DAO) and gastrointestinal failure (GIF) scores were observed before treatment and at day 3 and day 7 of treatment. The incidence of ICU hospital-acquired pneumonia (HAP-ICU), duration of mechanical ventilation (MV), length of ICU stay, 28-day mortality and adverse reactions of electroacupuncture were also observed in the two groups. Kaplan-Meier method was used for 28-day survival analysis. RESULTS: During the 7-day treatment and observation, 26 cases of 126 patients withdrew from the study, and 100 cases were actually enrolled, 50 cases in the observation group and 50 cases in the control group. IAP and DAO at day 3 of treatment in both groups were significantly lower than those before treatment [control group: IAP (cmH2O, 1 cmH2O = 0.098 kPa) was 13.75±2.76 vs. 18.11±3.97, DAO (U/L) was 129.88±24.81 vs. 158.01±22.64; observation group: IAP (cmH2O) was 13.56±2.19 vs. 18.50±3.54, DAO (U/L) was 129.11±29.32 vs. 159.36±28.65; all P < 0.01]. The gastrointestinal function parameters of the two groups improved gradually with the extension of treatment time, and the IAP, DAO and GIF scores at day 7 of treatment in the observation group were significantly lower than those in the control group [IAP (cmH2O): 11.28±3.61 vs. 12.68±3.23, DAO (U/L): 49.69±17.56 vs. 57.27±20.15, GIF score: 2.02±0.74 vs. 2.40±0.70, all P < 0.05). The duration of MV and the length of ICU stay in the observation group were significantly shorter than those in the control group [duration of MV (days): 15.72±4.60 vs. 18.08±4.54, length of ICU stay (days): 16.76±4.68 vs. 19.26±5.42, both P < 0.05], and the incidence of ICU-HAP and 28-day mortality were significantly lowered (12.0% vs. 30.0%, 22.0% vs. 32.0%, both P < 0.05). Survival analysis showed that the 28-day cumulative survival rate in the observation group was significantly higher than that in the control group (86.4% vs. 76.1%; Log-Rank test: χ2 = 37.954, P < 0.001). The patients in the observation group had no significant adverse reaction of electroacupuncture treatment. CONCLUSIONS: Electroacupuncture at corresponding acupoints can effectively improve gastrointestinal function in patients with AGI after sTBI, which is beneficial to shortening the length of ICU stay, promoting the recovery of the patients, and reducing the 28-day mortality.

Prevention, treatment, and risk factors of deep vein thrombosis in critically ill patients in Zhejiang province, China: a multicenter, prospective, observational study.

PURPOSE: The aim of this study is to investigate the prevention and treatment patterns of deep vein thrombosis (DVT) in critically ill patients and to explore the risk factors for DVT in people from Zhejiang Province, China. MATERIALS AND METHODS: This study prospectively enrolled patients admitted in intensive care units (ICUs) of 54 hospitals from 09/16/2019 to 01/16/2020. The risk of developing DVT and subsequent prophylaxis was evaluated. The primary outcome was DVT occurrence during ICU hospitalisation. Univariate and multivariate logistic regression were performed to determine the risk factors for DVT. RESULTS: A total of 940 patients were included in the study. Among 847 patients who received prophylaxis, 635 (75.0%) patients received physical prophylaxis and 199 (23.5%) patients received drug prophylaxis. Fifty-eight (6.2%) patients were diagnosed with DVT after admission to the ICU, and 36 patients were treated with anticoagulants (all patients received low molecular weight heparin [LMWH]). D-dimer levels (OR = 1.256, 95% CI: 1.132-1.990), basic prophylaxis (OR = 0.092, 95% CI: 0.016-0.536), and physical prophylaxis (OR = 0.159, 95% CI: 0.038-0.674) were independently associated with DVT in ICU patients. The short-term survival was similar between DVT and non-DVT patients. CONCLUSIONS: DVT prophylaxis is widely performed in ICU patients. Prophylaxis is an independent protective factor for DVT occurrence. The most common treatment of DVT patients is LMWH, although it might increase the rate of bleeding.Key messagesThis is the only multicenter and prospective study of DVT in ICUs in China.d-dimer levels were independently associated with DVT in ICU patients.Prophylaxis was an independent protective factor for DVT occurrence in ICU.

Clinical study on the safety and efficacy of high-dose tigecycline in the elderly patients with multidrug-resistant bacterial infections: A retrospective analysis.

Multidrug-resistant bacterial (MDRB) infections have been difficult to treat clinically. Tigecycline (TIG) has several advantages, especially in the treatment of severe infections. Many clinicians have considered increasing the TIG dose to improve the efficacy of this molecule. The safety and efficacy of high-dose TIG in elderly patients with MDRB infections were investigated in this study.We conducted a retrospective analysis of the elderly patients with MDRB infections who were treated at the First Affiliated Hospital. A total of 106 patients received a conventional dose (CD-TIG group: 50 mg every 12 hours) of TIG and 51 received a high dose (HD-TIG group: 100 mg every 12 hours). The data from all patients were collected for examining the clinical features and performing the microbiological analysis. The safety profile and efficacy of the HD regimen were investigated.The clinical efficacy and microbiological eradication in the patients with MDRB infection were higher in the HD-TIG group than the CD-TIG group. The independent predictors of clinical cure were the use of TIG at HD (odd ratio [OR], 5.129; 95% confidence interval [CI] [1.890, 13.921]; P = .001) and microbiological eradication (OR, 3.049; 95% CI, [1.251, 7.430]; P = .014). In the ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) subgroups, the sole independent predictor of clinical cure was the HD of TIG, and no significant adverse events were observed. The occurrence of multidrug-resistant Acinetobacter baumannii infection and an MIC value of 1 to 2 g/mL for TIG were independently associated with clinical failure in the VAP subgroup.HDs of TIG was found to associate with better clinical efficacy and microbiological eradication than its CDs in the elderly patients with MDRB infections. In the VAP and BSIs subgroups, administration of HDs of TIG was associated with better outcomes.