The dynamic monitoring of gastric residual volume by ultrasound was used to guide the early nutritional treatment of patients with severe mechanical ventilation to gradually achieve the standard / 中华危重病急救医学

Objective:To explore the application value of dynamic monitoring of gastric residual volume (GRV) in achieving different target energy in severe mechanical ventilation patients.Methods:A prospective randomized controlled study was conducted. Forty-two patients with mechanical ventilation admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from July to December 2022 were enrolled. According to the random number table method, patients were divided into GRV guided enteral nutrition by traditional gastric juice pumpback method (control group, 22 patients) and GRV guided enteral nutrition by bedside ultrasound (test group, 20 patients). General data were collected from both groups, and clinical indicators such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), neutrophil percentage (Neut%), procalcitonin (PCT), absolute lymphocytes (LYM), prealbumin (PA), and retinol-binding protein (RBP) were dynamically observed. Inflammation, infection, immunity, nutritional indicators, and the incidence of reflux/aspiration, ventilator-associated pneumonia (VAP) were compared between the two groups, and further compared the proportion of patients with respectively to reach the target energy 25%, 50%, and 70% on days 1, 3, and 5 of initiated enteral nutrition.Results:① There were no significant differences in gender, age, body mass index (BMI), duration of mechanical ventilation, and acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), severe nutritional risk score (NUTRIC) at admission between the two groups, indicating comparability. ② On day 1 of initiated enteral nutrition, there were no significant differences in infection, inflammation, immunity and nutrition indicators between the two groups. On day 3 of initiated enteral nutrition, the hs-CRP in the test group was lower than that control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 129.60±75.18 vs. 185.20±63.74, LYM: 1.00±0.84 vs. 0.60±0.41, PA (mg/L): 27.30±3.66 vs. 22.30±2.55, all P < 0.05]. On day 5 of initiated enteral nutrition, the hs-CRP, Neut%, PCT in the test group were lower than those control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 101.70±54.32 vs. 148.40±36.35, Neut%: (85.50±7.66)% vs. (92.90±6.01)%, PCT (μg/L): 0.7 (0.3, 2.7) vs. 3.6 (1.2, 7.5), LYM: 1.00±0.68 vs. 0.50±0.38, PA (mg/L): 27.10±4.57 vs. 20.80 ± 3.51, all P < 0.05]. There were no significantly differences in IL-6 and RBP between the two groups at different time points. ③ The proportion of 50% and 70% of achieved target energy in the test group on day 3, day 5 of initiated enteral nutrition were higher than those of the control group (70.0% vs. 36.4%, 70.0% vs. 36.4%, both P < 0.05). ④ The incidence of reflux/aspiration and VAP in the test group on day 5 of initiated enteral nutrition were significantly lower than those control group (incidence of reflux/aspiration: 5.0% vs. 28.6%, incidence of VAP: 10.0% vs. 36.4%, both P < 0.05). Conclusion:Dynamic monitoring of GRV by bedside ultrasound can accurately improve the proportion of 50% of achieved target energy on day 3 and 75% on day 5 in severe mechanical ventilation patients, improve the patient's inflammation, immune and nutritional status, and can prevent the occurrence of reflux/aspiration and VAP.

Macrophage polarization induced by short-chain fatty acid attenuates acute lung injury in sepsis / 中华危重病急救医学

Objective:To explore the effect of short-chain fatty acid (SCFA) on acute lung injury (ALI) in sepsis via macrophage polarization.Methods:① Clinical trial: 30 sepsis patients admitted to the intensive care unit (ICU) of General Hospital of Ningxia Medical University from January to December in 2022 and 10 non-sepsis patients in the same period were enrolled, stool samples were collected on the first day of admission, and SCFA butyric acid level in the two groups were studied by targeted metabolomics. ② Animal experiment: male C57BL/6J mice were selected and randomly divided into sham operation group (Sham group), sepsis caused by cecal ligation and perforation (CLP group) and SCFA intervention group (SCFA group, sodium butyrate 25 mg/kg was given by gavage 1 hour after CLP), with 6 animals in each group. Twenty-four hours after molding, the state of mice was evaluated by mouse sepsis score (MSS), the degree of pulmonary edema was evaluated by calculating the wet/dry ratio (W/D), and the pathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining, and lung injury score was performed. The serum levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6, IL-10), nuclear factor-κB (NF-κB), and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA expressions of inflammatory factors TNF-α, IL-1β, IL-6 and antioxidant factor nuclear factor E2-related factor 2 (Nrf2) in lung tissue. The expressions of macrophage polarization markers arginin-1 (ARG-1), CD206, inducible nitric oxide synthase (iNOS) and IL-1β in lung tissue were detected by immunohistochemistry.Results:① Compared with non-sepsis patients, SCFA-butyric acid level was significantly reduced in patients with sepsis (μg/g: 34.56±6.61 vs. 1 150.67±381.90, P < 0.01). ② Compared with the Sham group, MSS, lung W/D ratio, lung injury score, the levels of serum inflammatory factors TNF-α, TGF-β, NF-κB, IL-10, IL-6, IL-1β, the mRNA expressions of lung tissue inflammatory factors and antioxidant factor Nrf2, M1 macrophage polarization markers ARG-1, CD206 and M2 macrophage polarization markers iNOS and IL-1β were significantly increased in the CLP group. Compared with the CLP group, MSS, lung W/D ratio, lung injury score, the levels of serum inflammatory factors TNF-α, TGF-β, NF-κB, IL-10, IL-6, IL-1β, the mRNA expressions of lung tissue inflammatory factors and antioxidant factors Nrf2, and M1 macrophage polarization markers ARG-1 and CD206 were significantly reduced [MSS: 14.50±3.16 vs. 20.00±1.55, lung W/D ratio: 4.60±0.18 vs. 5.51±0.59, lung injury score: 47.56±2.36 vs. 88.30±6.04, serum TNF-α (ng/L): 27.99±0.58 vs. 69.55±18.53, serum TGF-β (μg/L): 9.82±2.16 vs. 18.73±1.83, serum NF-κB (μg/L): 1.23±0.09 vs. 1.95±0.28, serum IL-10 (ng/L): 78.39±2.29 vs. 140.22±19.82, serum IL-6 (ng/L): 300.64±77.60 vs. 1 442.52±494.14, serum IL-1β (ng/L): 33.13±0.99 vs. 38.39±1.31, lung IL-1β mRNA expression (IL-1β/β-actin): 1.01±0.01 vs. 2.24±0.62, lung IL-6 mRNA expression (IL-6/β-actin): 0.63±0.09 vs. 1.46±0.31, lung TNF-α mRNA expression (TNF-α/β-actin): 0.81±0.33 vs. 2.57±0.64, lung Nrf2 mRNA expression (Nrf2/β-actin): 1.59±0.25 vs. 2.96±0.89, ARG-1 positive area: (36.27±2.89)% vs. (49.75±5.03)%, CD206 positive area: (20.02±3.26)% vs. (44.24±3.61)%, all P < 0.05]. However, there was no significant difference in M2 macrophage polarization markers iNOS and IL-1β expression [iNOS positive area: (18.32±2.23)% vs. (21.77±3.57)%, IL-1β positive area: (40.42±4.78)% vs. (42.14±4.22)%, both P > 0.05]. Conclusion:SCFA may alleviate ALI in sepsis by reducing M1 polarization of pulmonary macrophages.

Application value of bedside ultrasound assessment of diaphragmatic dysfunction in sepsis patients / 中华急诊医学杂志

Objective:To evaluate the risk factors for diaphragmatic dysfunction of patients with sepsis and septic shock, and the application value of bedside ultrasound.Methods:Patients with sepsis and septic shock in the Intensive Care Unit (ICU), General Hospital of Ningxia Medical University from January 2020 to May 2021 were prospectively recruited as the research subjects, general postoperative patients and healthy volunteers were admitted as postoperative control and normal control groups. General clinical data were collected, patients with sepsis and septic shock were dynamically observed high sensitive c-reactive protein (hs-CRP), interleukin-6 (IL-6), serum albumin, transferrin, prealbumin levels, blood lactate, Pcv-aCO 2, ScvO 2, etc.; and indirect calorimetry was used to measure the resting energy level of the patient to calculate the missing energy value. Bedside ultrasound was used to dynamically evaluate the changes of diaphragm excursion (DE),inspiratory diaphragm thickness, and expiratory diaphragm thickness, to calculate relevant parameters. DE<10 mm or diaphragmatic thickness fraction (DTF) < 20% was diagnosed as diaphragmatic dysfunction. Results:(1) On day 1 in the ICU, the DE of the septic shock group, sepsis group and postoperative control group were significantly lower than that in the normal control group [10.3 (9.0, 13.6) mm, 12.3 (9.1, 15.0) mm, 12.9 (10.5, 15.7) mm vs. 22.0 (16.0, 24.6) mm, all P<0.05], and the incidence of DTF<20% was significantly higher than in the normal control group (32.7%, 41.9%, 33.3% vs. 0 %, all P<0.05), and the incidence of DE<10 mm in the septic shock group and sepsis group was significantly higher than that of postoperative control group and normal control group (36.7%, 35.5% vs. 10.0%, 0%, respectively, all P<0.05). On day 7, the DE in the septic shock group was significantly lower than that in the sepsis group [10.5 (6.8, 13.5) mm vs. 14.4 (10.6, 18.6) mm, P<0.05].(2) Correlation analysis of each index: The DE of patients with sepsis and septic shock on day 1, 3, and 7 was negatively correlated with the hs-CRP ( r=-0.253, -0.436, -0.455, all P<0.05); On day 3, DE was also negatively correlated with IL-6 ( r=-0.338, P=0.009); and DTF was negatively correlated with hs-CRP ( r=-0.375, P=0.004). On day 1, there was a positive correlation between DTF and serum transferrin levels in patients with sepsis and septic shock ( r=0.221, P=0.049). On day 3 and 7, the DE was positively correlated with serum prealbumin levels ( r=0.318, 0.408, both P<0.05). Conclusions:Patients with sepsis and septic shock have developed diaphragmatic dysfunction on day 1 in the ICU, which is mainly manifested as decreased in diaphragm mobility and diaphragmatic thickness fraction, and is related to inflammation and high protein catabolism.

Application value of lung ultrasound in the diagnosis and severity assessment of ventilator-associated pneumonia / 中华危重病急救医学

Objective:To explore the value of bedside lung ultrasound in the early diagnosis and severity assessment of ventilator-associated pneumonia (VAP).Methods:A prospective observational study was conducted in 60 patients with VAP (VAP group) and 62 patients without VAP (control group) who were admitted to department of intensive care unit of General Hospital of Ningxia Medical University from September 2018 to July 2020. The gender, age and underlying diseases of non-VAP group were matched with VAP group. The general clinical data such as gender, age, underlying diseases, department source of the patient, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score were recorded. The body temperature, white blood cell count (WBC), procalcitonin (PCT), oxygenation index (PaO 2/FiO 2), alveolar artery oxygen differential pressure (P A-aDO 2) were recorded. During mechanical ventilation, the patient's body temperature, WBC, sputum characteristics, and the change of the lung ultrasound were dynamically observed. With or without dynamic air bronchogram, lung ultrasound was considered to be positive as long as there were small subpleural consolidation or tissue-like sign. Ventilator-associated pneumonia lung ultrasound score (VPLUS) and lung ultrasound score (LUSS) were performed, and chest CT scan was completed on the same day. Use positive chest CT scan as the standard to evaluate the diagnostic efficacy of lung ultrasound, VPLUS score, and the combination of the two with PCT for VAP. LUSS was used to assess the severity of disease in patients with VAP. The correlation between LUSS and PaO 2/FiO 2, P A-aDO 2, APACHEⅡscore and SOFA score were analyzed. Results:① General information: compared with non-VAP group, VAP group had more emergency surgery patients [51.7% (31/60) vs. 33.9% (21/62), P = 0.047], APACHEⅡ score and SOFA score were significantly higher (APACHEⅡscore: 15.4±5.7 vs. 13.4±3.4, P = 0.021; SOFA score: 8.8±4.2 vs. 6.3±3.3, P < 0.001), body temperature tended to rise (℃: 38.3±0.8 vs. 38.0±0.9, P = 0.054), more patients had airway purulent secretions [65.0% (39/60) vs. 41.9% (26/62), P = 0.011], and mechanical ventilation time and length of ICU stay were longer [mechanical ventilation time (days): 10.5 (6.6, 15.0) vs. 4.3 (3.0, 6.0), P < 0.001; length of ICU stay (days): 14.8 (9.0, 18.0) vs. 6.0 (4.0, 9.1), P < 0.001], 28-day mortality rate was higher [31.7% (19/60) vs. 9.7% (6/62), P = 0.003].② Diagnostic efficacy evaluation: when lung ultrasound was positive, VPLUS≥3 and PCT > 0.5 μg/L were used separately for the diagnosis of VAP, the sensitivity was 73.3%, 75.0%, 61.7%, respectively; the specificity was 80.6%, 58.1% and 59.7%, respectively; the 95% confidence interval (95% CI) was 0.685-0.842, 0.574-0.748, 0.514-0.694, respectively, all P < 0.05, positive lung ultrasound had good sensitivity and specificity. When positive lung ultrasound or VPLUS≥3 were combined with PCT > 0.5 μg/L for tandem test, the specificity of VAP diagnosis was increased to 95.2% and 83.9%, respectively; but the specificity of VAP diagnosis of positive lung ultrasound combined with PCT > 0.5 μg/L was higher than VPLUS ≥3 combined with PCT > 0.5 μg/L (95.2% vs. 83.9%, P < 0.05).③ Correlation analysis: LUSS showed a significant positive correlation with APACHEⅡ and SOFA score ( r values were 0.407, 0.399, P values were 0.001, 0.002, respectively), LUSS had no relation with PaO 2/FiO 2 and P A-aDO 2 ( r values were 0.189, -0.064, P values were 0.629, 0.149, respectively). Conclusions:Lung ultrasound can early detect VAP , and its diagnostic specificity is significantly improved when combined with PCT > 0.5 μg/L. LUSS is closely related to the severity of disease in VAP patients, therefore, lung ultrasound may be an effective method for early diagnosis and efficacy evaluation of VAP patients.

LC-MSn analysis of metabolites of 1,2-bis (1,2-benzisoselenazolone-3(2H)-ketone)-ethane, a novel anti-cancer agent in rat / 药学学报

Abstract: This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.

Pharmacokinetics Study and Clinical Evaluation on Boanmycin / 中国药房

OBJECTIVE:To study the pharmacokinetics of boanmycin and to make a clinical evaluation on which.METHODS:36patients with malignant tumor were subjected to the first stage of clinical study after injected intramuscular injection.with0.5～7.5mg/m 2 boanmycin.Of which,8patients were chosen as the subjects for the pharmacokinetic study by microbioassay.RESULTS:Boanmycin had little influence on the functions of heart,liver,kidney and lungs and which had no inhibitory action on bone marrow.After intramuscular injection with5.29～7.65mg/m 2 boanmycin,parameters of pharma?cokinetics in the patients were determined as the following:t 1/2? was(14.036?4.409)min,t 1/2? was(39.160?5.599)min,AUC was(14.697?1.826)(?g?min)/ml and CLs was(0.781?0.102)L/min.CONCLUSION:Serum clearance of boanmycin shows two-compartment model.

Hospital Drug Supply to Meet Radiation Accident / 中国药房

OBJECTIVE: To explore a drug supply system to meet radiation accident.METHODS: According to the characteristics of drug utilization for radiation disease,a retrospective analysis was conducted on the drug demand and supply in the course of treating two patients with severe radiation disease.RESULTS: The characteristics of drug supply to meet demand of remedy of acute radiation sickness manifested as a great variety and wide scope of drugs involved and purchase without scheme because of uncertainties of dosages and course of treatment,and the time is urgent,and the drug supply is more difficult.Great importance should be attached to the reserving of drugs,information,capability,and pre-draft in building and operating the drug supply system to meet radiation accident.CONCLUSION: To build a drug supply system to meet radiation accident,reasonable organization and utilization of drugs resources is quite necessary.