The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure.

Introduction: Multiple organ dysfunction syndrome (MODS) is common in patients with sepsistic admitted to an intensive care unit (ICU) and greatly increases mortality. Pancreatic stone protein/regenerating protein (PSP/Reg) is a type of C-type lectin protein that is overexpressed during sepsis. This study aimed to evaluate the potential involvement of PSP/Reg in MODS development in patients with sepsis. Materials and methods: The relationship between circulating PSP/Reg levels, patient prognosis, and progression to MODS was analyzed in patients with sepsis admitted to the ICU of a general tertiary hospital. Furthermore, to examine the potential involvement of PSP/Reg in sepsis-induced MODS, a septic mouse model was established per the cecal ligation and puncture procedure, randomized into three groups, and subjected to a caudal vein injection of recombinant PSP/Reg at two different doses and phosphate-buffered saline. Survival analyses and disease severity scoring were performed to evaluate the survival status of the mice; enzyme-linked immunosorbent assays were performed to detect the levels of inflammatory factors and organ-damage markers in murine peripheral blood; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to measure apoptosis levels in lung, heart, liver, and kidney tissue sections and to visualize the degree of organ damage in the mouse model; myeloperoxidase activity assay, immunofluorescence staining, and flow cytometry were performed to detect neutrophil infiltration levels in vital murine organs and the activation indexes of neutrophils. Results and discussion: Our findings indicated that Circulating PSP/Reg levels were correlated with patient prognosis and sequential organ failure assessment scores. Furthermore, PSP/Reg administration increased disease severity scores, shortened survival time, increased the TUNEL-positive staining rate, and increased the levels of inflammatory factors, organ-damage markers, and neutrophil infiltration in the organs. Neutrophils can be activated by PSP/Reg to an inflammatory state, both in vivo and in vitro, which is characterized by the increased levels of intercellular adhesion molecule 1 and CD29. Conclusion: Patient prognosis and progression to MODS can be visualized by monitoring PSP/Reg levels upon ICU admission. Additionally, PSP/Reg administration in animal models exacerbates the inflammatory response and severity of multiorgan damage, which may be accomplished by promoting the inflammatory state of neutrophils.

[A clinical study of early continuous high-volume-hemofiltration in the treatment of severe acute pancreatitis].

OBJECTIVE: To evaluate the efficacy of early continuous high-volume-hemofiltration in the treatment of patients with severe acute pancreatitis (SAP). METHODS: Based on the method of prospective, randomized and controlled clinical trial, 60 patients with SAP between January 2005 and July 2011 from the First Affiliated Hospital of Nanchang University were divided into control group and hemofiltration group. The hemofiltration group was treated with early continuous high-volume-hemofiltration and not in the control group. The changes of vital signs, clinical symptoms and laboratory indicators were compared between the two groups before and after the treatment. RESULTS: After hemofiltration, the clinical symptoms such as abdominal pain, fever, tachycardia and respiratory distress in hemofiltration group were significantly remitted compared to those in the control group (P < 0.05). The APACHEIIscore (13.3 ± 1.0 vs 14.1 ± 1.2) and the level of TBil [(20.4 ± 11.3) µmol/L vs (28.1 ± 10.9) µmol/L], creatinine [(178.7 ± 71.8) µmol/L vs (215.6 ± 51.3) µmol/L], blood urea nitrogen [(10.1 ± 5.6) mmol/L vs (13.2 ± 3.8) mmol/L] and ALT [(51.3 ± 13.2) U/L vs (62.5 ± 14.3) U/L] were decreased compared to those in the control group (all P values < 0.05). The level of PaO2/FiO2 (197.3 ± 32.4 vs 178.3 ± 31.7) was increased (P < 0.05). After hemofiltration, heart rate was decreased gradually (P < 0.05) in the hemofiltration group than in the control group. Mean artery pressure (mAP) increased gradually (P < 0.05) in the hemofiltration group than in the control group. CONCLUSION: Early continuous high-volume-hemofiltration has significant effects on the treatment of SAP including the improvement of clinic symptoms, the blockade of development from systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS), improvement of organ function and prevention from the complications. It may become one of the important therapies for SAP.

[The clinical research on the application of the heating humidifier with heating wire in pipeline in patients with tracheal intubation].

OBJECTIVE: To explore the effect of the heating humidifier with heating wire in pipeline in patients with tracheal intubation. METHODS: The present research was a prospective study. One hundred and twenty patients with tracheal intubation and mechanical ventilation who could not reach the indication of extubation after weaning were randomly divided into two groups. The patients in the control group (n = 60) were treated by routine airway management which was intermittent airway instillation with normal saline to humidify the airway, and those in the experimental group(n = 60) were used heating humidifier with heating wire in pipeline for airway humidification. The temperature and humidity of inhaled gas, sputum viscosity, the number of tracheal catheter with sputum scab after extubation, as well as number of reintubated cases due to tube plugging, and the oxygenation index at different time points after oxygen inhalation were recorded. RESULTS: The temperature and humidity of inhaled gas in experimental group were higher than those in control group [temperature (centigrade): 36.9 ± 0.2 vs. 22.3 ± 2.1, humidity (mg/L): 44.0 ± 2.0 vs. 27.0 ± 4.0, both P < 0.01]. The number of sputum viscosity II (humidification in well) in experimental group was significantly more than that in the control group (49 vs. 15), but the number of sputum viscosity III (humidification in sufficient) in experimental group was significantly less than that in the control group (8 vs. 43, both P < 0.05). The number of tracheal catheter with sputum scab after extubation (5 cases) and reintubation for tracheal catheter plugging (0 case) in experimental group were significantly less than those in the control group (24 cases, 6 cases, P < 0.01). The oxygenation index (mm Hg, 1 mm Hg = 0.133 kPa) in experimental group was increased after oxygen inhalation, and higher than that in control group at 96 hours and 120 hours (96 hours: 349.0 ± 21.3 vs. 290.0 ± 20.7, 120 hours: 354.0 ± 25.6 vs. 309.0 ± 22.6, both P < 0.01). CONCLUSIONS: The humidify of heating humidifier with heating wire in pipeline for airway humidification in patients with tracheal intubation was better than that of intermittent airway instillation with normal saline.

[Effect of Shenfu injection on expression of lipopolysaccharide --induced microRNA-146a in alveolar macrophages].

OBJECTIVE: To study the effects of Shenfu injection (SF) on the expression of lipopolysaccharide(LPS)-induced microRNA-146a (miR-146a) in rat alveolar macrophages (AMs), and to extrapolate its potential anti-inflammatory mechanisms. METHODS: In vitro cultured rat AMs (NR8383 cells) were randomly divided into control group, LPS stimulation group, and SF stimulation group. The LPS stimulation group was challenged with a final concentration of 1 mg/L LPS, and to the control group an equal volume of phosphate buffer solution (PBS) was added instead. For SF treated group, SF in different concentrations (1 ml/L or 10 ml/L) was used during incubation of AMs for half an hour, and then LPS was added (1 mg/L final concentration). After 6 hours, the cells and were collected. MiRNA-146a expression [reverse transcription-polymerase chain reaction (RT-PCR)] in cells and tumor necrosis factor-α (TNF-α ) content [enzyme-linked immunosorbent assay (ELISA)] in culture supernatant were determined for each group. RESULTS: Both the expression of miR-146a and TNF-α content in LPS stimulation group were significantly elevated compared with control group [miR-146a (expression folds): 5.92 + 1.57 vs. 1.04 +0.38; TNF-α (ng/L): 636.93 _ 30.21 vs. 20.46 + 2.81; both P<0.05]. Compared with LPS stimulation group, the expression of miR-146a was significantly upregulated in cells in both 1 ml/L and 10 ml/L SF stimulation groups, but TNF- α content was significantly reduced in the supernatant [miR-146a (expression folds): 7.02 + 0.91, 8.11 ± 1.07 vs. 5.92 -1.57; TNF-α (ng/L): 447.24 +21.29, 357.83 +19.73 vs. 636.93 +30.21, all P<0.05] in a dose-dependent manner (both P<0.05). CONCLUSION: SF could up-regulate miR-146a expression in AMs in a dose-dependent manner, and it was speculated that miR-146a might be involved in the anti-inflammatory processes with SF treatment.

Correlation and Prognostic Assessment of Low T3 Syndrome and Norepinephrine Dosage for Patients with Sepsis: A Retrospective Single-Center (Cohort) Study.

Purpose: To investigate the correlation and prognostic significance of low triiodothyronine (T3) syndrome and norepinephrine dosage in patients with sepsis and septic shock. Methods: This single-center, retrospective, cohort study enrolled 169 patients with sepsis and septic shock that were admitted to the intensive care unit of First Hospital of Nanchang, Nanchang, China from June 2017 to July 2019. All included patients were followed up for 28 days or died, whichever was earlier. Patients with free T3 (FT3) of <3.1 pmol/L were considered with low T3 syndrome. The correlation and prognostic significance of the FT3 and maximum dosage of norepinephrine (MDN) within 72 h, as well as other clinical indicators, were analyzed by using correlation analysis, principal component analysis, receiver operating characteristic curve, Youden index, and logistic regression. Results: A total of 138 patients were allocated to the low T3 group. FT3 inversely correlated with the Sequential Organ Failure Assessment (SOFA) score within 24 h, fluid resuscitation volume within 24 h, and lactic acid levels, and positively correlated with the mean arterial pressure. The critical values of age, SOFA, and MDN for predicting the 28-day mortality were 79.5 years, 8.5 points, and 0.61 µg/kg/min, respectively. The mortality of the low T3 and normal T3 groups was similar. Considering the MDN of 0.61 µg/kg/min as the cutoff value, the mortality between the two groups was significantly different. Conclusion: Among patients with sepsis and septic shock, FT3 was inversely correlated with the disease severity. An MDN ≥ 0.61 µg/kg/min within 72 h may be an important prognostic indicator.

[A clinical study on organ protective effect of early high-volume hemofiltration (HVHF) in patients with multiple organ dysfunction syndrome (MODS) complicated by acute kidney injury (AKI)].

OBJECTIVE: To investigate the organ protective effect of early continuous HVHF in patients with MODS complicated by AKI. METHODS: 117 patients requested HVHF in ICU due to MODS/AKI were enrolled from June 2006 to June 2011 for clinical data collection. The patients were categorized, by RIFLE scale (R-risk of renal dysfunction, I-injury to the kidney, F-failure of kidney, L-loss of kidney function, E-end stage kidney disease), into three groups: RIFLE-R (n = 15), RIFLE-I (n = 23) and RIFLE-F (n = 79). The values of their serum creatinine (SCr), oxygenation index (PaO(2) /FiO(2) ), extravascular lung water index (EVLWI), blood lactic acid (Lac), prothrombin time (PT), aspartate aminotransferase (AST), acute physiology and chronic health evaluation II (APACHE II) score were recorded, at the beginning of, and within 72 hours after HVHF. The 90-day survival rate in each group was calculated. RESULTS: No significant difference was found between RIFLE-R and RIFLE-I group, within 72 hours after HVHF, in SCr, PaO(2) /FiO(2) , EVLWI, Lac, PT, AST, or APACHE II score. The mean values of SCr, EVLWI, Lac, PT, AST, APACHE II score, within 72 hours after HVHF in the RIFLE-F group were significantly higher in comparison with RIFLE-R, and RIFLE-I group [SCr (µmol/L): 260.50±35.51 vs. 83.61±21.07, 89.71±23.81 ; EVLWI (ml/kg): 12.18±2.11 vs. 10.94±1.50,10.76±1.92; Lac (mmol/L): 2.40±0.56 vs. 1.58±0.27, 1.68±0.35; PT (sec): 14.14±1.50 vs. 12.67±1.18, 12.51±0.94; AST (U/L): 96.19±18. 84 vs. 47.91±12.85, 56.39±13.44; APACHE II score: 20.17±2.61 vs. 17.79±2.65, 18.53±2.87, P< 0.05 or P< 0.01]; However, the PaO(2) /FiO(2) (mm Hg, 1 mm Hg = 0.133 kPa) value in RIFLE-F group was found significantly lower compared to RIFLE-R and RIFLE-I group (202.80±19.07 vs. 245.24±21.18, 250.63±25.56, P< 0.01). No statistical significant difference was found in the 90-day survival rate among RIFLE-R, RIFLE-I and RIFLE-F group (66.67%, 65.22%, 63.29%, respectively, P> 0.05). CONCLUSION: Early HVHF has protective effect against organs injury in patients with MODS and AKI.

Quantification analysis of pleural line movement for the diagnosis of pneumothorax.

BACKGROUND: There is no research on quantitative pleural line movement. In this study, we assume that tissue Doppler and its quantitative technology can quantify the pleural line movement and can be used to diagnose pneumothorax. AIM: To evaluate the quantitative assessment of pleural line movement measured by tissue Doppler imaging (TDI) for pneumothorax diagnosis. METHODS: Adult patients (n = 45) diagnosed with unilateral pneumothorax were included in this study. Each patient underwent TDI of both lungs. The pneumothorax side and contralateral normal lung side were compared using several indices obtained from TDI: peak pleural line velocity (PVmax), peak chest wall tissue velocity (CVmax), peak pleural line strain value (PSmax), peak chest wall tissue strain value (CSmax), PVmax/CVmax and PSmax/CSmax. The receiver operating characteristic analysis was used to evaluate the performance of these quantitative assessments for pneumothorax diagnosis. RESULTS: Various quantitative variables of the pneumothorax side were all lower than that of the non-pneumothorax side and included the PVmax (0.36 cm/s vs 0.59 cm/s, P < 0.001), PSmax (1.14% vs 1.90%, P = 0.001), PVmax/CVmax (1.06 vs 4.93, P < 0.001), and PSmax/CSmax (0.76 vs 1.74, P < 0.001). For the discrimination of pneumothorax, the cut-off values of the PVmax, PSmax, PVmax/CVmax, and PSmax/CSmax were calculated as 0.50 cm/s, 0.94%, 1.96, and 1.12, respectively. Similarly, the sensitivities and specificities of PVmax, PSmax, PVmax/CVmax, and PSmax/CSmax were 96% and 62%, 47% and 91%, 93% and 96%, and 82% and 93%, respectively. The area under the receiver operating characteristic curve were 0.84, 0.72, 0.99, and 0.91, respectively, for PVmax, PSmax, PVmax/CVmax, and PSmax/CSmax. CONCLUSION: Quantification analysis of pleural line movement using TDI is a useful tool for the diagnosis of pneumothorax.

Evaluation of Rhomboid Intercostal Block in Video-Assisted Thoracic Surgery: Comparing Three Concentrations of Ropivacaine.

Background: Ultrasound-guided rhombic intercostal block (RIB) is a novel regional block that provides analgesia for patients who have received video-assisted thoracoscopic surgery (VATS). The anesthetic characteristics of ultrasound-guided RIB with different concentrations of ropivacaine are not known. This research primarily hypothesizes that ultrasound-guided RIB, given in combination with the same volume of different concentrations of ropivacaine, would improve the whole quality of recovery-40 (QoR-40) among patients with VATS. Approaches: This double-blinded, single-center, prospective, and controlled trial randomized 100 patients undergoing VATS to receive RIB. One hundred patients who have received elective VATS and satisfied inclusion standards were fallen into four groups randomly: control group with no RIB and R0.2%, R0.3%, and R0.4%; they underwent common anesthesia plus the RIB with ropivacaine at 0.2%, 0.3%, and 0.4% in a volume of 30 ml. Outcomes: Groups R0.2%, R0.3%, and R0.4% displayed great diversities in the overall QoR-40 scores and QoR-40 dimensions (in addition to psychological support) by comparing with the control group (Group C) (p < 0.001 for all contrasts). Groups R0.3% and R0.4% displayed great diversities in the overall QoR-40 scores and QoR-40 dimensions (in addition to psychological support) by comparing with the R0.2% group (p < 0.001 for all contrasts). The overall QoR-40 scores and QoR-40 dimensions [physical comfort (p = 0.585)] did not vary greatly between Groups R0.3% and R0.4% (p > 0.05 for all contrasts). Groups R0.2%, R0.3%, and R0.4% showed significant differences in numerical rating scales (NRS) score region under the curve (AUC) at rest and on movement in 48 h when compared with the Group C (p < 0.001 for all contrasts). Groups R0.3% and R0.4% displayed great diversities in NRS score AUC at rest and on movement in 48 h when compared with the R0.2% group (p < 0.001 for all contrasts). The NRS mark AUC at rest and, on movement in 48 h, did not vary greatly between the Group R0.3% and R0.4% (p > 0.05 for all contrasts). Conclusion: In this study it was found that a dose of 0.3% ropivacaine is the best concentration for RIB for patients undergoing VATS. Through growing ropivacaine concentration, the analgesia of the RIB was not improved greatly. Clinicaltrials.gov Registration: https://clinicaltrials.gov/, identifier ChiCTR2100046254.

Reducing LncRNA-5657 expression inhibits the brain inflammatory reaction in septic rats.

Our preliminary study found that the long noncoding RNA (LncRNA)-5657 can reduce the expression of inflammatory factors during inflammatory reactions in rat glial cells. However, the role played by LncRNA-5657 during septic brain injury remains unclear. In the present study, rat models of septic encephalopathy were established by cecal ligation and puncture, and then the rats were treated with a hippocampal injection small hairpin RNA (shRNA) against LncRNA-5657 (sh-LnCRNA-5657). The sh-LncRNA-5657 treatment reduced the level of neuronal degeneration and necrosis in the rat hippocampus, reduced the immunoreactivities of aquaporin 4, heparanase, and metallopeptidase-9, and lowered the level of tumor necrosis factor-alpha. Glial cells were pre-treated with sh-LncRNA-5657 and then treated with 1 µg/mL lipopolysaccharide. Sh-LncRNA-5657 transfection decreased the expression of LncRNA-5657 in lipopolysaccharide-treated glial cells and decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6. These findings suggested that LncRNA-5657 expression can significantly reduce the inflammatory reaction during septic encephalopathy and induce protective effects against this disease. This study was approved by the Institutional Ethics Committee at the First Affiliated Hospital of Nanchang University of China (approval No. 2017-004) in 2017.

[Expression of microRNA-146a in lipopolysaccharide challenged alveolar macrophages in vitro].

OBJECTIVE: To investigate the expression of microRNA-146a (miRNA-146a) in NR8383 alveolar macrophages treated with lipopolysaccharides (LPS). METHODS: NR8383 alveolar macrophages were divided into two groups: LPS treated group and phosphate buffer saline (PBS) control group, and they cultured for 6 hours. The production of tumor necrosis factor-α (TNF-α) in the supernatant of cells was determined with enzyme-linked immunosorbent assay (ELISA), and the expression of miRNA-146a of cells was detected by real-time polymerase chain reaction (PCR). RESULTS: Compared with PBS control group, the TNF-α content (ng/L) in LPS treated group was significantly increased (650.26±40.53 vs. 6.23±1.76, P<0.01), and miRNA-146a in LPS treated group increased by about (5.33±0.81) folds (P<0.01). CONCLUSION: The expression of miRNA-146a was increased in LPS treated NR8383 cells, and miRNA-146a may be involved in the modulation inflammatory response of the NR8383 alveolar macrophage.

[Effect of high volume hemofiltration on expression of Toll-like receptor 4 in myocardium in endotoxin induced shock in dogs].

OBJECTIVE: To investigate the effects of high volume hemofiltration (HVHF) on the expression of Toll-like receptor 4 (TLR4) mRNA in myocardium in endotoxin (lipopolysaccharide, LPS) induced shock in dogs. METHODS: Sixteen healthy male dogs were injected with LPS 650 microg/kg via central vein to reproduce the model of endotoxin shock. All dogs were divided randomly into two groups: control group and therapy group, with 8 dogs in each group. Contents of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10 in circulation were measured by radioimmunological method. The expression levels of TLR4 mRNA in all group were measured by reverse transcription-polymerase chain reaction (RT-PCR). Change in myocardial histopathology was observed and analyzed with the aid of electron microscope. RESULTS: The contents of TNF-alpha (microg/L: 0.59+/-0.15, 0.51+/-0.12, 0.41+/-0.10), IL-6 (ng/L: 11.08+/-2.83, 9.82+/-2.58, 8.25+/-2.05), IL-10 (microg/L: 57.28+/-5.93, 53.81+/-5.83, 50.67+/-6.33) in therapy group were found to have decreased significantly at 1, 2, and 4 hours after HVHF compared with those when the model was completed [(0.84+/-0.16) microg/L, (16.97+/-2.50) ng/L, (70.86+/-5.43) microg/L], showing a continuous trend of lowering (all P<0.01). The contents of TNF-alpha, IL-6, IL-10 in therapy group were lower than those in control group significantly at any time point [TNF-alpha (microg/L): 0.75+/-0.14, 0.74+/-0.11, 0.72+/-0.11, IL-6 (ng/L): 15.33+/-3.20, 14.66+/-3.24, 14.20+/-3.33, IL-10 (microg/L): 71.54+/-4.73, 70.71+/-4.34, 69.35+/-4.60, all P<0.01]. Compared with control group, HVHF treatment group could down-regulate mRNA expression of TLR4 in myocardium (t=3.58, P<0.01). Correlation analysis revealed significant positive-correlation between tissue TLR4 mRNA expression and contents of TNF-alpha, IL-6, IL-10 in circulation (r(1)=0.785, r(2)=0.569, r(3)=0.653, all P<0.05). Injury to the myocardium was significantly ameliorated in therapy group compared with control group as shown by electron microscopic observation. CONCLUSION: HVHF can down-regulate mRNA expression of TLR4 in myocardium in LPS induced shock in dogs, and myocardial inflammatory response was alleviated resulting in amelioration of myocardial injury.

Impact of Shenfu injection on a composite of organ dysfunction development in critically ill patients with coronavirus disease 2019 (COVID-19): A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study aims to determine the protection provided by Shenfu injection (a traditional Chinese medicine) against development of organ dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19). TRIAL DESIGN: This study is a multicenter, randomized, controlled, open-label, two-arm ratio 1:1, parallel group clinical trial. PARTICIPANTS: The patients, who are aged from 18 to 75 years old, with a confirmed or suspected diagnosis of severe or critical COVID-19, will be consecutively recruited in the study, according to the guideline on diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People's Republic of China. Exclusion criteria include pregnant and breastfeeding women, atopy or allergies to Shenfu Injection (SFI), severe underlying disease (malignant tumor with multiple metastases, uncontrolled hemopathy, cachexia, severe malnutrition, HIV), active bleeding, obstructive pneumonia caused by lung tumor, severe pulmonary interstitial fibrosis, alveolar proteinosis and allergic alveolitis, continuous use of immunosuppressive drugs in last 6 months, organ transplantation, expected death within 48 hours, the patients considered unsuitable for this study by researchers. The study is conducted in 11 ICUs of designated hospitals for COVID-19, located in 5 cities of China. INTERVENTION AND COMPARATOR: The enrolled patients will randomly receive 100 ml SFI (study group) or identical volume of saline (control group) twice a day for seven consecutive days. Patients in the both groups will be given usual care and the necessary supportive therapies as recommended by the latest edition of the management guidelines for COVID-19 (the 7th version so far). MAIN OUTCOMES: The primary endpoint is a composite of newly developed or exacerbated organ dysfunction. This is defined as an increase in the sequential organ failure assessment (SOFA) score of two or more, indicating sepsis and involvement of at least one organ. The SOFA score will be measured for the 14 days after enrolment from the baseline (the score at randomization). The secondary endpoints are shown below: • SOFA score in total • Pneumonia severity index score • Dosage of vasoactive drugs • Ventilation free days within 28 days • Length of stay in intensive care unit • Total hospital costs to treat the patient • 28-day mortality • The incidence of adverse drug events related to SFI RANDOMISATION: The block randomization codes were generated by SAS V.9.1 for allocation of participants in this study. The ratio of random distribution is 1:1. The sealed envelope method is used for allocation concealment. BLINDING (MASKING): The patients and statistical personnel analyzing study data are both blinded. The blinding of group assignment is not adopted for the medical staff. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study is expected to recruit 300 patients with COVID-19, (150 in each group). TRIAL STATUS: Protocol version 2.0, February 15, 2020. Patient recruitment started on February 25, and will end on August 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000030043. Registered February 21, 2020, http://www.chictr.org.cn/showprojen.aspx?proj=49866 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

In vitro study on reversal of ovarian cancer cell resistance to cisplatin by naringin via the nuclear factor-κB signaling pathway.

The aim of the present study was to investigate the mechanism of action by which naringin reverses the resistance of ovarian cancer cells to cisplatin. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting assays were used to detect the effects of different concentrations of naringin on the expressions of nuclear factor (NF)-κB and P-glycoprotein (P-gp) in the SKOV3/CDDP cell line. Small interfering RNA (siRNA) targeting NF-κB was designed and synthesized to silence NF-κB, and recombinant plasmid vectors overexpressing NF-κB were constructed to transfect cells. RT-qPCR and western blotting assays were subsequently performed to detect the effects of NF-κB on the expression of P-gp at the mRNA and protein levels. Naringin was added to the NF-κB-overexpressing SKOV3/CDDP cells and cultured for 48 h, followed by the detection of the expression of P-gp. RT-PCR and western blotting results demonstrated that the gene and protein expressions of NF-κB and P-gp were significantly decreased in a dose-dependent manner by naringin treatment (P<0.05). In cells overexpressing NF-κB, P-gp expression was significantly elevated (P<0.05), and the expression of P-gp was significantly decreased when NF-κB was silenced (P<0.05). Treatment with naringin was able to significantly ameliorate the NF-κB-induced overexpression of P-gp (P<0.05). These results indicate that naringin is able to inhibit the expression of NF-κB and P-gp in SKOV3/CDDP cells. Such an inhibitory effect may increase gradually with concentration, and is associated with blockade of the NF-κB signaling pathway. This pathway may represent one of the mechanisms of action by which Naringin reverses resistance to platinum-based agents in ovarian cancer cells.

Rac2 deficiency attenuates CCl4-induced liver injury through suppressing inflammation and oxidative stress.

Oxidative stress is a leading cause to liver injury. Rac2 is a Ras-associated guanosine triphosphatase, an important molecule modulating a large number of cells and involved in the regulation of reactive oxygen species (ROS). For the study described here, we supposed that Rac2 knockout protects mice against CCl4-induced acute liver injury. We found that Rac2 expressed highly in CCl4-induced liver tissues. CCl4-treated Rac2 knockout (Rac2-/-) mice had reduced CD24 levels and steatosis. In addition, CCl4-induced high expression of pro-inflammatory cytokines and chemokine were reversed by Rac2 deficiency compared to CCl4-treated wild type (WT) mice. We also found that fibrosis-related signals of MMP-9, MMP-2 and TGF-ß1 were also down-regulated in Rac2 knockout mice induced by CCl4. Significantly, oxidative stress induced by CCl4 was also suppressed owing to the lack of Rac2, evidenced by enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels, superoxide radical, H2O2, xanthine oxidase (XO), xanthine dehydrogenase (XDH) and XO/XDH ratio. Moreover, c-Jun N-terminal protein kinase mitogen-activated protein kinases (JNK MAPK) was activated by CCl4, which was reversed in the liver of Rac2-/- mice through western blot and immunohistochemical analysis. In vitro, endotoxin (LPS) was treated to hepatocytes isolated from WT mice and Rac2-/- mice. The data further confirmed the role of Rac2 deficiency suppressed pro-inflammatory cytokines and chemokine, as well as fibrosis-related signals. Of note, production of ROS induced by LPS was reduced in Rac2-/- cells, accompanied with enhanced SOD1, SOD2 and reduced XO and phosphorylated-JNK expressions. Our results indicated that Rac2 played an essential role in acute liver injury induced by CCl4, providing the compelling information of the effects of Rac2 on liver injury, and revealing a novel regulatory mechanism for acute liver injury.

[Clinical characteristic analysis of the first human case infected by influenza A (H5N1) in Jiangxi Province].

OBJECTIVE: To describe the clinical, laboratory and radiological presentation of a human case infected by influenza A (H5N1), and to understand its management and prognosis. METHODS: The clinical and autopsy data of the first human case infected by influenza A (H5N1) in Jiangxi Province were collected and analyzed. RESULTS: The first case infected by influenza A (H5N1) in Jiangxi Province was confirmed by laboratory findings with reverse transcription-polymerase chain reaction (RT-PCR) and influenza A (H5N1) isolation. The patient had been healthy in the past and exposed to the environment of bird flu before illness. The initial symptoms included high fever with influenza-like symptoms, and then cough and purulent sputum mixed with blood appeared. The clinical situation deteriorated progressively with occurrence of diarrhea and dyspnea. Laboratory abnormalities included decrease of peripheral white blood cells and lymphocytes, urine protein, dramatic increase of enzymes associated with hepatic injury and myocarditis and decrease of serum albumin. Six days later, penicillin-resistant streptococcus pneumoniae was isolated from multiple sputum cultures. With the deterioration of clinical situation, several other bacteria and fungi were found in sputum culture. Pulmonary infiltrates were evident in right middle and lower lobe at day 5 after illness, and rapidly progressed to involve bilateral lungs as acute respiratory distress syndrome (ARDS)-like changes. The patient was treated with antiviral, antibacterial, and antifungal reagents, and corticosteroids and invasive mechanical ventilation were also administered, but without any improvement. The patient died 27 days after the onset of symptoms and an autopsy was performed. Pathologically, the lungs exhibited diffuse alveolar damage. The lymphocytes in the spleen, the lymph nodes and the tonsils were depleted prominently with histiocytic hyperplasia and hemophagocytic phenomena. Edema and degeneration of myocytes in the heart and extensive acute tubular necrosis in the kidney were observed. CONCLUSION: The prognosis was very poor if influenza A (H5N1) infected human cases was developed as ARDS with multiple organ damage or failure.

[Effect of high volume hemofiltration on pulmonary surfactant protein in endotoxin induced acute lung injury in dog].

OBJECTIVE: To explore the effect of high volume hemofiltration (HVHF) on pulmonary surfactant protein (SP) in endotoxin induced acute lung injury (ALI) in dogs. METHODS: Sixteen healthy male mongrel dogs were given lipopolysaccharide(LPS 650 mug/kg) via central vein within 30 minutes. After the reproduction of the model, they were divided into two groups randomly (n=8). One group received the treatment of HVHF and mechanical ventilation (MV, treatment group), while another received only MV (model group). Parameters of arterial blood gas and respiratory mechanics were recorded at basic values, after reproduction of the experimental model, and 1, 2 and 4 hours after HVHF. Content of SP-B in lung tissue homogenate was measured by protein Western blot. RESULTS: After injection of LPS, partial pressure of oxygen in artery (PaO(2)) and PaO(2)/fractional concentration of inspired oxygen (FiO(2)) began to decrease (both P<0.05). PaO(2)/FiO(2) <300 mm Hg (1 mm Hg=0.133 kPa) when ALI was reproduced. PaO(2) and PaO(2)/FiO(2) were higher in treatment group than those in model group 4 hours after HVHF (both P<0.01). Inspiratory resistance of airway (Raw) and peak inspiratory pressure (PIP) in model group were kept stable after MV. Lung dynamic compliance (Cdyn) and lung total compliance (Ctot) in model group were both decreased while ventilatory work of breathing (WOBvent) increased 4 hours after MV (all P<0.01). All parameters in the treatment group were kept stable and differences in Cdyn and Ctot were significant at 4 hours after HVHF compared to model group (P<0.01 and P<0.05). Content of SP-B in lung tissue homogenate was significantly higher in treatment group than that in model group (P<0.01). CONCLUSION: HVHF could effectively increase the content of SP-B in lung to prevent aggravation of respiratory mechanics and improve oxygenation.

Efficacy of coenzyme Q10 in mitigating spinal cord injury-induced osteoporosis.

Spinal cord injury (SCI)­induced osteoporosis may cause mild trauma to bone and increase the risk of bone fracture. The present study aimed to investigate the efficacy of coenzyme Q (CoQ10) on SCI­induced osteoporosis in rats. SCI was induced by surgical transection of the cord at the T10­12 level. Animals were treated with CoQ10 (10 mg/kg; intragastrically) daily from 12 h after the surgery and over 10 subsequent days. At the end of the experimental period, blood was collected from the animals and femurs and tibiae were removed for evaluation using biochemical assays. Treatment with CoQ10 prevented SCI­induced bone loss by rescuing the decreased levels of bone mineral density and bone mineral content observed in the SCI rats. Furthermore, CoQ10 administration reduced bone malondialdehyde levels with a concomitant increase in superoxide dismutase levels, thus alleviating SCI­induced oxidative injury. In addition, serum inflammatory cytokine levels were markedly increased in rats post­SCI, which was attenuated by treatment with CoQ10. Finally, the osteoclast­specific genes receptor activator of nuclear factor kappa­B ligand and cathepsin K were significantly upregulated and the osteoblast­specific gene core­binding factor alpha 1 in the femur was downregulated following SCI, which was effectively restored following treatment with CoQ10. The results suggested that CoQ10 treatment may be effective in attenuating SCI­induced osteoporosis.

[Study of changes in extravascular lung water index of patients suffered from H7N9 avian influenza with acute respiratory distress syndrome].

OBJECTIVE: To analyze the characteristic of changes in extravascular lung water index (EVLWI) of H7N9 avian influenza patients who complicated with acute respiratory distress syndrome (ARDS), and to approach the relevance between EVLWI and severity, pulmonary oxygenation in patients with lung injury. METHODS: Four H7N9 avian influenza patients administered from April to June in 2013 in First Affiliated Hospital of Nanchang University were studied. The patients who suffered from severe ARDS were administered with low tide volume ventilation plus positive end-expiratory pressure (PEEP), namely protected ventilation strategy, with monitoring hemodynamic parameters and EVLWI through pulse-indicated continuous cardiac output (PiCCO) catheter. During ventilation, patients' parameters, such as PEEP, fraction of inspired oxygen (FiO2), arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), EVLWI, and central venous pressure (CVP) were collected. RESULTS: All 4 H7N9 avian influenza patients were complicated with ARDS, 2 patients were classified to severe ARDS and administered with comprehensive therapies, specially protected ventilation strategy; ventilation duration was 9 days and 30 days respectively, and PiCCO monitoring was 9 days and 21 days respectively. EVLWI of 2 patients on the 1st, 2nd, 3rd day was 10.0±3.2 ml/kg, 12.0±2.9 ml/kg, 14.0±4.2 ml/kg, and 24.0±6.7 ml/kg, 24.0±6.1 ml/kg, 23.0±5.8 ml/kg, respectively. As their conditions became better, patients' EVLWI decreased to 5.5±2.7 ml/kg and 7.0±3.0 ml/kg, respectively at weaning. PEEP and FiO2 of 2 patients were down-regulated, PaO2/FiO2 increased to 334±64 mm Hg and 142±53 mm Hg at weaning. However, no significant changes in CI, SVRI, PVRI and CVP in the 2 patients were observed. CONCLUSIONS: EVLWI increases when H7N9 avian influenza patients are complicated with severe ARDS. As the conditions get better, EVLWI returns to normal value gradually. There is relevance between the motive changes in EVLWI and severity of ARDS and pulmonary oxygenation.

Lung recruitment maneuver effects on respiratory mechanics and extravascular lung water index in patients with acute respiratory distress syndrome.

BACKGROUND: Animal experiments showed that recruitment maneuver (RM) and protective ventilation strategy of the lung could improve oxygenation and reduce extravascular lung water. This study was to investigate the effects of RM on respiratory mechanics and extravascular lung water index (EVLWI) in patients with acute respiratory distress syndrome (ARDS). METHODS: Thirty patients with ARDS were randomized into a RM group and a non-RM group. In the RM group, after basic mechanical ventilation stabilized for 30 minutes, RM was performed and repeated once every 12 hours for 3 days. In the non-RM group, lung protective strategy was conducted without RM. Oxygenation index (PaO2/FiO2), peak inspiratory pressure (PIP), Plateau pressure (Pplat), static pulmonary compliance (Cst) and EVLWI of patients before treatment and at 12, 24, 48, 72 hours after the treatment were measured and compared between the groups. Hemodynamic changes were observed before and after RM. One-way ANOVA, Student's t test and Fisher's exact test were used to process the data. RESULTS: The levels of PaO2/FiO2 and Cst increased after treatment in the two groups, but they were higher in the RM group than in the non-RM group (P<0.05). The PIP and Pplat decreased after treatment in the two groups, but they were lower in the RM group than in the non-RM group (P<0.05). The EVLWI in the two groups showed downward trend after treatment (P<0.05), and the differences were signifcant at all time points (P<0.01); the EVLWI in the RM group was lower than that in the non-RM group at 12, 24, 48 and 72 hours (P<0.05 or P<0.01). Compared with pre-RM, hemodynamics changes during RM were significantly different (P<0.01); compared with pre-RM, the changes were not significantly different at 120 seconds after the end of RM (P>0.05). CONCLUSIONS: RM could reduce EVLWI, increase oxygenation and lung compliance. The effect of RM on hemodynamics was transient.