Artesunate alleviates sepsis-induced liver injury by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis.

BACKGROUND: The present study aimed to explore the regulatory effects of artesunate on macrophage polarization in sepsis. METHODS: Cell models and mice models were established using lipopolysaccharide (LPS), followed by treatment with various concentrations of artesunate. The phenotype of the macrophages was determined by flow cytometry. RNA immunoprecipitation was used to confirm the binding between MALAT1 and polypyrimidine tract-binding protein 1 (PTBP1), as well as between PTBP1 and interferon-induced helicase C domain-containing protein 1 (IFIH1). RESULTS: Treatment with artesunate inhibited M1 macrophage polarization in Kupffer cells subjected to LPS stimulation by downregulating MALAT1. Furthermore, MALAT1 abolished the inhibitory effect of artesunate on M1 macrophage polarization by recruiting PTBP1 to promote IFIH. In vivo experiments confirmed that artesunate alleviated septic liver injury by affecting macrophage polarization via MALAT1. CONCLUSION: The present study showed that artesunate alleviates LPS-induced sepsis in Kupffer cells by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis.

MicroRNA-30a inhibits cell proliferation in a sepsis-induced acute kidney injury model by targeting the YAP-TEAD complex.

Background: Acute kidney injury (AKI) is a primary feature of renal complications in patients with sepsis. MicroRNA (miRNA/miR)-30a is an essential regulator of cardiovascular diseases, tumors, phagocytosis, and other physical processes, but whether it participates in sepsis-induced AKI (sepsis-AKI) is unknown. We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI. Methods: The classical cecal ligation and puncture (CLP) method and lipopolysaccharide (LPS)-induced Human Kidney 2 (HK-2) cells were used to establish in vivo and in vitro sepsis-AKI models. Specific pathogen-free and mature male Sprague-Dawley (SD) rats, aged 6-8 weeks (weight 200-250 g), were randomly divided into five-time phase subgroups. Fluid resuscitation with 30 mL/kg 37 °C saline was administered after the operation, without antibiotics. Formalin-fixed, paraffin-embedded kidney sections were stained with hematoxylin and eosin. SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors, and compared with untreated normal controls. RNA, protein, and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and cell counting kit-8 methods. A Dual-Luciferase Assay Kit (Promega) was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics. Results: Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h (P <0.05). Tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were significantly increased in renal tissue 3 h after the operation in rats (P <0.05), and gradually decreased 6 h, 12 h, and 24 h after CLP. Levels of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment (P <0.05), and gradually decreased in HK-2 cells. One hour after LPS (10 µg/mL) treatment, TNF-α and IL-1ß levels in HK-2 cells were significantly up-regulated (P < 0.05), and they were markedly down-regulated after 3 h (P <0.05). IL-6 expression levels began to rise after LPS treatment of cells, peaked at 6 h (P <0.05), and then decreased to the initial level within a few hours. Stimulation with 10 µg/mL LPS promoted HK-2 cells proliferation, which was inhibited after miR-30a-3p-mimic transfection. Bioinformatics prediction identified 37 potential miR-30a-3p target genes, including transcriptional enhanced associate domain 1 (TEAD1). After transfection of HK-2 cells with miR-30a-3p mimics and miR-30a-3p inhibitor, TEAD1 transcript was significantly up- and down-regulated, respectively (both P <0.05). After LPS treatment (24 h), expression of TEAD1 in the inhibitors group was significantly increased (P <0.01), while that in the mimics group was significantly suppressed (P <0.01). In the dual luciferase reporter experiment, miR-30a-3p overexpression decreased fluorescence intensity (P <0.01) from TEAD1-wt-containing plasmids, but did not influence fluorescence intensity from TEAD1-muta-containing plasmids. LPS may promote HK-2 cells proliferation through the miR-30a-3p/TEAD1 pathway. Conclusion: In a background of expression of inflammatory factors, including TNF-α, IL-1ß, and IL-6, which were transiently increased in the sepsis-AKI model, miR-30a was down-regulated. Down-regulated miR-30a-3p may promote cell proliferation by targeting TEAD1 in LPS-induced HK-2 cells, demonstrating its potential as a biomarker for early sepsis-AKI diagnosis.

Minimally Invasive Treatment of Pelvic Fractures with Titanium Elastic Nailing: An Innovative Technology.

BACKGROUND: Minimally invasive treatment has become the most popular and effective treatment for pelvic fractures. This study aimed to evaluate the safety and efficacy of a new technique, titanium elastic nailing (TEN), for the minimally invasive treatment of pelvic fractures. METHOD: Twenty-four patients with pelvic fractures were referred to us between January 2020 to January 2022, including sixteen males and 8 females. Pelvic fractures were temporarily fixed by pelvic fixation belt accompanied by traction from the lower limb bone. Anterior pelvic ring injuries (superior ramus of pubis) and ilium fractures were treated with closed reduction and intramedullary fixation with minimally invasive TEN. Intraoperative C-arm, including pelvic anteroposterior, pelvic outlet, inlet and ilium oblique views, and O-arm fluoroscopy (intraoperative CT) were employed to assess fractures reduction and determine the location of the elastic titanium nail within the bone channel. RESULTS: By adopting closed reduction and minimally invasive incision techniques, pelvic fractures could be safely fixed by placing an elastic titanium nail in the osseous medullary cavity channels of the pelvis. Postoperative investigation indicated that the wounds of all patients were healed in the first stage without any occurrence of complications, such as injuries to the nerves, blood vessels, and important tissue structures. Patients are essential quickly after the operation and could perform the functional exercise in the early stages of the recovery. CONCLUSION: TEN can be used for minimally invasive treatment of pelvic fractures. This novel technique has no obvious complications and is worthwhile in clinical practice.

The treatment of complex intra-articular distal radius fractures with turning radius and distal volaris radius plate fixation.

BACKGROUND: Although distal radius fractures (DRFs) are clinically common, intra-articular DRFs accompanied by dorsally displaced free fragments are much less so. At present, it is very difficult to fix and stabilize the intra-articular distal radius fractures accompanying dorsally displaced free fragments with a plate. Our aim was to investigate the clinical effect of DRFs with distally displaced dorsal free mass treated with distal volaris radius (DVR) combined with turning of the radius via the distal palmar approach. METHODS: From 2015 to 2019, 25 patients with intra-articular distal radius fractures associated with dorsally displaced free fragments were selected and treated with distal volaris radius (DVR) combined with turning of the radius via the distal palmar approach. This study involved 14 males and 11 females, with an average age of 34.5 years (ranging from 21 to 50 years). The mean follow-up period was 16.5 months (ranging from 12 to 22 months). The dorsal displacement of the free fragments was analyzed by X-ray and three-dimensional computed tomography, allowing characterization of postoperative recovery effects by radial height, volar tilt and radial inclination. For the follow-up, we evaluated effects of the surgery by analyzing range of motion (ROM); Modified Mayo Wrist Score (MMWS); and Disabilities of Arm, Shoulder and Hand (DASH) score. Postoperative wound recovery and complications were also monitored to evaluate the clinical therapeutic effects of the surgical procedures. RESULTS: X-ray showed that all patients showed reduced fractures, well-healed wounds and recovered function with no obvious complications. Based on the follow-up, patients had a mean radial height of 10.5 mm (ranging from 8.1 to 12.6 mm), mean MMWS of 78.8° (ranging from 61° to 90°), mean DASH score of 16.25 (ranging from 11 to 21), mean ROM for volar flexion of 76.5° (ranging from 62° to 81°), mean ROM for dorsiflexion of 77.1° (ranging from 59 to 83) and mean VAS score of 1.4 (ranging from 1 to 3). CONCLUSION: Treatment of the intra-articular distal radius fractures accompanying dorsally displaced free fragments with turning of the radius and the DVR plate system via the distal palmar approach is effective and has no obvious complications.

PAI-1/PIAS3/Stat3/miR-34a forms a positive feedback loop to promote EMT-mediated metastasis through Stat3 signaling in Non-small cell lung cancer.

AIM: This study intented to clarify the intracellular effect of PAI-1 on Non-small cell lung cancer (NSCLC) metastasis and the precise mechanism involved. METHODS: The metastatic properties of NSCLC cells were determined by transwell assays and wound-healing assay in vitro. The mRNA and protein expressions of genes were analyzed by Real-time qPCR and western blot, respectively. Pulmonary metastasis model of NSCLC cells was established to evaluate the pro-metastasis effect of PAI-1 and anti-metastatic effect of miR-34a in vivo. The gene targets of miR-34a were confirmed by luciferase reporter assays. Chromatin immunoprecipitation assay was employed to detect the transcriptional regulation of miR-34a. Co-immunoprecipitation assay was performed to observe the interaction of proteins. RESULTS: PAI-1, which was elevated in NSCLC patients with recurrence and metastasis, augmented NSCLC metastasis and was negatively related to the prognosis of NSCLC. miR-34a, which was decreased in NSCLC patients with metastasis, attenuated NSCLC metastasis and was positively correlated with the prognosis of NSCLC. Moreover, PAI-1 was identified as the target gene of miR-34a and activated the Stat3 signaling pathway to promote epithelial-mesenchymal transition (EMT) in NSCLC cells. PAI-1 interacted with PIAS3 to regulate Stat3-dependent gene expression and miR-34a was transcriptionally suppressed by Stat3 to form a positive regulatory loop through Stat3 signaling. CONCLUSION: Our findings suggest that PAI-1 and miR-34a, which can be clinically utilized as biomarkers for the clinical prognosis or diagnosis of NSCLC, are potential targets for the treatment of NSCLC.

Selective denitrification of flue gas by O3 and ethanol mixtures in a duct: Investigation of processes and mechanisms.

A novel selective denitrification process, referred as O3-ethanol oxidation method, was developed by injecting O3 and ethanol mixtures into the simulated flue gas duct. The organic radicals, generated through the ethanol oxidation by O3, can oxidize NO into NO2, and finally into important industrial raw, namely, nitrate organics or aqueous nitrate acids. The residual ethanol in the tail can be recycled. The CO3(2-), HCO3(-) and SO2 in the flue gas hardly exhibit any effect on the NOX removal. Compared to the conventional O3 oxidation method, the present method shows higher selective oxidation of NO, higher NO(X) removal and less O3 consumption as well as proves lower initial investment and operating costs with more compact equipment.

Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland China.

INTRODUCTION: Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality. METHODS: We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included. RESULTS: A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027-1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691-4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142-5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141-4.420) were significantly associated with mortality. CONCLUSIONS: Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.

Characteristics of critically ill patients in ICUs in mainland China.

OBJECTIVES: We sought to describe the demographics, case mix, interventions, and clinical outcome of critically ill patients admitted to ICUs in Mainland China. DESIGN: A 2-month (July 1, 2009, to August 31, 2009) prospective, observational cohort study. SETTING: Twenty-two ICUs in Mainland China. PATIENTS: Adult patients admitted to participating ICUs during the study period with an ICU length of stay >24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, including demographics, underlying diseases, severity of illness, admission status, complications, intervention and treatment during ICU stay, and clinical outcome were recorded in case report form. The primary outcome measure was all-cause hospital mortality. Independent predictors for hospital mortality were determined with multivariate logistic regression analysis. One thousand two hundred ninety-seven patients met the inclusion criteria for the study, 821 (63.3%) were male, and mean age was 58.5 ± 19.2 yrs. Mean Acute Physiology and Chronic Health Evaluation II score was 18.0 ± 8.1, and mean Sequential Organ Failure Assessment score was 6.5 ± 3.8. One third of the patients were postoperative ICU admissions. Seven hundred sixty-five patients (59.0%) developed infections, followed by severe sepsis or septic shock (484, 37.3%), acute kidney injury (398, 30.7%), and acute lung injury/acute respiratory distress syndrome (351, 27.1%). Mechanical ventilation was used in almost three fourths of the patients, whereas any type of renal replacement therapy was used in 173 patients (13.3%). Hospital mortality was 20.3%. Multivariate logistic regression analysis found that Acute Physiology and Chronic Health Evaluation II score, solid tumor, severe sepsis/septic shock, acute lung injury/acute respiratory distress syndrome, and acute kidney injury were independent risk factors for hospital mortality. CONCLUSIONS: Critically ill patients in ICUs in Mainland China exhibited a case mix similar to those of Western countries, although there are significant differences in intensive care unit admission rates and disease severity between Western and Chinese ICUs.

[Effects of reduced glutathione on plasma level of cytokines and pulmonary ultrastructure in rats with sepsis].

OBJECTIVE: To investigate the protection mechanism of reduced glutathione (GSH) in acute lung injury in rats with sepsis. METHODS: Sepsis in Sprague-Dawley (SD) rats were reproduced by cecal ligation and puncture (CLP). They were randomly divided into four groups, sham-operated group, model group, GSH treatment group and levofloxacin (LEV) treatment group. Heart blood of 7 rats in all groups was collected at 3, 6, 12, 24 hours after operation. The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured. The lung ultrastructure changes were observed with electron microscope at 24 hours in all groups. RESULTS: Compared with the sham-operated group, the plasma level of TNF-alpha increased more obviously at 6 hours of the model group [(227+/-28) microg/L vs. (132+/-9) microg/L, P<0.01]. Compared with the model group, the plasma level of TNF-alpha in the GSH treatment group decreased obviously [(144+/-28) microg/L], and it was obviously lower than that of LEV treatment group [(214+/-48) microg/L , both P<0.01] . No obvious difference of plasma level of TNF-alpha was found at 3, 12, 24 hours among all the groups. Compared with the sham-operated group, the plasma level of IL-6 of the model group raised obviously at 3 hours [(267.65+/-72.87) microg/L vs. (135.43+/-40.08) microg/L, P<0.01]. In the GSH treatment group, the plasma level of IL-6 [(191.97+/-62.98) microg/L] was lower than that of the model group and the LEV treatment group [(268.75+/-74.67) microg/L, both P<0.05]. The plasma level of IL-6 was not obviously different among all groups at 6, 12, 24 hours. In the model group, the injury of pulmonary ultrastructure was obvious, especially in the mitochondria of the pulmonary cells. In the GSH treatment group, the change in ultrastructure of the lung was slight. CONCLUSION: TNF-alpha and IL-6 play significant role in the development of pulmonary ultrastructure injury in acute lung injury of septic rats. Treatment with GSH was effective in preventing such injury.