Endothelial cell-derived extracellular vesicles expressing surface VCAM1 promote sepsis-related acute lung injury by targeting and reprogramming monocytes.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common life-threatening syndrome with no effective pharmacotherapy. Sepsis-related ARDS is the main type of ARDS and is more fatal than other types. Extracellular vesicles (EVs) are considered novel mediators in the development of inflammatory diseases. Our previous research suggested that endothelial cell-derived EVs (EC-EVs) play a crucial role in ALI/ARDS development, but the mechanism remains largely unknown. Here, we demonstrated that the number of circulating EC-EVs was increased in sepsis, exacerbating lung injury by targeting monocytes and reprogramming them towards proinflammatory macrophages. Bioinformatics analysis and further mechanistic studies revealed that vascular cell adhesion molecule 1 (VCAM1), overexpressed on EC-EVs during sepsis, activated the NF-κB pathway by interacting with integrin subunit alpha 4 (ITGA4) on the monocyte surface, rather than the tissue resident macrophage surface, thereby regulating monocyte differentiation. This effect could be attenuated by decreasing VCAM1 levels in EC-EVs or blocking ITGA4 on monocytes. Furthermore, the number of VCAM1+ EC-EVs was significantly increased in patients with sepsis-related ARDS. These findings not only shed light on a previously unidentified mechanism underling sepsis-related ALI/ARDS, but also provide potential novel targets and strategies for its precise treatment.

Ultralow RuO2 Doped NiS2 Heterojunction as a Multifunctional Electrocatalyst for Hydrogen Evolution linking to Biomass Organics Oxidation.

Hydrogen energy and biomass energy are green and sustainable forms that can solve the energy crisis all over the world. Electrocatalytic water splitting is a marvelous way to produce hydrogen and biomass platform molecules can be added into the electrolyte to reduce the overpotential and meanwhile are converted into some useful organics, but the key point is the design of electrocatalyst. Herein, ultralow noble metal Ru is doped into NiS2 to form RuO2 @NiS2 heterojunction. Amongst them, the 0.06 RuO2 @NiS2 has low overpotentials of 363 mV for OER and 71 mV for HER in 1 m KOH, which are superior to the RuO2 and Pt/C. Besides, the 0.06 RuO2 @NiS2 shows a low overpotential of 173 mV in 1 m KOH+0.1 m glycerol, and the glycerol is oxidized to glyceraldehyde and formic acid via the high Faraday efficiency GlyOR process, and the splitting voltage is only 1.17 V. In addition, the 0.06 RuO2 @NiS2 has a low overpotential of 206 mV in 1 m KOH+0.1 m glucose, and the glucose is converted to glucaric acid, lactic acid, and formic acid. This work has a "one stone three birds" effect for the production of hydrogen, low splitting voltage, and high-value-added biomass chemicals.

[Research progress on the regulatory mechanism of endothelial derived extracellular vesicles in acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by a variety of internal and external injury factors in the lung, and its morbidity and mortality have remained stubbornly high. Recent studies have shown that endothelial-derived extracellular vesicles are an important mediator of pathological signal transduction and play an important regulatory role in the occurrence, development and prognosis of ARDS. Now our paper reviewed the regulatory mechanism of endothelial-derived extracellular vesicles in ARDS.

Multiparametric transrectal ultrasound for the diagnosis of peripheral zone prostate cancer and clinically significant prostate cancer: novel scoring systems.

BACKGROUND: To evaluate the diagnostic performance of multiparametric transrectal ultrasound (TRUS) and to design diagnostic scoring systems based on four modes of TRUS to predict peripheral zone prostate cancer (PCa) and clinically significant prostate cancer (csPCa). METHODS: A development cohort involved 124 nodules from 116 patients, and a validation cohort involved 72 nodules from 67 patients. Predictors for PCa and csPCa were extracted to construct PCa and csPCa models based on regression analysis of the development cohort. An external validation was performed to assess the performance of models using area under the curve (AUC). Then, PCa and csPCa diagnostic scoring systems were established to predict PCa and csPCa. The diagnostic accuracy was compared between PCa and csPCa scores and PI-RADS V2, using receiver operating characteristics (ROC) and decision curve analysis (DCA). RESULTS: Regression models were established as follows: PCa = - 8.284 + 4.674 × Margin + 1.707 × Adler grade + 3.072 × Enhancement patterns + 2.544 × SR; csPCa = - 7.201 + 2.680 × Margin + 2.583 × Enhancement patterns + 2.194 × SR. The PCa score ranged from 0 to 6 points, and the csPCa score ranged from 0 to 3 points. A PCa score of 5 or higher and a csPCa score of 3 had the greatest diagnostic performance. In the validation cohort, the AUC for the PCa score and PI-RADS V2 in diagnosing PCa were 0.879 (95% confidence interval [CI] 0.790-0.967) and 0.873 (95%CI 0.778-0.969). For the diagnosis of csPCa, the AUC for the csPCa score and PI-RADS V2 were 0.806 (95%CI 0.700-0.912) and 0.829 (95%CI 0.727-0.931). CONCLUSIONS: The multiparametric TRUS diagnostic scoring systems permitted better identifications of peripheral zone PCa and csPCa, and their performances were comparable to that of PI-RADS V2.

Clinically significant prostate cancer (csPCa) detection with various prostate sampling schemes based on different csPCa definitions.

BACKGROUND: Combining targeted biopsy (TB) with systematic biopsy (SB) is currently recommended as the first-line biopsy method by the European Association of Urology (EAU) guidelines in patients diagnosed with prostate cancer (PCa) with an abnormal magnetic resonance imaging (MRI). The combined SB and TB indeed detected an additional number of patients with clinically significant prostate cancer (csPCa); however, it did so at the expense of a concomitant increase in biopsy cores. Our study aimed to evaluate if ipsilateral SB (ipsi-SB) + TB or contralateral SB (contra-SB) + TB could achieve almost equal csPCa detection rates as SB + TB using fewer cores based on a different csPCa definition. METHODS: Patients with at least one positive prostate lesion were prospectively diagnosed by MRI. The combination of TB and SB was conducted in all patients. We compared the csPCa detection rates of the following four hypothetical biopsy sampling schemes with those of SB + TB: SB, TB, ipsi-SB + TB, and contra-SB + TB. RESULTS: The study enrolled 279 men. The median core of SB, TB, ipsi-SB + TB, and contra-SB + TB was 10, 2, 7 and 7, respectively (P < 0.001). ipsi-SB + TB detected significantly more patients with csPCa than contra-SB + TB based on the EAU guidelines (P = 0.042). They were almost equal on the basis of the Epstein criteria (P = 1.000). Compared with SB + TB, each remaining method detected significantly fewer patients with csPCa regardless of the definition (P < 0.001) except ipsi-SB + TB on the grounds of D1 (P = 0.066). Ten additional subjects were identified with a higher Gleason score (GS) on contra-SB + TB, and only one was considered as significantly upgraded (GS = 6 on ipsi-SB + TB to a GS of 8 on contra-SB + TB). CONCLUSIONS: Ipsi-SB + TB could acquire an almost equivalent csPCa detection value to SB + TB using significantly fewer cores when csPCa was defined according to the EAU guidelines. Given that there was only one significantly upgrading patient on contra-SB, our results suggested that contra-SB could be avoided.

[Effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock].

OBJECTIVE: To investigate the effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock. METHODS: An observational study was conducted. The inpatients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital, Affiliated Hospital of Yangzhou University and Jiangdu People's Hospital from October 1st, 2018 to September 30th, 2020 were enrolled. The general data including gender, age, body mass index (BMI), patient source, site of infection, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score and arterial blood lactic acid (Lac) at ICU admission, fluid resuscitation dose, completion time of initial 30 mL/kg fluid resuscitation, mechanical ventilation, incidence of acute kidney injury (AKI), continuous renal replacement therapy (CRRT), length of ICU stay and 28-day mortality. The relationship between the completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score (the difference between SOFA score 3 hours of fluid resuscitation and initial SOFA score) was analyzed. In addition, according to the completion time (T) of initial 30 mL/kg fluid resuscitation, the patients were divided into T ≤ 1 hour group, 1 hour < T ≤ 2 hours group, 2 hours < T ≤ 3 hours group and T > 3 hours group, and the observation parameters among the groups were compared. RESULTS: (1) A total of 131 patients were enrolled, including 94 males and 37 females with an average age of (68.3±15.0) years old. The median APACHE II score was 27 (21, 34), the median of initial SOFA score was 12 (10, 14), the median of initial Lac was 5.0 (3.4, 7.1) mmol/L, and the most common source of infection was lung, with a total of 87 patients (66.41%). The completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score fitted the Logistic curve (Y = -1.062 6X2+4.407 9X+0.961 8), which suggested that the early or late completion time of initial fluid resuscitation had adverse effects on the prognosis of patients with septic shock. (2) There was no significant difference in infection site, initial APACHE II score, initial Lac, and initial SOFA score among different completion time of initial 30 mL/kg fluid resuscitation groups. The respiratory support rate, the incidence of AKI and the ratio of CRRT in the T ≤ 1 hour group were significantly higher than those in the 1 hour < T ≤ 2 hours group, 2 hours < T ≤ 3 hours group and T > 3 hours group (respiratory support rate: 78.57% vs. 75.51%, 42.86%, 75.00%; incidence of AKI: 57.14% vs. 20.41%, 21.43%, 50.00%; ratio of CRRT: 35.71% vs. 0%, 7.14%, 16.67%), the differences among the groups were statistically significant (all P < 0.05). The 28-day mortality was the highest in the T ≤ 1 hour group (64.29%), and the lowest in the 1 hour < T ≤ 2 hours group (22.45%), 35.71% in the 2 hours < T ≤ 3 hours group, 33.33% in the T > 3 hours, and the difference among the groups was statistically significant (P < 0.01). CONCLUSIONS: Completion of initial 30 mL/kg fluid resuscitation in 1-2 hours after septic shock may reduce the 28-day mortality and improve organ dysfunction, and initial fluid resuscitation prematurely or too late may increase 28-day mortality. But further research and verification are needed.

Initial fluid resuscitation (30 mL/kg) in patients with septic shock: More or less?

OBJECTIVES: The 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is limited evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock. METHODS: This was a multicenter prospective observational study of adult patients with septic shock who were admitted to four intensive care units (ICUs) in a total of three Jiangsu Province teaching hospitals over a 3-year span from May 8, 2018, to June 15, 2021. Each enrolled patients with septic shock was categorized into the low-volume (below 20 mL/kg fluid), medium-volume (20-30 mL/kg fluid) or high-volume (above 30 mL/kg fluid) fluid group according to the initial infusion dose given for fluid resuscitation. Various demographic attributes and other variables were collected from medical records. Logistic regression and Kaplan-Meier curve analysis were used to determine the relationship between initial fluid resuscitation doses and patient outcomes. MEASUREMENTS AND MAIN RESULTS: A total of 302 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the high-volume group (48.3%) and lowest in the medium-volume group (26.3%, P < 0.05). Patients who completed 30 mL/kg initial fluid resuscitation in the first 1-2 h had the lowest 28-day mortality rate (22.8%, P < 0.05). Logistic regression showed that a medium initial fluid volume dose was an independent protective factor, with the odds ratio (OR) indicating significantly decreased mortality (OR, 0.507; 95% confidence interval, 0.310-0.828; P = 0.007; P < 0.05). A Kaplan-Meier curve stratified by initial fluid resuscitation dose was constructed for the probability of 28-day mortality. The medium-volume fluid group showed a significantly lower 28-day mortality rate than the high-volume group or the low-volume group (log-rank test, P = 0.0016). CONCLUSION: In septic shock patients, an initial fluid resuscitation rate of 20-30 mL/kg within the first hour may be associated with reduced 28-day mortality; however, this result needs to be confirmed by further high-quality randomized controlled clinical trials. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674.

High-flow nasal cannula for acute exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: The evidence for the safety of high-flow nasal cannula (HFNC) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients is conflicting. OBJECTIVES: To evaluate the intubation and mortality risks of HFNC compared to non-invasive ventilation (NIV) and conventional oxygen therapy (COT) for AECOPD patients. METHODS: A search of electronic databases was performed. Studies that used HFNC to treat AECOPD patients were identified. RESULTS: Seven RCTs and one observational study were included. There were no differences in intubation risk (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.49 to 1.78, p = 0.84, very low certainty) and mortality risk (RR 0.91, 95% CI 0.46 to 1.79, p = 0.77, very low certainty) for HFNC compared with NIV. No data were available for intubation or mortality risk for HFNC compared with COT. CONCLUSION: For AECOPD patients, low-quality evidence indicates that HFNC does not increase intubation and mortality risks compared to NIV.

Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro.

INTRODUCTION: Mesenchymal stem cells (MSCs) exert immunomodulatory functions by inducing the development and differentiation of naive T cells into T cells with an anti-inflammatory regulatory T cell (Treg) phenotype. Our previous study showed that hepatocyte growth factor (HGF) secreted by MSCs had immunomodulatory effects in the context of lipopolysaccharide (LPS) stimulation. We hypothesized that HGF is a key factor in the MSC-mediated regulation of the T helper 17 (Th17) cell/regulatory T (Treg) cell balance. METHODS: We investigated the effects of MSCs on the differentiation of CD4+ T cells and the functions of Th17/Treg cells in response to LPS stimulation by performing in vitro coculture experiments. MSCs were added to the upper chambers of cell culture inserts, and CD4+ T cells were plated in the lower chambers, followed by treatment with LPS or an anti-HGF antibody. Th17 (CD4+CD3+RORrt+) and Treg (CD4+CD25+Foxp3+) cell frequencies were analysed by flow cytometry, and the expression of Th17 cell- and Treg cell-related cytokines in the CD4+ T cells or culture medium was measured by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Neutrophil functions were determined by flow cytometry after a coculture with Th17/Treg cells. RESULTS: The percentage of CD4+CD25+Foxp3+ cells was significantly increased in the CD4+ T cell population, while the percentage of CD4+CD3+RORrt+ cells was significantly decreased after MSC coculture. However, the MSC-induced effect was significantly inhibited by the anti-HGF antibody (p < 0.05). Furthermore, MSCs significantly inhibited the CD4+ T cell expression of IL-17 and IL-6 but increased the expression of IL-10 (p < 0.05 or p < 0.01); these effects were inhibited by the anti-HGF antibody (p < 0.05). In addition, CD4+ T cells cocultured with MSCs significantly inhibited neutrophil phagocytic and oxidative burst activities (p < 0.05 or p < 0.01); however, these MSC-induced effects were inhibited by the anti-HGF antibody (p < 0.05). CONCLUSION: These data suggested that MSCs induced the conversion of fully differentiated Th17 cells into functional Treg cells and thereby modulated the Th17/Treg cell balance in the CD4+ T cell population, which was partly attributed to HGF secreted by the MSCs.

A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury.

PURPOSE: Therapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury. METHODS: We searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool. RESULTS: Twenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007). CONCLUSIONS: Our meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.

The Value of Shadowing and the Twinkling Artifact in the Diagnosis of Ureteral Stones: A Single-center Study.

OBJECTIVE: To determine and evaluate the value of shadowing and the twinkling artifact (TA) for the diagnosis of ureteral stones. MATERIALS AND METHODS: Related ultrasound images from 117 patients with suspected ureteral stones were consecutively collected with optimized machine settings, confirmed by computed tomography and then retrospectively reviewed by 12 physicians who were classified into 3 groups according to their experience levels: elementary, intermediate, and advanced. The shadowing/TA grades were separately evaluated by all the participating physicians in a blinded manner, and the consistency was verified using Kendall's coefficient of concordance (Kendall's W). Furthermore, the diagnostic performance was compared among the groups stratified by physicians' clinical experience levels and ureteral stone sizes. RESULTS: Using shadowing/TA as indicators for ureteral stones, Kendall's W for the TA evaluation was higher than that for shadowing among all the participating physicians and subgroups (P <.05). Furthermore, with no difference in specificity at 100%, the sensitivity of the isolated TA was superior to that of shadowing in groups stratified by the physicians' clinical experience levels and stone sizes, respectively (P <.05). However, for the respective comparisons of shadowing and the TA among groups stratified by stone sizes, as ureteral stones became larger, the detection sensitivities all significantly increased (P ≤.001). CONCLUSION: Among physicians, subjective evaluation of the TA is more consistent and has better diagnostic sensitivity than that of shadowing for the diagnosis of ureteral stones, and the stone size may play an important role in the detection sensitivity of these 2 indicators.

Sonographic Alteration of Basal Ganglia in Different Forms of Primary Focal Dystonia: A Cross-sectional Study.

BACKGROUND: Few studies have addressed whether abnormalities in the lenticular nucleus (LN) are characteristic transcranial sonography (TCS) echo features in patients with primary dystonia. This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia. METHODS: cross-sectional observational study was performed between December 2013 and December 2014 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects. TCS was performed in patients and control subjects. Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups. RESULTS: Thirteen individuals were excluded due to poor temporal bone windows, and two subjects were excluded due to disagreement in evaluation by sonologists. Totally, 70 patients (cervical dystonia, n = 30; blepharospasm, n = 30; oromandibular dystonia, n = 10) and 50 normal controls were included in the final analysis. LN hyperechogenicity was observed in 51% (36/70) of patients with primary focal dystonia, compared with 12% (6/50) of controls (P < 0.001). Substantia nigra hyperechogenicity did not differ between the two groups. LN hyperechogenicity was observed in 73% (22/30) of patients with cervical dystonia, a greater prevalence than in patients with blepharospasm (33%, 10/30, P = 0.002) and oromandibular dystonia (40%, 4/10, P = 0.126). LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls (73% vs. 12%, P < 0.001); however, no significant difference was detected in patients with blepharospasm (33% vs. 12%, P = 0.021) or oromandibular dystonia (40% vs. 12%, P = 0.088). CONCLUSIONS: LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls. It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.

[Comparative study on polytene chromosomes of two isolates of Simulium quinquestriatus].

The salivary glands were exposed and isolated from the larvae of Simulium quinquestriatus and stained in carbol fuchsin, squashed between slide and coverslide. Slides were examined and photographed under microscope to measure the polytene chromosomes. Systematic analysis was made. Results indicated that the number of the polytene chromosomes of both isolates is three. The main characteristic chromosomal structures are homologized. Only the banding types of II L are different.