Trendelenburg maneuver predicts fluid responsiveness in patients on veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Evaluation of fluid responsiveness during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support is crucial. The aim of this study was to investigate whether changes in left ventricular outflow tract velocity-time integral (ΔVTI), induced by a Trendelenburg maneuver, could predict fluid responsiveness during VA-ECMO. METHODS: This prospective study was conducted in patients with VA-ECMO support. The protocol included four sequential steps: (1) baseline-1, a supine position with a 15° upward bed angulation; (2) Trendelenburg maneuver, 15° downward bed angulation; (3) baseline-2, the same position as baseline-1, and (4) fluid challenge, administration of 500 mL gelatin over 15 min without postural change. Hemodynamic parameters were recorded at each step. Fluid responsiveness was defined as ΔVTI of 15% or more, after volume expansion. RESULTS: From June 2018 to December 2019, 22 patients with VA-ECMO were included, and a total of 39 measurements were performed. Of these, 22 measurements (56%) met fluid responsiveness. The R2 of the linear regression was 0.76, between ΔVTIs induced by Trendelenburg maneuver and the fluid challenge. The area under the receiver operating characteristic curve of ΔVTI induced by Trendelenburg maneuver to predict fluid responsiveness was 0.93 [95% confidence interval (CI) 0.81-0.98], with a sensitivity of 82% (95% CI 60-95%), and specificity of 88% (95% CI 64-99%), at a best threshold of 10% (95% CI 6-12%). CONCLUSIONS: Changes in VTI induced by the Trendelenburg maneuver could effectively predict fluid responsiveness in VA-ECMO patients. Trial registration ClinicalTrials.gov, NCT03553459 (the TEMPLE study). Registered on May 30, 2018.

Correction to: MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming.

An amendment to this paper has been published and can be accessed via the original article.

miR-17-5p and miR-20a-5p suppress postoperative metastasis of hepatocellular carcinoma via blocking HGF/ERBB3-NF-κB positive feedback loop.

Dysregulation of microRNA (miRNA) is a frequent event in hepatocellular carcinoma (HCC), but little is known whether it is a bystander or an actual player on residual HCC metastasis during liver microenvironment remodeling initiated by hepatectomy. Methods: The differently expressed miRNAs and mRNAs were identified from RNA-seq data. Western blot, qRT-PCR, fluorescence in situ hybridization, immunofluorescence and immunohistochemical were used to detect the expression of miRNA and mRNA in cell lines and patient tissues. The biological functions were investigated in vitro and in vivo. Chromatin immunoprecipitation, proximity ligation and luciferase reporter assay were used to explore the specific binding of target genes. The expression of HGF/ERBB3 signaling was detected by Western blot. Results: In this study, HGF induced by hepatectomy was shown to promote metastasis of residual HCC cells. miR-17-5p and miR-20a-5p were confirmed to play inhibitory roles on HCC metastasis. And ERBB3 was found to be the common target of miR-17-5p and miR-20a-5p. HCC cells with lower levels of miR-17-5p and miR-20a-5p or higher level of ERBB3 were often more sensitive to response HGF stimuli and to facilitate metastatic colonization both in vitro and in vivo experimental systems. Furthermore, HGF reinforced ERBB3 expression by NF-κB transcriptional activity in a positive feedback loop. Of particular importance, HCC patients with lower levels of miR-17-5p and miR-20a-5p or higher level of ERBB3 had significantly shorter OS and PFS survivals after surgical resection. Conclusion: miR-17-5p and miR-20a-5p could suppress postoperative metastasis of hepatocellular carcinoma via blocking HGF/ERBB3-NF-κB positive feedback loop and offer a new probable strategy for metastasis prevention after HCC resection.

MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming.

BACKGROUND: MicroRNA-612 (miR-612) has been proven to suppress EMT, stemness, and tumor metastasis of hepatocellular carcinoma (HCC) via PI3K/AKT2 and Sp1/Nanog signaling. However, its biological roles on HCC progression are far from elucidated. METHODS: We found direct downstream target of miR-612, hadha by RNA immunoprecipitation and sequencing. To explore its biological characteristic, potential molecular mechanism, and clinical relevance in HCC patients, we performed several in-vitro and in-vivo models, as well as human tissue chip. RESULTS: Ectopic expression of miR-612 could partially reverse the level of HADHA, then suppress function of pseudopods, and diminish metastatic and invasive potential of HCC by lipid reprogramming. In detail, miR-612 might reduce invadopodia formation via HADHA-mediated cell membrane cholesterol alteration and accompanied with the inhibition of Wnt/ß-catenin regulated EMT occurrence. Our results showed that the maximum oxygen consumption rates (OCR) of HCCLM3miR-612-OE and HCCLM3hadha-KD cells were decreased nearly by 40% and 60% of their counterparts (p < 0.05). The levels of acetyl CoA were significantly decreased, about 1/3 (p > 0.05) or 1/2 (p < 0.05) of their controls, in exogenous miR-612 or hadha-shRNA transfected HCCLM3 cell lines. Besides, overexpression of hadha cell lines had a high expression level of total cholesterol, especially 27-hydroxycholesterol (p < 0.005). SREBP2 protein expression level as well as its downstream targets, HMGCS1, HMGCR, MVD, SQLE were all deregulated by HADHA. Meanwhile, the ATP levels were reduced to 1/2 and 1/4 in HCCLM3miR-612-OE (p < 0.05) and HCCLM3hadha-KD (p < 0.01) respectively. Moreover, patients with low miR-612 levels and high HADHA levels had a poor prognosis with shorter overall survival. CONCLUSION: miR-612 can suppress the formation of invadopodia, EMT, and HCC metastasis and by HADHA-mediated lipid programming, which may provide a new insight of miR-612 on tumor metastasis and progression.

miR-612 suppresses stem cell-like property of hepatocellular carcinoma cells by modulating Sp1/Nanog signaling.

In our previous study we found that miR-612 negatively regulated stem cell-like property and tumor metastasis of hepatocellular carcinoma cells (HCC). In this study, we try to elucidate underlying mechanism of the regulation, and find that miR-612 inversely modulate the mRNA and protein level of epithelial cell adhesion molecule as well as CD133, negatively regulate the numbers and sizes of tumor spheres, directly inhibit the protein level of Sp1, and subsequently reduce transcription activity of Nanog. Of importance, the higher levels of Sp1 and Nanog in biopsies are the more unfavorable prognoses of HCC patients are found after tumor resection. Taken together, miR-612 has a suppressive role on HCC stemness via Sp1/Nanog signaling pathway.

Targeting autophagy as a potential therapeutic approach for immune thrombocytopenia therapy.

Autophagy involves the sequestration and lysosomal degradation of various cytoplasmic structures, including damaged organelles and invading microorganisms. Autophagy is not only an essential cell-intrinsic mechanism for protecting against internal and external stress conditions but is also key in the cellular response against microbes, in antigen processing for major histocompatibility complex (MHC) presentation, and in lymphocyte development, survival, and proliferation. In recent years, perturbations in autophagy have been implicated in a number of diseases, including autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Immune thrombocytopenia (ITP) is a multifactorial disease characterized by autoimmune responses to self-platelet membrane proteins. Recently, our unpublished original data demonstrated aberrant expression of molecules in the autophagy pathway in ITP patients compared with controls, and we found a close correlation between the pathogenesis of ITP and the autophagy pathway. The potential of targeting the autophagy pathway in ITP as a novel therapeutic approach has been discussed.

Magnetic resonance imaging of temporomandibular joint: morphometric study of asymptomatic volunteers.

BACKGROUND: The aims of this study were to determine the best suited magnetic resonance imaging scanning plane, scanning sequence, and imaging modality for the evaluation of the temporomandibular joint (TMJ) and quantitatively assess the relationship of articular disk position to condyle position. METHODS: One hundred four TMJs in 52 symptom-free heads were examined by magnetic resonance imaging. The best scanning plane, scanning sequence, and scanning parameter were determined according to the imaging time and image quality. Bilateral symmetry of the articular disk and mandibular condyle was measured by using the automatic measurement of 3.0-T GE Excite Signa MR scanner. RESULTS: Fast spin-echo sequence, oblique sagittal imaging plane, and proton density imaging were the best suited scanning sequence, scanning planes, and imaging modality, respectively. The thicknesses of the anterior and posterior bands and for the intermediate zone were not statistically different for both sides. The posterior band of the disk was found to originate in an area adjacent to the 12-o'clock position of the condyle (± 5 degrees), whereas the anterior band of the disk originated adjacent to 1-o'clock position (28 ± 6 degrees). The anteroposterior diameter and mediolateral diameter of the condylar processes were not statistically different for both sides. The axial condylar angle between the plane of the greatest mediolateral diameter of the condylar processes and the midsagittal plane were also not statistically different for both sides. CONCLUSIONS: The magnetic resonance images can depict clearly major regional anatomic structures and position in the TMJ, which can be used in the early diagnosis for the TMJ disorder.

[Effect of acupuncture of Ho (ST 36)-plus Mu (CV 12)-acupoints on hypothalamic gonadotropin-releasing hormone mRNA and SP mRNA expression in stress-induced gastric ulcer rats].

OBJECTIVE: To observe the effect of acupuncture of "Zusanli" [ST 36, Ho (Sea)-acupoint] and "Zhongwan" (CV 12, front Mu-acupoint) on the expression of hypothalamic gonadotropin-releasing hormone (GnRH) mRNA and SP mRNA in stress-induced gastric ulcer (GU) rats. METHODS: Sixty male Wistar rats were randomly divided into normal control group, simple bundling group, GU model group, CV 12 group, ST 36 group and CV 12 + ST 36 (Ho- and front Mu-acupoint combination) group, with 10 cases in each group. GU model was established by binding the rat's four limbs to an animal board and to immerse it to cool water for 24 h. Manual acupuncture stimulation was applied to CV 12, bilateral ST 36 or CV 12 + ST 36 for 20 min, once daily for 2 days. The GU index was evaluated by using Guth's method (1979). GnRH mRNA and SP mRNA expression of the hypothalamus tissue was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with the normal group, the GU index values in the simple bundling group and the model group were significantly higher (P < 0.01); while in comparison with the model group, the GU index values were significantly decreased in the CV 12, ST 36 and CV 12 + ST 36 groups (P < 0.05, P < 0.01). Following stress stimulation, hypothalamic GnRH mRNA expression levels in the simple bundling group and the model group were remarkably increased (P < 0.05, P < 0.01), whereas those of hypothalamic SP mRNA expression had no apparent changes in these two groups (P > 0.05). After manual acupuncture intervention, hypothalamic GnRH mRNA expression levels in the CV 12, ST 36 and CV 12 + ST 36 groups were evidently down-regulated and SP mRNA expression levels in the ST 36 and CV 12+ ST 36 groups were remarkably upregulated in comparison with the model group (P < 0.01). No significant differences were found between the CV 12 and ST 36 groups in the GU index, among the CV 12, ST 36 and CV 12 + ST 36 groups in GnRH mRNA expression, and between the CV 12 and model groups in the expression levels of SP mRNA (P > 0.05). CONCLUSION: Acupuncture of CV 12 and ST 36 can relieve stress-induced gastric ulcer in the rat, which is closely with its effect in down-regulating hypothalamic GnRH mRNA expression.

Clinical characteristics of adenovirus associated lower respiratory tract infection in children.

BACKGROUND: Acute lower respiratory tract infection (ALRI) due to adenovirus infection is a low frequency event but often causes severe outcome. This study was undertaken to uncover the clinical and epidemiological features of adenovirus infection in children. METHODS: Hospitalized children with ALRI were analyzed through continuous monitoring from 2006 to 2012. Nasopharyngeal aspirates were examined by direct immunofluorescence to detect respiratory agents including respiratory syncytial virus, adenovirus, influenza virus types A/B, parainfluenza virus types 1/2/3. Chlamydia pneumonia, Mycoplasma pneumonia and Chlamydia trachomatis were determined by real-time PCR. A retrospective analysis was made of 479 patients with positive infection of adenovirus. RESULTS: The positive detection rate of adenovirus was 0.63% in patients with ALRI. The incidence rate of adenovirus-associated acute lower respiratory tract infection peaked at the second six months of life. The morbidity was much higher in winter, spring and summer than in autumn. Patients with pneumonia accounted for 73.90% of the patients. More than one-third of the patients developed severe pneumonia, whereas no death was found. Features of severe adenovirus-associated lower respiratory tract infection included persistent high fever with serious infective symptoms, and hepatic dysfunction was one of the most common complications. Mixed infection of atypical pathogens was common (18.58%) in this study. CONCLUSIONS: Adenovirus is a critical pathogen that can cause severe respiratory infections even in immunocompetent children. Coinfection of adenovirus with atypical pathogens is common. Antibiotic treatment with azithromycin or erythromycin is necessary in patients with mixed infection of atypical pathogens.

[Decreasing effect of electro-acupuncture at Sanyin points on inflammatory cytokines in autoimmune prostatitis rats].

OBJECTIVE: To observe the changes of inflammatory cytokines in autoimmune prostatitis (AIP) rats treated by electro-acupuncture (EA) at Sanyin points. METHODS: We selected 40 Wistar male rats in this study, 10 as normal controls, and the other 30 made AIP models by intradermal injection of protein purification liquid from the prostate of allogeneic male rats with dual immune adjuvant. Then we randomly divided the AIP models into a model, a Cernilton control and an EA group of equal number, the latter two groups treated by Cernilton enema and EA, respectively. After 15 days of treatment, all the animals were sacrificed for detection of the levels of TNF-alpha, iNOS, MDA and T-AOC in the prostate tissue. RESULTS: Compared with the normal controls, the model rats showed significantly elevated TNF-alpha expression ([15.31 +/- 1.36] vs [32.20 +/- 1.65] pg/ml, P < 0.01), iNOS activity ([0.81 +/- 0.33] vs [1.25 +/- 0.23] U/ml, P < 0.01) and MDA content ([0.66 +/- 0.14] vs [0.91 +/- 0.21] nmol/ml, P < 0.05), but markedly reduced T-AOC activity ([1.56 +/- 0.16] vs [1.11 +/- 0.15] U/ml, P < 0.01). In comparison with the model group, the EA group exhibited significantly reduced levels of TNF-alpha ([17.32 +/- 2.69 ] pg/ml, P < 0.01), iNOS ([0.98 +/- 0.5 ] U/ml, P < 0.05) and MDA ([0.70 +/- 0.20] nmol/ml, P < 0.05), but remarkably increased level of T-AOC ([1.44 +/- 0.26] U/ml, P < 0.05). CONCLUSION: Electro-acupuncture at Sanyin points can protect the prostate tissue from morphological damage and reduce inflammatory reaction by decreasing pro-inflammatory cytokine activity, vascular permeability and inflammatory cell infiltration and increasing the activity of the antioxidant defense system.

[Clinical significance of rapid detecting bone marrow BCL2/IGH and BCL6/IGH fusion genes in patients with diffuse large B cell lymphoma by multiplex PCR].

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin's lymphoma (NHL), characterized by great heterogeneity in clinical manifestations and molecular genetics. This study was aimed to explore the clinical significance of applying multiplex PCR to detect BCL2/IGH and BCL6/IGH fusion genes in DLBCL. Multiplex PCR was used to detect bone marrow samples from 80 cases of DLBCL. The results showed that 12 patients (15%) carried BCL2/IGH or BCL6/IGH fusion genes, BCL2/IGH was found in 6 patients (7.5%), and BCL6/IGH in another 6 patients (7.5%). The patients with different molecular markers displayed different clinical features and outcomes. It is concluded that multiple PCR is rapid and accurate method to identify gene abnormalities in DLBCL, but further studying a quantitative or semi-quantitative assay for the expression of fusion genes is needed.

An enhanced preparation and purification of the major antioxidants baicalein and wogonin from Scutellariae radix.

A simple, rapid and improved method was developed to isolate high-purity baicalein and wogonin from Scutellariae radix. The method involves endogenous baicalinase-catalysed hydrolysis (EBCH), partition, automated low-pressure preparative chromatography (LPPC) and recrystallisation without multiple and tedious column chromatography. This process was optimised for large scale production of baicalein and wogonin with high yields, low costs and process automation. The transformation ratio of baicalin and wogonoside reached 98.21% and 96.60% after EBCH, leading to an increase of 5.41-fold in baicalein and 3.89-fold in wogonin, compared to a raw sample without hydrolysis. The purity of final products was more than 98% after one-step LPPC and recrystallisation. The experimental results show that EBCH-LPPC is an effective method for preparing high purity antioxidants.

[Surgical site infection in pancreas surgery and the use of perioperative antibiotics].

OBJECTIVE: To analyze the pathogen profiles and the use of perioperative antibiotics after surgical site infection (SSI) in pancreas operation. METHOD: We retrospectively analyzed the pathogen profiles and the use of perioperative antibiotics in 48 SSI patients who received pancreas operations from Jan 2001 to Dec 2005. RESULTS: Totally 79 strains of pathogens (74 strains of bacteria) were isolated, including 17 strains of methicillin-resistant Staphylococcus aureus (MRSA), 17 strains of enterococcus species, 12 strains of Escherichia species, and 5 strains of enterobacteriaceae. Combination of the third generation of cephalosporins and antianaerobic agents were the main prophylactic therapies, with an average duration of (4.7 +/- 1.2) days. Most SSI episodes happened 6-14 days postoperatively (median 9 days). Celiac infections were most common (n=39). Therapeutic antibiotics gave priority to combined-antibiotics of the third cephalosporins and antianaerobic antibiotics, glycopeptides and carbapenems. CONCLUSIONS: SSI commonly occurs on the 6-14 postoperative day, with MRSA and enterococci as the common pathogens of SSI after pancreas surgery. Antibiotic resistance should be considered when applying prophylactic therapies.