[Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases].

Objective: To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated. Results: A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% -20.5% ), respectively. Conclusion: Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

[The clinical characteristics of neutrophil extracellular trap in patients with severe cerebral venous sinus thrombosis and its prognostic value in acute and subacute patients].

Objective: To explore the clinical characteristics of neutrophil extracellular trap (NET) in patients with severe cerebral venous sinus thrombosis (CVST) and to study their prognostic value in the acute and subacute phases. Methods: This study is a retrospective case series analysis. Clinical and pathological data of 52 patients with severe cerebral venous sinus thrombosis who underwent endovascular treatment in the Department of Neurosurgery, Tianjin Huanhu Hospital from June 2019 to June 2022 were retrospectively analyzed. There were 20 males and 32 females, with an age of (40.1±13.6) years(range:18 to 66 years). Forty-five healthy physical examinees were included in the control group. High-resolution MRI was used to stage the thrombus, with 11 cases in the acute group, 28 cases in the subacute group, and 13 cases in the chronic group. Thrombus specimens were obtained through endovascular treatment, and the fluorescence intensity of NET in peripheral blood at different time points was analyzed by immunofluorescence contrast,including the double-stranded DNA structure and adhesion protein components (citrolinated histone H3 (CitH3), myeloperoxidase-DNA complex(MPO-DNA), neutrophil elastase (NE)). The NET markers were determined by ELISA. Spearman rank correlation analysis was used to analyze the correlation between the NET markers in peripheral blood of patients with severe cerebral venous sinus thrombosis in the acute and subacute phases and the volume of venous sinus thrombus, the degree of venous sinus recanalization after treatment, and the discharge modified Rankin scale(mRS)score. The accuracy of NET markers in predicting the prognosis of patients with severe cerebral venous sinus thrombosis was analyzed by drawing receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: The results of immunofluorescence staining and ELISA showed that no NET structure was formed in the peripheral blood of the control group, while CitH3, MPO-DNA and NE levels in the peripheral blood of CVST patients were increased, among which the acute stage group was the highest, followed by the subacute group, and the chronic group was the lowest. Spearman correlation analysis showed that CitH3, MPO-DNA and NE levels in peripheral blood of patients in acute group and subacute group were positively correlated with thrombus volume and mRS score at discharge (P<0.05). The levels of CitH3 and MPO-DNA in peripheral blood of patients with complete venous sinus recanalization were lower than those of patients with partial venous sinus recanalization (P<0.01). ROC curve analysis results showed that MPO-DNA and NE had no predictive ability for the prognosis of CVST patients (P values were 0.614 and 0.324, respectively), and the AUC of CitH3 was 0.800 (95%CI: 0.638~0.962, P=0.032), the best cut-off value was 13.5 µg/L, the sensitivity was 100%, and the specificity was 58.8%. Conclusions: A large number of NET are formed in patients with severe cerebral venous sinus thrombosis in acute stage. Patients with severe cerebral venous sinus thrombosis in acute stage and subacute stage with high peripheral blood NET content has a low rate of complete sinus revascularization and poor neurological function recovery after treatment.

[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events. Results: A total of 81.82% (n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546-1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% (n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients (n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion: Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Assessment of hesitancy to COVID-19 vaccine in patients with rheumatic arthritis.

OBJECTIVE: The COVID-19 pandemic caused by SARS-CoV-2 in 2019 has greatly impacted global health, leading to high morbidity and mortality rates. Rheumatoid arthritis (RA) patients have faced numerous challenges during the pandemic, including concerns about infection, limited medical resources, and shortages of medication. While vaccination is a crucial strategy against COVID-19, the reasons behind vaccine hesitancy (VH) among people with RA remain largely unexplored. SUBJECTS AND METHODS: We conducted a cross-sectional, single-arm study in China from July 18 to August 18, 2021. Using a self-administered questionnaire and a convenient sampling method, we investigated vaccine attitudes and VH among RA patients. The questionnaire developed by the investigators was validated by two public health experts and one senior rheumatologist. It covered sociodemographics, disease-related variables, vaccination attitudes, and willingness, etc. We employed Chi-squared and regression analyses to identify factors associated with VH toward COVID-19 vaccination. RESULTS: A total of 184 RA patients were enrolled in the survey, with 113 (61.41%) expressing unwillingness to be vaccinated. The Chi-squared test revealed significant differences in employment status and related systemic damage (p < 0.05). Among the unvaccinated RA patients, 71.68% believed COVID-19 vaccination might impact their disease. Binary and multicollinearity logistic regression analyses showed that the acute stage of RA (p < 0.001, OR = -3.165, 95% CI: 0.035 - 0.164) and fear of disease development caused by drug discontinuation during vaccination (p < 0.001, OR = -3.591, 95% CI: 0.005 - 0.157) were the restricting factors influencing the COVID-19 vaccine inoculation rate in RA patients. CONCLUSIONS: The COVID-19 vaccination rate among RA patients in China is low due to limited knowledge, misconceptions, and insufficient promotion. Boosting confidence and understanding of the vaccine's effectiveness and safety is crucial to improve vaccination success.

[Efficacy of transcatheter pulmonary valve perforation in neonates with pulmonary atresia with intact ventricular septum].

Objective: To explore the efficacy and safety of transcatheter pulmonary valve perforation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The clinical data on surgical treatment and follow-up in 16 patients with PA-IVS who underwent transcatheter pulmonary valve perforation in Women and Children's Hospital, Qingdao University from October 2018 to October 2021 were analyzed retrospectively. The right ventricular systolic pressure and percutaneous oxygen saturation (SpO2) were compared before and after operation. In addition, the SpO2 and echocardiographic data at preoperative and the last follow-up were compared. Comparisons between groups were performed using paired-samples t test. Results: Among the 16 patients (10 males and 6 females) with the age at operation of 19 (14, 26) days, 12 cases underwent transcatheter pulmonary valve perforation successfully, 2 cases were transferred to surgery department for open-heart pulmonary valvulotomy, and the remaining 2 cases were transmitted to surgery department for transthoracic pulmonary valve perforation. The age at operation of the 12 patients who underwent transcatheter pulmonary valve perforation was 18 (14, 27) days, and the weight was (3.6±0.4) kg. The immediate postoperative right ventricular systolic pressure decreased significantly ((57±16) vs. (95±19) mmHg (1 mmHg=0.133 kPa), t=7.49, P<0.001), and the postoperative SpO2 was improved effectively (0.90±0.48 vs.0.75±0.09, t=-5.61, P<0.001). The follow-up time was 22 (7, 33) months for 12 patients who underwent transcatheter pulmonary valve perforation successfully. At the last follow-up, the ratio of right to left ventricular transverse diameter was significantly higher than that before operative (0.55±0.05 vs. 0.45±0.05, t=-3.27,P=0.007). Furthermore, the Z-scores of pulmonary valvular diameter (-0.78±0.23 vs. -1.73±0.56, t=-8.52, P<0.001) and the tricuspid valvular diameter (-0.52±0.12 vs. -1.46±0.38, t=-10.40, P<0.001) were all significantly higher than preoperative data. At last, all the patients achieved biventricular circulation without death or major complications. Conclusion: Transcatheter pulmonary valve perforation is a safe and effective therapy for neonatal PA-IVS, and its curative effect has been confirmed by the medium follow-up data.

A minimized and efficient low temperature loading device for indentation.

A minimized and efficient low temperature loading device cooling with Peltier coolers for indentation test is developed. Both specimen and indentation tip are immersed in 50% methanol-water solution, totally eliminating the contact thermal drift problem. Low temperature indentation tests down to 253.8 K can be realized within 10 min. The size of the device is miniaturized within 50 × 40 × 30 mm3, and no vacuum environment is required. Monocrystalline copper is tested to perform the feasibility of the device. Based on the simple structure and stable experimental effect, the developed device can be integrated into various types of current indentation devices to attach low temperature testing ability.

[Progress in screening and follow-up studies of pulmonary ground glass nodules].

With the wide application of high-resolution chest CT in health check-up, the ground glass nodule(GGN) has been increasingly detected. GGNs have a complex etiology and image features, which can develop fast or very slowly. Therefore, whether to follow up or to resect it is usually very difficult to be determined. Overdiagnosis or overtreatment frequently happens. According to the development of GGNs, the process can be clinically divided into four stages: biological onset stage (pre-detection stage), observational stage, clinical treatment stage and postoperative follow-up stage. This review summarizes the progress on the natural development process, imaging monitoring and differentiation, the optimal time of surgical treatment for GGNs based on the decision of multidisciplinary team. This revie wmay be helpful for clinicians to understand the rule of GGN development in the follow-up, and find an optimal time to give surgical intervention for improving the prognosis of and life quality of the GGN patients.

[Evaluation of papilledema and visual improvement in patients with idiopathic intracranial hypertension after venous sinus stenting].

Objective: To evaluate the improvement of papilledema and visual acuities in patients with idiopathic intracranial hypertension (IIH) after venous sinus stenting. Methods: The clinical data of 8 IIH patients who met the inclusion criteria underwent venous sinus stenting between January 2013 and December 2016 at Department of Neurosurgery, Tianjin Huanhu Hospital were analyzed retrospectively. There were 6 females and 3 males,aged (32.9±14.4)years (range:19 to 57 years).The thickness of the retinal nerve fiber layer (RNFL) was measured by optical coherence tomography. Fundus,visual acuity and visual field examination were performed before and after operation. If pressure gradient ≥10 mmHg(1 mmHg=0.133 kPa) across the venous stenosis was indicated by intraoperative pressure measurement,the patient would be treated with venous sinus stenting. Intracranial pressure was measured by lumbar puncture 3 to 7 days after operation. RNFL thickness and eye examination were detected 6 months after surgery. CT venogram was used to observe the sinus venous conditions. Paired t test was used to compare the data before and after surgery. Results: All the 8 patients underwent venous sinus stenting successfully. The mean pressure gradient across the venous stenosis was reduced from (24±9.2) mmHg to (2.6±2.0) mmHg (t=8.02,P<0.01). Intracranial pressure decreased from preoperative (41.4±12.7) cmH2O(1 cmH2O=0.098 kPa) to postoperative (12.9±3.3) cmH2O (t=7.08, P<0.01). The RNFL thickness decreased from (275.3±68.3)µm to (131.4±31.8)µm(t=5.80,P<0.05) 6 months after surgery and the baseline visual acuity was improved from(M(QR))0.24 (0.25) to 0.65 (0.23)(Z=-2.52,P<0.05).Papilledema was significantly improved in 6 patients,and no significant change in 2 patients. CT venogram indicated adjacent stent restenosis in 1 patient. Conclusion: Venous sinus stenting can effectively improve papilledema and visual acuity caused by IIH.

[Correlation between early eeg dual-frequency index monitoring combined with lactic acid clearance rate and delayed encephalopathy with acute severe carbon monoxide poisoning].

Objective: To analyze the correlation and predictive value between early BIS monitoring combined with lactic acid resolution (LCR) and delayed encephalopathy with acute severe carbon monoxide poisoning (ASCMP) . Methods: Select 96 cases of our hospital ASCMP patients were analyzed retrospectively in March 2020, and follow-up of 60 days, according to the outcome in patients with acute carbon monoxide poisoning (DEACMP) delayed encephalopathy group with good prognosis, compare two groups of general information, admission BIS average 24 h and 24 h after treatment the LCR, According to the 24h LCR test results, patients were divided into high LCR group (LCR>15%) and low LCR group (LCR≤15%) , analysis the BIS average, the correlation of the LCR with DEACMP and both individual and joint of DEACMP predictive value, Comparing clinical data of patients with high LCR and low LCR. Results: The mean BIS value of the DEACMP group 24 hours after admission was significantly lower than that of the group with good prognosis (P< 0.05) . LCR of DEACMP group was significantly lower than that of the group with good prognosis after 24 h treatment (P<0.05) . The prevalence of DEACMP in patients with high LCR was significantly lower than that with low LCR (P<0.01) ; In the early stage, BIS mean, LCR and DEACMP were negatively correlated (P< 0.05) , and the area under the curve predicted by BIS mean, LCR and their combination on DEACMP was 0.799, 0.847 and 0.902, respectively. Conclusion: Early BIS monitoring combined with LCR has a significant correlation with DEACMP, and the combined effect of the two is better. Early BIS combined with LCR detection can provide effective guidance for the prognosis assessment of ASCMP patients.

Target inhibition on GSK-3ß by miR-9 to modulate proliferation and apoptosis of bladder cancer cells.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Target inhibition on GSK-3ß by miR-9 to modulate proliferation and apoptosis of bladder cancer cells, by Z.-C. Dong, D. Zhang, S.-B. Wang, Z.-Q. Lin, published in Eur Rev Med Pharmacol Sci 2018; 22 (10): 3018-3026-DOI: 10.26355/eurrev_201805_15059-PMID: 29863246" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15059.

Friction properties of in vivo human skin from visualized friction testing.

Investigations on mechanical behaviors of intravital human skin are of significance in various fields. However, due to the great complexity and the individual variation of human skin, traditional experimental mechanics often fails to work in such research objects. In this study, the friction property considering the skin-uplift effect of human skin was in vivo studied experimentally and theoretically. An in situ and noninvasive friction experiment was performed in vivo on human skin, where the projected contact morphology was captured through a novel specially developed optical system. According to the contact morphology, a model taking uplift resistance into account is proposed based on Greenwood model, in which the contact area was depicted as a combination of two ellipses to better characterize the skin deformation. Moreover, since the model degrades into Greenwood model in small deformation, it can be considered as an extension from the perspective of small deformation to large deformation. Based on the model, the adhesion friction and deformation friction have been separated according to the ratio of indentation depth to probe radius. The results show that the friction property of skin varies with the indentation depth changing, and the deformation friction is positively correlated with the ratio of indentation depth to probe radius.

Effects of dietary Enteromorpha powder supplementation on productive performance, egg quality, and antioxidant performance during the late laying period in Zi geese.

This study investigated the effects of dietary Enteromorpha powder supplementation on the productive performance, egg quality, and antioxidant performance of Zi geese during the late laying period. Three hundred twelve Zi geese (1 yr old) were randomly allocated into 2 cohorts to form a control group and an experimental group (with each cohort including 6 replicates and 21 female geese and 5 male geese in each replicate). The control group was fed a basal diet, and the experimental group was fed a diet containing 3% Enteromorpha powder. The data showed that Enteromorpha powder supplementation significantly improved egg production, laying rate, average daily egg weight (P < 0.01), and egg yolk color (P < 0.05). Supplementation decreased the ADFI and feed conversion rate (P < 0.01). Compared with the control group, glutathione peroxidase (GSH-Px) activity was significantly higher in serum and ovary tissue (P < 0.05), but GSH-Px activity was lower in liver tissue (P < 0.01). Malondialdehyde was reduced in liver and ovary tissue (P < 0.05) in the Enteromorpha powder supplementation group. Meanwhile, the expression of the CAT gene was significantly upregulated in the liver (P < 0.01) in the Enteromorpha group. These results indicate that dietary Enteromorpha powder supplementation improved productive performance and reduced the level of lipid peroxidation in Zi geese during the late laying period.

MiR-130b/TNF-α/NF-κB/VEGFA loop inhibits prostate cancer angiogenesis.

BACKGROUND: Angiogenesis is a critical biological process essential for solid cancer growth and metastasis. It has been shown that microRNAs (miRNAs) play a vital role in a variety of biological processes in cancers. However, whether miR-130b is involved in prostate cancer angiogenesis remains ill-defined. METHODS: We performed the miRNA microarray to analyze miRNA expression in human prostate cancer specimens. In vitro gain-of-function assays and loss-of-function assays were conducted to explore the potential functions of miR-130b in human prostate cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether tumor necrosis factor-α (TNF-α) was a direct target of miR-130b. The Matrigel plug and tumor vascular imaging assays were performed to confirm the anti-angiogenic activity of miR-130b in nude mice. RESULTS: We found that miR-130b was one of the miRNAs being most significantly downregulated. Subsequently, we found that miR-130b expression was markedly downregulated in human prostate cancer cell lines. Down-regulation of miR-130b in prostate cancer cells significantly promoted the proliferation, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs), while ectopic expression of miR-130b blocked prostate cancer angiogenesis in vitro and in vivo. Mechanistic analyses indicated that tumor necrosis factor-α (TNF-α) was regulated by miR-130b directly. MiR-130b attenuated nuclear factor-κB (NF-κB) signaling and its downstream gene vascular endothelial growth factor-A (VEGFA) by directly inhibiting TNF-α expression. Additionally, subsequent investigations identified that the ectopic level of VEGFA markedly abrogated the anti-angiogenic effect induced by miR-130b. Interestingly, VEGFA could in turn decrease the expression of miR-130b, thus forming a negative feedback loop that drives the angiogenesis of prostate cancer. CONCLUSION: These findings show that miR-130b/TNF-α/NF-κB/VEGFA feedback loop is significantly correlated with angiogenesis in prostate cancer and miR-130b could be regarded as potential therapeutic target for prostate cancer anti-angiogenesis treatment.

[MicroRNA-26a-5p targets Wnt5a to regulate osteogenic differentiation of human periodontal ligament stem cell from inflammatory microenvironment].

Objective: To investigate the effect of microRNA-26a-5p on osteogenic differentiation of human periodontal ligament stem cells (hPDLSC) and its related mechanisms. Methods: hPDLSC in periodontal tissues from healthy adults and hPDLSC from periodontitis patients (PPDLSC) were isolated and cultured in vitro, respectively. The PPDLSC were divided into Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups. Group Ⅰ is control group, and the other four groups were transiently transfected with miR-NC, miR-26a-5p, antimiR-NC and antimiR-26a-5p lentiviral vectors, respectively. The osteogenic differentiation abilities of the cells in vitro were determined by alizarin red staining, alkaline phosphatase (ALP) activity assay and real-time quantitative PCR (qPCR). Totally 40 male mice (6-weeks) were equally divided into five groups with 8 mice in each group. The PPDLSCs cells (1×10(7)/ml) in Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups, which adhered to hydroxyapatine-tricalcium phosphate (HA-TCP), were implanted into the nude mice subcutaneously and the animal models were constructed to analyze the effect of miR-26a-5p on the osteogenic differentiation of PPDLSCs in vivo. PPDLSCs were divided into A, B, C, D groups, and transfected with miR-26a-5p+Wnt5a-Wt, miR-NC+Wnt5a-Wt, miR-26a-5p+Wnt5a-Mut and miR-NC+Wnt5a-Mut in each of the above mentioned 5 groups, respectively. The luciferase activity assay was used to detect the relative luciferase in A, B, C and D groups to analyze the targeting relationship between miR-26a-5p and Wnt5a. Osteogenic differentiation related proteins expression were analyzed by western blotting. Results: hPDLSC and PPDLSC were observed consistent with the characteristics of mesenchymal stem cells and had osteogenic differentiation ability in vitro. Compared with hPDLSC [(89.87±8.12)%], the osteogenic capacity of PPDLSC [(31.46±6.56)%] was significantly lower (P<0.05). The ALP activity (1.88±0.59), calcified nodules (79.88±5.92), the expression of the osteogenic differentiation markers Runt-related transcription factor 2 (Runx2) (2.40±0.70), ALP (2.10±0.60) and osteocalcin (3.00±0.90) mRNA in the PPDLSC from Group Ⅲ were significantly higher in comparison with the control group [(0.88±0.34), (29.69±2.65), (1.30±0.30), (0.09±0.25), (1.71±0.50)], while those from Group Ⅴ[(0.44±0.07), (14.83±3.05), (0.50±0.11), (0.30±0.08) and (0.80±0.17)] were significantly lower (P<0.05). In vivo studies in nude mice showed that the proportion of the osteogenic region [(34.96±5.65)%] in the miR-26a-5p group was significantly increased in comparison with the control group [(23.28±3.03)%], while in the antimiR-26a-5p group [(8.02±2.27)%] was significantly lower (P<0.05). The luciferase activity of the Group A (0.46±0.06) was significantly lower than Group B (3.46±0.45) (P<0.05). Compared with the control group, the expression levels of Wnt5a protein, calmodulin kinase Ⅱ and protein kinase C proteins in the Group Ⅲ were significantly decreased, while those in the GroupⅤ were significantly increased (P<0.05). Conclusions: MicroRNA-26a-5p could promote osteogenic differentiation of PPDLSC in vivo and in vitro, and its mechanism might be inhibiting the activation of Wnt/Ca(2+) signaling pathway by targeting Wnt5a.

[Significance of intestinal fatty acid binding protein in evaluation of intestinal barrier dysfunction of mice at early stage of severe burn injury].

Objective: To investigate the significance of intestinal fatty acid binding protein (IFABP) in the evaluation of intestinal barrier dysfunction of mice at the early stage of severe burn injury. Methods: Thirty-six 8-week-old C57BL/6 male mice were collected and divided into normal control group (n=6) and scald group (n=30) according to random number table. Back of each mouse in scald group was placed into hot water of 90 ℃ for 10 s, causing full-thickness scald (hereinafter refer to as burn) of 30% total body surface area, while mice in normal control group were not inflicted with burns. Six mice in normal control group were taken, and 6 mice in scald group at 1, 2, 6, 12, and 24 h post injury were taken respectively. The portal vein blood of each mouse was extracted and the plasma was separated to measure intestinal permeability with fluorescin isothiocyanate-dextran fluorescence probe tracing method and plasma IFABP content by enzyme-linked immunosorbent assay. The distal ileum tissue of mice in normal control group and scald group at each time point post injury was collected to observe the morphology of the intestinal mucosa tissue by hematoxylin-eosin staining. Data were processed with one-way analysis of variance and Student-Newman-Keuls test, and pearson correlation test was used to analyze the correlation between intestinal permeability and plasma IFABP content of burned mice. Results: (1) At 1, 2, 6, 12, and 24 h post injury, the intestinal permeability of mice in scald group was 2.7±0.8, 5.4±2.5, 7.3±4.2, 12.4±6.1, 1.4±0.7, respectively, obviously higher than 1.0±0.4 of normal control group (P<0.05 or P<0.01). The intestinal permeability of mice in scald group showed an increasing trend post injury, reaching the peak at 12 h post injury, and rapidly falling back at 24 h post injury. (2) At 1, 2, 6, 12, and 24 h post injury, the plasma IFABP content of mice in scald group was (64±11), (59±12), (76±18), (111±22), and (66±10) ng/mL, obviously higher than (35±8) ng/mL in normal control group (P<0.05 or P<0.01). The plasma IFABP content of mice in scald group showed an increasing trend post injury, reaching the peak at 12 h post injury, and rapidly decreasing at 24 h post injury. (3) Uniform thickness of mucosa, intact epithelia, regularly arranged villi, and no inflammatory cell infiltration were observed in ileum of mice in normal control group. In ileum of mice in scald group, shortened villi of mucosa with different degrees, edema of lamina propria, and infiltration of neutrophils were observed at 1 and 2 h post injury; obviously damaged and partially exfoliated ileal mucosa, disorderly arranged and broken villi, degenerated and necrotic epithelial cells, dilated central lacteal, and infiltration of lymphocytes and neutrophils were observed at 6 and 12 h post injury; the damage of ileal mucosa was alleviated, and basically intact epithelia, dilated central lacteal, and infiltration of inflammatory cells were observed at 24 h post injury. (4) There was a significantly positive correlation between the intestinal permeability and the plasma IFABP content of burned mice (r=0.841, P<0.05). Conclusions: The plasma IFABP can be used as a good biological indicator for the evaluation of intestinal barrier dysfunction of mice at the early stage of severe burn injury.

MiR-592 functions as a tumor suppressor in acute myeloid leukemia by targeting ROCK1 and predicts patients' prognosis.

OBJECTIVE: Dysregulation of miR-592 has been reported in several tumors. However, its role in acute myeloid leukemia (AML) remains unknown. The present study aimed at investigating the expression pattern and biological function of miR-592 in AML and to elucidate the mechanism involved. PATIENTS AND METHODS: qRT-PCR was used to analyze the expression of miR-592 in bone marrow and serum obtained from AML patients and healthy controls. The associations between serum miR-592 expression and clinical features and prognosis of AML patients were statistically analyzed. Then we detected the effect of miR-592 on proliferation, metastasis and apoptosis by CCK-8 assay, Transwell assays and flow cytometry, respectively. Dual-luciferase reporter assays were performed to validate the regulation of a putative target of miR-592. Rescue experiments were performed to confirm whether ROCK1 was a direct and functional target of miR-592 in AML. RESULTS: We found that the expression level of miR-592 was significantly lower in AML patients and AML cell lines. Low expression of serum miR-592 was associated with advanced French-American-British classification, cytogenetics and poor prognosis. Multivariate analysis confirmed that serum miR-592 expression was an independent prognostic factor for AML patients. Functionally, overexpression of miR-592 suppressed AML cell growth and metastasis, and promoted apoptosis. Further mechanistic investigation showed ROCK1 was a direct target gene of miR-592. Finally, ROCK1 overexpression rescued the effect of miR-592-mediated AML cell proliferation and metastasis. CONCLUSIONS: These findings suggest that miR-592 acted as a tumor suppressor by targeting ROCK1 and may serve as a potential biomarker in AML.

[Effects of different doses of dopamine on organ function of rats at early stage of severe scald].

Objective: To explore the effects of different doses of dopamine on organ function of rats at early stage of severe scald. Methods: Thirty-two male Wistar rats aged 8 to 12 weeks were divided into sham injury (SI) group, simple resuscitation (SR) group, small dose (SD) group, and moderate dose (MD) group according to the random number table, with 8 rats in each group. After rats in the 4 groups were performed cardiac catheterization, rats in group SI were sham injured on the back by immersing in 37 ℃ warm water for 18 s, and rats in the other 3 groups were inflicted with 30% total body surface area (TBSA) full-thickness scald on the back by immersing in 97 ℃ hot water for 18 s. Rats in group SI were not treated after the injury, while rats in the other 3 groups were performed fluid resuscitation for 24 h through jugular vein catheter with micro syringe pump according to the Parkland formula. They were given 4.0 mL·kg(-1)·% TBSA(-1) normal saline during the first 24 h, of which they were given half of the total amount for the first 8 h, and they were given half of the total amount for the second and third 8 h. Rats in group SR were infused normal saline only, while rats in group SD and group MD were infused normal saline+ 1.25 µg·kg(-1)·min(-1)dopamine and normal saline+ 6.00 µg·kg(-1)·min(-1) dopamine respectively. Volume of 0.5 mL venous blood of all rats were taken through the cardiac catheter with serum separated at post injury hour (PIH) 1, 3, 6, 12, and 24. Serum content of cardiac troponin I (cTnI) was determined by enzyme-linked immunosorbent assay; serum content of diamine oxidase (DAO) was detected by ultraviolet spectrophotometer; serum content of ß(2)-microglobulin (ß(2)-MG) was determined by latex-enhanced immunoturbidimetric assay; serum content of total bile acid (TBA) was determined by enzyme colorimetry; serum content of lactic acid, malondialdehyde, and myeloperoxidase (MPO) was determined by ultraviolet spectrophotometer. Data were processed with analysis of variance for repeated measurement, one-way analysis of variance, least significant difference test, and Bonferroni correction. Results: (1) At PIH 1, 3, 6, 12, and 24, serum content of cTnI of rats in group SR, group SD, and group MD [(2.69±0.19), (3.04±0.19), (4.96±0.25), (6.88±0.28), (4.75±0.31) µg/L, (2.70±0.14), (3.08±0.13), (5.06±0.19), (7.11±0.21), (4.89±0.16) µg/L, (2.18±0.14), (2.54±0.09), (3.97±0.14), (5.46±0.34), (3.32±0.33) µg/L] were higher than that in group SI [(1.70±0.08), (1.70±0.08), (1.69±0.11), (1.69±0.08), (1.70±0.08) µg/L, P<0.05], serum content of cTnI of rats in group SR and group SD was similar (P>0.05), and serum content of cTnI of rats in group MD was lower than that in group SR and group SD (P<0.05). (2) At PIH 1 to 24, serum content of DAO of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of DAO of rats in group SR and group MD was similar (P>0.05), and serum content of DAO of rats in group SD was lower than that in group SR and group MD (P<0.05). (3) At PIH 1 to 24, serum content of ß(2)-MG of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of ß(2)-MG of rats in group SR and group MD was similar (P>0.05), and serum content of ß(2)-MG of rats in group SD was lower than that in group SR and group MD (P<0.05). (4) At PIH 1 to 24, serum content of TBA of rats in group SR, group SD, and group MD was similar (P>0.05) and higher than that in group SI (P<0.05). (5) At PIH 1 to 24, serum content of lactic acid of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of lactic acid of rats in group SR and group MD was similar (P>0.05), and serum content of lactic acid of rats in group SD was lower than that in group SR and group MD (P<0.05). (6) At PIH 1 to 24, serum content of malondialdehyde and MPO of rats in group SR, group SD, and group MD was higher than that in group SI (P<0.05), serum content of malondialdehyde and MPO of rats in group SR and group MD was similar (P>0.05), and serum content of malondialdehyde and MPO of rats in group SD was significantly lower than that in group SR and group MD (P<0.05). Conclusions: With effective liquid recovery, dopamine of MD can improve early cardiac function of rats with severe scald, while dopamine of SD can alleviate tissue ischemia and hypoxia, reduce oxygen free radical damage in internal organs, and improve functions of intestine and kidney.

In vivo adhesive behavior of human facial skin by a modified indentation test.

A better understanding of the adhesive behavior of human facial skin is important for dermatological or cosmetic applications. For their in vivo experimental characterization and analysis, the indentation test is an effective and widely used method. In this study, our independently developed transparent indenter and curved surface optical imaging technique are improved, by which the contact area of facial skin can be in vivo and in situ obtained during an indentation test. Thanks to the modified indentation technique, the real contact radii of human facial skin under different conditions (normal, as-moistened, moistened after 30 min) are obtained, and their adhesive behavior is studied. Moreover, we modify the classical elastic adhesion theory (JKR theory) based on the Neo-hookean model considering the fact that the hyperelastic model is usually more appropriate for skin research. It is evidenced that the adhesion properties highly influence the contact area as well as the adhesive force/energy, and our modified hyperelastic adhesion theoretical model shows a better agreement with the experimental values of contact radius under each condition.

Suicide-related behaviours in schizophrenia in China: a comprehensive meta-analysis.

AIMS: Suicide-related behaviours are common in schizophrenia and are significantly associated with premature death. The objective of this meta-analysis study was to estimate the pooled prevalence of suicide-related behaviours in schizophrenia patients in China. METHODS: The relevant literature was searched systematically via the relevant electronic databases (PubMed, Embase, PsycINFO, Chinese National Knowledge Infrastructure, Wanfang Databases and Chinese Biological Medical Literature Database) from their inception until 14 September 2016. Only original studies that reported the prevalence of suicide-related behaviours including suicidal ideation (SI), suicide plan, suicide attempt (SA) and completed suicide were selected. RESULTS: Nineteen articles met the inclusion criteria and were analysed. The pooled lifetime prevalence of SI and SA were 25.8% (95% CI 14.7-41.1%) and 14.6% (95% CI 9.1-22.8%), respectively. The 1-month prevalence of SI was 22.0% (95% CI 18.2-26.4%). Subgroup analyses of lifetime SI and SA showed that gender, sample size, survey year, study location and source of patients have no significant mediating effects on the results. CONCLUSIONS: Suicide-related behaviours are common in Chinese schizophrenia patients. Due to the high mortality risk, regular screening and effective suicide prevention programmes are warranted.

[Airway epithelial ATG5 suppresses asthmatic inflammation in mice].

Objective: To explore the role and mechanisms of airway epithelium-localized ATG5 in asthmatic airway injury and inflammation. Methods: CC10-rtTA/(tetO)7-cre-ATG5(f/f)(atg5(△/△)) mice and atg5(+/+) mice were randomly assigned to control and asthma groups, respectively. Mice of the asthma group were treated with house dust mite extract (HDM), and allergic inflammation, mucus hyperproduction, and markers of autophagy, apoptosis, and necroptosis were examined. Results: Airway epithelium-specific ATG5 deficiency significantly increased the number of BALF total inflammatory cells (171.25±41.50) and eosinophils (114.54±19.61), compared with the control asthma group (42.64±8.72) (P<0.01) and (18.71±7.54) (P<0.01), respectively. Histological analyses showed that airway inflammation deteriorated significantly in atg5(△/△) asthma group (2.00±0.45) compared to atg5(+/+) group (1.23±0.26) (P<0.01). Meanwhile, Th2-related cytokines and mucus production were increased in atg5(△/△) asthma group. These mice displayed enhanced necroptosis markers RIP and RIP3, while the autophagic protein LC3B and apoptotic markers caspase-9 and -3 were not significantly changed. Conclusion: Airway epithelium-localized ATG5 suppresses allergic airway inflammation, likely via modulation of necroptosis, while independent of autophagy and apoptosis.