Retraction Note: LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression.

The article "LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression", by R.-F. Zhang, J.-W. Liu, S.-P. Yu, D. Sun, X.-H. Wang, J.-S. Fu, Z. Xie, published in Eur Rev Med Pharmacol Sci 2019; 23 (16): 6774-6782-DOI: 10.26355/eurrev_201908_18715-PMID: 31486475 has been retracted by the authors for the following reasons: - The data presented in the manuscript require further validation, which may affect the results. After careful consideration, we have decided to withdraw it to ensure its reliability and reproducibility. All authors concur with this decision. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18715.

[Screening for asymptomatic atrial fibrillation in elder community populations in Dalian: a single center study].

Objective: We aimed to determine the epidemiological characteristics of asymptomatic AF in elder community population (≥65 years old) to analyze the detection rate of different screening methods. Methods: The study was a prospective cohort study. The elder (≥65 years old) residents who voluntarily participated in free physical examination in Dalian community were selected. The participants were randomly divided into screening group (including intensive screening group and single screening group) and control group. The control group received interrogation, medical history collection and routine 12-lead electrocardiogram (ECG) examination. Screening group received an additional single-lead ambulatory ECG equipment worn for 5-7 days. Intensive screening group received two equal-length wearings in 2020 and 2021 respectively, while one screening group only wore once in 2020. Results: Finally 3 340 residents ((70.7±5.0) years old) which consisted of 1 488 males (44.55%) were enrolled. There were 1 945 residents in screening group, including 859 in intensive screening group and 1 086 in one-time screening group. The control group included 1 395 people. Detection rate of asymptomatic AF was significantly higher in screening group than control group (79(4.06%) vs. 24(1.72%), P<0.001). Higher detection rate was found in screening group than control group in AF risk factors (1 or 2-3) subgroups and CHA2DS2-VASc score (2-3 or≥4) subgroups (P<0.05). Additionally, no difference was found between intensive screening group and single screening group (42(4.89%) vs. 37(3.41%), P=0.100). Intensive screening increased detection rate (7(6.93%) vs. 1(0.58%), P=0.009) only in residents those with low thrombosis risk (CHA2DS2-VaSc<2). Conclusions: Screening in elderly (≥65 years old) can significantly improve the detection rate of asymptomatic AF by wearing single lead dynamic ECG device. The rate increased significantly with the increase of risk factors associated with AF by single screening. In addition, repeat screening of the same method may only improve detection rates in the group with low risk thrombotic scores and non-combination of AF risk factors.Screening methods that are appropriate for different populations may require further exploration.

[Analysis of chromosome aberrations in peripheral blood lymphocyte of medical radiation workers in a tertiary hospital].

Objective: To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors. Methods: From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed. Results: The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group (Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ(2)=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ(2)=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ(2)=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant (P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ(2)=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages (P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion: Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.

Ferroptosis in neurodegenerative diseases: inhibitors as promising candidate mitigators.

OBJECTIVE: Ferroptosis is a new form of iron-dependent programmed cell death, characterized by intracellular iron overload and lipid peroxidation. Several studies have revealed that ferroptosis is associated with the occurrence and development of various neurodegenerative diseases (NDs). Therefore, this paper reviews the mechanism and related genes of ferroptosis, focusing on the research of antiferroptosis drugs in NDs to provide theoretical support for future experimental research and clinical application. MATERIALS AND METHODS: This work focuses on ferroptosis, and the authors searched the literature on PubMed related to ferroptosis using the keywords "neurodegenerative diseases" and "neurons". All articles were from August 2022 and earlier, excluding irrelevant or retracted articles, and articles from the last five years were used as the main inclusion criteria. RESULTS: After collection and summary, it was found that ferroptosis in NDs was not only related to iron metabolism, lipid metabolism, and amino acid metabolism but also related to genes such as Nrf2, FSP1, VDACs, and p53. We also summarized drugs that inhibited ferroptosis in NDs and classified them according to their mechanism of action. CONCLUSIONS: Ferroptosis was involved in the progression of NDs through its production mechanism and related genes. Targeting ferroptosis might be a new strategy for treating NDs.

[Epidemiological investigation on allergic diseases related to animal dander of cats, dogs and horses].

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ2=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ2=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.

[Phenotype and genetic mutation analysis of an inherited protein C deficiency pedigree].

Objective: A phenotypic and gene mutation study was carried out to investigate the molecular mechanism of inherited protein C deficiency in a family with the disorder. Methods: The proband was a 21-year-old male who was admitted to hospital due to swelling of the left lower limb for 3 months and hemoptysis with chest tightness for more than 1 week. The clinical diagnosis was pulmonary embolism and deep vein thrombosis of the left lower limb. Plasma protein C activity, protein S activity and antithrombin Ⅲ activity were detected in the patient and their family members. Whole exon sequencing was used to analyze a total of 199 genes associated with thrombus susceptibility of the patient. After the mutation was found and Sanger sequencing was used to verify whether the family members carried the same gene mutations as the patient. The conservation of amino acid mutation sites was analyzed by using the software ClustalX-2.1-win. The damage of mutations to protein function was analyzed by PROVEAN and PolyPhen-2 online bioinformatics software. Finally, PyMOL 2.3 software was used to analyze the protein model. Results: The patient and four family members all had the identical heterozygous missense mutation c.1019 C>T (p. Thr340Met) in exon 9 of the protein C gene, resulting in various degrees of protein C deficiency. The Thr340 amino acid was discovered to be poorly conserved in seven homologous species after investigation with the clustalx-2.1-win software. P. Thr340Met was found to be a detrimental mutation by both PROVEAN and PolyPhen-2 online bioinformatics program. The mutation of Thr340 to Met340 caused the hydrogen bond between Thr340 and Gln226 to dissolve, changing the spatial arrangement of protein C, which might be the main explanation for the lower protein C activity, according to the protein model. Conclusions: Protein C deficiency in this family was caused by a hybrid missense mutation C. 1019 C>T (p. Thr340Met). Protein C deficiency may present in varying severity among mutation carriers at the same locus of the protein C gene. Whole-exome sequencing may be considered in young patients with spontaneous venous thromboembolism, even if there is no relevant family history.

[Roles of interleukin-6/signal transduction and activator of transcription 3 pathway and ß-catenin in mechanical stress-induced hypertrophic scar formation in mice].

Objective: To establish mechanical stress-induced hypertrophic scar mouse models, and to examine the roles of interleukin-6/signal transduction and activator of transcription 3 (IL-6/STAT3) pathway and ß-catenin. Methods: The experimental research method was used. Sixteen female C57/BL6 mice of 12-week-old were collected and two straight full-thickness skin incisions of 2 cm in length were inflicted on the back of each mouse. On the fourth day post injury, the two wounds on the back of each mouse were divided into mechanical traction group and blank control group according to the random number table method, with 16 wounds in each group. The wounds in mechanical traction group were given continuous mechanical traction for 14 days, while the wounds in blank control group were given no treatment. After 14 days of mechanical traction for wounds in mechanical traction group, the appearances of the scar tissue in wounds of 2 groups were visually observed, and the areas of scars were measured; the morphological changes of the scar tissue in wounds of 2 groups were observed by hematoxylin-eosin staining, and the cross-sectional areas of scars were measured; the content of IL-6 in supernatant of the scar tissue in wounds of 2 groups was detected by enzyme-linked immunosorbent assay; the protein expression of phosphorylated STAT3 (p-STAT3) of the scar tissue in wounds of 2 groups was detected by Western blotting; and the expression of ß-catenin of the scar tissue in wounds of 2 groups was detected by immunohistochemistry. Data were statistically analyzed with paired sample t test. Results: Red hairless area similar to human scar tissue formed in wounds of mechanical traction group after 14 days of mechanical traction, with large area of scar, thickened local area, hardened texture, and some even slightly raised, while scar in wounds of blank control group was linear and not obvious. After 14 days of mechanical traction for wounds in mechanical traction group, the scar area of wounds in mechanical traction group was (5.65±0.95) mm2, which was significantly larger than (1.07±0.28) mm2 in blank control group (t=26.333, P<0.01). After 14 days of mechanical traction for wounds in mechanical traction group, the skin appendages of scar tissue were absent, and the dermis hyperplasia was active and obviously thickened, while skin appendages of scar tissue of wounds in blank control group were still present, with unconspicuous dermis hyperplasia; the cross-sectional area of scar in wounds of mechanical traction group was (0.82±0.23) mm2, which was significantly larger than (0.29±0.07) mm2 of blank control group (t=8.879, P<0.01). After 14 days of mechanical traction for wounds in mechanical traction group, the content of IL-6 in the supernatant of scar tissue and the protein expression of p-STAT3 in scar tissue of wounds in mechanical traction group were significantly higher than those in blank control group (t=37.552, 25.863, P<0.01). The expression of ß-catenin was high in the scar tissue of wounds in mechanical traction group after 14 days of mechanical traction, while that in blank control group was low. Conclusions: The study successfully establishes mechanical stress-induced hypertrophic scar mouse models. Mechanical stress can participate in wound healing and induce scar hyperplasia of mice wounds through continuous or overexpression of IL-6/STAT3 pathway, and ß-catenin can also promote the formation of hypertrophic scar.

Urinary biomarkers of early renal injury in antiretroviral-naïve HIV-positive persons in Shanghai, China: comparison with the general population.

OBJECTIVES: People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. METHODS: We performed a cross-sectional study of 166 antiretroviral-naïve PLWH and 99 HIV-negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2 . We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. RESULTS: Eighty-three pairs were successfully matched based on PSM. Compared with the HIV-negative group, the HIV-positive group had higher ratios of N-acetyl-ß-D-glucosaminidase (NAG) to urine creatinine (UCr), alpha1-microglobulin (α1-M) to UCr, kidney injury marker-1 (KIM-1) to UCr, neutrophil gelatinase-associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm-Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs  = 0.32; P < 0.001) and α1-M:UCr (rs  = 0.24; P = 0.002) ratios, and negative correlations were observed between CD4 cell count and NAG:UCr (rs  = -0.34; P < 0.001), KIM-1:UCr (rs  = -0.16; P = 0.042) and α1-M:UCr (rs  = -0.36; P < 0.001) ratios. In multivariate linear regression analyses, older age, lower total cholesterol and higher HIV RNA were independently associated with higher NAG:UCr; older age, lower total cholesterol and lower CD4 cell count were independently associated with higher α1-M:UCr. CONCLUSIONS: In comparioson with HIV-negative participants, PLWH were more likely to have tubular injury. Early antiretroviral treatment might mitigate the development of kidney injury.

A retrospective cohort study of early mortality among patients with HIV/TB co-infection in Shanghai municipality.

OBJECTIVES: Tuberculosis (TB) is the most common and fatal opportunistic co-infection among HIV-infected individuals. While TB-associated mortality predominantly occurs in the first 90 days after admission, such a correlation remains unclear in HIV/TB co-infected patients. Thus, we aimed to investigate the 90-day mortality and associated risk factors among HIV/TB co-infected patients in China. METHODS: Adult patients with HIV and a newly confirmed TB diagnosis admitted to the Shanghai Public Health Clinical Center between September 2009 and August 2017 were enrolled. Clinical and laboratory characteristics, key treatments and outcomes were collected retrospectively. The associations between different factors and early mortality were analysed. RESULTS: Of the 485 laboratory-confirmed HIV/TB patients [median (range) age = 39 (19-79) years], 413 (85.15%) were male. Diagnosis was confirmed by culture, pathology and acid-fast bacilli smear alone in 362 (74.6%), 6 (1.2%) and 117 (24.1%) patients, respectively. Multiple drug-/rifampin-resistant TB was detected in 21 (5.8%) of the 367 patients with a positive culture. Rifampin or rifabutin was administered to 402 (82.9%) patients. Additionally, 66 (13.6%) and 86 (17.7%) died within 90 days and 1 year of admission, respectively. Of the 64 TB-related deaths, 59 (92.2%) occurred within 90 days of admission. In Cox regression, central nervous system (CNS) TB [odds ratio (OR) = 2.49, 95% confidence interval (CI): 1.46-4.23, P < 0.001], no antiretroviral therapy (ART) within 3 months after admission (OR = 11, 95% CI: 6.4-18.9, P < 0.001), and plasma albumin level < 25 g/L (OR = 1.91, 95% CI: 1.07-3.40, P = 0.021) were associated with early death. CONCLUSIONS: Tuberculosis co-infection was prevalent and fatal in HIV-infected patients, with most deaths occurring within 90 days of admission. Early mortality was associated with CNS-TB, no ART, and serum albumin level < 25 g/L.

Protective effects of miRNA-589 on cerebral ischemia-reperfusion injury.

To uncover the potential influence of microRNA-589 (miRNA-589) on cerebral ischemia-reperfusion injury (IRI) and the underlying mechanism, BV2 cells were stimulated by lipopolysaccharide (LPS) or conditioned medium (CM) of primary cortical neurons undergoing oxygen-glucose deprivation (OGD). Regulatory effects of miRNA-589 on the release of inflammatory factors in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The interaction between miRNA-589 and TRAF6 was finally assessed by dual-luciferase reporter gene assay. MiRNA-589 was downregulated in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD. Overexpression of miRNA-589 reduced the release of inflammatory factors in LPS or CM-induced BV2 cells. TRAF6 was verified to be the downstream gene of miRNA-589, and its level was negatively regulated by miRNA-589. MiRNA-589 is downregulated following cerebral IRI and alleviates inflammatory response through negatively regulating TRAF6.

Overexpression of ACE2 prevents hypoxia-induced pulmonary hypertension in rats by inhibiting proliferation and immigration of PASMCs.

OBJECTIVE: Imbalance of the ratio of angiotensin converting enzyme (ACE) and ACE2 may lead to pathological conditions in lung. However, its effect on hypoxia-induced pulmonary hypertension (HPH) remains unclear. Therefore, the aim of this study was to investigate the effects of ACE2 overexpression on rat primary pulmonary arterial smooth muscle cells (PASMCs) and HPH rat model. MATERIALS AND METHODS: ACE and ACE2 expression in rat PASMCs under hypoxia condition, as well as in HPH rat model, was detected. The overexpressed ACE2 gene was transfected into PASMCs by Lentiviral. Later, the proliferation and migration of PASMCs were evaluated. Meanwhile, the overexpressed ACE2 gene was transfected into rats and exposed to hypoxia for four weeks. Finally, the right ventricular systolic pressure, the right ventricular hypertrophy, and the percentage of the medial wall thickness were measured to evaluate the development of HPH. RESULTS: Imbalance of the expression of ACE/ACE2 was indicated in rat PASMCs under hypoxia condition and in the HPH rat model, respectively. The overexpression of ACE2 significantly inhibited PASMCs proliferation and migration. Moreover, the overexpressed ACE2 could significantly attenuate pulmonary hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy in HPH rat model. CONCLUSIONS: ACE2 is related to the formation of pulmonary vascular remodeling and pulmonary hypertension. Furthermore, it may prevent hypoxia-induced pulmonary hypertension by inhibiting the proliferation of PASMCs.

Synthesis and biological activities of novel trifluoromethylpyridine amide derivatives containing sulfur moieties.

A series of trifluoromethylpyridine amide derivatives containing sulfur moieties (thioether, sulfone and sulfoxide) was designed and synthesized. Their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Ralstonia solanacearum (R. solanacearum) and insecticidal activities against P. xylostella were evaluated. Notably, the half-maximal effective concentration (EC50) value of sulfone-containing compound F10 is 83 mg L-1 against Xoo, which is better than that of commercial thiodiazole copper (97 mg L-1) and bismerthiazol (112 mg L-1). Thioether-containing compounds E1, E3, E5, E6, E10, E11 and E13 showed much higher activities against R. solanacearum with the EC50 value from 40 to 78 mg L-1, which are much lower than that of thiodiazole copper (87 mg L-1) and bismerthiazol (124 mg L-1). Generally, most of the sulfone-containing compounds and sulfoxide-containing compounds showed higher activities against Xoo than that of the corresponding thioether-containing compound, but most of the thioether-containing compounds contributed higher antibacterial activities against R. solanacearum. Furthermore, title compounds E3, E11, E24 and G2 showed good insecticidal activities of 75%, 70%, 70% and 75%, respectively.

LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression.

OBJECTIVE: The aim of this study was to detect the expression of long non-coding ribonucleic acid (lncRNA) urothelial carcinoma associated 1 (UCA1) in the plasma of patients with osteoporosis (OST), and to investigate its influences on the proliferation and differentiation of osteoblasts and its mechanism. PATIENTS AND METHODS: Plasma samples were collected from 52 OST patients treated in our hospital and 30 healthy subjects receiving a physical examination, respectively. The expression level of lncRNA UCA1 in OST patients and healthy subjects were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Furthermore, osteoblast MC3T3-E1 cell lines with a stable knockout of UCA1 in mice were constructed using small-interfering RNA (siRNA). The influence of UCA1 knockout on the proliferation of osteoblasts was detected using cell counting kit-8 (CCK-8) assay. Meanwhile, the proportion of EdU-positive cells in osteoblasts of the control group and UCA1 knockout group was detected using EdU staining. Moreover, the messenger RNA (mRNA) levels of differentiation-related genes, including Runt-related transcription factor 2 (Runx2), Collagen1α1, osteoclast (OC), osteoprotegerin (OPG), osteopontin (OPN) and Osterix (OSX), were detected via RT-PCR. The protein expression level of Runx2 was detected via Western blotting. In addition, osteoblasts were cultured with a bone-derived medium for 14 d. Then, the differentiation status was detected via alizarin red staining and alkaline phosphatase staining. Finally, the expression of bone morphogenetic protein-2 (BMP-2)/(Smad1/5/8) signaling pathway was analyzed using Western blotting. RESULTS: The expression of plasma lncRNA UCA1 was significantly increased in OST patients (p<0.05). Cell experiments revealed that UCA1 siRNA intervention could significantly promote the proliferation and differentiation of osteoblast MC3T3-E1 cell lines. In addition, Western blotting showed that the pro-apoptotic effect of UCA1 might be mediated by the BMP-2/(Smad1/5/8) signaling pathway in osteoblasts. CONCLUSIONS: Inhibiting lncRNA UCA1 can promote the proliferation and differentiation of osteoblasts by activating the BMP-2/(Smad1/5/8) signaling pathway in osteoblasts. Therefore, UCA1 is expected to be a new therapeutic target for OST.

[Effect of esmolol in septic shock patients with tachycardia: a randomized clinical trial].

Objective: To investigate the effect of esmolol in septic shock patients with tachycardia. Methods: A prospective randomized controlled trial was conducted. Screening septic shock patients that admitted to Department of General Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from June 2016 to August 2017. After 24 h resuscitation therapy, 100 cases of septic shock patients with tachycardia (heart rate>100 bpm) were divided into esmolol group (n=50) and control group (n=50) with random number table. Patients in esmolol group accepted standard treatment plus esmolol injection with an initial dose of 25 mg/h. Heart rate target is 80 to 100 bpm. Patients in esmolol group continued to use esmolol for 7 days or to the day the patient left the ICU when the heart rate didn't achieve the target. Patients in control group were given standard treatment. Primary outcome was 28 d mortality. Secondary outcomes included heart rate, norepinephrine dosages, lactate level, inflammatory markers in per day during the trial; acute physiology and chronic health evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) on day 1, 3, 5, 7; length of hospital stay, length of mechanical ventilation, medication time of vasoactive agent. The data were compared with t test or rank sum test between the two groups. Results: The 28 d mortality of esmolol group and control group was 62%, 68%, respectively(χ(2)=0.529, P=0.529). Logistic regression analysis showed that primary heart rate (increase of 10 bpm, OR=1.568, 95%CI: 1.039-1.238, P=0.027), primary APACHEⅡ (OR=1.134, 95%CI: 1.026-1.239, P=0.005), integral heart rate (per 10 bpm, OR=2.207, 95%CI: 1.400-3.479, P=0.001) were independent risk factors for 28 d mortality. Compared with control group, the esmolol group had a lower heart rate on day 1-7; but over all, there was no statistically significant difference in heart rate between the two groups (P>0.05). There was no significant difference in total does of norepinephrine, lactate level, inflammatory markers, APACHE Ⅱ, SOFA, length of hospital stay between the two groups (all P>0.05). Conclusion: Tachycardia significantly increases the risk of death in patients with septic shock, esmolol may decrease the mortality by controlling heart rate.

The efficacy of trans-esophageal echocardiography in treatment of nonvalvular atrial fibrillation with left atrial appendage occlusion.

The article "The efficacy of trans-esophageal echocardiography in treatment of nonvalvular atrial fibrillation with left atrial appendage occlusion" by Y. Song, S.-C. Qin, X. Fu, Z.-M. Jiang, K. Chen, X.-L. Wang, R.-F. Zhang, Y. Liuang, R.-F. Zhang, Y. Liu, published in Eur Rev Med Pharmacol Sci 2018; 22 (16): 5335-5338 has been withdrawn.

GAS5 promotes podocyte injury in sepsis by inhibiting PTEN expression.

OBJECTIVE: To investigate the potential role of long noncoding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) in sepsis-induced podocyte injury and its underlying mechanism. MATERIALS AND METHODS: The sepsis model was established by lipopolysaccharide (LPS) induction in podocytes. The expression levels of Nephrin and GAS5 were detected by quantitative Real-time polymerase chain reaction (qRT-PCR) after LPS induction in podocytes for 12 h, 24 h and 36 h, respectively. Western blot was used to detect the expression level of Nephrin in sepsis-induced podocytes. The mRNA expressions of GAS5 and Nephrin in podocytes were detected after transfection of GAS5 siRNA. Albumin influx in podocytes after GAS5 knockdown was detected by Transwell assay. Western blot was used to detect the protein expression of Snail in sepsis after GAS5 knockdown. The target gene of GAS5 was predicted by bioinformatics analysis. QRT-PCR and Western blot were used to detect the protein and mRNA levels of PTEN (phosphatase and tensin homolog deleted on chromosome ten). Nephrin expression and the albumin inflow after PTEN knockdown were then measured. The expression of PI3K/AKT/GSK3ß was also detected after GAS5 was downregulated while PTEN was upregulated. RESULTS: LPS stimulation downregulated the mRNA expression of Nephrin in podocytes and achieved the lowest level at 24 h. The protein expression change of Nephrin was consistent with its mRNA expression. In the septic state, the albumin influx of podocytes remarkably increased, but the function of podocyte barrier was weakened. Besides, GAS5 expression decreased in a time-dependent manner in LPS-induced podocytes. After GAS5 knockdown by siRNA, Nephrin expression and the function of podocyte barrier were significantly reduced. Snail expression was also upregulated in septic state, and GAS5 knockdown increased the expressions of phosphorylated Snail and PI3K/AKT/GSK3ß. After knockdown of GAS5, the mRNA and protein levels of PTEN significantly decreased, which was contract to the expression of Snail. However, overexpression of PTEN could reverse the promotive effect of GAS5 on PI3K/AKT activation. CONCLUSIONS: GAS5 expression decreased in sepsis-induced podocyte injury, and GAS5 was involved in regulating sepsis-induced podocyte injury by reducing PTEN expression.

The efficacy of trans-esophageal echocardiography in treatment of nonvalvular atrial fibrillation with left atrial appendage occlusion.

OBJECTIVE: To investigate the efficacy of transesophageal echocardiography (TEE) in the treatment of nonvalvular atrial fibrillation with left atrial appendage (LAA) occlusion. PATIENTS AND METHODS: Forty-nine patients with nonvalvular atrial fibrillation were selected from January 2015 to December 2015 to serve as control group, and 49 patients with nonvalvular atrial fibrillation were selected from January 2016 to December 2016 to serve as observation group. Patients in both groups were treated with LAA occlusion. After surgery, patients in control group received 2D-transesophageal echocardiography (2D-TEE), while patients in observation group received 3D-TEE. LAA diameter, maximum depth, postoperative parameters, and postoperative complications were compared between two groups. RESULTS: The maximum LAA diameter can be measured from different angles in control group, and maximum depth cannot be measured in control group. No significant differences in maximum LAA diameter and maximum depth were found between two groups from different angles (p<0.05). No significant difference in left ventricular end diastolic diameter (LVEDd), left atrial diameter (LA-d), left ventricular ejection fraction (LVEF), mitral regurgitation volume (MV Reg V), E peak and pulmonary vein diastolic flow velocity (PVd) were found between those two groups (p<0.05). The overall occurrence of postoperative complications in observation group and control group were 0.00% and 12.24%, respectively, significant difference was found between those two groups (p<0.05). CONCLUSIONS: Compared with 2D-TEE, the application of 3D-TEE in treatment of nonvalvular atrial fibrillation with left atrial appendage occlusion is more conducive to the selection of the size of the reservoir, and can reduce the occurrence of postoperative complications.

Research on correlation between GALNT3 gene and osteoporosis.

OBJECTIVE: The aim of this study was to explore the correlation between GALNT3 gene and osteoporosis. PATIENTS AND METHODS: In this study, 184 cases of osteoporosis that were treated at our hospital from 2013 to 2014 were selected as research subjects in the observation group. In addition, 84 healthy people were selected as the control group from 2013 to 2014. The bone mineral density of the observation and control groups were detected by x-rays and the expression levels and differences of mRNA of the GALNT3 gene and protein in their body was detected using fluorescence quantitative polymerase chain reaction (qPCR), enzyme-linked immunoassay, and Western blotting. RESULTS: X-ray results suggest that when compared to the healthy group, bone mineral density of patients in the observation group was significantly lower than that of research subjects in the control group, with significant differences. The fluorescence qPCR results suggest that the expression levels of mRNA of the GALNT3 gene in patients with osteoporosis were significantly lower than that in the healthy group (p<0.05). Enzyme-linked immunosorbent assay (ELISA) results suggest that the expression levels of the GALNT3 gene in patients with osteoporosis (1.26±0.32) µg/L was significantly lower than that in the healthy group (12.41±0.28) µg/L, with significant differences (p<0.05). The Western blotting results agreed with the ELISA results. We also found in our research that the bone mineral density of patients with osteoporosis significantly correlated with the expression levels of the GALNT3 gene (r=0.95). CONCLUSIONS: Therefore, the GALNT3 gene significantly correlated with osteoporosis and the low expression of GALNT3 gene can promote the occurrence and deterioration of osteoporosis.

MiR-204 promotes fracture healing via enhancing cell viability of osteoblasts.

OBJECTIVE: To investigate the effects and related mechanisms of miR-204 on fracture healing. MATERIALS AND METHODS: Mouse osteoblastic cell line MC3T3-E1 was used in our experiment. Three groups were established to investigate the potential function between miR-204 and osteoblastic cells: miR-NC group (negative control), miR-204 mimics group (MC3T3-E1 cells transfected with miR-204 mimics) and miR-204 mimics + inhibitor group (MC3T3-E1 cells transfected with miR-204 mimics and inhibitor). After incubation, cell viability, activity of caspase-3, and migration ability of MC3T3-E1 cells, were measured. Further, the expression levels of Runt-related transcription factor 2 (RUNX2) and Osterix (OSX) were detected and analyzed. RESULTS: Compared with miR-NC group, the cell viability and migration ability of MC3T3-E1 cells were enhanced while the activity of caspase-3 was respectively mitigated. Besides, the expression level of RUNX2 and OSX was increased by treatment of miR-204 mimics. However, these variations of the indicators were reversed by the intervention using miR-204 inhibitor. CONCLUSIONS: We revealed the promotion effect of miR-204 on fracture healing, indicating that miR-204 could be a potential therapeutic target for the treatment of a fracture.

Low-level laser irradiation promotes the differentiation of bone marrow stromal cells into osteoblasts through the APN/Wnt/ß-catenin pathway.

OBJECTIVE: The relationship between adiponectin (APN) pathway and Wnt pathway was explored through BMSCs, and the effect of low-level laser irradiation (LLLI) on bone marrow stromal cells (BMSCs) and its mechanism were further studied. MATERIALS AND METHODS: 3-week-old Sprague-Dawley (SD) rats were selected, and mesenchymal stem cells were separately cultured and purified. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze cell proliferation. After osteogenic and adipogenic induction, cultures were conducted, respectively, cells were stained with alizarin red and oil red O. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expressions of osteogenesis-related genes, runt-related transcription factor 2 (RUNX2), and osteocalcin (OC) and those of adipogenesis-related genes, peroxisome proliferator-activated receptor-gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (c/EBPα). Western blotting was used to detect the expressions of ß-catenin in the cytoplasm and nucleus. The lentiviral expression vector of adiponectin receptors (APN-R) was constructed, and the expression of APN receptor genes was silenced. The expressions of ß-catenin in APN receptors and the nucleus within cells were detected. RESULTS: LLLI promoted the bone formation by inducing the differentiation direction of mesenchymal stem cells, increasing the number of osteoblasts in the bone marrow and inhibiting the reduction of the number of adipocytes. LLLI regulates the Wnt pathway, promotes the entry of ß-catenin into the nucleus, activates the osteogenic effect of the Wnt pathway so as to promote the bone formation of osteoblasts and inhibit bone resorption of osteoclasts. LLLI promotes the entry of ß-catenin into the nucleus and the osteogenic differentiation of BMSCs through the APN pathway. CONCLUSIONS: In summary, LLLI can promote osteogenesis and inhibit adipocytes formation, thus attenuating bone resorption of osteoclasts. The mechanism of LLLI is that it promotes the entry of ß-catenin into the nucleus and regulates the Wnt pathway and the differentiation direction of mesenchymal stem cells through the APN signal pathway, thus promoting bone formation.