Plasma miR-15b-5p, miR-338-5p, and miR-764 as Biomarkers for Hepatocellular Carcinoma.

BACKGROUND: Recently, increasing research evidence indicates that miRNA plays important roles in oncogenesis of hepatocellular carcinoma (HCC). The objective of this study was to investigate the potential of plasma miRNAs as biomarkers for HCC determination. MATERIAL AND METHODS: This trial included 4 phases: (i) miRNAs in tumor tissues were screened with a miRNA array for determining candidate miRNAs. (ii) Candidate miRNAs were measured by RT-qPCR in plasma of 10 HCC patients before and after surgery (7-10 days) for target miRNAs that displayed a pattern of postoperative decrease. (iii) Plasma levels of target miRNAs in 37 HCC patients, 29 cirrhosis patients, and 31 healthy controls were measured by RT-qPCR for determining potential biomarkers. (iv) The powers of biomarkers for differentiating HCC were validated and the correlations with clinicopathological variables of HCC patients were analyzed. RESULTS: miRNA array demonstrated an abnormal expression of 92 miRNAs in tumor tissues compared to adjacent non-tumor tissues. Of those molecules with an over-expressed level in tumor tissues and preoperative plasmas, a decrease in postoperative plasma was observed in miR-15b-5p, miR-338-5p, and miR-764. Plasma levels of these miRNAs in HCC patients were higher than in the other 2 groups (P<0.05). Receiver-operator characteristic (ROC) curve analyses suggested these plasma miRNAs could be useful biomarkers for determining HCC. miR-338-5p yielded an area under the ROC curve (AUC) of 0.799 (74.5% sensitivity and 82.8% specificity) and 0.909 (72.3% sensitivity and 99.68% specificity) to discriminate HCC patients from cirrhosis patients and healthy controls, respectively. The expression level of miR-338-5p was negatively correlated with the level of AFP (r=-0.306, P=0.036), and the expression level of miR-764 was positively correlated with the tumor size (r=0.371, P=0.01). CONCLUSIONS: Circulating miR-15b-5p, miR-338-5p, and miR-764 may be biomarkers for diagnosis of HCC.

Comparative clinical trial of Langenlianqiao oral liquid and Lianhuaqingwen capsule in the treatment of mild cases of coronavirus disease 2019 (COVID-19).

OBJECTIVE: To evaluate the clinical efficacy of Langenlianqiao (LGLQ) oral liquid treatment and provide a reference basis for the clincal treatment of coronavirus disease 2019 (COVID-19). DESIGN: An experimental clinical study was conducted on three groups with confirmed diagnoses of COVID-19. SITE: This study was conducted at Changde Hospital. PARTICIPANTS: A total of 253 patients were enrolled in this study. METHODS: The patients were divided into the LGLQ treatment group (100 cases), the Lianhuaqingwen (LHQW) treatment group (100 cases) and the placebo control group (53 cases), according to the treatment each group received. The occurrence of major clinical symptoms, the duration of symptom disappearance, the number of days in hospitalisation and the duration of infection were compared among the three groups. RESULTS: Compared with the placebo control group (10.0 [1.2] d, 9.4 [1.3] d), the duration of infection and hospitalisation effectively decreased in the LGLQ group (6.8 [0.6] d, 7.4 [0.8] d) and the LHQW group (6.8 [1.0] d, 7.3 [1.0] d). Furthermore, the incidence of fatigue in the LGLQ group (4.0%) was lower compared to the LHQW group (14.0%) and the placebo control group (15.1%), but this difference was not statistically significant (P = 0.580 for LGLQ vs. LHQW, P = 0.246 for LGLQ vs. placebo). In the treatment of cough, the LGLQ group showed a significantly different effect compared to both the LHQW group (P = 0.014) and the placebo group (P = 0.016). Additionally, for dry cough specifically, LHQW was effective in reducing its incidence compared to the placebo control group (P < 0.05), while LGLQ showed no statistically significant difference from either LHQW (P = 0.39) or the placebo group (P = 0.14). However, neither the LGLQ group nor the LHQW group showed a reduction in the duration of symptom disappearance in patients with pre-existing symptoms (P > 0.05). CONCLUSIONS: Compared with the placebo control group, the LGLQ group showed an improvement in the clinical symptoms of COVID-19 and a decrease in the duration of hospitalisation and infection, which confirmed that the LGLQ treatment had the same antiviral effect as the LHQW treatment. This may provide in-depth insights for antiviral therapy research.

ANXA2 promotes osteogenic differentiation and inhibits cellular senescence of periodontal ligament cells (PDLCs) in high glucose conditions.

Background: Periodontal ligament cells (PDLCs) are a major component of the periodontal ligament and have an important role in the regeneration of periodontal tissue and maintenance of homeostasis. High glucose can affect the activity and function of PDLCs in a variety of ways; therefore, it is particularly important to find ways to alleviate the effects of high glucose on PDLCs. Annexin A2 (ANXA2) is a calcium- and phospholipid-binding protein involved in a variety of cellular functions and processes, including cellular cytokinesis, cytophagy, migration, and proliferation. Aim: The aim of this study was to exploring whether ANXA2 attenuates the deleterious effects of high glucose on PDLCs and promotes osteogenic differentiation capacity. Methods and results: Osteogenic differentiation potential, cellular senescence, oxidative stress, and cellular autophagy were detected. Culturing PDLCs with medium containing different glucose concentrations (CTRL, 8 mM, 10 mM, 25 mM, and 40 mM) revealed that high glucose decreased the protein expression of ANXA2 (p < 0.0001). In addition, high glucose decreased the osteogenic differentiation potential of PDLCs as evidenced by decreased calcium deposition (p = 0.0003), lowered ALP activity (p = 0.0010), and a decline in the expression of osteogenesis-related genes (p = 0.0008). Moreover, ß-Galactosidase staining and expression of p16, p21 and p53 genes showed that it increased cellular senescence in PDLCs (p < 0.0001). Meanwhile high glucose increased oxidative stress in PDLCs as shown by ROS (p < 0.0001). However, these damages caused by high glucose were inhibited after the addition of 1 µM recombinant ANXA2 (rANXA2), and we found that rANXA2 enhanced autophagy in PDLCs under high glucose conditions. Conclusions and discussion: Therefore, our present study demonstrates that alterations in ANXA2 under high glucose conditions may be a factor in the decreased osteogenic differentiation potential of PDLCs. Meanwhile, ANXA2 is associated with autophagy, oxidative stress, and cellular senescence under high glucose conditions.

Discovery of 4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-ol derivatives as EGFR and HDAC dual inhibitors.

In patients with non-small cell lung cancer (NSCLC), the standard therapy consists of selective tyrosine kinase inhibitors that target epidermal growth factor receptors (EGFR). Nonetheless, their clinical utility is primarily limited by the development of resistance to drugs. HDAC inhibitors have been shown in studies to reduce the level of EGFR that is expressed and downregulate the EGFR-induced phosphorylation of AKT and ERK. Therefore, dual inhibitors of EGFR and HDAC provide a potential approach as combination treatment synergistically inhibited the growth of NSCLC. Herein, we examined the EGFR inhibition effect of twenty compounds which designed and synthesized by us previously. Among them, compounds 12c and 12d exhibited powerful antiproliferative activity against the NCI-H1975 cell line with IC50 values of 0.48 ± 0.07 and 0.35 ± 0.02 µM, correspondingly. In cell-free kinase assays, both 12c and 12d demonstrated target-specific EGFR inhibition against wild type (EGFRwt). Furthermore, the expression of EGFR and phosphorylation of the EGF-induced pathways were significantly suppressed under the treatment of 12c and 12d. Besides, both histones H3 and H4 exhibited increased levels of acetylation following 12c and 12d treatment. The animal experiments shown that 12d could prevent the growth of tumor, inhibited the expression of EGFR and the phosphorylation levels of p70 S6K, AKT and p38 MAPK in vivo, and did not cause organ damage to the mice during the experiment. Overall, the results illustrated that compound 12c and 12d could serve as effective EGFR and HDAC dual inhibitors in NSCLC cells. Our work offers an alternative strategy for NSCLC therapy.

Oxalic acid activated bone meal for immobilization of Pb and Cd contaminated soils.

Bone meal (BM) is a cost-effective and low-carbon material to remediate heavy metal contaminated soils. Moreover, its immobilization efficiency for heavy metals still requires improvement. This study aimed to assess the activation effect of oxalic acid on the BM to develop an oxalic acid-activated bone meal (ABM) for improving immobilization efficiency. Several series of tests, including the available phosphorus content test, toxicity characteristic leaching procedure (TCLP), modified European Community Bureau of Reference (BCR) sequential extraction procedure, and X-ray diffraction (XRD) analysis, are used to investigate the effect of activation on the immobilization ability and chemical speciation of lead (Pb) and cadmium (Cd) in soils and the different mechanisms of Pb/Cd immobilization using the ABM and BM. The results indicate that the ABM possesses a higher solubility than the BM. The activation of BM achieves optimal effect when using 1 mol/L oxalic acid solution with a liquid-solid ratio of 2:1. The TCLP and BCR test results show that the ABM significantly outperforms the BM in terms of Pb immobilization. The leaching concentration of Pb from ABM immobilized soils can meet regulatory limits in China and the USA, and it is also 30 to 75% lower than that from BM immobilized soils. Regarding Cd immobilization, ABM outperforms BM after 90 days of curing. The XRD analysis shows that heavy metal phosphates are the primary products of Pb and Cd immobilized by ABM, whereas heavy metal carbonates are the main products after the immobilization by BM.

Relationship between ambient air pollution and preterm birth: a retrospective birth cohort study in Yan'an, China.

Preterm birth (PTB) has been associated with exposure to air pollution, but it is unclear whether effects might vary among air pollution sources in a valley city, and yet few studies have investigated refined susceptible windows for PTB. We performed a retrospective birth cohort study in Yan'an city, a typical valley city in the west of China, and analyze the effects of air pollutants on premature delivery, identify critical windows for maternal air pollutants exposure and PTB. The pregnant women who gave birth in the Affiliated Hospital of Yan'an University and Yan'an people's Hospital from January 1, 2018 to December 31, 2019 were selected as the research objects. A questionnaire survey and medical records were conducted. The daily average concentrations of particulate matter with aerodynamic diameters of ≤ 2.5 µm (PM2.5) and ≤ 10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and ozone (O3) in Yan'an City from January 1, 2017 to December 31, 2019 were collected. After controlling the confounding factors of PTB by logistic regression model, the effect of air pollutants on preterm birth was analyzed. After controlling the confounding factors such as maternal age, gestational times and gestational hypertension syndrome, PTB was associated with exposure to third trimester PM10 (adjusted odds ratio [aOR] = 1.019, 95% confidence interval [95%CI] = 1.004-1.035). PTB risk increased with second trimester exposure to SO2 (aOR = 1.039, CI = 1.011-1.068), also with third trimester (aOR = 1.031, CI = 1.010-1.053). PTB was also associated with third trimester O3 (aOR = 1.023, CI = 1.005-1.041). This study indicates that maternal exposure to PM10, SO2 and O3 might lead to increased risk of PTB, and critical exposure windows were inconsistent.

[Effect of flurbiprofen combined different concentrations of ropivacaine local infiltration on postoperative analgesia after laparoscopic cholecystectomy].

OBJECTIVE: To investigate the effects of postoperative analgesia after laparoscopic cholecystectomy using intravenous flurbiprofen combined with different concentrations of ropivacaine incision infiltration. METHODS: Eighty patients who underwent traditional laparoscopic cholecystectomy received standard general anesthesia. At the end of surgery, patients were randomly divided into four groups: group Con (control group: no analgesics was administered, n=20); group F (flurbiprofen group: 100 mg of flurbiprofen was given intravenously with no incision infiltration, n=20); group FR(0.25) (100 mg of flurbiprofen was given intravenously, combined with 0.25% ropivacaine incision infiltration, 2 mL per incision, 6 mL in total, n=20) and group FR(0.5) (100 mg of flurbiprofen was given intravenously, combined with 0.5% ropivacaine incision infiltration, 2 mL per incision, 6 mL in total, n=20). The intensity of postoperative pain was evaluated using numeric rating scale (NRS) in a double-blinded manner. Intramuscularly 50 mg of meperidin was administered as rescue medication when NRS was above 4. The NRS and the associated side effects were observed and recorded at the end of 0, 2, 6, 12, 24, and 48 hours postoperatively (T(0 h)h,T(2 h),T(6 h),T(12 h),T(24 h),and T(48 h)). RESULTS: There was no obvious difference among the four groups in respect of gender, age, body weight, baseline blood pressure, heart rate(HR), and total doses of sufentanil and remifentanil during operation and surgical time(P>0.05).There were significant differences among group FR(0.25)(2.34 ± 0.89,3.01 ± 1.27,2.79 ± 0.94), group FR(0.5)(2.42 ± 0.79, 2.69 ± 0.96, 2.03 ± 0.87)and group Con(3.42 ± 1.23, 5.98 ± 1.46, 4.53 ± 0.92)in NRS at T(2 h), T(6 h), and T(12 h)(P<0.05).Systolic blood pressures (SBP) of patients in group FR(0.25) [(114.19 ± .74) mmHg,(108.31 ± 7.62) mmHg) and group FR(0.5) [(115.26 ± 8.95) mmHg,(111.25 ± 9.12) mmHg] were significantly lower than those of patients in group Con [(137.11 ± 8.71) mmHg,(125.16 ± 8.92) mmHg] at T(2 h) and T(6 h)(P<0.05). Compared with group Con [(81.24 ± 6.64) beats/min], heart rate(HR) was also lower in patients of group FR(0.25) [(69.14 ± 5.92) beats/min] and group FR(0.5) [(70.16 ± 5.25) beats/min] at T(6 h)(P<0.05). There was no obvious adverse effect in all the four groups. CONCLUSION: Intravenous flurbiprofen combined with ropivacaine infiltration could significantly reduce postoperative pain after laparoscopic cholecystectomy, providing more stable hemodynamics. Compared with 0.25% ropivacaine, 0.5% ropivacaine infiltration combined with intravenous flurbiprofen has better and longer analgesic effects.