Effect of ontological insecurity on vaccination behavior against COVID-19: a hospital-based cross-sectional study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has brought great uncertainty to our society and it may have disrupted people's ontological security. Consequently, this hospital-based study concerns the impact of ontological insecurity on vaccination behavior against COVID-19. STUDY DESIGN: This cross-sectional study was conducted among hospital inpatients. METHODS: A questionnaire survey addressing inpatient ontological insecurity and vaccination behavior against COVID-19 was administered in Taizhou, China. A total of 1223 questionnaires were collected; specifically, 1185 of them were credible, for a validity rate of 96.9%. RESULTS: The score of ontological insecurity was 13.27 ± 7.84, which was higher in participants who did not recommend vaccination for others than those who did (12.95 ± 8.25 vs 14.00 ± 6.78, P = 0.022). There was no difference between the vaccinated and unvaccinated groups (13.22 ± 7.96 vs 13.35 ± 7.67, P = 0.779). Lower ontological insecurity (odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.08-1.81) and being inoculated with COVID-19 vaccines (OR = 2.17, 95% CI: 1.67-2.82) were significantly associated with recommendation of COVID-19 vaccines to others after adjusting for sex, age, education, and occupation. Associations between low ontological insecurity and recommendations for COVID-19 vaccines were observed in men, adults aged 18-59 years, non-farmers, and vaccine recipients. CONCLUSIONS: This study suggests that the ontological insecurity of participants affects their behavior of recommending the COVID-19 vaccination to others rather than getting vaccinated themselves. This promotion of vaccination can be considered from the perspective of improving ontological security in China.

Gelatin methacryloyl hydrogel eye pad loaded with amniotic extract prevents symblepharon in rabbit eyes.

OBJECTIVE: The aim was to evaluate the ability of gelatin methacryloyl (GelMA) hydrogel eye pads loaded with amniotic extract to prevent symblepharon in rabbits. MATERIALS AND METHODS: Forty-eight rabbits were divided into 3 groups. After ocular alkali burn, Group A (n=16) was treated with amniotic extract-loaded hydrogel eye pads placed in the conjunctival sac, Group B (n=16) was treated with amniotic membrane transplantation, and Group C (n=16) received no treatment. At 1, 2, 3, and 4 weeks post-injury, 4 rabbits from each group were selected to evaluate for symblepharon, determine epithelial healing rate and corneal neovascularization, conduct histopathology, and to quantify the expression of TGF-ß1. RESULTS: At 1 week post-injury, the epithelial healing rate in Groups A and B was higher than Group C (p=0.002, 0.001, respectively). At 2 weeks, corneal neovascularization in Group B was less than Group C (p=0.004). At 3 and 4 weeks, no symblepharon has been found in Group A, but it was found in some eyes in Group B and C (p=0.009, 0.013). Further, the expression of TGF-ß1 in Group A was lower than in Group B and C (p<0.001). H&E staining showed that the controls in Group C had more edema and inflammatory cell infiltration in the first 2 weeks, relative to Groups A and B. At 4 weeks, Masson's Trichrome staining showed that fibers were most regularly aligned in Group A and that immuno-histochemical staining found that proliferating cell nuclear antigen was highest expressed in Group C. CONCLUSIONS: Treatment with GelMA hydrogel eye pads loaded with amniotic extract shortly after chemical injury prevented symblepharon in rabbits.

LncRNA LINP1 promotes proliferation and inhibits apoptosis of gastric cancer cells by repressing RBM5.

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, "LncRNA LINP1 promotes proliferation and inhibits apoptosis of gastric cancer cells by repressing RBM5, by X.-C. Lu, H.-Y. Zhou, J. Wu, Y. Jin, X.-M. Yao, X.-Y. Wu, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 137-144-DOI: 10.26355/eurrev_202001_19904-PMID: 31957826" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19904.

Long non-coding RNA AB073614 promotes metastasis of gastric cancer cells by upregulating IGF-2.

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, "Long non-coding RNA AB073614 promotes metastasis of gastric cancer cells by upregulating IGF-2, by X.-Y. Wu, H.-Y. Zhou, X.-M. Yao, X.-D. Chen, J. Wu, X.-C. Lu, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 145-150-DOI: 10.26355/eurrev_202001_19905-PMID: 31957827" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19905.

The expressions of miR-151a-5p and miR-23b in lung cancer tissues and their effects on the biological functions of lung cancer A549 cells.

OBJECTIVE: To investigate the expressions of miR-151a-5p and miR-23b in lung cancer tissues and their effects on the biological functions of lung cancer A549 cells. PATIENTS AND METHODS: Samples of lung cancer tissue (55 cases) and pericarcinomatous tissue (55 cases) were collected in thoracic surgery in our hospital from May 2017 to November 2018. The expression levels of miR-151a-5p and miR-23b in lung cancer tissues and pericarcinomatous tissues were detected by RT-PCR. Lung cancer cells A549 were transfected. Before transfection, the cells were divided into a negative control group (NC group, transfected with miRNA NC), a group transfected with miR-151a-5p inhibitor and a group transfected with miR-23b inhibitor. MTS Cell Proliferation Colorimetric Assay Kit (CCK8) was used to detect cell proliferation and draw the growth curve. Transwell chamber was used to detect the invasion ability in vitro, and BD flow cytometry was used to detect apoptosis in each group. RESULTS: The expression levels of miR-151a-5p and miR-23b in lung cancer tissues were significantly higher than those in pericarcinomatous tissues (p<0.001). After 48 h to 72 h, the cell growth of both the miR-151a-5p inhibitor group and the miR-23b inhibitor group was significantly lower than that of the NC group (p<0.001). The numbers of invasion of miR-151a-5p inhibitor group and miR-23b inhibitor group were significantly lower than that of NC group (p<0.00). The apoptosis rates of miR-151a-5p inhibitor group and miR-23b inhibitor group were significantly higher than that of NC group (p<0.001). CONCLUSIONS: Both miR-151a-5p and miR-23b are highly expressed in lung cancer, and the inhibition of miR-151a-5p and miR-23b can restrain the proliferation, invasion and migration of lung cancer A549 cells, thereby promoting the apoptosis of lung cancer A549 cells.

MicroRNA-493-5p suppresses colorectal cancer progression via the PI3K-Akt-FoxO3a signaling pathway.

OBJECTIVE: MicroRNA493-5p (miR-493-5p) appears to have an essential role in the abnormal cell proliferation and migration observed in the development and progression of various cancers. However, the function and mechanism of action of miR-493-5p in colorectal cancer (CRC) is unclear. PATIENTS AND METHODS: MiR-493-5p expression was analyzed in CRC patient tissue samples and cell lines by fluorescence quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). SW480 and Caco-2 cells were transfected with miR-493-5p mimics or treated with the phosphoinositide 3-kinase (PI3K) agonist 740Y-P. Cell proliferation was determined by colony formation and cell proliferation assays and cell migration and invasion by transwell migration and wound-healing assays. The Luciferase reporter assay was used to verify the association between the expression of miR-493-5p and PI3K activity. Expression levels of PI3K, protein kinase B(Akt), and forkhead box O 3a (FoxO3a) proteins were measured by Western blot analysis and immunofluorescence assay. RESULTS: MiR-493-5p expression was significantly downregulated in CRC tissue samples and cell lines which was associated with progression of CRC. The proliferation, migration, and invasion of CRC cells were inhibited by miR-493-5p overexpression. The finding that miR-493-5p upregulation decreased PI3K, Akt, and FoxO3a protein expression revealed that it directly targets PI3K. Additionally, the miR-493-5p-mediated suppression of CRC cell proliferation, migration and invasion was counteracted by the PI3K agonist, indicating that miR-493-5p suppresses CRC progression by inhibiting the PI3K-Akt-FoxO3a signaling pathway. CONCLUSIONS: MiR-493-5p suppresses the proliferation, migration, invasion, and progression of CRC via the PI3K-Akt-FoxO3a signaling pathway.

LncRNA NEAT1 facilitates the progression of sepsis through up-regulating TSP-1 via sponging miR-370-3p.

OBJECTIVE: Sepsis is a systemic inflammatory disease. LncRNA NEAT1 has been reported to be up-regulated in sepsis patients. Nevertheless, the modulatory network of NEAT1 in sepsis remains to be revealed. PATIENTS AND METHODS: The abundance of long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1), miR-370-3p, and thrombospondin-1 (TSP-1) were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in sepsis patients and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Enzyme-linked immunosorbent assay (ELISA) was performed to examine the concentration of cytokines in RAW 264.7 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry assay, and Western blot assay were conducted to detect the proliferation and apoptosis of RAW 264.7 cells. Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay were conducted to confirm the combination between miR-370-3p and NEAT1 or TSP-1 in RAW 264.7 cells. RESULTS: The enrichment of NEAT1 was enhanced in sepsis patients and LPS-stimulated RAW 264.7 cells. NEAT1 contributed to LPS-induced inflammation and apoptosis of RAW 264.7 cells. MiR-370-3p bound to NEAT1, and it was negatively regulated by NEAT1 in RAW 264.7 cells. LPS promoted the inflammation and apoptosis while restrained the proliferation of RAW 264.7 cells via NEAT1/miR-370-3p axis. TSP-1 was a target of miR-370-3p in RAW 264.7 cells, and miR-370-3p suppressed the inflammation and apoptosis while it facilitated the proliferation of LPS-induced RAW 264.7 cells via TSP-1. CONCLUSIONS: LncRNA NEAT1 promoted the inflammation and apoptosis while restrained the proliferation of LPS-stimulated RAW 264.7 cells through the miR-370-3p/TSP-1 axis.

LncRNA LINP1 promotes proliferation and inhibits apoptosis of gastric cancer cells by repressing RBM5.

OBJECTIVE: Recent studies have revealed that long non-coding RNAs (lncRNAs) play a crucial role in tumor progression. Gastric cancer (GC) is one of the common types of malignancies worldwide. This study aimed to identify the exact function of lncRNA LINP1 in the progression of GC. PATIENTS AND METHODS: LINP1 expression in paired cancer tissues and adjacent normal tissues of GC patients was detected by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR). The effect of LINP1 silence on proliferation and apoptosis of GC cells was detected. Meanwhile, the underlying mechanism of LINP1 function was explored by RT-qPCR and Western blot assay. Furthermore, tumor formation assay was performed to examine the ability of LINP1 in tumor formation in vivo. RESULTS: LINP1 expression was remarkably up-regulated in GC tissues compared with adjacent normal tissues. The growth ability of GC cells was significantly inhibited after silencing of LINP1 in vitro. Besides, the apoptosis of GC cells was markedly induced after silencing of LINP1. The silence of LINP1 significantly up-regulated the expression of RBM5 in GC cells. Meanwhile, RBM5 expression in GC tissues was remarkably lower than that of the adjacent normal tissues. Furthermore, tumor formation assay showed that knockdown of LINP1 markedly inhibited tumor formation in vivo. CONCLUSIONS: These results suggested that LINP1 could down-regulate RBM5. Meanwhile, LINP1 remarkably promoted growth ability and suppressed apoptosis of GC in vitro and in vivo. Our findings might provide a novel regulator and therapeutic strategy for GC patients.

Long non-coding RNA AB073614 promotes metastasis of gastric cancer cells by upregulating IGF-2.

OBJECTIVE: Recently, long non-coding RNAs (lncRNAs) have been widely studied for their vital roles in human diseases. In this study, we investigated the effect of lncRNA AB073614 on the metastasis of gastric cancer (GC), and explored the possible underlying mechanism. PATIENTS AND METHODS: AB073614 expression in GC tissue samples was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). The roles of AB073614 in GC metastasis were identified through wound healing assay and transwell assay, respectively. Moreover, RT-qPCR and Western blot assay were used to explore the potential mechanism. RESULTS: AB073614 expression level in GC samples was significantly higher than that of adjacent ones. Besides, the migration and invasion of GC cells were obviously repressed after AB073614 was knocked down. After AB073614 was knocked down in vitro, the mRNA and protein expressions of insulin-like growth factor 2 (IGF-2) was remarkably down-regulated. Furthermore, a negative correlation was found between the expression level of IGF-2 and AB073614 in GC tissues. CONCLUSIONS: AB073614 could promote GC cell migration and invasion via up-regulating IGF-2. Our findings might provide a potential therapeutic target for GC patients.

Controlling nutritional status (CONUT) score-based nomogram to predict overall survival of patients with HBV-associated hepatocellular carcinoma after curative hepatectomy.

PURPOSE: As a novel immune-nutritional biomarker, the controlling nutritional status (CONUT) score has been reported to predict outcomes in cancer patients. We aimed to elucidate the prognostic value of preoperative CONUT score and construct a CONUT score-based nomogram to predict individual survival of patients with hepatitis B viral (HBV)-associated hepatocellular carcinoma (HCC) after curative hepatectomy. METHODS: Preoperative CONUT score was retrospectively calculated in 380 HBV-associated HCC patients undergoing radical resection between 2006 and 2012. Patients were assigned to two groups: CONUT-low ( < 2) and CONUT-high ( ≥ 2), according to the optimal cut-off value determined using receiver operating characteristic analysis. Associations of CONUT score with oncological outcomes were evaluated. The Cox proportional hazard model was used to identify predictors of survival and a new nomogram was developed based on the independent prognostic factors for overall survival (OS). RESULTS: The CONUT score exhibited a higher area under the curve value than the other immune-nutritional parameters. The CONUT-high group had significant poorer OS and recurrence-free survival compared with CONUT-low group (P < 0.001 and P = 0.016, respectively). Multivariate analyses identified CONUT score, liver cirrhosis, tumor size and differentiation as independent prognostic factors for OS. And the nomogram based on these four variables had superior discriminative ability to predict survival compared with other conventional staging systems. CONCLUSIONS: Preoperative CONUT score is an effective independent predictor of OS in patients with resected HBV-related HCC. This novel nomogram based on CONUT may provide accurate and individualized survival prediction for HCC patients undergoing surgical resection.

Mechanism of metformin enhancing the sensitivity of human pancreatic cancer cells to gem-citabine by regulating the PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: To investigate the effect of metformin (MET) on enhancing the sensitivity of human pancreatic cancer cells to gemcitabine (GEM) by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MATERIALS AND METHODS: The GEM-resistant human pancreatic cancer PANC-1/GEM cell line was established, and the proliferation ability of PANC-1 and PANC-1/GEM cell lines was detected using the Cell Counting Kit-8 (CCK-8), which was then detected by flow cytometry after they were labeled by Ki67. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting were adopted to detect the difference in the mTOR expression between PANC-1 and PANC-1/GEM cell lines. The proliferation ability of PANC-1/GEM/MET and PANC-1/GEM cell lines was determined using CCK-8 after drug-resistant cell lines were treated with 20 mmol/L MET combined with 0.4 µmol/L GEM or 0.4 µmol/L GEM alone for 48 h. Colony formation assay was applied to detect the proliferation ability of cells. The difference in the expression of mTOR/PI3K/Akt between PANC-1/GEM/MET and PANC-1/GEM cell lines was tested via qRT-PCR and Western blotting, respectively. RESULTS: Compared with PANC-1 cells, PANC-1/GEM cells had significantly enhanced proliferation ability (p<0.01). Flow cytometry results showed that the proliferation ability of PANC-1/GEM cells was notably enhanced (p<0.01). The expression level and phosphorylation level of mTOR in drug-resistant cell lines were increased (p<0.01). After the drug-resistant cell lines were treated with 20 mmol/L MET for 48 h, the proliferation ability of PANC-1/GEM/MET cells was evidently decreased compared with that of PANC-1/GEM cells (p<0.01). The messenger ribonucleic acid (mRNA) and protein expression levels of mTOR/PI3K/Akt were markedly down-regulated (p<0.01). CONCLUSIONS: MET can regulate the PI3K/Akt/mTOR signaling pathway to enhance the sensitivity of human pancreatic cancer cells to GEM.

Effect of SOCS1 on diabetic renal injury through regulating TLR signaling pathway.

OBJECTIVE: To clarify the effect of suppressor of cytokine signaling 1 (SOCS1) on diabetic nephropathy (DN)-induced renal injury by regulating the Toll-like receptor (TLR) signaling pathway. MATERIALS AND METHODS: The Sprague-Dawley rats were divided into control group (n=10) and DN group (established with streptozotocin injection, n=20). The DN rats were administrated with SOCS1 lentivirus to upregulate the in vivo expression. The rat blood glucose was detected to confirm the successful preparation of the DN model. The hepatic and renal function indexes, including blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and creatinine (CR) were detected. The pathological lesions in the kidney were observed via hematoxylin-eosin (HE) staining. Besides, the serum levels of the inflammatory factors in rats were detected via enzyme-linked immunosorbent assay (ELISA). The relative levels of genes in the TLR signaling pathway were detected via RT-PCR and Western blotting. RESULTS: The blood glucose level in rats of the DN group was significantly enhanced, indicating the successful modeling. The expression of SOCS1 was significantly upregulated in rats administrated with SOCS1 lentivirus. The contents of BUN, ALP, ALT, and CR in rats of SOCS1 overexpression group were significantly lower than those in the DN group. The inflammatory infiltration in the kidney and the glomerular injury were pronounced in the DN group. The serum levels of interleukin-1 (IL-1), interferon-γ (INF-γ), and tumor necrosis factor-α (TNF-α) were significantly declined in SOCS1 overexpression group. Besides, the mRNA expressions of myeloid differential protein-88 (MyD88), TLR2, and INF-γ, and the protein expression of TLR2 were all remarkably downregulated in SOCS1 overexpression group. CONCLUSIONS: SOCS1 can promote renal injury repair in DN rats by inhibiting the TLR pathway. Therefore, SOCS1 is expected to be a new target for the repair of DN renal injury.

Neurotrophin-3 improves fracture healing in rats.

OBJECTIVE: This study aimed at investigating the role of Neurotrophin-3 (NT-3) in the bone fracture healing of rats and to provide a reference for clinical treatment. MATERIALS AND METHODS: 40 Sprague-Dawley (SD) rats were randomly divided into control group and NT-3 group. The tibia fracture model was made in NT-3 group, and the tibia bone mineral density (BMD) was measured before and after the surgery. The biomechanics indexes were inspected after the surgery, including elasticity modulus, max load, and bending rigidity. The levels of bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-ß1 in serum were examined by enzyme-linked immunosorbent assay (ELISA). Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the levels of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) mRNA expression in callus tissue. The pathological profile of tibia fracture healing was characterized after the surgery. RESULTS: The levels of BMD in NT-3 group were significantly higher than that in control group after the surgery (p < 0.05). The levels of elasticity modulus, maximum load, stiffness of shinbone, BMP-2 and TGF-ß1 were significantly higher in NT-3 group than those in control group after the surgery (p < 0.05). Compared with the control group, the expression of HIF-1α mRNA was significantly lower and the expression of VEGF mRNA was significantly higher in NT-3 group after the surgery (p < 0.05). Histological study showed that the periosteal reaction, capillary proliferation, cartilage cells production and ossification were happened after treating NT-3 for tibia fracture model rats. CONCLUSIONS: NT-3 can significantly improve fracture healing in rats.

Expression and clinical significance of long-non-coding RNA GHET1 in pancreatic cancer.

OBJECTIVE: To investigate the expression level and biological function of long non-coding RNA gastric carcinoma high expressed transcript 1 (lncRNA-GHET1) in pancreatic ductal adenocarcinoma (pancreatic cancer for short), to analyze the correlation between the expression of GHET1 and clinicopathological features and to explore the role and clinical significance of GHET1 in the development and progression of pancreatic cancer. PATIENTS AND METHODS: The relative expression of GHET1 in 5 human pancreatic cancer cell lines was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The specific interference sequence of GHET1 was designed and transiently transfected into pancreatic cancer cells. qRT-PCR assay was used to detect the interference efficiency. Cell counting kit-8 (CCK-8) assay was used to detect the effect of the interference with GHET1 on the proliferation of pancreatic cancer cells. Flow cytometry was used to detect the effect of the interference with GHET1 on the cycle distribution and apoptosis. qRT-PCR was used to detect the relative expression of GHET1 in pancreatic cancer tissues compared with that in cancer-adjacent tissues. The correlation between the expression of GHET1 and the pathological features of pancreatic cancer patients was analyzed. RESULTS: The expression of GHET1 in human pancreatic cancer cells was relatively high. The results of CCK-8 showed that the proliferation of tumor cells was inhibited after the interference with GHET1 expression. The results of flow cytometry showed that the expression of GHET1 was blocked at G1/G0 phase, and the apoptosis rate was increased. The results of qRT-PCR showed that the expression of GHET1 was upregulated in pancreatic cancer tissues of 49 out of 64 patients compared with that in cancer-adjacent tissues, and the highly expressed GHET1 was positively correlated with the tumor, node and metastasis (TNM) staging of pancreatic cancer. CONCLUSIONS: Highly expressed GHET1 promotes the proliferation of pancreatic cancer, inhibits apoptosis and is related to TNM staging. The expression of GHET1 can be used as a potential molecular marker for the prognosis and therapeutic target of pancreatic cancer.

Prognostic significance of preoperative albumin-to-globulin ratio in patients with cholangiocarcinoma.

BACKGROUND: This study aimed to assess the prognostic value of the serum albumin to globulin ratio (AGR) in cholangiocarcinoma patients after surgery. METHODS: We retrospectively enrolled 123 cholangiocarcinoma patients who underwent surgical treatment between June 2003 and September2014 at the Third Affiliated Hospital of Sun Yat-sen University. Univariate and multivariate analyses using the Cox regression model were performed to determine the prognostic value of AGR. RESULTS: Univariate analysis suggested that AGR was a predictive factor for (overall survival) OS but not for recurrence free survival (RFS). After adjustment for other risk factors, multivariate analysis showed that AGR remained independently associated with OS. The optimal cut-off point for AGR was determined to be 1.44. Kaplan-Meier curves showed that there was a significantly lower mean survival time in the low AGR group compared to the high AGR group. A low AGR was found to be significantly associated with high alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin levels and an advanced American Joint Committee on Cancer TNM stage, but a low hemoglobin level. CONCLUSION: In summary, patients with higher AGRs have better outcomes than those with lower AGRs. Preoperative AGR can be a reliable marker for evaluating the prognosis of cholangiocarcinoma patients.

Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression.

OBJECTIVE: Although 5-fluorouracil (5-FU) is widely used in the treatment of various cancers, drug resistance remains a limitation for its anti-cancer activity. Mammalian target of rapamycin (mTOR) is deregulated in diverse human cancers, including gallbladder carcinoma and mTOR inhibitors show promising anti-cancer activities with proliferation inhibitory effects. This study aims to clarify the benefit of the combination of 5-FU and the mTOR inhibitor, OSI-027, on gallbladder carcinoma cell proliferation. MATERIALS AND METHODS: Two gallbladder carcinoma cell lines and two agents (5-FU and OSI-027) were used in the present study. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. The expression of MDR1 protein was determined by western blot analysis. RESULTS: The combination of OSI-027 with 5-FU showed a synergistic anti-proliferative effect on the gallbladder cancer cells, RBE and GBC-SD cells. Upon 5-FU treatment, MDR1 expression was upregulated and OSI-027 could reverse 5-FU-induced MDR1 upregulation. Moreover, MDR1 depletion sensitized gallbladder carcinoma cells to 5-FU stimulation and attenuated the synergistic effect of OSI-027 and 5-FU. Finally, we determined that OSI-027 downregulated MDR1 expression by suppressing its synthesis rather than by promoting its degradation. CONCLUSIONS: Dual mTORC1/mTORC2 inhibitors such as OSI-027 are promising therapeutic agents in combination with 5-FU for the treatment of human gallbladder cancer.

Protective effect and mechanism of hydrogen treatment on lung epithelial barrier dysfunction in rats with sepsis.

This study aimed to explore the protective effect of hydrogen and to investigate the underlying mechanism of its preliminary effect on the alveolar epithelial barrier function in septic rats. Forty-five male Sprague-Dawley rats were divided randomly into three groups (N = 15): control [saline injection (intraperitoneal, ip), air drawing; SA], acute lung injury group [lipopolysaccharide (LPS) injection (ip, 15 mg/kg), air drawing; LA], and acute lung injury combined with hydrogen drawing group [LPS injection (ip, 15 mg/kg), 2% hydrogen drawing; LH]. The rats were euthanized after 6 h of treatment, and the extravascular lung water (EVLW), pulmonary alveolar-arterial oxygen pressure (A-aDO2), and respiratory index (RI) of each group were measured. The aquaporin-1 (AQP-1) protein expression in the lung tissues was detected using immunohistochemistry and western blotting, and the correlation between the EVLW and AQP-1 was analyzed. The lung morphology was observed with light and electron microscopy. In the LA group, EVLW (0.87 ± 0.17), A-aDO2 (113.21 ± 13.92), RI (0.65 ± 0.26), and AQP-1 expression increased. Additionally, thickened alveolar walls, significant invasion of inflammatory cells around the vessels, capillary ectasia, hyperemia/hemorrhage in the alveolar space, significantly swollen mitochondria, and increased vacuolar degeneration were observed. A significant negative correlation between AQP-1 expression and EVLW was observed (R2 = 0.8806). Compared with the LA group, EVLW (0.71 ± 0.19), A-aDO2 (132.42 ± 17.39), RI (0.75 ± 0.24), and inflammatory reaction decreased and AQP-1 expression increased in the LH group. The damage to pulmonary epithelial cells improved after hydrogen treatment in rats with sepsis; hydrogen could protect the pulmonary epithelial barrier function by acting on AQP-1.

Reference intervals of bone turnover markers determined by using their curve-fitting valley for adult females in China.

SUMMARY: The reference values for bone turnover markers (BTMs) have a significant role in the diagnosis, monitoring, and treatment of metabolic bone disease. This study proposes that the peak value of bone mineral density and the trough value for the BTM curve can be used to determine the reference range of BTM. INTRODUCTION: The aim of this study is to determine the reference intervals of BTMs for adult females in China with an attempt to reference the peak bone mineral density (BMD) with the corresponding BTM valley. METHODS: This study included 546 premenopausal and 394 postmenopausal women. The levels of several BTMs were determined, and the BMD was measured using a dual-energy X-ray absorptiometry. RESULTS: The BTMs of postmenopausal women were 17-96 % higher than premenopausal women. The change of BTM with age presented an optimal goodness-of-fit according to the cubic regression model (R (2) = 0.074-0.346, all P = 0.000). All kinds of BTM levels were positively correlated with age in premenopausal women aged 27-56 years old (r = 0.167-0.502, P = 0.023-0.000). Except for uCTX, the BTM reference value determined using a curve-fitting valley was significantly lower than the reference values for premenopausal women. The BTM reference values determined in this study were also significantly different from the reference values given by the manufacturers of the reagents used. CONCLUSIONS: This study found that the changes of level with age of BTMs in Chinese women present an optimal goodness-of-fit according to the cubic regression model. The fitting valley corresponds to the BMD fitting peak and may possibly be an effective means of determining the BTM reference intervals.

Age-related changes in biochemical markers of bone turnover and gonadotropin levels and their relationship among Chinese adult women.

UNLABELLED: The relationship between the levels of gonadotropic hormones and bone metabolism in Chinese adult women is unclear. Our research shows that a significant positive correlation exists between the levels of gonadotropic hormones and various bone turnover indicators. Follicle-stimulating hormone (FSH) has been found to have a greater influence on all types of bone turnover indicator than luteinizing hormone (LH). Further, FSH has a greater influence on bone formation indicators than on bone resorption indicators. INTRODUCTION: The aim of this study was to investigate the relationship between serum FSH and LH and biochemical markers of bone turnover in native Chinese adult women. METHODS: We conducted a cross-sectional study of 694 healthy Chinese women aged between 20 and 82 years. Serum FSH, LH, bone-specific alkaline phosphatase (BAP), osteocalcin (OC), N-terminal telopeptides of type I collagen, C-terminal telopeptides of type I collagen, urinary NTX, urinary CTX, and urinary deoxypyridinoline (uDPD) were determined. RESULTS: All types of bone turnover indicator were significantly positively correlated with FSH (r = 0.164-0.626, all P = 0.000) and LH (r = 0.130-0.618, all P = 0.013-0.000). The correlation coefficient between serum FSH and BAP was the highest (r = 0.626), and that between serum FSH and uDPD was the lowest (r = 0.164). The serum gonadotropic hormone levels were higher; concentrations of bone turnover indicators were higher. The extent of the influence of FSH on various bone turnover indicators was approximately seven to 20 times greater than that of LH on these indicators. FSH could explain 43% and 22% of the changes in BAP and OC, respectively; whereas, LH could explain only 2.1% and 1.1%, respectively. FSH could explain approximately 1.9-11.8% of the changes in bone resorption indicators; however, LH had almost no effect on them. CONCLUSIONS: Gonadotropic hormone levels are correlated with the rate of bone turnover in Chinese women: the higher the serum gonadotropic hormone levels in circulation, the higher the levels of bone turnover indicators. FSH has a greater influence on all types of bone turnover indicator than LH; moreover, it has a greater influence on bone formation indicators than on bone resorption indicators.