Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia.

OBJECTIVE: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. METHODS: Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. RESULTS: A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ. CONCLUSION: Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.

PECAM-1 drives ß-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives ß-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. METHODS: The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3ß/ß-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. RESULTS: DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted ß-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3ß signaling was enhanced to inhibit the degradation of ß-catenin, which regulates the process of EndMT. CONCLUSIONS: PECAM-1 defects and/or internalization are key events for ß-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3ß signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Video Abstract.

Construction of a risk prediction model for non-variceal upper gastrointestinal bleeding and rebleeding based on multi-dimensional indicators and its application research.

OBJECTIVE: To construct a predictive model for the risk of rebleeding in non-variceal upper gastrointestinal bleeding (NVUGIB) based on multidimensional indicators to provide an assessment tool for early screening of rebleeding in NVUGIB. METHODS: Retrospective analysis of the 3-month follow-up data of 85 patients with NVUGIB diagnosed at the Fifth Hospital of Wuhan from January 2019 to December 2021 who were discharged from the hospital after medical treatment. Patients were divided into a rebleeding group (n=45) and a non-rebleeding group (n=95) based on whether they rebleed during follow-up. The demographic characteristics, clinical characteristics and biochemical indicators of the two groups were compared. A multivariate logistic regression was used to analyze the influencing factors of NVUGIB rebleeding. A nomograph model was built using the screening results. The area under the working characteristic curve of the subject (AUC) was used to analyze the model differentiation, evaluate the model specificity and sensitivity, and verify the prediction performance of the model with the validation set. RESULTS: There were significant differences in age, hematemesis, red blood cell count (RBC), platelet (PLT), albumin (Alb), prothrombin time (PT), TT, fibrinogen (Fib), plasma D-dimer (D-D), and blood lactate (LAC) levels between the two groups (all P<0.05). Logistic regression analysis shows that, age ≥75, hematemesis more than 5 times, PLT≤100*109/L, D-D>0.5 mg/L were associated with greater risk of rebleeding. The nomogram model was constructed based on the above four indicators. The AUC of the training set (n=98) for predicting the risk of NVUGIB rebleeding was 0.887 (95% CI: 0.812-0.962), the specificity was 0.882, and the sensitivity was 0.833. The AUC of the validation set (n=42) was 0.881 (95% CI: 0.777-0.986), the specificity was 0.815, and the sensitivity was 0.867. After 500 times of sampling by bootstrap method, the mean absolute error of the calibration curve of the validation set model was 0.031, indicating that the calibration curve and the ideal curve fit well, and the predicted value of the model was in good agreement with the actual value. CONCLUSION: Age ≥75, hematemesis >5 times, lower PLT, and higher D-D levels rise the risk of rebleeding in NVUGIB patients and have some reference value in clinical diagnosis and disease assessment.

The rapid inhibition of B-cell activation markers by belimumab was associated with disease control in systemic lupus erythematosus patients.

Objective: To examine the kinetics of B cell subsets and activation markers in the early stage of belimumab treatment and their correction with treatment response. Methods: We enrolled 27 systemic lupus erythematosus (SLE) patients receiving 6 months belimumab treatment. Flow cytometry was used to test their B cell subsets and activation markers (including CD40, CD80, CD95, CD21low, CD22, p-SYK and p-AKT). Results: During belimumab treatment, SLEDAI-2K declined, the proportions of CD19+ B cells and naïve B cells decreased, whereas the switched memory B cells and non-switched B cells increased. The larger variations of the B cell subsets and the activation markers were in the first 1 month than the other later time frames. The ratio of p-SYK/p-AKT on non-switched B cell at 1 month was associated with the SLEDAI-2K decline rate in the 6 months of belimumab treatment. Conclusion: B cell hyperactivity was rapidly inhibited in the early stage of belimumab treatment, and the ratio of p-SYK/p-AKT may predict SLEDAI-2K decline. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04893161?term=NCT04893161&draw=2&rank=1; identifier: NCT04893161.

Tofacitinib for new-onset adult patients with anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis.

OBJECTIVE: We aimed to investigate the efficacy and safety of tofacitinib in adult anti-melanoma differentiation-associated 5 gene (Anti-MDA5) antibody-positive dermatomyositis (DM) patients and evaluate the effects of tofacitinib on peripheral lymphocyte subsets. METHODS: An open-label study was conducted of 15 new-onset, untreated adult patients with anti-MDA5-positive DM for tofacitinib with a dose of 5mg twice per day. The primary outcome was defined by the total improvement score after treatment for 6 months, classified according to the 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) response criteria for adult DM and polymyositis. Secondary outcomes after 6 months treatment comprised the change in predicted forced vital capacity, the percentage of predicted carbon monoxide diffusion capacity, ferritin level and peripheral blood lymphocyte subsets measured by flow cytometry. RESULTS: Disease responses occurred in 10 patients (71.4%) after 6 months. The median total improvement score was 43.75 (41.875-59.375). Two patients achieved major improvement, seven achieved moderate and one minimal. The serum ferritin level (p = 0.008), DLCO% (p = 0.009) was improved and a marked increase in total lymphocyte cells (p = 0.045) and CD8+ T cells (p = 0.006) was measured after 6 months treatment compared to baseline. CONCLUSION: Tofacitinib demonstrates efficacy for new-onset, untreated adult patients with anti-MDA5-positive DM and stimulates proliferation of peripheral lymphocyte subsets (especially total lymphocyte cells and CD8+ T cells) after 6 months treatment. Further studies are warranted to validate the current findings. Key Points • Treatment of anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis is always challenging. • This prospective, open-label clinical trial demonstrates tofacitinib is an effective and safe agent for new-onset adult patients with anti-MDA5-positive DM. • Tofacitinib treatment results in an increase in peripheral lymphocyte numbers, especially CD8+ T cells at 6 months compared with pre-treatment levels.

Millet-based crop planting strategies in the Songhua River Region during the liaojin (907-1234 AD) dynasties: A case of the Luotong Mountain City site.

Introduction: Millet-based dryland agriculture is the traditional mode of agricultural cultivation in northern China and has been of great significance to the emergence and development of Chinese civilization. However, although they are both millet-based agricultural production methods, with various subtypes in different regions of northern China. In the Songhua River Region in northeast China, the ecological environment and abundant natural resources led to the slow development of agriculture, and it was only after the Liaojin Dynasties that a mature farming industry was formed. Material and Method: We used the plant flotation instrument to flotation the soil samples unearthed in the Luotong Mountain City, a Liaojin period site in Songhua River Region, northeast China, and collected the charred plant seeds. Then observing them with the electron microscope, we identified and counted the plant seeds in this site. Result: It was found that this region is still a millet-based crop utilization structure, and a total of 11 types of charred agricultural crop seeds were excavated from flotation at the Luotong Mountain City site. And the barnyard millet crops occupy a prominent advantage, with ubiquity of more than 91%. Discussion: The ancestors of this region were still engaged in a millet-based agricultural strategy during this period, with a certain lag compared to the Central Plains'agricultural strategy where Triticeae crops had become dominant. In addition, the crop structure with the millet-based agriculture of the region is also somewhat different from that of the Central Plains. Through comparative studies of surrounding sites and reference to historical documents, it was found that this difference in crop structure is a phenomenon unique to the Songhua River Region and is related to the dietary habits of the local settled Jurchen nomads, who ate barnyard millet meal.

Peripheral immunophenotypes associated with the flare in the systemic lupus erythematosus patients with low disease activity state.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by clinical heterogeneity and flare unpredictability. It was still unclear for the association between SLE flare and immunophenotypes. Flow cytometric analysis defined the B and T subsets of the low disease activity state (LDAS) patients and healthy controls. Principal components analysis (PCA) and cluster analysis (CA) distinguished the immunophenotypes. Compared with the 66 healthy controls, the 93 LDAS patients had higher proportions of plasma cells, double negative B cells, naïve B cells and CD8+T cells, and lower proportions of unswitched memory B cells and CD4+T cells. PCA showed the abnormalities of T and B cell axes. CA divided the patients into 3 groups. The memory B cells group had the lower flare risk compared with the non-memory B cells group (including naïve B cells group and T cells group). The immunophenotypes were associated with SLE flare in the LDAS patients.

Alterations of peripheral blood B cell subsets in Chinese patients with adult idiopathic inflammatory myopathies.

OBJECTIVES: Abnormalities and hyperactivation of B cells have been described in idiopathic inflammatory myopathies (IIM). However, little is known about changes in the homeostasis of peripheral blood B cells in adult IIM patients. The aim of this study was to identify phenotypic alterations of B cell subsets and their relation to the overall clinical profile. METHODS: Blood samples were collected from 25 adult IIM patients and 15 healthy controls. Peripheral B cell subsets were classified into non-switched memory B cells (CD19+CD27+lgD+), switched memory B cells (CD19+CD27+lgD-), double-negative (DN) memory B cells (CD19+CD27-lgD-) and naïve B cells (CD19+CD27-lgD+) based on their surface phenotype as measured by flow cytometry. The clinical profile of IIM and its correlation with B cell subsets was further evaluated. RESULTS: Frequencies of CD19+ B cells and naïve B cells were increased in adult IIM patients compared with healthy controls (p=0.005 and p<0.001, respectively) and the frequency of memory B cells was decreased (p<0.001). Moreover, patients with a rash had lower non-switched memory B cells proportion (p=0.032). Patients with anti-MDA5+ antibodies had higher CD19+ B cells proportion than anti-ARS+ patients (p=0.046). Patients who were not receiving treatment had elevated levels of CD19+ B cells and naïve B cells along with reduced non-switched memory B cells compared with patients who were receiving treatment (p=0.021, p=0.036 and p=0.032, respectively). CONCLUSIONS: Our findings demonstrate abnormalities in the homeostasis of the B cell subsets present in adult IIM patients, characterised by expanded CD19+ B cells and naïve B cells but reduced memory B cells. Phenotypic abnormalities of B cell subsets are associated with the presence of a rash, with anti-MDA5 positivity and with treatment.

Elevated CD19+Siglec-10+ B cell levels are correlated with systemic lupus erythematosus disease activity.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell dysregulation and the breakdown of self-tolerance, leading to pathogenic autoantibody production. Human Siglec-10 is a member of the sialic acid-binding immunoglobulin-type lectin (Siglec) family and a B cell surface coreceptor that inhibits B cell receptor-induced signalling. However, to date, no report has investigated CD19+Siglec-10+ B cells in SLE patients. Thus, this study aimed to measure the population of CD19+Siglec-10+ B cells in patients with SLE and its correlation with disease activity. METHODS: Flow cytometry was employed to measure the population of CD19+Siglec-10+ B cells in peripheral blood mononuclear cells (PBMCs) of both SLE patients and healthy controls (HCs). The correlation of the proportion of CD19+Siglec-10+ B cells with the values of SLE disease activity was analysed. PBMCs from HCs were challenged with serum from active SLE, inactive SLE, or HCs, and the proportion of CD19+Siglec-10+ B cells was then assessed. The effect of dexamethasone (DEX) or hydroxychloroquine (HCQ) treatment on the proportion of CD19+Siglec-10+ B cells in PBMCs from SLE patients was also determined. RESULTS: The proportion of CD19+Siglec-10+ B cells in SLE patients was significantly elevated (P < 0.05), correlated positively with the SLEDAI score (r = 0.304; P = 0.018) and negatively with complement component 3 (C3) (r = -0.283; P = 0.04). In vitro assays indicated that sera from active SLE patients could significantly enhance the proportion of CD19+Siglec-10+ B cells (P < 0.05), while HCQ treatment significantly attenuated their proportions (P < 0.01). CONCLUSIONS: The elevation of CD19+Siglec-10+ B cells and their correlation with disease activity may suggest a role for Siglec-10 in the pathogenesis and progression of SLE and provide a serum biomarker for SLE activity.

Study of the effect of pain on postoperative rehabilitation of patients with uterine malignant tumor.

Objective: The relationship between acute postoperative pain (APSP) and health-related quality of life (HRQoL) in patients with uterine malignant tumor after operation was evaluated with self-rating scales, and the influencing factors of postoperative rehabilitation were screened. Methods: A total of 102 patients undergoing elective surgery for Gynecology in the First Affiliated Hospital of Guangxi Medical University were included in this study. PCS, SAS, NRS and EQ-5D scales were evaluated 1 day before surgery, and NRS and EQ-5D scales were evaluated 1,3,7,14, and 30 days after surgery. In addition, the general and perioperative information of patients was collected from the medical record system of the hospital. Results: From the 1st to the 30th day after operation, the NRS and EQ-5D-5L scores of patients decreased gradually, and EQ-VAS scores increased gradually. NRS score was correlated with EQ-5D score (P < 0.01). Postoperative hospital stay, Education level, PCS score and NRS score (Overall state and Active state) were the principal influencing factors of EQ-5D score (P < 0.05). Patients in the pain group had a later time to get out of bed and eat, a higher incidence of postoperative complications, and a longer postoperative hospital stay (P < 0.05). Endoscopic surgery can reduce postoperative pain and promote postoperative rehabilitation (χ 2 = 37.631, P < 0.001). Conclusions: The postoperative rehabilitation of patients in the pain group was poor. Minimally invasive surgery can reduce postoperative pain and promote postoperative rehabilitation. EQ-5D score can be used as a subjective index to evaluate postoperative rehabilitation. Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR2000032759).

[Retracted] MicroRNA­107 inhibits tumor growth and metastasis by targeting the BDNF­mediated PI3K/AKT pathway in human non­small lung cancer.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data featured in Fig. 7, and the tumour images in Fig. 2, were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory response. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 49: 1325­1333, 2016; DOI: 10.3892/ijo.2016.3628].

LncRNA SNHG6/miR-125b-5p/BMPR1B Axis: A New Therapeutic Target for Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a significant cause of patient morbidity. The exactly pathobiological features of this condition has yet to be completely elucidated. METHODS: Breast cancer data obtained from The Cancer Genome Atlas (TCGA) database were evaluated for lncRNA SNHG6 expression. Normal human breast epithelial cell line (MCF-10A) and other breast cancer cell lines (BT-549, MDA-MB-231, Hs 578t, ZR-75-30, SK-BR-3, MCF-7) were also assessed for lncRNA SNHG6 expressions. Cellular proliferative ability was evaluated with colony formation and CCK-8 assays. The ability of cells to migrate was scrutinized with the wound healing and Boyden chamber cell migration assays. qRT-PCR enabled for detection of lncRNA SNHG6, miR-125b-5p and BMPR1B mRNA expressions. Protein BMPR1B expressions were further assessed using Western Blotting. Direct binding sites between transcripts were determined using dual-luciferase reporter assays. We also constructed a xenograft mouse model to further dissect the vivo implications of lncRNA SNHG6. Ki-67 and c-Caspase-3 expressions were detected using immunohistochemistry staining. RESULTS: Breast cancer cell lines demonstrated higher lncRNA SNHG6 expressions, particularly TNBC cell lines, in contrast to normal breast epithelial cell lines. This finding coincided with those noted on analysis of TCGA breast cancer data. lncRNA SNHG6 knockdown inhibited TNBC cell proliferation, migration, while promoted cell apoptosis. Furthermore, suppressed lncRNA SNHG6 expressions resulted in lower tumor weights and volumes in a xenograft mouse model, as evidenced by Ki-67 and c-Caspase-3 expression profiles in tumor tissues. miR-125b-5p and lncRNA SNHG6/BMPR1B both possessed direct binding sites for each other which was validated utilizing a dual-luciferase reporter assay. Decreasing lncRNA SNHG6 expression in TNBC cells upregulated miR-125b-5p expression. Another side, inhibiting miR-125b-5p upregulated BMPR1B expression in these cells. Moreover, knocking down lncRNA SNHG6 downregulated BMPR1B expression in TNBC cells, and the finding was rescued in cells which were exposed to miR-125b-5p inhibitor. Downregulating miR-125b-5p mitigated the effect of suppressing lncRNA SNHG6 on TNBC cell proliferation, migration, and apoptosis. CONCLUSION: Downregulation of lncRNA SNHG6 could inhibit TNBC cell proliferative, migratory capabilities and promote apoptosis capability, likely through modulation of the miR-125b-5p/BMPR1B axis. This axis may be targeted in formulating new therapies for TNBC.

Immune Cell Infiltration-Based Characterization of Triple-Negative Breast Cancer Predicts Prognosis and Chemotherapy Response Markers.

Breast cancer represents the number one cause of cancer-associated mortality globally. The most aggressive molecular subtype is triple negative breast cancer (TNBC), of which limited therapeutic options are available. It is well known that breast cancer prognosis and tumor sensitivity toward immunotherapy are dictated by the tumor microenvironment. Breast cancer gene expression profiles were extracted from the METABRIC dataset and two TNBC clusters displaying unique immune features were identified. Activated immune cells formed a large proportion of cells in the high infiltration cluster, which correlated to a good prognosis. Differentially expressed genes (DEGs) extracted between two heterogeneous subtypes were used to further explore the underlying immune mechanism and to identify prognostic biomarkers. Functional enrichment analysis revealed that the DEGs were predominately related to some processes involved in activation and regulation of innate immune signaling. Using network analysis, we identified two modules in which genes were selected for further prognostic investigation. Validation by independent datasets revealed that CXCL9 and CXCL13 were good prognostic biomarkers for TNBC. We also performed comparisons between the above two genes and immune markers (CYT, APM, TILs, and TIS), as well as cell checkpoint marker expressions, and found a statistically significant correlation between them in both METABRIC and TCGA datasets. The potential of CXCL9 and CXCL13 to predict chemotherapy sensitivity was also evaluated. We found that the CXCL9 and CXCL13 were good predictors for chemotherapy and their expressions were higher in chemotherapy-responsive patients in contrast to those who were not responsive. In brief, immune infiltrate characterization on TNBC revealed heterogeneous subtypes with unique immune features allowed for the identification of informative and reliable characteristics representative of the local immune tumor microenvironment and were potential candidates to guide the management of TNBC patients.

Uncoupled bone remodeling is characteristic of bone damage in premenopausal women with new-onset systemic lupus erythematosus.

OBJECTIVE: To investigate the mechanism underlying systemic lupus erythematosus (SLE)-related bone loss by evaluating the bone mineral density (BMD) and bone turnover markers (BTMs) in premenopausal patients with new-onset SLE without any treatment. METHODS: BMD and BTMs of 106 premenopausal patients with new-onset SLE and 64 gender-, age- and body mass index (BMI)-matched healthy controls were analyzed. BMD was determined using dual energy X-ray absorptiometry (DXA). Serum BTMs were measured. RESULTS: Hip and lumbar spine BMD in premenopausal patients with new-onset SLE was significantly decreased compared with healthy controls. Higher rate of osteoporosis was observed in new-onset SLE patients (25% vs. 1%). Moreover, uncoupled bone remodeling evidenced by an increase in bone resorption marker ß-CTX (685.9 ± 709.6 pg/mL vs. 395.4 ± 326.0 pg/mL, P < 0.05) and decrease in bone formation markers PINP (37.4 ± 33.0 ng/mL vs. 46.1 ± 20.9 ng/mL, P < 0.05) and OC (11.4 ± 9.8 ng/mL vs. 18.2 ± 8.6 ng/mL, P < 0.05) was observed in premenopausal patients with new-onset SLE compared with healthy controls. Univariate correlation analyses showed negative correlations between OC and SLE Disease Activity Index (SLEDAI), and positive correlations between ß-CTX and SLEDAI. SLE patients positive for dsDNA, nucleosome showed lower OC and higher ß-CTX. CONCLUSION: Premenopausal patients with new-onset SLE had decreased BMD and abnormal bone metabolism with increased ß-CTX and decreased OC and P1NP levels, indicating uncoupled bone remodeling in new-onset SLE patients. Disease activity and abnormal immunity, especially the amount of antibodies in SLE patients, were strongly associated with abnormality of bone metabolism.

Crocin Improves Endothelial Mitochondrial Dysfunction via GPx1/ROS/KCa3.1 Signal Axis in Diabetes.

Mitochondrial dysfunction contributes to excessive reactive oxygen species (ROS) generation, which is a dramatic cause to promote endothelial dysfunction in diabetes. It was previously demonstrated that crocin protected the endothelium based on its diverse medicinal properties, but its effect on the mitochondrion and the potential mechanism are not fully understood. In this study, mitochondrial function was analyzed during the process of excessive ROS generation in high glucose (HG)-cultured human umbilical vein endothelial cells (HUVECs). The role played by KCa3.1 was further investigated by the inhibition and/or gene silence of KCa3.1 in this process. In addition, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase 2 (NOX2), superoxide dismutase 1 (SOD1), and glutathione peroxidase 1 (GPx1) were also detected in this study. Our data showed that crocin improved mitochondrial dysfunction and maintained normal mitochondrial morphology by enhancing the mitochondrial membrane potential (MMP), mitochondrial mass, and mitochondrial fusion. Furthermore, KCa3.1 was confirmed to be located in the mitochondrion, and the blockade and/or silencing of KCa3.1 improved mitochondrial dysfunction and reduced excessive ROS generation but did not affect NOX2 and/or the SOD1 system. Intriguingly, it was confirmed that KCa3.1 expression was elevated by ROS overproduction in the endothelium under HG and/or diabetes conditions, while crocin significantly suppressed this elevation by promoting GPx1 and subsequently eliminating ROS generation. In addition, crocin enhanced CD31, thrombomodulin (TM), and p-/t-endothelial nitric oxide synthase (eNOS) expressions as well as NO generation and decreased vascular tone. Hence, crocin improved mitochondrial dysfunction through inhibiting ROS-induced KCa3.1 overexpression in the endothelium, which in turn reduced more ROS generation and final endothelial dysfunction in diabetes.

ITGBL1 promotes gastric cancer cell proliferation and invasion via Akt signal pathway.

Integrin beta- like 1 (ITGBL1), an extracellular matrix protein, plays an oncogenic role in diverse forms of cancers. To this end, we examined the importance of ITGBL1 in gastric cancer (GC). The upregulated expression of ITGBL1 in GC was associated with a poor prognosis. Moreover, upregulation of ITGBL1 enhanced cell mobility while silencing it exerted an opposite effect. Up-regulation of ITGBL1 significantly promoted phosphorylation of Akt, decreased the ratio of phosphorylated Akt in AGS/ITGBL1-shRNA and N87/ITGBL1-shRNA cells, enhanced cell mobility and proliferation. Silencing ITGBL1 had an opposite effect on Akt phosphorylation, cell mobility, and proliferation. These findings show that ITGBL1 regulates mobility and proliferation of GC likely through activation of Akt signaling.

Cav 1.3 damages the osteogenic differentiation in osteoporotic rats by negatively regulating Spred 2-mediated autophagy-induced cell senescence.

Cav 1.3 can affect the classical osteoclast differentiation pathway through calcium signalling pathway. Here, we performed cell transfection, real-time fluorescence quantitative PCR (qPCR), flow cytometry, SA-ß-Gal staining, Alizarin Red S staining, ALP activity test, immunofluorescence, Western blot and cell viability assay to analyse cell viability, cell cycle, osteogenesis differentiation and autophagy activities in vitro. Meanwhile, GST-pull down and CHIP experiments were conducted to explore the influence of Cav 1.3 and Sprouty-related EVH1 domain 2 (Spred 2) on bone marrow-derived mesenchymal stem cells (BMSCs). The results showed that OS lead to the decreased of bone mineral density and differentiation ability of BMSCs in rats. Cav 1.3 was up-regulated in OS rats. Overexpression of Cav 1.3 inhibited the activity of BMSCs, the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN), as well as promoted the cell cycle arrest and senescence. Furthermore, the negative correlation between Cav 1.3 and Spred 2 was found through GST-pull down and CHIP. Overexpression of Spred 2 increased the expressions of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 of BMSCs, which ultimately promoted the cell activity of BMSCs and ALP, RUNX2, OCN expression. In conclusion, Cav 1.3 negatively regulates Spred 2-mediated autophagy and cell senescence, and damages the activity and osteogenic differentiation of BMSCs in OS rats.

Characterization of Corosolic Acid as a KPC-2 Inhibitor That Increases the Susceptibility of KPC-2-Positive Bacteria to Carbapenems.

The emergence of KPC-producing Gram-negative bacteria in clinical practice highlights the need to search for novel antimicrobials and new anti-infection strategies. In this study, we constructed a laboratory KPC-2-positive strain, E. coli BL21(DE3) (pET28a-KPC-2) and identified the activity of KPC-2 in this strain. Using enzyme inhibition assays, checkerboard MIC assays, growth curves, time-killing assays and combined disk test, we found that the natural compound corosolic acid (CA) significantly inhibited the activity of the class A ß-lactamase KPC-2, which is common among clinical isolates. CA treatment increased the antibacterial or bactericidal activity of imipenem and meropenem against E. coli BL21(DE3) (pET28a-KPC-2) in vitro (FIC index = 0.17 ± 0.03 for both carbapenems). In addition, the mouse intraperitoneal infection model confirmed that the combination therapy significantly reduced the bacterial load in the livers and spleens following subcutaneous administration. Our results showed that CA can be used to extend the life of carbapenems, providing a viable strategy for severe infections caused by KPC-2-positive bacteria.