COVID-19 vaccination willingness among people living with HIV in Shijiazhuang, China: a cross-sectional survey.

Objectives: The COVID-19 pandemic imposed an enormous disease and economic burden worldwide. SARS-CoV-2 vaccination is essential to containing the pandemic. People living with HIV (PLWH) may be more vulnerable to severe COVID-19 outcomes; thus, understanding their vaccination willingness and influencing factors is helpful in developing targeted vaccination strategies. Methods: A cross-sectional study was conducted between 15 June and 30 August 2022 in Shijiazhuang, China. Variables included socio-demographic characteristics, health status characteristics, HIV-related characteristics, knowledge, and attitudes toward COVID-19 vaccination and COVID-19 vaccination status. Multivariable logistic regression was used to confirm factors associated with COVID-19 vaccination willingness among PLWH. Results: A total of 1,428 PLWH were included, with a 90.48% willingness to receive the COVID-19 vaccination. PLWH were more unwilling to receive COVID-19 vaccination for those who were female or had a fair/poor health status, had an allergic history and comorbidities, were unconvinced and unsure about the effectiveness of vaccines, were unconvinced and unsure about the safety of vaccines, were convinced and unsure about whether COVID-19 vaccination would affect ART efficacy, or did not know at least a type of domestic COVID-19 vaccine. Approximately 93.00% of PLWH have received at least one dose of the COVID-19 vaccine among PLWH, and 213 PLWH (14.92%) reported at least one adverse reaction within 7 days. Conclusion: In conclusion, our study reported a relatively high willingness to receive the COVID-19 vaccination among PLWH in Shijiazhuang. However, a small number of PLWH still held hesitancy; thus, more tailored policies or guidelines from the government should be performed to enhance the COVID-19 vaccination rate among PLWH.

Insulin promotes growth in breast cancer cells through the type I IGF receptor in insulin receptor deficient cells.

Breast cancer is the most common cancer in women. The upregulation of insulin-like growth factor (IGF) system observed in certain types of breast cancers was linked to growth, metastasis, and survival resulting in multiple strategies designed to target the type I IGF receptor (IGF-1R) in breast cancer. These attempts failed to prove beneficial and it has been suggested that insulin receptor (IR) could also play an important role in breast cancer biology. To better understand the IR's role in breast cancer cells, the receptor was deleted from MCF-7L cells using CRISPR technology, and fluorescence-assisted cell sorting was used to obtain clone 35 (CL35). It was found that CL35 activated signaling pathways upon insulin stimulation despite the absence of IR expression. We hypothesized that CL35 used a surrogate receptor for sustained growth and development. IGF-1R was able to activate insulin signaling and growth in CL35. Thus, insulin may play a central role in regulating breast cancer growth due to its ability to activate all the receptors of the IGF family. These findings argue that dual targeting of IR and IGF-IR may be required to inhibit breast cancer growth.

Apocynum venetum leaf extract alleviated doxorubicin-induced cardiotoxicity by regulating organic acid metabolism in gut microbiota.

Apocynum venetum leaf is commonly utilized for its beneficial effects in reducing blood pressure, inducing sedation, promoting diuresis, anti-aging, and cardioprotection, which also exhibit positive effects on the gut microbiota. The gut microbiota plays a role as an endocrine organ by producing bioactive metabolites that can directly or indirectly impact host physiology, specifically cardiovascular diseases. In this study, main chemical components of A. venetum leaf extract (AVLE) were identified by LC-MS, and an orally administered AVLE was employed to treat mice with doxorubicin (Dox)-induced cardiotoxicity. The results showed that AVLE contained hyperoside and oganic acids. The pharmacological findings revealed that AVLE regulated the gut microbiota, resulting in a significant increase in the levels of two organic acids, indole-3-propionic acid (IPA) and acetic acid (AA). Both IPA and AA exhibited the ability to reduce BNP, CK, and LDH levels in mice with Dox-induced cardiotoxicity. Moreover, IPA demonstrated an improvement in Dox-induced cardiac injury by inhibiting apoptosis, while AA promoted increased secretion of ghrelin through the parasympathetic nervous system, subsequently reducing cardiac fibrosis by decreasing collagen I, collagen III, and activin A. Hence, our study demonstrates that AVLE exerts a beneficial cardioprotective effect by modulating the gut microbiota, providing a potential novel target for the treatment and prevention of Dox-induced cardiotoxicity.

Regional assessments of supraspinatus muscle stiffness in normal adults using shear wave elastography.

Objectives: To provide normal references for regional shear wave elastography assessments of supraspinatus muscle in a population. Methods: Shear wave elastography images of supraspinatus muscles were evaluated on 100 shoulders of 50 normal adults in a fixed position with 30° shoulder abduction both at rest and contraction. Shear wave velocity values and activity values of intramuscular tendon, anterior superficial, anterior deep, posterior superficial, posterior deep, and central subregions were measured. The possible differences in hand dominance, sexes, stratified age groups, and internal muscular-component subregions were discussed. Results: The results showed that shear wave velocity values at rest and activity values differed significantly among supraspinatus muscular-component subregions. Shear wave velocity values at rest were normally highest in posterior deep and lowest in central subregions, whereas activity values were highest in central subregions. The results also showed evaluation of the intramuscular tendon using shear wave elastography to be practicable. The differences in shear wave velocity values at rest between the dominant and nondominant sides were not significant in each subregion, while the values at rest of the majority of subregions were significantly greater in males than in females. Stratified by age groups of 10 years, the shear wave velocity values at rest of some subregions tended to increase with age, with uncorrelations possibly related to insufficient sample sizes and different intensities of limb activities. Conclusions: This study suggested that regional assessments of supraspinatus stiffness using shear wave elastography are feasible, with further research supporting that it can provide information on the surgery, training, and rehabilitation of rotator cuff tears.

Diagnostic value and characteristic analysis of serum nucleocapsid antigen in COVID-19 patients.

Background: To date, several types of laboratory tests for coronavirus disease 2019 (COVID-19) diagnosis have been developed. However, the clinical importance of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen (N-Ag) remains to be fully elucidated. In this study, we sought to investigate the value of serum SARS-CoV-2 N-Ag for COVID-19 diagnosis and to analyze N-Ag characteristics in COVID-19 individuals. Methods: Serum samples collected from 215 COVID-19 patients and 65 non-COVID-19 individuals were used to quantitatively detect N-Ag via chemiluminescent immunoassay according to the manufacturer's instructions. Results: The sensitivity and specificity of the N-Ag assay were 64.75% (95% confidence interval (95% CI) [55.94-72.66%]) and 100% (95% CI [93.05-100.00%]), respectively, according to the cut-off value recommended by the manufacturer. The receiver operating characteristic (ROC) curve showed a sensitivity of 100.00% (95% CI [94.42-100.00%]) and a specificity of 71.31% (95% CI [62.73-78.59%]). The positive rates and levels of serum SARS-CoV-2 N-Ag were not related to sex, comorbidity status or disease severity of COVID-19 (all P < 0.001). Compared with RT‒PCR, there was a lower positive rate of serum N-Ag for acute COVID-19 patients (P < 0.001). The positive rate and levels of serum SARS-CoV-2 N-Ag in acute patients were significantly higher than those in convalescent patients (all P < 0.001). In addition, the positive rate of serum SARS-CoV-2 N-Ag in acute COVID-19 patients was higher than that of serum antibodies (IgM, IgG, IgA and neutralizing antibodies (Nab)) against SARS-CoV-2 (all P < 0.001). However, the positive rate of serum SARS-CoV-2 N-Ag in convalescent COVID-19 patients was significantly lower than that of antibodies (all P < 0.001). Conclusion: Serum N-Ag can be used as a biomarker for early COVID-19 diagnosis based on appropriate cut-off values. In addition, our study also demonstrated the relationship between serum N-Ag and clinical characteristics.

IGF-1 Stimulates Glycolytic ATP Production in MCF-7L Cells.

The Insulin-like Growth Factor (IGF) system in breast cancer progression has been a matter of interest for decades, but targeting this system did not result in a successful clinical strategy. The system's complexity and homology of its two receptors-insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF-1R)-are possible causes. The IGF system maintains cell proliferation and also regulates metabolism, making it a pathway to explore. To understand the metabolic phenotype of breast cancer cells, we quantified their real-time ATP production rate upon acute stimulation with ligands-insulin-like growth factor 1 (1GF-1) and insulin. MCF-7L cells express both IGF-1R and IR, while tamoxifen-resistant MCF-7L (MCF-7L TamR) cells have downregulated IGF-1R with unchanged IR levels. Treating MCF-7L cells with 5 nM IGF-1 increased the glycolytic ATP production rate, while 10 nM insulin did not affect metabolism when compared with the control. Neither treatment altered ATP production in MCF-7L TamR cells. This study provides evidence of the relationship between metabolic dysfunction, cancer, and the IGF axis. In these cells, IGF-1R, and not IR, regulates ATP production.

Discrete Element Simulation of the Relationship betweenComposition, ITZ Property, and Tensile Behavior ofEco-Friendly UHPC Matrix.

To combat global warming, the development of eco-friendly ultra-high performance concrete (UHPC) has become one of the current research hotspots. Understanding the relationship between composition and performance of eco-friendly UHPC from a meso-mechanical point will be of great significance in proposing a more scientific and effective mix design theory. In this paper, the 3D discrete element model (DEM) of an eco-friendly UHPC matrix was constructed. The mechanism of the effect of the interface transition zone (ITZ) properties on the tensile behavior of an eco-friendly UHPC matrix was studied. The relationship between composition, ITZ property, and tensile behavior of eco-friendly UHPC matrix was analyzed. The results show that ITZ strength influences the tensile strength and cracking behavior of eco-friendly UHPC matrix. The effect of ITZ on the tensile properties of eco-friendly UHPC matrix is more significant than that of normal concrete. The tensile strength of UHPC will be increased by 48% when the ITZ property is changed from normal condition to perfect. Improving the reactivity of the binder system of UHPC will improve the performance of ITZ. The cement content in UHPC was reduced from 80% to 35%, and the σITZ/σPaste was reduced from 0.7 to 0.32. Both nanomaterials and chemical activators can promote the hydration reaction of the binder material, which in turn leads to better ITZ strength and tensile properties for an eco-friendly UHPC matrix.

Receptor for hyaluronan-mediated motility (RHAMM) defines an invasive niche associated with tumor progression and predicts poor outcomes in breast cancer patients.

Breast cancer invasion and metastasis result from a complex interplay between tumor cells and the tumor microenvironment (TME). Key oncogenic changes in the TME include aberrant synthesis, processing, and signaling of hyaluronan (HA). Hyaluronan-mediated motility receptor (RHAMM, CD168; HMMR) is an HA receptor enabling tumor cells to sense and respond to this aberrant TME during breast cancer progression. Previous studies have associated RHAMM expression with breast tumor progression; however, cause and effect mechanisms are incompletely established. Focused gene expression analysis of an internal breast cancer patient cohort confirmed that increased RHAMM expression correlates with aggressive clinicopathological features. To probe mechanisms, we developed a novel 27-gene RHAMM-related signature (RRS) by intersecting differentially expressed genes in lymph node (LN)-positive patient cases with the transcriptome of a RHAMM-dependent model of cell transformation, which we validated in an independent cohort. We demonstrate that the RRS predicts for poor survival and is enriched for cell cycle and TME-interaction pathways. Further analyses using CRISPR/Cas9-generated RHAMM-/- breast cancer cells provided direct evidence that RHAMM promotes invasion in vitro and in vivo. Immunohistochemistry studies highlighted heterogeneous RHAMM protein expression, and spatial transcriptomics associated the RRS with RHAMM-high microanatomic foci. We conclude that RHAMM upregulation leads to the formation of 'invasive niches', which are enriched in RRS-related pathways that drive invasion and could be targeted to limit invasive progression and improve patient outcomes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Suppression of Insulin Receptor Substrate 1 Inhibits Breast Cancer Growth In Vitro and in Female Athymic Mice.

Targeting the type I insulin-like growth factor receptor (IGF-IR) has not been successful in breast cancer. Data suggest the highly homologous insulin receptor (IR) may be an alternate growth stimulatory pathway used by cancer cells. Since both receptors phosphorylate the insulin receptor substrate 1 (IRS-1) protein as an immediate consequence of ligand binding, disruption of both receptors could be accomplished by suppression of IRS-1. IRS-1 gene deletion by CRISPR/Cas9 editing resulted in suppression of IGF-I, insulin, and estrogen-stimulated growth in hormone-dependent MCF-7L breast cancer cells. A doxycycline-inducible IRS-1 shRNA lentiviral construct was also used to infect MCF-7L breast cancer cells. IRS-1 shRNA downregulation resulted in decreased responses to IGF-I, insulin, and estradiol in monolayer and anchorage-independent growth assays. Decreased IRS-1 levels also suppressed estradiol-stimulated gene expression and estrogen receptor binding to DNA. Xenograft growth was also inhibited by induction of IRS-1 shRNA. These data show that IRS-1 is a critical regulator of endocrine responsive breast cancer. Efforts to target this adaptor protein could have broader growth inhibitory effects and receptor targeting.

Booster shot of inactivated SARS-CoV-2 vaccine induces potent immune responses in people living with HIV.

This study aimed to investigate the immunogenicity to SARS-CoV-2 and evasive subvariants BA.4/5 in people living with HIV (PLWH) following a third booster shot of inactivated SARS-CoV-2 vaccine. We conducted a cross-sectional study in 318 PLWH and 241 healthy controls (HC) using SARS-CoV-2 immunoassays. Vaccine-induced immunological responses were compared before and after the third dose. Serum levels of IgG anti-RBD and inhibition rate of NAb were significantly elevated at the "post-third dose" sampling time compared with the pre-third dose in PLWH, but were relatively decreased in contrast with those of HCs. Induced humoral and cellular responses attenuated over time after triple-dose vaccination. The neutralizing capacity against BA.4/5 was also intensified but remained below the positive inhibition threshold. Seropositivity of SARS-CoV-2-specific antibodies in PLWH was prominently lower than that in HC. We also identified age, CD4 cell counts, time after the last vaccination, and WHO staging type of PLWH as independent factors associated with the seropositivity of antibodies. PLWH receiving booster shot of inactivated vaccines generate higher antibody responses than the second dose, but lower than that in HCs. Decreased anti-BA.4/5 responses than that of WT impede the protective effect of the third dose on Omicron prevalence.

Pregnancy and fetal outcomes of chronic hepatitis C mothers with viremia in China.

BACKGROUND: Data that assess maternal and infant outcomes in hepatitis C virus (HCV)-infected mothers are limited. AIM: To investigate the frequency of complications and the associated risk factors. METHODS: We performed a cohort study to compare pregnancy and fetal outcomes of HCV-viremic mothers with those of healthy mothers. Risk factors were analyzed with logistic regression. RESULTS: Among 112 consecutive HCV antibody-positive mothers screened, we enrolled 79 viremic mothers. We randomly selected 115 healthy mothers from the birth registry as the control. Compared to healthy mothers, HCV mothers had a significantly higher frequency of anemia [2.6% (3/115) vs 19.0% (15/79), P < 0.001] during pregnancy, medical conditions that required caesarian section [27.8% (32/115) vs 48.1% (38/79), P = 0.004], and nuchal cords [9.6% (11/115) vs 34.2% (27/79), P < 0.001]. In addition, the mean neonatal weight in the HCV group was significantly lower (3278.3 ± 462.0 vs 3105.1 ± 459.4 gms; P = 0.006), and the mean head circumference was smaller (33.3 ± 0.6 vs 33.1 ± 0.7 cm; P = 0.03). In a multivariate model, HCV-infected mothers were more likely to suffer anemia [adjusted odds ratio (OR): 18.1, 95% confidence interval (CI): 4.3-76.6], require caesarian sections (adjusted OR: 2.6, 95%CI: 1.4-4.9), and have nuchal cords (adjusted OR: 5.6, 95%CI: 2.4-13.0). Their neonates were also more likely to have smaller head circumferences (adjusted OR: 2.1, 95%CI: 1.1-4.3) and lower birth weights than the average (≤ 3250 gms) with an adjusted OR of 2.2 (95%CI: 1.2-4.0). The vertical transmission rate was 1% in HCV-infected mothers. CONCLUSION: Maternal HCV infections may associate with pregnancy and obstetric complications. We demonstrated a previously unreported association between maternal HCV viremia and a smaller neonatal head circumference, suggesting fetal growth restriction.

Effects of Targeted Intervention plus Comprehensive Nursing on the Quality of Life and Nursing Satisfaction in Multiple Traumas.

Objective: To explore the effect of targeted intervention plus comprehensive nursing on quality of life and nursing satisfaction of patients with multiple traumas. Methods: Totally 68 cases with multiple traumas admitted to Xishan People's Hospital from September 2018 to September 2019 were recruited and randomized into a control group and a study group via the random number table method, with 34 cases in each group. The control group received conventional nursing, and the study group adopted targeted intervention plus comprehensive nursing. Results: The study group showed significantly lower life scores and Hospital Anxiety and Depression Scale (HADS) scores after the intervention, as compared to the control group. The average Newcastle Nursing Service Satisfaction Scale (NSNS) scores, various self-care ability scores, and comprehensive self-care ability scores were higher than those of the control group. Significantly lower Numerical Rating Scale (NRS) scores were observed in the study group at 7 d and 10 d of intervention than those of the control group. Conclusion: Targeted intervention plus comprehensive nursing enhances the quality of life of patients and nursing satisfaction, which merits clinical promotion.

Lowered Cd toxicity, uptake and expression of metal transporter genes in maize plant by ACC deaminase-producing bacteria Achromobacter sp.

In this study, an ACC deaminase-producing bacterial strain Achromobacter sp. A1 was isolated from maize rhizosphere soil, characterized and evaluated for the effects on cadmium (Cd) immobilization in solution/rhizosphere, physiological characteristics and the tissue Cd contents in maize and the molecular mechanisms involved by hydroponic and pot experiments. ACC deaminase activity of strain A1 was significantly enhanced by Cd addition and Cd concentration decreased (55.54-63.62%) in solution supplemented with various Cd concentrations. Strain A1 significantly increased the maize dry weights (30.77-105%) and chlorophyll content (7.46-14.46%), decreased MDA content (25.16-36.87%) and ethylene production (20.93-35.86%) in hydroponic experiment. Strain A1 significantly reduced the above-ground tissue Cd uptake by 12.64-33.68% and 42-48% in hydroponic and pot experiments, reduced the DTPA-extractable Cd content and elevated invertase, urease and catalase activity in rhizosphere soils. In addition, the expression levels of Cd transporter genes HMA3 and Nramp5 were significantly reduced in root and shoot after strain A1 inoculation. These results indicate that strain A1 has great potential for application as a novel and environmentally friendly inoculant to immobilize Cd and reduce maize Cd uptake in Cd-contaminated environments, and will improve the understanding of the relative molecular mechanisms underlying the response to strain A1 in maize plant.

Major adverse kidney events within 30 days in patients with acute pancreatitis: a tertiary-center cohort study.

BACKGROUND: To evaluate the event rate of major adverse kidney events within 30 days (MAKE30) in acute pancreatitis (AP) and its potential risk factors. METHODS: A retrospective analysis of a tertiary center data on all AP patients admitted within 72 h after onset of abdominal pain between June 2015 and June 2019 was conducted. MAKE30 - a composite of death, new renal replacement therapy (RRT), or persistent renal dysfunction (PRD) - and its individual components were retrieved at discharge or 30 days. Logistic regression analysis was used to assess the risk factors for MAKE30. RESULTS: 295 patients were enrolled and 16% experienced MAKE30. For individual components, the incidence was 3% for death, 15% for new RRT, and 5% for PRD. In multivariate logistic regression analysis, hyperchloremia at admission [OR = 8.38 (1.07-65.64); P = 0.043] and SOFA score [OR 1.63 (1.18-2.26); P = 0.003] were independent risk factors in predicting MAKE30. Further analysis showed that patients with hyperchloremia had more requirements of RRT (57% vs. 10%, P < 0.001), more PRD (14% vs. 4%, P = 0.034). CONCLUSION: MAKE30 is a common event in AP patients. Hyperchloremia and SOFA score at admission were two independent risk factors for MAKE30.

The room-temperature, ambient-pressure conversion of CO2 into value-added pharmaceutical products quinazoline-2,4(1H,3H)-diones.

As global warming due to CO2 emissions has become a widely recognized concern, CO2 capture, sequestration, neutralization, and conversion have become possible solutions to address this concern. Among these approaches, the conversion of CO2 into fuels or value-added products has attracted considerable attention. In this work, we report the high-efficiency conversion of CO2 to important industrial raw materials for pharmaceutical compounds, quinazoline-2,4(1H,3H)-diones, via reactions with 2-aminobenzonitriles at room temperature and under ambient pressure, with high conversion yields (91.5-99.3%). 1,8-Diazabicyclo-[5.4.0]-undec-7-ene (DBU), 1,1,3,3-tetramethylguanidine (TMG), and cholinium (Ch) ammonium-based ionic liquids (ILs) are employed as catalysts during the process. Cations with a pKa value near 11.9 and anions with a pKa value range of 10 to 15 are necessary for the reaction. The experimental results indicate that the ionic liquid pair [HDBU+][3-Cl-PhO-] has high efficiency under very mild conditions, obtaining high product yields of 91.5% at 25 °C and 1 atm and 99.3% at 30 °C and 1 atm. More importantly, the catalysts retain high efficiency and activity after 5 consecutive cycles. To gain insightful understanding of the reaction, density functional theory (DFT) calculations were conducted to study the reaction mechanism. The computational results indicate that the catalytic process contains three stages: cyano activation, intramolecular rearrangement, and intramolecular cyclization. Of these, the rate-determining step is cyano activation, which shows an energy barrier of 24.5 kcal mol-1. Tuning the types of ions in ILs can effectively reduce this energy barrier and allow high efficiencies.

Epidemiological investigation and intergenerational clinical characteristics of 24 coronavirus disease patients associated with a supermarket cluster: a retrospective study.

BACKGROUND: In view of the ongoing coronavirus disease (COVID-19) pandemic, it remains unclear whether the severity of illness and time interval from symptom onset to release from quarantine differ between cases that originated from clusters and cases reported in other areas. This study aimed to assess epidemiological and intergenerational clinical characteristics of COVID-19 patients associated with cluster outbreaks to provide valuable data for the prevention and control of COVID-19. METHODS: We identified the first employee with COVID-19 at a supermarket and screened the close contacts of this index patient. Confirmed cases were divided into two groups according to the generation (first generation comprising supermarket employees [group A] and second or third generations comprising family members or friends of the supermarket employees [group B]). The epidemiological and clinical characteristics of the two groups were retrospectively compared. RESULTS: A total of 8437 people were screened, and 24 COVID-19 patients were identified. Seven patients (29.2%) were asymptomatic; three patients were responsible for six symptomatic cases. The interval from the confirmation of the first case to symptom onset in symptomatic patients was 5-11 days. The clinical manifestations of symptomatic patients upon admission were non-specific. All patients (including the seven asymptomatic patients) were admitted based on chest computed tomography features indicative of pneumonia. There were 11 cases in group A (first generation) and 13 cases in group B (second generation, 11 cases; third generation, 2 cases), with no significant differences in clinical and epidemiological characteristics between the two groups, except for sex, duration from symptom onset to hospitalization, and underlying disease (P > 0.05). CONCLUSIONS: For cluster outbreaks, it is important to comprehensively screen close the contacts of the index patient. Special attention should be paid to asymptomatic cases. The clinical management of cluster patients is similar to that of other COVID-19 patients.

[Low temperature affects airway mucin secretion and promotes acute exacerbation of chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) has a high incidence, and leads to irreversible lung dysfunction. Preventing COPD acute exacerbation (AECOPD) and delaying the progression of the disease are the focus of treatment. However, there is still a lack of precise and effective preventive measures. A significant feature of AECOPD is the high incidence in winter. The traditional concept is that cold air in winter can be accompanied by increased virus replication, environmental pollution, and reduced air humidity. Various confounding factors intertwine to promote the occurrence of AECOPD, and the impact of low temperature itself has been neglected. In recent years, with the development of molecular biology, more and more studies have found that abnormal secretion of airway mucin can lead to obstruction of mucus clearance, increase the chance of infection, and participate in the development of COPD. Low temperature can affect mucin secretion through various mechanisms. This article summarizes the particularity of COPD airway temperature and the related ways of low temperature leading to mucin changes. It draws people's attention to low temperature in order to carry out basic research and provide new intervention methods for predicting and preventing the occurrence of AECOPD.

The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9.

BACKGROUND: For the study, we determine the potential biomarkers and uncover the regulatory mechanisms of lncRNA MALAT1 / miR-145 / SOX9 axis on the abilities of cell growth and cell metastasis of colorectal cancer. METHODS: Previously published dataset GSE18105 from GEO database was used for microarray analysis to identify differential-expressed lncRNAs and mRNAs. The miRNA which had targeted relationships with both lncRNA and mRNA was predicted using miRCode and Targetscan. The association between lncRNA and miRNA, miRNA and mRNA was verified using dual-luciferase reporter assay. Expression levels of lncRNA MALAT1, miR-145 and SOX9 were examined by quantitative RT-PCR analysis. The cell viability of two cancer cell lines was compared by CCK-8 assay. Colony formation was hired to detected cell proliferation. The cell cycle distribution and apoptotic cell rate were conducted by flow cytometry assay. Wound healing as well as transwell assay were compare the cell migration and cell invasion respectively among groups. The effect of MALAT1 on colorectal cancer in vivo was constructed by xenograft model. RESULTS: Significantly dysregulated lncRNAs and mRNAs were identified by microarray analysis. By experimental verification, MALAT1 and SOX9 were expressed in a high percentage of colorectal cancer tumors and cells, while miR-145 was in a low expression. We also identified miR-145 as a target of MALAT1 and SOX9. MALAT1 played a role in regulating cancer process by functioning as a competing endogenous RNA. Silencing MALAT1 could effectively decrease the expression level of SOX9, thus suppress cell viability and metastasis. Down-regulated MALAT1 could induce resistance of G1 phase in cell cycle, and facilitation of colorectal cancer cell apoptosis. Nude mice injected with cells transfected with si-MALAT1 had smaller tumor on size and weight. CONCLUSIONS: The regulatory function of lncRNA MALAT1 / miR-145 / SOX9 axis was revealed in colorectal cancer based on bioinformatics analysis. LncRNA MALAT1 could facilitate colorectal cancer cell proliferation, invasion and migration by down-regulating miR-145 and up-regulating SOX9. LncRNA MALAT1 could suppress cell cycle and apoptosis through MALAT1 / miR-145 / SOX9 axis.

Upregulation of microRNA-351 exerts protective effects during sepsis by ameliorating skeletal muscle wasting through the Tead-4-mediated blockade of the Hippo signaling pathway.

Sepsis-induced skeletal muscle wasting may lead to various severe clinical consequences. Understanding molecular mechanisms of the regulation of the loss of skeletal muscle mass in septic patients remains a significant clinical challenge. The current study was conducted to establish septic mice models to explore the relationship between microRNA (miR)-351 and the transcription element apical (TEA) domain transcription factor (Tead)-4 gene and to investigate its effects on the skeletal muscle through mediating the Hippo signaling pathway in mice with acute sepsis. A total of 60 mice were collected to establish mouse models of acute sepsis. The positive expression rate of Tead-4 and the apoptotic index (AI) were measured. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship between miR-351 and Tead-4. Furthermore, the muscle fiber diameter (MFD) and area (MFA) and the content of 3-methylhistidine (3-MH) and tyrosine (Tyr) were assessed. The expression levels of miR-351, p38-MAPK, Yes-associated protein, Tead-4, B-cell lymphoma X protein (Bax), and Caspase-3 were determined with quantitative RT-PCR and Western blot analysis. Finally, cell viability, apoptosis, and levels of inflammatory factors, including IL-1ß, IL-6, IGF-1, TNF-α, and monocyte chemoattractant protein-1 were detected by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and ELISA. Initially, Tead-4 protein expression was higher in skeletal muscle tissues of mice with acute sepsis. Tead-4 was identified to negatively regulate miR-351. Upregulation of miR-351 increased MFA and MFD, muscle weight water content, Bcl-2 expression levels, and cell viability. Up-regulation of miR-351 reduced AI; 3-MH and Tyr content; positive expression of Tead-4 protein; the expression levels of p38-MAPK, Yap, Tead-4, Bax, and Caspase-3; apoptosis; and inflammatory responses. The current study demonstrated that up-regulation of miR-351 inhibits the degradation of skeletal muscle protein and the atrophy of skeletal muscle in mice with acute sepsis by targeting Tead-4 through suppression of the Hippo signaling pathway. Thus, miR-351 overexpression may be a future therapeutic strategy for acute sepsis.-Zhang, L.-N., Tian, H., Zhou, X.-L., Tian, S.-C., Zhang, X.-H., Wu, T.-J. Upregulation of microRNA-351 exerts protective effects during sepsis by ameliorating skeletal muscle wasting through the Tead-4-mediated blockade of the Hippo signaling pathway.

Correlation between oral health and quality of life among the elderly in Southwest China from 2013 to 2015.

The aim of this study was to evaluate the oral health among the elderly in Southwest China and to analyze the correlation between common oral diseases and quality of life (QOL) in the same population, thus providing recommendations to improve their oral health and life quality.Elderly people (>60 years' old) were randomly recruited into our study, and we performed oral health examinations and diagnoses, using the Community Periodontal Index (CPI) to assess the periodontal condition, and Oral Health Impact Profile-14 (OHIP-14) to score life quality associated with oral health. Then we analyzed correlations between oral health and QOL as well as body mass index (BMI).A total of 687 subjects participated in our study and 212 (30.9%) were diagnosed with gingivitis or subgingival calculus, 291 (42.4%) with moderate chronic periodontitis, 136 (19.8%) with severe chronic periodontitis, 514 (74.8%) with dental caries, and 648 (94.3%) with dentition defects. A total of 653 (95.1%) qualified OHIP-14 scores were collected, with a median score of 13. The scores of the severe and moderate periodontitis were similar to the dentition defects, but higher than the scores for gingivitis and subgingival calculus. Considering the most common side effect, 11% of the subjects with severe chronic periodontitis were reported to be "unsatisfied with eating," and 48.4% of the participants with dentition defects complained about "troubles with pronunciation." A logistic regression analysis revealed that underweight (BMI <20) correlated with dental caries (odds ratio [OR]: 0.167, P = .040) and dentition defects (OR: 0.119, P = .016).The general oral health condition was poor among the elderly in Southwest China. Periodontitis and dentition defects have considerable negative effects on the QOL among this population.