Serum hyaluronic acid and procollagen III, N-terminal propeptide levels are highly associated with disease severity and predict the progression of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19). Methods: A total of 420 confirmed COVID-19 patients were included in the study. According to the "Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)", the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data. Results: Male patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P<0.05). Expectedly, serum inflammatory factors (NLR, PLR, LMR, CLR, PCT, CRP), coagulation markers (APTT, PT, TT, FIB, D-Dimer), Myocardial damage markers (hs-TNT, LDH) were significantly increased (P<0.05) in severe COVID-19 patients. Surprisedly, those patients showed obviously elevated levels of common tumor markers (ProGRP, CYFRA21-1, SCC, NSE) (P<0.05). In this case, the levels of tumor marker reflected more the condition of inflammation than the growth of tumor. More importantly, HA and PIIIN-P were highly associated with COVID-19 severity. The AUC of the ROC curve for the diagnosis of severe COVID-19 by HA and PIIIN-P was 0.826. Meanwhile, HA was positively correlated with myocardial damage markers (hs-TNT, LDH). PIIIN-P was positively correlated with myocardial damage markers (hs-TNT, LDH) and inflammatory factors (NLR, PLR, LMR, CLR, ProGRP, SCC, PCT, CRP). On the contrary, PIIIN-P was negatively correlated with pulmonary function indexes (oxygenation index and oxygen saturation of hemoglobin). Conclusion: HA and PIIIN-P are highly associated with disease severity and progression of COVID-19 and can be used as new markers for the prediction of severe COVID-19.

S100 Calcium-Binding Protein A8 Functions as a Tumor-Promoting Factor in Renal Cell Carcinoma via Activating NF-κB Signaling Pathway.

BACKGROUND: Renal cell carcinoma (RCC), arising from the renal tubular epithelium, is one of the most common types of genitourinary malignancies. Based on the Gene Expression Omnibus (GEO) database (GSE100666), S100 calcium-binding protein A8 (S100A8) was highly expressed in RCC tissues. S100A8, an inflammatory regulatory factor, has emerged as an important mediator associated with the occurrence and development of cancer. MATERIALS AND METHODS: The Gene Expression Omnibus (GEO) database was used to identify the key genes and investigate the main signaling pathways in RCC. Human RCC samples and corresponding adjacent normal tissues were collected in our hospital. The expression of S100A8 in human RCC samples was detected using western blotting and immunohistochemical analysis. S100A8 overexpression or knockdown was mediated by using Lipofectamine 3000 in human renal cell carcinoma cell line 786-O and ACHN cells. Basic experiments, including MTT and cell apoptosis assays, were utilized for investigating the function of S100A8 in RCC. Furthermore, the levels of inflammation were also evaluated in 786-O and ACHN cells. RESULTS: In the current study, we found that downregulation of S100A8 inhibited proliferation and promoted apoptosis in 786-O and ACHN RCC cells. Of note, S100A8 silencing downregulated the phosphorylation of NF-κB p65, thereby decreasing the levels of TNF-α, cleaved caspase1, and MMP9. By contrast, S100A8 upregulation could increase these expressions. CONCLUSION: Overall, S100A8 knockdown restrained RCC malignant biological properties, which was associated with the deactivation of the NF-κB signaling pathway. This present study demonstrates new insights that S100A8 may be a potential therapeutic target in RCC.

Psychological capital and alienation among patients with COVID-19 infection: the mediating role of social support.

BACKGROUND: COVID-19 infection continues all over the world, causing serious physical and psychological impacts to patients. Patients with COVID-19 infection suffer from various negative emotional experiences such as anxiety, depression, mania, and alienation, which seriously affect their normal life and is detrimental to the prognosis. Our study is aimed to investigate the effect of psychological capital on alienation among patients with COVID-19 and the mediating role of social support in this relationship. METHODS: The data were collected in China by the convenient sampling. A sample of 259 COVID-19 patients completed the psychological capital, social support and social alienation scale and the structural equation model was adopted to verify the research hypotheses. RESULTS: Psychological capital was significantly and negatively related to the COVID-19 patients' social alienation (p < .01). And social support partially mediated the correlation between psychological capital and patients' social alienation (p < .01). CONCLUSION: Psychological capital is critical to predicting COVID-19 patients' social alienation. Social support plays an intermediary role and explains how psychological capital alleviates the sense of social alienation among patients with COVID-19 infection.

IL-11 drives the phenotypic transformation of tracheal epithelial cells and fibroblasts to enhance abnormal repair after tracheal injury.

Tracheal stenosis (TS) is a multifactorial and heterogeneous disease that can easily lead to respiratory failure and even death. Interleukin-11 (IL-11) has recently received increased attention as a fibrogenic factor, but its function in TS is uncertain. This study aimed to investigate the role of IL-11 in TS regulation based on clinical samples from patients with TS and a rat model of TS produced by nylon brush scraping. Using lentiviral vectors expressing shRNA (lentivirus-shRNA) targeting the IL-11 receptor (IL-11Rα), we lowered IL-11Rα levels in the rat trachea. Histological and immunostaining methods were used to evaluate the effects of IL-11Rα knockdown on tracheal injury, molecular phenotype, and fibrosis in TS rats. We show that IL-11 was significantly elevated in circulating serum and granulation tissue in patients with TS. In vitro, TGFß1 dose-dependently stimulated IL-11 secretion from human tracheal epithelial cells (Beas-2b) and primary rat tracheal fibroblasts (PRTF). IL-11 transformed the epithelial cell phenotype to the mesenchymal cell phenotype by activating the ß-catenin pathway. Furthermore, IL-11 activated the atypical ERK signaling pathway, stimulated fibroblasts proliferation, and transformed fibroblasts into alpha-smooth muscle actin (α-SMA) positive myofibroblasts. IL-11-neutralizing antibodies (IL-11NAb) or ERK inhibitors (U0126) inhibited IL-11 activity and downregulated fibrotic responses involving TGFß/SMAD signaling. In vivo, IL-11Rα knockdown rats showed unobstructed tracheal lumen, relatively intact epithelial structure, and significantly reduced granulation tissue proliferation and collagen fiber deposition. Our findings confirm that IL-11 may be a target for future drug prevention and treatment of tracheal stenosis.

Latent profile analysis of security among patients with COVID-19 infection in mobile cabin hospitals and its relationship with psychological capital.

Aim: COVID-19 patients' security is related to their mental health. However, the classification of this group's sense of security is still unclear. The aim of our research is to clarify the subtypes of security of patients infected with COVID-19, explore the factors affecting profile membership, and examine the relationship between security and psychological capital for the purpose of providing a reference for improving patients' sense of security and mental health. Methods: A total of 650 COVID-19 patients in a mobile cabin hospital were selected for a cross-sectional survey from April to May 2022. They completed online self-report questionnaires that included a demographic questionnaire, security scale, and psychological capital scale. Data analysis included latent profile analysis, variance analysis, the Chi-square test, multiple comparisons, multivariate logistical regression, and hierarchical regression analysis. Results: Three latent profiles were identified-low security (Class 1), moderate security (Class 2), and high security (Class 3)-accounting for 12.00, 49.51, and 38.49% of the total surveyed patients, respectively. In terms of the score of security and its two dimensions, Class 3 was higher than Class 2, and Class 2 was higher than Class 1 (all P < 0.001). Patients with difficulty falling asleep, sleep quality as usual, and lower tenacity were more likely to be grouped into Class 1 rather than Class 3; Patients from families with a per capita monthly household income <3,000 and lower self-efficacy and hope were more likely to be grouped into Classes 1 and 2 than into Class 3. Psychological capital was an important predictor of security, which could independently explain 18.70% of the variation in the patients' security. Conclusions: Security has different classification features among patients with COVID-19 infection in mobile cabin hospitals. The security of over half of the patients surveyed is at the lower or middle level, and psychological capital is an important predictor of the patients' security. Medical staff should actively pay attention to patients with low security and help them to improve their security level and psychological capital.

Genital Microbiota of Women From Six Ethnic Groups With and Without Human Papillomavirus Infection in Shangri-La, China.

Background: A diversity of microorganisms is associated with human health and exists in a state of dynamic equilibrium. This diversity has direct implications for the assessment of susceptibility to infectious diseases, especially human papillomavirus (HPV) infection. Methods: Here, we investigated the relationships between HPV infection and vaginal, cervical, and gut microbiota composition and assessed the levels of genital immune mediators. We selected a multiethnic area in Yunnan Province, China, to collect samples from healthy women of childbearing age. A total of 82 healthy women of childbearing age were included in this study. Vaginal, cervical, and rectal swabs were collected to analyze the microbial community, and cytokines were analyzed in some samples. Findings: Different proportions and types of HPV infection were detected in cervical (44%), vaginal (18%), and rectal (18%) swabs. HPV detected in cervical swabs was generally a high-risk type, while low-risk HPV types were primarily detected in vaginal and rectal swabs. There were some differences in this proportion as well as in the microbial community composition among different ethnic groups. Rectal samples exhibited the highest diversity index, while vaginal samples displayed the lowest diversity index. Lactobacillus dominated most of the vaginal samples, was decreased in HPV-positive samples, and differed among different ethnic groups. However, the sequence proportion of Lactobacillus in the cervix exhibited the opposite trend in those affected by HPV infection. The dynamic balance between the potential pathogens Gardnerella and Lactobacillus determines the health of the female genital system. Interpretation: This study constitutes the first step toward personalized medicine for women's reproductive health, wherein differences between the genital microbiomes of individuals would be considered in risk assessment and for subsequent disease diagnosis and treatment.

Cord blood 25(OH)D3, cord blood total immunoglobulin E levels, and food allergies in infancy: A birth cohort study in Chongqing, China.

Background: Food allergy (FA) in infants has become a common disease worldwide. There are many controversies surrounding the relationships among levels of cord blood 25-hydroxy vitamin D3 [25(OH)D3], total immunoglobulin E (IgE), and FA. Methods: In this study, we recruited pregnant women in the third trimester undergoing obstetric examination in Chongqing City, Western China. Healthy full-term singleton births between May to August 2018 and November 2018 to January 2019 were included in the summer-birth and winter-birth cohorts, respectively. Questionnaires on vitamin D status in pregnancy and family allergies were used to investigate the pregnant women. The levels of <12 ng/mL, 12～20 ng/mL, and >20 ng/mL 25(OH)D3 in cord blood detected by liquid chromatography tandem mass spectrometry were considered deficient, insufficient, and sufficient, respectively. The electrochemiluminescence method was used to detect the total lgE levels in cord blood, classified into low-IgE (<0.35 IU/mL) and high-IgE (≥0.35 IU/mL) levels, respectively. Within postnatal 6 months, allergic symptoms in infants were investigated using questionnaire during the infants' monthly physical examinations. Suspected cases of FA underwent a history inquiry, skin prick test, food elimination test, and open-food challenge for diagnosis of FA. Multivariate logistic regression was used to analyze the risk factors of FA in infants. Results: In this study, we recruited 741 pairs of pregnant women and infants, including 343 infants in the summer-birth cohort and 398 infants in the winter-birth cohort. The incidence of FA within postnatal 6 months was 6.88%, showing significantly higher incidence of FA in the winter-birth cohorts than in the summer-birth cohorts (10.3% vs. 2.9%, χ2 = 15.682, P = 0.000). Among the 741 infants, 47.1%, 27.5%, and 13.8% of infants had deficient, insufficient, and sufficient 25(OH)D3, respectively, in the cord blood; 81.5% and 18.5% of infants had total low-IgE and total high-IgE levels, respectively, in the cord blood. No significant correlation was found between the 25(OH)D3 and IgE levels (r = -0.038, P = 0.300). Logistic regression analysis showed that winter birth [odds ratio (OR) 95% confidence interval (CI): 4.292 (2.003～8.359)] compared with infants in summer birth group, and sufficient (>20 ng/mL) 25(OH)D3 levels in cord blood [OR (95% CI): 2.355 (1.129～4.911) compared with infants in the deficient group (<12 ng/mL) and 3.782 (1.680～8.514) compared with infants in the insufficient group (12～20 ng/mL)] were independent risk factors for FA in infants within postnatal 6 months. Conclusions: Winter birth and sufficient 25(OH)D3 levels in infant cord blood were independent risk factors for FA in infants. 25(OH)D3 and total IgE levels in cord blood cannot be used as predictors of FA in early infancy.

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in children with autism spectrum disorder. / å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥çš„è¡€æ¸ èƒ°å²›ç´ æ ·ç”Ÿé•¿å› å­-1å’Œèƒ°å²›ç´ æ ·ç”Ÿé•¿å› å­ç»“åˆè›‹ç™½-3æ°´å¹³ç ”ç©¶.

OBJECTIVES: To study the serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in children with autism spectrum disorder (ASD) and their association with the core symptoms of ASD. METHODS: A total of 150 ASD children aged 2-7 years (ASD group) and 165 healthy children matched for age and sex (control group) who were recruited at the outpatient service of Chongqing Health Center for Women and Children were enrolled as subjects. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the core symptoms of the ASD children. Chemiluminescence was used to measure the serum levels of IGF-1 and IGFBP-3 in both groups. RESULTS: The ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). The children with severe ASD had significantly lower serum levels of IGF-1 and IGFBP-3 than those with mild-to-moderate ASD (P<0.001). For the children aged 2-3 years, the ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). Boys had a significantly lower serum level of IGF-1 than girls in both ASD and control groups (P<0.05). The serum levels of IGF-1 and IGFBP-3 were negatively correlated with the total score of CARS (r=-0.32 and -0.40 respectively, P<0.001). CONCLUSIONS: The reduction in serum IGF-1 level in early childhood may be associated with the development of ASD, and the serum levels of IGF-1 and IGFBP-3 are associated with the core symptoms of ASD children.

Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent.

BACKGROUND: Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS. METHODS: A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO2) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6-8 h after the ascent. RESULTS: Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P < 0.001), height (168.4 ± 5.9 vs. 171.3 ± 6.1 cm, P = 0.019), weight (62.0 ± 10.0 vs. 66.7 ± 8.6 kg, P = 0.014) and proportion of smokers (23.4% vs. 51.9%, P = 0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR) =6.32, P < 0.001), SpO2 change upon exercise at low altitude (OR = 0.63, P = 0.002) and systolic BP change after the ascent (OR = 0.96, P = 0.029). Women had larger reduction in SpO2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO2 after exercise was associated with both AMS incidence (P = 0.001) and AMS score (P < 0.001) in men but not in women. CONCLUSIONS: Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women. TRIAL REGISTRATION: Chinese Clinical Trial Registration, ChiCTR1900025728 . Registered 6 September 2019.

Clinical efficacy of the modified Helicobacter pylori eradication therapy for Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: a meta analysis.

BACKGROUND: Helicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP. METHODS: We searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I) statistic. RESULTS: A total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29-0.47). The combined estimate is I = 57% (P < 0.01). The study subjects were categorized by factors (area of patients). The pooled response rate of the sub-groups (Korea, Japan, China, and Western countries) was 0.63 (95% CI: 0.50-0.76), 0.16 (95% CI: 0.05-0.30), 0.38 (95% CI: 0.20-0.55), and 0.57 (95% CI: 0.08-1.00). The response rate showed that the modified HP eradication therapy was effective for patients with HP-negative gastric MALT lymphoma, especially in Korea and Western countries. CONCLUSION: Therefore, the modified HP eradication therapy can be considered an optional therapy for patients with low-grade HP-negative gastric MALT lymphoma. However, several limitations were revealed in the meta-analysis. Further systematic reviews and research are required.

[Adsorption of Cr(â ¥) in Water by Maifanite Modified with Different LDHs Coatings].

Under alkaline conditions, the hydrothermal coprecipitation method was used to form different layered double hydroxides (LDHs) by combining different bivalent and trivalent metal compounds, such as ZnCl2, MgCl2, AlCl3, and FeCl3, and then LDHs were coated on the surface of the original maifanite. The effect of LDHs coating-modified maifanite on the improvement of Cr(Ⅵ) adsorption in water was studied using isothermal adsorption, desorption, non-isothermal adsorption, adsorption kinetics, pH, and competitive adsorption tests, respectively. The results show that the maximum theoretical adsorption capacity of modified maifanite for Cr(Ⅵ) is close to ten times that of original maifanite at 15℃. The adsorption effect of ZnAl-LDHs coating-loaded modified maifanite is better than that of other LDHs-coating modified maifanites. In contrast, the results of the desorption experiments show that maifanite coated with LDHs enhances the reuse of substrates. The thermodynamic parameters of the substrate for Cr(Ⅵ) adsorption in the experiment were △Gθ < 0, △Hθ < 0, △Sθ > 0, indicating that the substrate adsorption process of Cr(Ⅵ) is spontaneous and exothermic. Based on the adsorption kinetics study, the adsorption process of Cr(Ⅵ) by maifanite could be fitted using a pseudo-secondary reaction process. The adsorption type was mainly chemisorption. By selecting the suitable metal ion combination method to prepare different LDHs-coating modified maifanites, the Cr(Ⅵ) performance can effectively be improved.

Tibial plateau fractures in elderly people: an institutional retrospective study.

BACKGROUND: Tibial plateau fractures are the most common intra-articular fractures, which require careful evaluation and preoperative planning. The treatment of tibial plateau fractures in elderly patients is challenging, and the comprehension of epidemiology and morphology can be helpful. This study described the characteristics of geriatric tibial plateau fractures. METHODS: A total of 327 (23.24%) patients aged ≥60 years were reviewed in our level one trauma center over a 4-year period (from January 2013 to November 2016). The following parameters were collected and evaluated: (1) demographic data, (2) injury mechanisms and (3) fracture classifications. RESULTS: Females accounted for 60.86% in all included elderly patients. Electric-bike accidents were the cause of 32.42% of all these injuries, and 39.62% of these led to high-energy injuries. The most common type of fracture was Schatzker II (54.74%). According to the three-column classification, single lateral column fracture (28.75%) and four-quadrant fracture (involving lateral, medial, posterolateral and posteromedial fractures) (23.24%) were the two most frequent patterns. In all cases, 67.58% involved the posterior column, and the prevalence of posterolateral and posteromedial fractures were 62.69% and 37.92% respectively. Isolated posterior column fractures accounted for 12.54% of patients in total, which mostly consisted of posterolateral fracture in older females (85.37%). CONCLUSIONS: The majority of elderly patients with tibial plateau fractures are females, and Electric-bike accidents are an important cause of injury. Geriatric tibial plateau fractures have unique distribution in classification.

The relationship between inflammatory factors, oxidative stress and DIO-1 concentration in patients with chronic renal failure accompanied with or without euthyroid sick syndrome.

Objective To investigate the relationship between inflammatory factors, oxidative stress and type 1 deiodinase (DIO-1) concentration in patients with chronic renal failure (CRF) with or without euthyroid sick syndrome (ESS). Methods This study recruited patients with CRF and divided them into two groups: group 1 had low free triiodothyronine (FT3) levels; and group 2 had normal FT3 levels. Group 3 consisted of healthy volunteers. Serum levels of interleukin (IL)-6, IL-1ß, tumour necrosis factor (TNF)-α, 8-isoprostane and DIO-1 were measured using enzyme-linked immunosorbent assays. Multiple regression analysis was used to analyse correlations between parameters. Results Sixty patients were enrolled into each group and the groups were comparable in terms of vital signs, white blood cell count, free thyroxine and thyroid stimulating hormone concentrations. The serum DIO-1 concentration was significantly higher in group 2 than in groups 1 and 3. Multivariate regression analysis revealed that the DIO-1 concentration was inversely correlated with the TNF-α concentration. Conclusions Patients with CRF without ESS showed higher concentrations of DIO-1 than patients with ESS. The DIO-1 concentration was inversely correlated with the TNF-α concentration, which might indicate that the inflammatory response was milder in the patients with CRF without ESS than in those with ESS.

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study.

BACKGROUND/AIMS: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. METHODS: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. RESULTS: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. CONCLUSION: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

Downregulation of MicroRNA-330 Correlates with the Radiation Sensitivity and Prognosis of Patients with Brain Metastasis from Lung Cancer.

BACKGROUND: The present study sought to explore the role of microRNA-330 (miR-330) in predicting the radiation response and prognosis of patients with brain metastasis (BM) from lung cancer (LC). METHODS: Patients with BM from LC were identified and classified into radiation-sensitive and radiation-resistant groups according to the overall survival rate, local and distant recurrence rate after conventional whole-brain radiation therapy. Quantitative realtime polymerase chain reaction (qRT-PCR) was used to detect miR-330 expression in serum. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic value of miR-330 for the radiation sensitivity of brain metastasis from LC. Related clinical factors for radiation sensitivity were assessed by logistic regression analysis, and a survival analysis was conducted using COX regression and the Kaplan-Meier method. RESULTS: MiR-330 exhibited lower expression in the radiation-sensitive group than in the radiation-resistant group. The area under the ROC curve of miR-330 for predicting radiation sensitivity was 0.898 (optimal cut-off value, 0.815), with a sensitivity of 71.7% and a specificity of 90.1%. After radiation therapy, patients with low miR-330 expression, compared to patients with high miR-330 expression, displayed a lower survival rate and a median survival time. MiR-330 expression was correlated with extracranial metastasis, maximum BM diameter, tumor-node-metastasis (TNM) stage and node (N) stage. Logistic regression and COX regression analyses revealed that extracranial metastasis, TNM stage, N stage and miR-330 expression were factors that influenced both radiation sensitivity and individual prognostic factors in patients with BM from LC. CONCLUSIONS: These findings indicate that the downregulation of miR-330 correlates with radiation sensitivity and poor prognosis in patients with BM from LC.

Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by targeting PDCD4 gene.

This study aims to explore the effects of microRNA-21 (miR-21) on radiosensitivity in non-small cell lung cancer (NSCLC) by targeting programmed cell deanth 4 (PDCD4) and regulating PI3K/AKT/mTOR signaling pathway. Cancer tissues and adjacent normal tissues were collected from 97 NSCLC patients who received a standard radiotherapy regimen. TUNEL assay was applied to determine cell apoptosis in tissues. The qRT-PCR assay was used to detect the expressions of miR-21 expression and PDCD4 mRNA. The protein expressions of PDCD4 and PI3K/AKT/mTOR signaling pathway-related proteins were determined by Western blotting. Colony formation assay was used to observe the sensitivity to radiotherapy of NSCLC cells. Flow cytometry was adopted to testify cell apoptosis. Compared with adjacent normal tissues, miR-21 expression was significantly increased and the mRNA and protein expressions of PDCD4 were decreased in NSCLC tissues. Higher miR-21 expression was associated with attenuated radiation efficacy and shorter median survival time. PDCD4 was the target gene of miR-21. The miR-21 mimics and siRNA-PDCD4 decreased the sensitivity to radiotherapy and cell apoptosis of A549 and H1299 cells and activated PI3K/AKT/mTOR pathway. The sensitivity of A549 and H1299 cells was strengthened in the miR-21 inhibitors group and the PI3K/AKT/mTOR inhibitors group. The siRNA-PDCD4 could reverse the effects of miR-21 inhibitors on sensitivity to radiotherapy and cell apoptosis of NSCLC cells. Our findings provide strong evidence that miR-21 could inhibit PDCD4 expression and activate PI3K/AKT/mTOR signaling pathway, thereby affecting the radiation sensitivity of NSCLC cells.

Up-Regulation of MicroRNA-133a Inhibits the MEK/ERK Signaling Pathway to Promote Cell Apoptosis and Enhance Radio-Sensitivity by Targeting EGFR in Esophageal Cancer In Vivo and In Vitro.

This study aims to explore how microRNA-133a (miR-133a) affects cell apoptosis and radio-sensitivity by targeting EGFR via regulating MEK/ERK pathway in esophageal cancer (EC). A total of 358 EC patients were selected and assigned into the resistant and sensitive groups. Human EC KYSE 150 cell line was assigned into the blank, negative control (NC), miR-133a mimic, miR-133a inhibitors, si-EGFR, miR-133a inhibitors + si-EGFR groups after transfection. MiR-133a and EGFR mRNA expressions were detected by qRT-PCR and EGFR, MEK/ERK pathway-related protein expressions were detected by Western blotting. The radio-sensitivity and cell apoptosis were testified by clone formation and flow cytometry. MiR-133a was up-regulated but EGFR was down-regulated in the sensitive group than in the resistant group. Compared with the blank and NC groups, the miR-133a mimic and si-EGFR groups exhibited increased cell apoptosis rate but decreased EGFR, p-MEK1/2, and p-ERK1/2 protein expressions; while opposite trend was observed in the miR-133a inhibitors group. Compared with the miR-133a inhibitors group, the miR-133a inhibitors + si-EGFR group presented reduced cell survival rate, EGFR, p-MEK1/2, and p-ERK1/2 protein expressions but increased cell apoptosis rate. These results indicated that miR-133a could inhibit the MEK/ERK pathway to promote cell apoptosis and enhance radio-sensitivity by targeting EGFR in EC. J. Cell. Biochem. 118: 2625-2634, 2017. © 2017 Wiley Periodicals, Inc.

The impact of smoking on levels of chronic periodontitis-associated biomarkers.

OBJECTIVE: To investigate the effect of smoking on the expression levels of matrix metalloproteinase (MMP)-1, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and the concentrations of TNF-α and IL-10 in patients with chronic periodontitis (ChP). METHODS: This is an ex-vivo study. Our study consisted of 78 cases, all of which were diagnosed with ChP and were selected according to the inclusion and exclusion criteria. Among these 78 cases, 38 patients were classified into the smoking group (S-ChP group), and 40 patients in the non-smoking group (NS-ChP group). The clinical periodontal parameters of all patients were recorded, including the plaque index (PLI), probing depth (PD), loss of attachment (LA) and sulcus bleeding index (SBI). Serum was collected from forearm blood to establish a Porphyromonas gingivalis (Pg) internalizing KB cell model. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of MMP-1, MMP-9 and TIMP-1 in the KB cell lysis solution as well as IL-10 and TNF-α in the gingival crevicular fluid (GCF). RESULTS: Fewer Pg internalizing KB cell colonies were observed in the NS-ChP group than in the S-ChP group (P<0.01). When 400µL serum was added, there were remarkable differences in the concentrations of MMP-1 and TIMP-1 secreted from the KB cells between the S-ChP and NS-ChP groups (MMP-1: t=-21.71, P<0.01; TIMP-1: t=64.35, P<0.001). Additionally, when 800µL serum was added, there were significant differences in the concentrations of MMP-1, MMP-9 and TIMP-1 in the KB cells between the S-ChP and NS-ChP groups (MMP-1: t=-81.89, P<0.001; MMP-9: t=-15.67, P<0.001; TIMP-1: t=109.4, P<0.001). The TNF-α levels were higher, but the IL-10 levels were lower in the GCF from the ChP patients in the S-ChP group than those in the NS-ChP group (both P<0.001). CONCLUSION: The serum of S-ChP patients can enhance the concentrations of MMP-1 and MMP-9, but reduce TIMP-1 secreted from Pg internalizing KB cells. However, the concentration of TNF-α was increased and IL-10 was decreased. Abnormal concentrations of ChP-associated biomarkers may be conducive to the development and progression of ChP.

Effects of CYP3A5 genetic polymorphism and smoking on the prognosis of non-small-cell lung cancer.

OBJECTIVE: We aimed to explore the impacts of the rs776746 polymorphism in the CYP3A5 gene and smoking on the prognosis of non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Our study enrolled 104 early NSCLC patients undergoing surgery and 107 advanced NSCLC patients undergoing chemotherapy, hospitalized between December 2009 and December 2012 at the First Affiliated Hospital of Liaoning Medical University. All subjects with complete follow-up data were pathologically diagnosed. The rs776746 polymorphism and different genotypes (*1/*1, *1/*3, and *3/*3) were identified by polymerase chain-reaction restriction fragment-length polymorphism. RESULTS: Clinical response to chemotherapy in NSCLC patients with *1/*1 + *1/*3 genotypes were significantly worse than in those with the *3/*3 genotype (17.78% vs 56.45%, P<0.001), and after Bonferroni adjustment, the differences still showed significance (P c<0.01). The mortality risk of NSCLC patients undergoing chemotherapy with the *3/*3 genotype was 0.617 times those with *1/*1 + *1/*3 genotypes (relative risk [RR] 0.617, 95% confidence interval [CI] 0.402-0.948; P=0.028), while the mortality risk of smoking patients was 1.743 times greater than that of nonsmoker patients (RR 1.743, 95% CI 1.133-2.679; P=0.042). Furthermore, a 3.087-fold mortality risk was found in NSCLC patients undergoing surgery with the *3/*3 genotype compared with those with *1/*1 + *1/*3 genotypes (RR 3.087, 95% CI 1.197-7.961; P=0.020). In NSCLC patients undergoing surgery, the mortality risk of smokers was 1.896 times greater than nonsmokers (RR 1.896, 95% CI 1.040-3.455; P=0.037). CONCLUSION: Our study demonstrated that the CYP3A5 rs776746 polymorphism and smoking may influence the prognosis of NSCLC patients undergoing chemotherapy and surgery.

Expression of miRNA-26b in the diagnosis and prognosis of patients with non-small-cell lung cancer.

OBJECTIVE: To investigate the correlation between miR-26b and non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: NSCLC tissues and normal lung tissues that were more than 7 cm adjacent from tumor were collected from 154 NSCLC patients. Additionally, 63 normal specimens from benign lung disease were selected as the control group. Real-time fluorescent quantitative PCR was used to detect miR-26b expression in tissues. RESULT: miR-26b expression in NSCLC tissues was significantly lower than in other two types of tissues. Receiver operating characteristic curve analysis showed that the area under the curve was 0.856 with sensitivity and specificity of 79.9 and 79.4%, respectively. miR-26b expression was a risk factor for poor prognosis of NSCLC. CONCLUSION: The expression of miR-26b is downregulated in NSCLC tissues, and it might be useful in the diagnosis and prognosis of NSCLC patients.