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Background/purpose: Dental plaque is the main cause leading to the dental caries and periodontal diseases. The main purpose of this study was to test the efficacy of oral spray containing the antimicrobial peptide P-113 on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment. Materials and methods: This study was divided into two parts. In Part A, we investigated the user experiences with the P-113 containing oral spray. In part B, 14 subjects in the experimental group used the P-113-containing oral spray, while 14 subjects in the control group used a placebo without the P-113 in a 4-week clinical trial. Participants were asked to use the P-113-containing oral spray or placebo 3 times per day and 5 times per use. Moreover, 3 check-ups and 2 washouts were carried out to evaluate the DMFT score, dental plaque weight, dental plaque index, and gingival index. Results: In part A, up to 91.8% of the subjects in the experimental group were satisfied with the use of the P-113-containing oral spray. In part B, based on our PacBio SMRT sequencing platform and DADA2 analysis, the numbers of Streptococcus and Porphyromonas in the experimental group were lower than those in the control group. In addition, decreased dental plaque weight, dental plaque index, and gingival index were all observed in the experimental group. Conclusion: The P-113-containing oral spray has the potential to reduce the dental caries and periodontal disease-related bacteria and to control the dental plaque formation.

Abstract TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

Objective To understand the distribution of body mass index （BMI） in non-dialysis patients with chronic kidney disease （CKD） and explore the possible influencing factors. MethodsA total of 369 patients participated in this cohort study for more than 6 months. And uni/multifactorial comparisons were made for distribution of BMI, diet/exercise profiles, nature/type of food and frequency of exercise. Results The level of BMI was excess （n = 84, 22.76%）, normal （n = 263, 71.27%） and too-low （n = 22, 5.97%）. No statistically significant inter-group differences existed in nature/type of food. Statistically significant inter-group differences in exercise frequency existed （P = 0.008）. Regression models were constructed by combining the above-mentioned influencing factors and other potential factors. The model revealed that exercise frequency （β = −0.201, P＜0.01） and beverage intake （β = 0.110, P = 0.032） were independent influencing factors of BMI. Conclusion BMI is generally normal for non-dialysis CKD patients at our center. And the number of BMI overload is greater than that of underload. Exercise frequency and beverage intake may be independent influencing factors of BMI.

Background/purpose: Oral health is related to general health and a person’s overall well-being. The aim of the present study was to explore the association between oral health status and bite force among young adults. Materials and methods: Maximum bite force (MBF) was measured using Dental Prescale II in conjunction with a pressure-sensitive film and bite force analyzer in 40 young adults aged 20 to 40. Supragingival dental plaque was collected and cultured. Plaque weight, pH, and colony counts were assessed. The decayed, missing, and filled teeth index (DMFT) and body mass index (BMI) were recorded. Results: Bite force was negatively correlated with the number of missing teeth and the sum of missing and filled teeth. When the filled-to-remaining-teeth ratio (F/R ratio) was less than 8%, the bite force was significantly higher compared to an F/R ratio of 8–25%. Additionally, the amount of total bacteria was positively correlated with total bite force, and the quantity of Streptococcus mutans (S. mutans) along with total bacteria was positively correlated with bite force in the molar region (∗P

Background/purpose: 3D-printed bone tissue engineering is becoming recognized as a key approach in dentistry for creating customized bone regeneration treatments fitting patients bone defects requirements. 3D bioprinting offers an innovative method to fabricate detailed 3D structures, closely emulating the native bone micro-environment and better bone regeneration. This study aimed to develop an 3D-bioprintable scaffold using a combination of alginate and β-tricalcium phosphate (β-TCP) with the Cellink® BioX printer, aiming to advance the field of tissue engineering. Materials and methods: The physical and biological properties of the resulting 3D-printed scaffolds were evaluated at 10 %, 12 %, and 15 % alginate combined with 10 % β-TCP. The scaffolds were characterized through printability, swelling behavior, degradability, and element analysis. The biological assessment included cell viability, alkaline phosphatase (ALP) activity. Results: 10 % alginate/β-TCP 3D printed at 25 °C scaffold demonstrated the optimal condition for printability, swelling capability, and degradability of cell growth and nutrient diffusion. Addition of β-TCP particles significantly improved the 3D printed material viscosity over only alginate (P

Abstract Background Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. Purpose Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3–5. Methods This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3–5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. Results 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. Conclusion Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3–5.

BackgroundChinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3–5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear.MethodsPatients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)

Background/purpose: Salivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored. Materials and methods: Immunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC in vitro and in vivo. Results: We found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells in vitro. MUC1 knockdown significantly inhibited tumor growth in vivo, and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway. Conclusion: Our results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC.

Abstract We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child–Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002–1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003–1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006–1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009–1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029–1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child–Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761–0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

Background/purpose: Artificial Intelligence (AI) can optimize treatment approaches in dental healthcare due to its high level of accuracy and wide range of applications. This study seeks to propose a new deep learning (DL) ensemble model based on deep Convolutional Neural Network (CNN) algorithms to predict tooth position, detect shape, detect remaining interproximal bone level, and detect radiographic bone loss (RBL) using periapical and bitewing radiographs. Materials and methods: 270 patients from January 2015 to December 2020, and all images were deidentified without private information for this study. A total of 8000 periapical radiographs with 27,964 teeth were included for our model. AI algorithms utilizing the YOLOv5 model and VIA labeling platform, including VGG-16 and U-Net architecture, were created as a novel ensemble model. Results of AI analysis were compared with clinicians' assessments. Results: DL-trained ensemble model accuracy was approximately 90% for periapical radiographs. Accuracy for tooth position detection was 88.8%, tooth shape detection 86.3%, periodontal bone level detection 92.61% and radiographic bone loss detection 97.0%. AI models were superior to mean accuracy values from 76% to 78% when detection was performed by dentists. Conclusion: The proposed DL-trained ensemble model provides a critical cornerstone for radiographic detection and a valuable adjunct to periodontal diagnosis. High accuracy and reliability indicate model's strong potential to enhance clinical professional performance and build more efficient dental health services.

Abstract Background Single-nucleotide polymorphisms (SNPs) in various genetic loci are associated with childhood obesity; however, their influence on adolescent growth patterns has rarely been explored. This study investigated whether genetic variants could predict tri-ponderal mass index (TMI)-derived growth trajectories and the interaction between genetic and dietary factors. Methods We conducted Taiwan Puberty Longitudinal Study, a prospective cohort that recruited 1,135 children since 2018. Anthropometric measurements were recorded every three months, while dietary nutrition assessment and biological sampling for genotyping were collected during the first visit. TMI growth trajectory groups were identified using growth mixture modeling. A multinomial logistic regression model for different growth trajectories was used to examine the effect of candidate SNPs, and the most related SNPs were used to establish the genetic risk score. We then explored the effect of the genetic risk score in subgroup analysis according to dietary calories and different dietary consumption patterns. Results Three TMI-based growth trajectory groups were identified among adolescents. The “increased weight” trajectory group accounted for approximately 9.7% of the participants. FTO/rs7206790 was associated with the increased weight growth trajectory after adjusting for the baseline TMI and other correlated covariates (OR: 2.13, 95% CI: 1.08–4.21). We generated the genetic risk score using 4 SNPs (FTO/rs7206790, ADCY9/rs2531995, TFAP2B/rs4715210, and TMEM18/rs6548238) and selected the threshold of 10 points to define risk categories. There were 11.66% and 3.24% of participants belonged to the increased weight trajectory in high- and low-risk groups, respectively; and the predictive ability of the genetic risk score was notable among low calories intake participants (OR: 1.90, 95% CI: 1.18–3.05 vs. OR: 1.17, 95% CI: 0.78–1.75 in high calories intake group). Conclusion Our results offer a new perspective on the genetic and dietary basis of changes in adolescent obesity status. Individualized interventions for obesity prevention may be considered among high-risk children.

ABSTRACT Objective: An increasing amount of literature indicates that the serum calcium level may be related to metabolic syndrome (MetS) and obesity. This study aimed to examine the relationship between the serum calcium level and MetS in adults in Taiwan. Subjects and methods: We conducted a cross-sectional study and enrolled 1,580 participants (54.4% women; mean age, 33.28 ± 12.21 years) who underwent health examinations in northern Taiwan between 2012 and 2016. Logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of MetS and its components in groups of patients in the tertiles of the serum calcium level. Results: In total, 167 participants (10.6%) had MetS. The odds of high systolic blood pressure (BP), blood glucose, and triglyceride (TG) levels significantly increased as the serum calcium level increased. Compared with the participants in the lowest tertile of the serum calcium level (tertile 1), those in the second tertile (OR = 1.47, 95% CI: 0.97-2.23) and third tertile (OR = 1.63, 95% CI: 1.06-2.53) had a significantly higher risk of MetS. Further analyses revealed a significant association between MetS and an increased serum calcium level in those in the overweight and obese groups. However, there was no association between the serum calcium levels and MetS in those in the normal weight group. Conclusion: This study demonstrated that a higher serum calcium level is associated with an increased risk of MetS and its components in adults with overweight and obesity.

PurposeThe study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves.MethodsA retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. ResultsA total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p

Introduction: To overcome the genuine bioinert properties of zirconia ceramic, functionalization of the surface with the bioactive protein fibronectin was conducted.Methods: Glow discharge plasma (GDP)-Argon was first used to clean the zirconia surface. Then allylamine was treated at three different powers of 50 W, 75 W, and 85 W and immersed into 2 different fibronectin concentrations (5 µg/ml and 10 µg/ml).Results and Discussion: After surface treatment, irregularly folded protein-like substances were attached on the fibronectin coated disks, and a granular pattern was observed for allylamine grafted samples. Infrared spectroscopy detected C-O, N-O, N-H, C-H, and O-H functional groups for fibronectin treated samples. Surface roughness rose and hydrophilicity improved after the surface modification, with MTT assay showing the highest level of cell viability for the A50F10 group. Cell differentiation markers also showed that fibronectin grafted disks with A50F10 and A85F10 were the most active, which in turn encouraged late-stage mineralization activity on 21d. Up-regulation of osteogenic related mRNA expression from 1d to 10d can be observed in RT-qPCR data for ALP, OC, DLX5, SP7, OPG and RANK biomarkers. These physical and biological properties clearly indicate that an allylamine and fibronectin composite grafted surface significantly stimulated the bioactivity of osteoblast-like cells, and can be utilized for future dental implant applications.

Abstract Background Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. Methods In this ambispective intervention cohort study,1,200 patients with CKD stages 1–5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1–2 and trimonthly in stage 3–5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. Discussion This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. Trial registration Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378

Studies have shown that downregulation of nuclear-enriched autosomal transcript 1 (Neat1) may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice. Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear. Therefore, the effects of Neat1 on neuronal apoptosis were observed. C57BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro, and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro. The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons, and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed. The experiment was divided into four groups: the control group, without any treatment, received normal culture; the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol; the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol. The protein expression levels of neurons p53-induced death domain protein 1 (PIDD1, a pro-apoptotic protein), caspase-2 (an apoptotic priming protein), cytochrome C (a pro-apoptotic protein), and cleaved caspase-3 (an apoptotic executive protein) were measured in each group using the western blot assay. To observe changes in the intracellular distribution of cytochrome C, the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay. Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. The results showed that the apoptosis rate, PIDD1, caspase-2, and cleaved caspase-3 expression levels significantly decreased, and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group; however, Neat1 downregulation reversed these changes. Compared with the Neat1 downregulation group, the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased, and the mitochondrial cytochrome C level significantly increased. These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway, reducing the activation of caspase-3, and preventing neuronal apoptosis after oxygen and glucose deprivation, which might reduce secondary brain injury after traumatic brain injury. All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China, on December 19, 2020 (approval No. 2020-895).

BackgroundTime-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy.MethodsThis is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks.ResultsThe change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 μmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction.ConclusionPreliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.

Abstract Objectives The least amount of contrast medium (CM) should be used under the premise of adequate diagnosis. The purpose of this study is to evaluate the feasibility of utilizing ultra-low-dose (224 mgI/kg) CM for pancreatic artery depiction using the combination of advanced virtual monoenergetic imaging (VMI+) and high-concentration (400 mgI/mL) CM. Materials and methods 41 patients who underwent both normal dose CM (ND-CM, 320 mgI/kg) and low dose CM (LD-CM, 224 mgI/kg) thoracoabdominal enhanced CT for tumor follow-up were prospectively included. The VMI+ at the energy level of 40-kev for LD-CM images was reconstructed. CT attenuation, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the abdominal artery, celiac artery, and superior mesenteric artery (SMA) and qualitative scores of pancreatic arteries depiction were recorded and compared among the three groups (ND-CM, LD-CM, and VMI+ LD-CM images). ANOVA and Friedman tests were used for statistical analysis. Results All quantitative and qualitative parameters on LD-CM images were lower than that on ND-CM images (all p 0.05). VMI+ LD-CM images had the highest mean CT and CNR values of all arteries (all p

Background and objectivesCerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the ‘glymphatic system’. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients.MethodsWe conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity.ResultsThe median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p

Abstract A major number of studies have demonstrated Beta-tricalcium phosphate (β-TCP) biocompatibility, bioactivity, and osteoconductivity characteristics in bone regeneration. The aim of this research was to enhance β-TCP's biocompatibility, and evaluate its physicochemical properties by argon glow discharge plasma (GDP) plasma surface treatment without modifying its surface. Treated β-TCP was analyzed by scanning electron microscopy (SEM), energy-dispersive spectrometry, X-ray photoelectron spectroscopy (XPS), X-ray diffraction analysis, and Fourier transform infrared spectroscopy characterization. To evaluate treated β-TCP biocompatibility and osteoblastic differentiation, water-soluble tetrazolium salts-1 (WST-1), immunofluorescence, alkaline phosphatase (ALP) assay, and quantitative real-time polymerase chain reaction (QPCR) were done using human mesenchymal stem cells (hMSCs). The results indicated a slight enhancement of the β-TCP by GDP sputtering, which resulted in a higher Ca/P ratio (2.05) than the control. Furthermore, when compared with control β-TCP, we observed an improvement of WST-1 on all days (p

BackgroundDental caries and periodontal disease remain the most prevalent oral health problems in the world. Chewing xylitol gum may help reduce the risk of caries and periodontitis for dental health benefits. However, little evidence has shown healthy food estimation by sequencing 16S rDNA in oral microbial communities. This study investigated the clinical effect of xylitol chewing gum on dental plaque accumulation and microbiota composition using the PacBio full-length sequencing platform in 24 young adults (N = 24). The participants were randomly assigned to xylitol chewing gum and control (no chewing gum) groups. Participants in the chewing gum group chewed ten pieces of gum (a total of 6.2 g xylitol/day). Dental plaque from all teeth was collected for weighing, measuring the pH value, and analysis of microbial communities at the beginning (baseline, M0) and end of the 2-week (effect, M1) study period.ResultsThe results suggested a 20% reduction in dental plaque accumulation (p < 0.05) among participants chewing xylitol gum for 2 weeks, and the relative abundance of Firmicutes (a type of pathogenic bacteria associated with caries) decreased by 10.26% (p < 0.05) and that of Bacteroidetes and Actinobacteria (two types of pathogenic bacteria associated with periodontitis) decreased by 6.32% (p < 0.001) and 1.66% (p < 0.05), respectively. Moreover, the relative abundance of Fusobacteria was increased by 9.24% (p < 0.001), which has been proven to have a higher proportion in dental plaque of healthy adults. However, the dental plaque pH value stayed in a healthy range for the two groups.ConclusionIn conclusion, chewing xylitol gum would benefit cariogenic and periodontal bacterial reduction in the oral cavity, which could help to prevent the diseases related to these bacteria.

BackgroundNeuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC–MSCs) in treating NMOSD.MethodsThe trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC—MSCs. Patients will be treated with three different doses of hUC–MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years.DiscussionAlthough hUC–MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC–MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC–MSC in treating NMOSD and might be able to determine the optimal dose of hUC–MSC for NMOSD patients.Trial registrationThe study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

Ground-penetrating radar (GPR) has been used in a wide range of shallow detection applications, such as underground geological mapping, highway detection, and hydrogeology survey. In recent years, GPR has been most widely utilized in tunnel geological prediction because it has the advantages of high resolution, intuitionistic results, and fast scanning. In addition, GPR signal is a typical nonstationary and time-varying signal, with its electromagnetic wave exhibiting strong absorption attenuation and dispersion as it propagated in complex surrounding rock. At the same time, the GPR response is often characterized by a weak signal and a strong interference because of numerous system interferences in the tunnel detection environment, which lead to difficulties in data processing and interpretation. Therefore, interference elimination is always a difficult problem when GPR is applied to tunnel geological prediction. In this study, through the introduction of shearlet transform (ST) to GPR signal processing, an adaptive thresholding method is proposed to eliminate random interference on the basis of the energy difference between effective and interference signals in the shearlet domain at different scales and directions. The advantages of this method in random interference removal are verified by forward simulation data. On this basis, the interference signal, as well as its energy proximity and frequency anomaly, common in advanced tunnel geological prediction is taken as an example to illustrate the effect of wavelet transform (WT) on its removal. In this manner, WT and ST are combined to suppress interference. First, WT is used to separate abnormal frequency interference. Then, ST based on the adaptive thresholding method is used to suppress random interference. The results of practical engineering cases of karst cave detection in the field show that the method proposed in this study can remove the interference signal, retain the effective signal, and highlight the abnormal geological area on the basis of the processed waveform stacking diagram to improve the interpretation accuracy of GPR data.

Graphical Abstract

Background: N6-Methyladenosine (m6A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. But its role in neuromyelitis optica spectrum disorders (NMOSD) is not known.Aims: To explore the mechanism of m6A in NMOSD patients.Methods: This study assessed the m6A methylation levels in blood from two groups: NMOSD patients and healthy controls. Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) and RNA-seq were performed to assess differences in m6A methylation between NMOSD patients and healthy controls. Ultra-high performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS) method was performed to check m6A level. Differential m6A methylation genes were validated by MeRIP-qPCR.Results: Compared with that in the control group, the total m6A level was decreased in the NMOSD group. Genes with upregulated methylation were primarily enriched in processes associated with RNA splicing, mRNA processing, and innate immune response, while genes with downregulated methylation were enriched in processes associated with the regulation of transcription, DNA-templating, and the positive regulation of I-kappa B kinase/NF-kappa B signalling.Conclusion: These findings demonstrate that differential m6A methylation may act on functional genes to regulate immune homeostasis in NMOSD.

Guided-bone regeneration (GBR) is increasingly using three-dimensional (3D) printing by fused deposition modeling (FDM) to build the filaments used for treatment. Polylactic acid (PLA) and beta-tricalcium phosphate (β-TCP) are widely used as base materials in 3D printing, necessitating that they are studied together in the context of GBR treatment. This study sought to test and compare the properties and efficacy of different ratios of β-TCP and PLA used to make the 3D-printed filament material to find the most effective combination of materials for GBR treatment. Several ratios of PLA to β-TCP were tested, including PLA/β-TCP ratios of 95%/5% (PLA-5), 90%/10% (PLA-10), 85%/15% (PLA-15), and 80%/20% (PLA-20), and quantitative real-time polymerase chain reaction (qPCR) in vitro testing was done to characterize the material. After adding β-TCP to PLA, mechanical testing indicated that tensile and elongation strengths decreased, hardness was retained, and cell proliferation was promoted. The effect of PLA and β-TCP on increasing alkaline phosphatase (ALP) activity was significantly greater in a ratio of 10% β-TCP/90% PLA at 5 days (p < 0.05) than in any other ratios tested. This is supported by results from qPCR testing, which showed early osteoblast-like differentiation of DLX5, RUNX2, OPG, OC, and collagen type 1 (COL-1) expression levels similar to cells cultured on PLA-10. Our results demonstrated that 3D printing of filaments produced in a ratio of 90% PLA to 10% β-TCP was more effective for GBR than that of filaments produced only using PLA.

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.

Abstract Open heart surgeries are common for treating ischemic and heart valve disease. During cardiac surgery, cardiopulmonary bypass (CPB) can temporarily take over the function of heart and lungs. However, elevated red blood cell (RBC) aggregation may lead to the common side-effects such as microinfarction. We investigated blood physical properties changes and the correlation between blood microstructure, viscoelastic response and biochemical changes following surgery with CPB. We examined shear-rate dependent blood viscosity, elasticity and RBC aggregate size in the pre-surgery disease state, post-surgery state and long-term recovery state of cardiac surgical patients. Within a week following surgery, the patient hematocrit was significantly lower due to CPB. Despite lower RBC concentration, the RBC aggregate shape became larger and more rounded, which is correlated to the elevated plasma fibrinogen related to systemic inflammatory response. During the same period, the hematocrit-adjusted low shear rate viscosity increased significantly, as did the yield stress, indicating more solid-like behavior for blood. Six months to one year later, all the physical and biochemical properties measured returned to baseline.

Abstract Background Inhaled corticosteroids are recommended as the first-line controller medication for childhood asthma owing to their multiple clinical benefits. However, heterogeneity in the response towards these drugs remains a significant clinical problem. Methods Children aged 5 to 18 years with mild to moderate persistent asthma were recruited into the Taiwanese Consortium of Childhood Asthma Study. Their responses to inhaled corticosteroids were assessed based on their improvements in the asthma control test and peak expiratory flow. The predictors of responsiveness were demographic and clinical features that were available in primary care settings. We have developed a prediction model using logistic regression and have simplified it to formulate a practical tool. We assessed its predictive performance using the area under the receiver operating characteristic curve. Results Of the 73 asthmatic children with baseline and follow-up outcome measurements for inhaled corticosteroids treatment, 24 (33%) were defined as non-responders. The tool we have developed consisted of three predictors yielding a total score between 0 and 5, which are comprised of the following parameters: the age at physician-diagnosis of asthma, sex, and exhaled nitric oxide. Sensitivity and specificity of the tool for prediction of inhaled corticosteroids non-responsiveness, for a score of 3, were 0.75 and 0.69, respectively. The areas under the receiver operating characteristic curve for the prediction tool was 0.763. Conclusions Our prediction tool represents a simple and low-cost method for predicting the response of inhaled corticosteroids treatment in asthmatic children.

Abstract Background Chloroquine, a bitter tastant, inhibits Ca2+ signaling, resulting in suppression of B cell activation; however, the inhibitory mechanism remains unclear. Results In this study, thapsigargin (TG), but not caffeine, induced sustained intracellular Ca2+ increases in mouse splenic primary B lymphocytes, which were markedly inhibited by chloroquine. Under Ca2+-free conditions, TG elicited transient Ca2+ increases, which additionally elevated upon the restoration of 2 mM Ca2+. The former were from release of intracellular Ca2+ store and the latter from Ca2+ influx. TG-induced release was inhibited by 2-APB (an inhibitor of inositol-3-phosphate receptors, IP3Rs) and chloroquine, and TG-caused influx was inhibited by pyrazole (Pyr3, an inhibitor of transient receptor potential C3 (TRPC3) and stromal interaction molecule (STIM)/Orai channels) and chloroquine. Moreover, chloroquine also blocked Ca2+ increases induced by the engagement of B cell receptor (BCR) with anti-IgM. Conclusions These results indicate that chloroquine inhibits Ca2+ elevations in splenic B cells through inhibiting Ca2+ permeable IP3R and TRPC3 and/or STIM/Orai channels. These findings suggest that chloroquine would be a potent immunosuppressant.

Introduction. Parkinson’s disease (PD) is a common neurodegenerative disorder that may increase the risk of falls, functional limitation, and balance deficits. Tai Chi was used as an option for improving balance in people with PD. The aim of this meta-analysis was to evaluate the effects of Tai Chi on falls, balance, and functional mobility in individuals with PD. Method. The literature search was conducted in PubMed, the Cochrane Library, CINAHL, PEDro, Medline, Embase, sportDISCUS, Trip, and the National Digital Library of Theses and Dissertations in Taiwan. Randomized controlled trials (RCTs) analyzing the effects of Tai Chi, compared to no intervention or to other physical training, on falls, functional mobility, and balance in PD patients were selected. The outcome measurements included fall rates, Berg Balance Scale (BBS), Functional Reach (FR) test, and the Timed Up and Go (TUG) test. Two reviewers independently assessed the methodological quality and extracted data from the studies using the PEDro scale. Results. Five RCTs that included a total of 355 PD patients were included in this review. The quality of evidence in these studies was rated as moderate to high. Compared to no intervention or other physical training, Tai Chi significantly decreased fall rates (odds ratio = 0.47, 95% confidence interval (CI) 0.30 to 0.74, and p=0.001) and significantly improved balance and functional mobility (BBS mean difference (MD) = 3.47, 95% CI 2.11 to 4.80, and p

The objective of this study was to evaluate and compare the biomechanical behavior of internal fixation techniques in bilateral sagittal split ramus osteotomies (BSSROs) for mandibular setback. Artificial polyurethane mandibles were used in this study. The distal segment of the mandible was repositioned in an 8-mm setback position. All mandibles were divided into three groups: Group 1 had a straight plate with a four-hole monocortical fixation, Group 2 had a curved plate with a four-hole monocortical fixation, and Group 3 had a three–inverted L-type bicortical screw fixation. Vertical loads were applied on the incisal edge by a material testing system. The resistance force at 1, 3, 5, and 10 mm of displacement was analyzed. From the experimental results, Group 1 showed significantly lower results than Groups 2 and 3. No significant difference was observed between Groups 2 and 3 at 1, 3, and 5 mm of displacement. However, at 10 mm of displacement, the resistance force of Group 3 was greater than that of Group 2. For BSSROs, this study concluded that curved plate fixation exhibited the same rigidity as the inverted-L bicortical screw fixation did at ≤5 mm displacement.

Background/Aims: Bitter-tasting chloroquine can suppress T cell activation by inhibiting Ca2+ signaling. However, the mechanism of inhibition remains largely unclear. Methods: In this study, CD4+ T cells were isolated from the thymus, and the calcium content of CD4+ thymocytes was measured using fura-2 AM and a TILL imaging system. Pyrazole-3 (Pyr3), thapsigargin (TG), and caffeine were used to assess the effects of chloroquine on the intracellular Ca2+ content of CD4+ T cells. Results: In murine CD4+ thymocytes, chloroquine decreased the TG-triggered intracellular Ca2+ increase in a dose-dependent manner. In the absence of chloroquine under Ca2+-free conditions (0 mM Ca2+ and 0.5 mM EGTA), TG induced a transient Ca2+ increase. After restoration of the extracellular Ca2+ concentration to 2 mM, a dramatic Ca2+ increase occurred. This elevation was completely blocked by chloroquine and was markedly inhibited by Pyr3, a selective antagonist of transient receptor potential C3 (TRPC3) channel and stromal interaction molecule (STIM)/Orai channel. Furthermore, the TG-induced transient Ca2+ increase under Ca2+-free conditions was eliminated in the presence of chloroquine. Chloroquine also blocked the dialyzed inositol-1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ increase. However, chloroquine was not able to decrease the caffeine-induced Ca2+ increase. Conclusion: These data indicate that chloroquine inhibits the elevation of intracellular Ca2+ in thymic CD4+ T cells by inhibiting IP3 receptor-mediated Ca2+ release from intracellular stores and TRPC3 channel-mediated and/or STIM/Orai channel-mediated Ca2+ influx.

Background: Lung cancer is a serious threat to human health and life worldwide. Anxiety is common amongst palliative care patients with lung cancer and adversely affects quality of life. Acupuncture is an effective and safe treatment method used for the treatment of depressive mood status. We aimed to assess the influence of electrical acupuncture stimulation on self-reported anxiety in palliative care among patients with lung cancer. Methods: This pilot study had an experimental, 3-group, research plan. A total of 188 participants were enrolled from the Shanghai Pulmonary Hospital, Tongji University, Shanghai, China from 2014-2015. This pilot study had an experimental, 3-group, research plan. In TEAS group, participants received standardized palliative care and electrical acupuncture stimulation in Zusanli, Sanyinjiao and Hegu acupoints. Group MS received standardized palliative care and muscle stimulation nearby nonacupoint. Controlled group received standardized palliative care. The patients maintained their assigned acupuncture stimulation for 7 days. Demographic Instrument, Karnofsky Performance Scale Index, SF-16 health questionnaire and Self-Rating Anxiety Scale (SAS) were used. Results: The mean SAS scores in TEAS Group before and after electrical intervention in palliative care intervention were 31.17±7.55,34.58±13.98 and 27.86±6.73, (P=0.00) QoL score showed elevation from 57.13 in 8th day to 60.12 in 28th day, rising further to 5%. Comfort Score showed continuous elevation trend for 28 days. Conclusion: Electric acupuncture stimulation could reduce the anxiety of patients, promote rehabilitation and increase the quality of life among patients with lung cancer in palliative care.

Background: Cardiac function is an important predictor for life expectancy in elderly subjects. Tai Chi Chuan (TCC) is a generalized tolerable exercise for the aged population. The current study evaluated the effects of TCC on the vascular compliance and resistance as well as cardiac function of a general healthy elderly population. Materials and methods: A total of 122 consecutive subjects were enrolled from the general population. Yang style TCC was practiced three times a week for 1 hour each session for a duration of 5 months. Subjects were categorized as “adherents” (n=33) if they participated in >48 (80%) sessions, or as “non-adherents” (n=34). Biochemistry data, including fasting glucose, serum cholesterol, triglycerides, uric acid, were recorded before and after the 5-month intervention. Hemodynamic variables, including vascular compliance, resistance, cardiac output, stroke volume, and left ventricular ejection fraction, were obtained before and after the program using a Dynapulse 200 M monitor. Results: Serum triglyceride levels declined after TCC practice (the changes in triglycerides were −3.12 mg/dL and 18.8 mg/dL for the adherent and non-adherent groups, respectively; p=0.03). Significant differences between the adherent and non-adherent groups existed in left ventricular contractility, cardiac output, cardiac index, stroke volume, and brachial artery compliance (p

BackgroundPrevious studies revealed that reduction of airway caliber in infancy might increase the risks for wheezing and asthma. However, the evidence for the predictive effects of pulmonary function on respiratory health in children was still inconsistent.MethodsWe conducted a population-based prospective cohort study among children in 14 Taiwanese communities. There were 3,160 children completed pulmonary function tests in 2007 and follow-up questionnaire in 2009. Poisson regression models were performed to estimate the effect of pulmonary function on the development of bronchitis and asthma.ResultsAfter adjustment for potential confounders, pulmonary function indices consistently showed protective effects on respiratory diseases in children. The incidence rate ratios of bronchitis and asthma were 0.86 (95% CI 0.79-0.95) and 0.91 (95% CI 0.82-0.99) for forced expiratory volume in 1 second (FEV₁). Similar adverse effects of maximal mid-expiratory flow (MMEF) were also observed on bronchitis (RR = 0.73, 95% CI 0.67-0.81) and asthma (RR = 0.85, 95% CI 0.77-0.93). We found significant decreasing trends in categorized FEV₁ (p for trend = 0.02) and categories of MMEF (p for trend = 0.01) for incident bronchitis. Significant modification effects of traffic-related air pollution were noted for FEV₁ and MMEF on bronchitis and also for MMEF on asthma.ConclusionsChildren with high pulmonary function would have lower risks on the development of bronchitis and asthma. The protective effect of high pulmonary function would be modified by traffic-related air pollution exposure.