Identification and experimental validation of key m6A modification regulators as potential biomarkers of osteoporosis

Osteoporosis (OP) is a severe systemic bone metabolic disease that occurs worldwide. During the coronavirus pandemic, prioritization of urgent services and delay of elective care attenuated routine screening and monitoring of OP patients. There is an urgent need for novel and effective screening diagnostic biomarkers that require minimal technical and time investments. Several studies have indicated that N6-methyladenosine (m6A) regulators play essential roles in metabolic diseases, including OP. The aim of this study was to identify key m6A regulators as biomarkers of OP through gene expression data analysis and experimental verification. GSE56815 dataset was served as the training dataset for 40 women with high bone mineral density (BMD) and 40 women with low BMD. The expression levels of 14 major m6A regulators were analyzed to screen for differentially expressed m6A regulators in the two groups. The impact of m6A modification on bone metabolism microenvironment characteristics was explored, including osteoblast-related and osteoclast-related gene sets. Most m6A regulators and bone metabolism-related gene sets were dysregulated in the low-BMD samples, and their relationship was also tightly linked. In addition, consensus cluster analysis was performed, and two distinct m6A modification patterns were identified in the low-BMD samples. Subsequently, by univariate and multivariate logistic regression analyses, we identified four key m6A regulators, namely, METTL16, CBLL1, FTO, and YTHDF2. We built a diagnostic model based on the four m6A regulators. CBLL1 and YTHDF2 were protective factors, whereas METTL16 and FTO were risk factors, and the ROC curve and test dataset validated that this model had moderate accuracy in distinguishing high- and low-BMD samples. Furthermore, a regulatory network was constructed of the four hub m6A regulators and 26 m6A target bone metabolism-related genes, which enhanced our understanding of the regulatory mechanisms of m6A modification in OP. Finally, the expression of the four key m6A regulators was validated in vivo and in vitro, which is consistent with the bioinformatic analysis results. Our findings identified four key m6A regulators that are essential for bone metabolism and have specific diagnostic value in OP. These modules could be used as biomarkers of OP in the future

The Predictive Potentiality of Salivary Microbiome for the Recurrence of Early Childhood Caries

The aim of this study was to investigate the variation of the salivary microbiota in the recurrence of early childhood caries (ECC), and to explore and verify the potential microbial indicators of ECC recurrence. Saliva samples from kindergarten children were tracked every 6 months for 1 year. Finally, in total 28 children and 84 samples were placed on the analysis phase: 7 children with ECC recurrence made up the ECC-recurrence (ER) group, 6 children without ECC recurrence constituted the non-ECC-recurrence (NER) group, and 15 children who kept ECC-free were set as the ECC-free (EF) group. DNA amplicons of the V3-V4 hypervariable region of the bacterial 16S rDNA were generated and sequencing was performed using Illumina MiSeq PE250 platform. No statistically significant differences of the Shannon indices were found in both cross-sectional and longitudinal comparisons. Furthermore, both principal coordinates analysis (PCoA) and heatmap plots demonstrated that the salivary microbial community structure might have potentiality to predict ECC recurrence at an early phase. The relative abundance of Fusobacterium, Prevotella, Leptotrichia, and Capnocytophaga differed significantly between the ER and NER groups at baseline. The values of area under the curve (AUC) of the four genera and their combined synthesis in the prediction for ECC recurrence were 0.857, 0.833, 0.786, 0.833, and 0.952, respectively. The relative abundance of Fusobacterium, Prevotella, Leptotrichia, and Capnocytophaga and their combination showed satisfactory accuracy in the prediction for ECC recurrence, indicating that salivary microbiome had predictive potentiality for recurrence of this disease. These findings might facilitate more effective strategy to be taken in the management of the recurrence of ECC

Long-term outcomes of laparoscopic liver resection versus open liver resection for hepatocellular carcinoma: A single-center 10-year experience

BackgroundLaparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) has increased. However, the long-term outcomes of LLR for HCCs should be validated further. Besides, the validity of laparoscopic minor liver resection in difficult segments (1, 4a, 7, 8) (LMLR-DS) and laparoscopic major hepatectomy (LMH) for HCCs need to be studied.MethodsA total of 1773 HCC patients were collected: 683 received LLR and 1090 received OLR. Propensity score matching (PSM) with 1:1 ratio was used to eliminate the selection bias. Short-term and long-term outcomes were compared. In subgroup analyses, the validity of LMLR-DS or LMH for HCCs was studied.ResultsAfter PSM, 567 patients were in LLR or OLR group. LLR had lower intraoperative blood-loss and shorter postoperative hospital-stays than OLR. The postoperative complications were lower in LLR group (23.8% vs. 32.8%, P=0.001). The Overall survival (OS) and disease-free survival (DFS) had no significant difference between LLR and OLR groups (P=0.973, P=0.812). The cumulative 1-, 3-, and 5-year OR rates were 87.9%, 68.9%, and 57.7% for LLR group, and 85.9%, 68.8%, 58.8% for OLR group. The cumulative 1-, 3-, and 5-year DFS rates were 73.0%, 51.5%, 40.6% for LLR group, and 70.3%, 49.0%, 42.4% for OLR group. In subgroup analyses, 178 patients were in LMLR-DS or open surgery (OMLR-DS) group after PSM. LMLR-DS had lower intraoperative blood-loss and shorter postoperative hospital-stays than OMLR-DS. The postoperative complications were lower in LMLR-DS group. The OS and DFS had no difference between LMLR-DS and OMLR-DS groups. The cumulative 5-year OR and DFS rates were 61.6%, 43.9% for LMLR-DS group, and 66.5%, 47.7% for OMLR-DS group. In another subgroup analyses, 115 patients were in LMH or open major hepatectomy (OMH) group. LMH had lower blood-loss and shorter postoperative hospital-stays than OMH. The complications, OS and DFS had no significantly differences between two groups. The cumulative 5-year OR and DFS rates were 44.3%, 29.9% for LMH group, and 44.7%, 33.2% for OMH group.ConclusionsLLR for HCCs showed better short-term outcomes and comparable long-term outcomes with OLR, even for patients who received LMLR-DS or LMH. LLR could be reliable and recommended for HCC treatment

New Process with Argon Injected into Ladle around the Tapping Hole for Controlling Slag Carry-over during Continuous Casting Ladle

A new process with argon injected into the ladle around the tapping hole for controlling slag carry-over in a teeming ladle was presented. Physical modeling was used to study the mechanism of controlling slag carry-over, and the feasibility of the new process was also investigated by industrial trials. The results show that vortex forms firstly, and then converts to drain sink. With argon injected into the ladle around the tapping hole, an argon ring was formed, and the rotating angular velocity of the melt close to the tapping hole reduced dramatically, and even vanished when the melt passed the argon ring. Therefore, the new controlling slag carry-over process can eliminate the slag carry-over caused by vortex. The velocity of the melt toward the tapping hole was reduced due to the bubble buoyancy as the melt passed the argon ring. So, the new process can decrease the critical height of slag carry-over caused by drain sink. The application feasibility of the new controlling slag carry-over process is verified by the plant trials. Compared to the traditional teeming ladle process, the new controlling slag carry-over process shows much better efficiency on decreasing the steel residual in the poured ladle

Determinants of catastrophic dental health expenditure in China

This study explored catastrophic health expenditure in China, due to out-of-pocket payments for dental care, and its associated individual- and contextual-level factors. We pooled data from 31,566 adults who participated in the third National Oral Health Survey with province-level data from different sources. We defined catastrophic dental health expenditure (CDHE) as payments for dental services and/or medication for dental problems during the last year that exceeded the 10% and 20% of the household income. The association of individual and contextual factors with catastrophic dental health expenditure was evaluated using two-level logistic regression models with individuals nested within provinces. Socioeconomic position (education and household income), household size and dental status (pain in teeth or mouth and number of teeth) were the individual-level factors associated with CDHE among the full sample of participants; and, also, among those who used dental services in the past year. Greater gross domestic product per capita was the only contextual factor associated with CDHE, and only at the lower income threshold. This study shows that out-of-pocket expenses for dental services may put a considerable, and unnecessary, burden on households' finances. Our findings also help characterise those households more likely to face catastrophic expenditure on health if they have to pay for dental services

Elemental segregation and subsequent precipitation during solidification of continuous cast Nb–V–Ti high-strength low-alloy steels

In this study, elemental segregation during solidification and subsequent precipitation behaviour in a continuous cast Nb–V–Ti high-strength low-alloy steel was investigated by optical microscopy, scanning electron microscopy with energy dispersive X-ray spectroscopy and thermodynamic modelling. It is known that for steels with low carbon contents the pearlite that forms on slow cooling does so where the interdendritic liquid was present prior to final solidification. The alloying elements of Nb, Ti, Mn and V segregate into the interdendritic liquid during solidification, while Al preferentially segregates into the solidifying solid phase. The composition analysis on the slab samples verified the predicted element segregation behaviour, with a smaller difference in the concentrations of Mn and V in the pearlite and dendritic ferrite regions being observed compared to the Nb levels. Small (30–100 nm) spherical or irregular shaped Nb-rich precipitates (Nb(C, N) and (Nb, V)(C, N)) were mainly found in the pearlite regions, while angular Al-rich (60–300 nm) precipitates were found in the dendritic ferrite regions, in the form of AlN and complex AlN–V(C, N) precipitates. Small isolated ferrite regions surrounded by pearlite were observed in the microstructure and has two origins: one type is dendritic ferrite that appears as an isolated island due to a sectioning effect when observing the two-dimensional microstructure; the other is a ferrite idiomorph that forms in the interdendritic region due to the low carbon content of the steel. Accordingly, in these isolated ferrite islands two different precipitation behaviours are found; predominantly Al-rich particles in the dendritic regions or predominantly Nb-rich precipitates in the interdendritic ferrite idiomorphs. No Al-rich precipitates were observed in the interdendritic regions (pearlite or isolated ferrite idiomorphs) despite the Thermo-Calc predictions indicating a higher volume fraction of AlN in these regions compared to the dendritic regions. This is believed to be due to back diffusion of nitrogen after solidification reducing the available nitrogen, which reacts with the high Nb levels present

Clinical analysis of perioperative complications of 26 cases of liver cancer after ALPPS

Objective To analyze the characteristics of perioperative liver function and complications in hepatocellular carcinoma (HCC) patients undergoing associating liver partition and portal vein ligation for staged hepatectomy (ALPPS, two-stage, hepatectomy and portal vein ligation). Methods Twenty-six patients undergoing ALPPS due to advanced HCC in our hospital from July 2014 to June 2017 were enrolled in this study. The indexes of liver function and their trends were observed in the perioperative period. The occurrence, development, treatment and outcomes of complications were also observed. Results The trend of liver function showed that after the first and second operations, alanine aminotransferase (ALT) level reached a peak on the first 1~2 d after surgery, and then decreased rapidly; total bilirubin (TB) reached the highest level on the 3rd~4th days after the first operation, maintained at a high level on the first 1 to 5 d after the second stage of surgery, and then gradually decreased to normal. One patient developed a "bilirubin-transaminase discrepancy" phenomenon in which the transaminase levels were gradually decreased while TB level was progressively elevated in 6 d after the secondary operation, and then developed into liver failure. In terms of complications, the highest incidence was pleural effusion, including 9 cases (34.6%, with 8 on the 3rd to 7th days after operation, and thoracic drainage in 1 case) in the first stage, and 12 cases (46.2%, with 10 cases on the 8th to 12th days postoperatively, and thoracic puncture drainage or drainage in 11 case) after the second operation. The incidence of infectious complications was 15.4% in the first phase and 26.9% after the second operation, and the lung infection was most common. Conclusion After ALPPS, transaminase and bilirubin show a trend of first rise and then falling within 1 week after operation. Pleural effusion is the most common complication after operation, and easy to occur in the first week after the first operation and second week after the second stage of surgery. Therefore, active prevention of lung infection is helpful to reducing the incidence of perioperative infection complications

Meeting the oral health needs of 12-year-olds in China:Human resources for oral health

Abstract Background An appropriate level of human resources for oral health [HROH] is required to meet the oral health needs of population, and enable maximum improvement in health outcomes. The aim of this study was to estimate the required HROH to meet the oral health needs of the World Health Organization [WHO] reference group of 12-year-olds in China and consider the implications for education, practice, policy and HROH nationally. Methods We estimated the need of HROH to meet the needs of 12-year-olds based on secondary analysis of the epidemiological and questionnaire data from the 3rd Chinese National Oral Health Survey, including caries experience and periodontal factors (calculus), dentally-related behaviour (frequency of toothbrushing and sugar intake), and social factors (parental education). Children’s risk for dental caries was classified in four levels from low (level 1) to high (level 4). We built maximum and minimum intervention models of dental care for each risk level, informed by contemporary evidence-based practice. The needs-led HROH model we used in the present study incorporated need for treatment and risk-based prevention using timings verified by experts in China. These findings were used to estimate HROH for the survey sample, extrapolated to 12-year-olds nationally and the total population, taking account of urban and rural coverage, based on different levels of clinical commitment (60-90%). Results We found that between 40,139 and 51,906 dental professionals were required to deliver care for 12-year-olds nationally based on 80% clinical commitment. We demonstrated that the majority of need for HROH was in the rural population (72.5%). Over 93% of HROH time was dedicated to prevention within the model. Extrapolating the results to the total population, the estimate for HROH nationally was 3.16–4.09 million to achieve national coverage; however, current HROH are only able to serve an estimated 5% of the population with minimum intervention based on a HROH spending 90% of their time in providing clinical care. Conclusions The findings highlight the gap between dental workforce needs and workforce capacity in China. Significant implications for health policy and human resources for oral health in this country with a developing health system are discussed including the need for public health action

Finite-Time Projective Synchronization and Parameter Identification of Fractional-Order Complex Networks with Unknown External Disturbances

This paper is devoted to exploring the finite-time projective synchronization (FTPS) of fractional-order complex dynamical networks (FOCDNs) with unknown parameters and external disturbances. Based on the stability theory of fractional-order differential systems, synchronization criteria between drive-response networks were obtained and both the uncertain parameters and external disturbances were identified or conquered simultaneously. Moreover, the upper limit of the settling-time function was obtained. Finally, a numerical example was given to verify the effectiveness of the results