The Application of Computer Technology to Clinical Practice Guideline Implementation: A Scoping Review.

Implementation of clinical practice guidelines (CPG) is a complex and challenging task. Computer technology, including artificial intelligence (AI), has been explored to promote the CPG implementation. This study has reviewed the main domains where computer technology and AI has been applied to CPG implementation. PubMed, Embase, Web of science, the Cochrane Library, China National Knowledge Infrastructure database, WanFang DATA, VIP database, and China Biology Medicine disc database were searched from inception to December 2021. Studies involving the utilization of computer technology and AI to promote the implementation of CPGs were eligible for review. A total of 10429 published articles were identified, 117 met the inclusion criteria. 21 (17.9%) focused on the utilization of AI techniques to classify or extract the relative content of CPGs, such as recommendation sentence, condition-action sentences. 47 (40.2%) focused on the utilization of computer technology to represent guideline knowledge to make it understandable by computer. 15 (12.8%) focused on the utilization of AI techniques to verify the relative content of CPGs, such as conciliation of multiple single-disease guidelines for comorbid patients. 34 (29.1%) focused on the utilization of AI techniques to integrate guideline knowledge into different resources, such as clinical decision support systems. We conclude that the application of computer technology and AI to CPG implementation mainly concentrated on the guideline content classification and extraction, guideline knowledge representation, guideline knowledge verification, and guideline knowledge integration. The AI methods used for guideline content classification and extraction were pattern-based algorithm and machine learning. In guideline knowledge representation, guideline knowledge verification, and guideline knowledge integration, computer techniques of knowledge representation were the most used.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Ten interleukins and risk of prostate cancer.

Background: Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them. Methods: We conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively. Results: The odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (ß, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (ß, 0.002; 95% CI, -0.011, 0.014; P=0.755). Conclusion: This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.

Comparative Efficacy and Safety of Thrombolytic Agents for Pulmonary Embolism: A Bayesian Network Meta-Analysis.

BACKGROUND: Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis. METHODS: A search was conducted of the following databases: PubMed, The Cochrane Library, Embase, and Web of Science to collect randomized controlled trials (RCTs) comparing thrombolytic agents with heparin or other thrombolytic agents in patients with acute PE; the clinical outcomes included patient mortality, recurrent PE, pulmonary artery systolic pressure (PASP) after treatment, and major and minor bleeding. The measurement duration of outcome indicators was the longest follow-up period. Thereafter, a network meta-analysis was performed using a Bayesian network framework. RESULTS: A total of 29 RCTs (3,067 patients) were included, of which 6 studies (304 patients) were massive PE, 14 studies (2,173 patients) were submassive PE, 1 study (83 patients) included massive and submassive PE, and 8 studies (507 patients) were PE of unknown type. The treatment regimens included thrombolytic therapy (alteplase, reteplase, tenecteplase, streptokinase, and urokinase) and anticoagulant therapy alone. The results showed that the mortality using thrombolytic agents (except tenecteplase) was significantly lower compared with heparin. The recurrence of PE with alteplase was significantly lower compared with heparin (RR = 0.23, 95% CI, 0.04, 0.65). The PASP after using alteplase was significantly lower compared with heparin (mean difference = -11.36, 95% CI, -21.45, -1.56). Compared with heparin, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.27, 95% CI, 1.36, 7.39); compared with streptokinase, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.22, 95% CI, 1.01, 11.10). CONCLUSION: For patients with acute PE, four thrombolytic agents (alteplase, reteplase, streptokinase, and urokinase) appeared to be superior in efficacy compared with anticoagulants alone due to a reduction in mortality and no increase in bleeding risk. Alteplase may be a better choice because it not only reduced mortality but also reduced PE recurrence rate and treated PASP. Tenecteplase did not reduce mortality compared with anticoagulants alone and may not be a good choice of thrombolytic agent due to an increase in minor bleeding compared with streptokinase and anticoagulants alone. Thrombolytic drugs should be rationally selected to optimize the thrombolytic regimen and achieve as good a balance as possible between thrombolysis and bleeding.

The Role of the Cerebellum in Drug Reward: A Review.

Drug abuse remains a global problem; nonetheless, its mechanism has not yet been fully understood. Recent studies have reported on the non-motor functions of the cerebellum, and evidence from neuroimaging and behavioral studies has suggested the role of cerebellum in drug reward, which has received increasing attention. Furthermore, emerging technological developments have aided in clarifying the various circuits and functions of the cerebellum. Exploring the role of the cerebellum in drug reward can improve our understanding of the mechanism underlying addiction and facilitate the development of new treatment schemes. This review summarizes the anatomy of the cerebellum and its connections to brain regions considered important in addiction. Subsequently, we investigate the neurological reasons elucidating why the cerebellum is a potential target for drug reward. Additionally, we expound the molecular targets of addictive drugs in the cerebellum, mainly glutamate and endocannabinoids. Unlike previous studies, this article focuses on the influence of alcohol, nicotine, morphine, cannabis, and cocaine on the cerebellum from multiple viewpoints, including imaging and behavioral changes, molecular signals, neurotransmitters, and synaptic transmission. We aim to clarify some drug-induced cerebellar changes to supplement the previous research regarding the relationship between addiction and the cerebellum. Finally, we discuss the limitations and prospects of drug reward research on the cerebellum to provide novel insights into studying the cerebellum and its role in addiction. We recommend that future addiction network models should include the cerebellum to provide new therapeutic targets for treating addiction.

Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.

BACKGROUND: Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. METHODS: We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. RESULTS: The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI. CONCLUSION: This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.

Coffee and caffeine consumption and risk of renal cell carcinoma: A Mendelian randomization study.

Background: The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association. Materials and methods: In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources. Results: The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292). Conclusion: Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

The causal association between smoking, alcohol consumption and risk of bladder cancer: A univariable and multivariable Mendelian randomization study.

Smoking and alcohol consumption are associated with bladder cancer risk in observational studies. We conducted a two-sample univariable and multivariable Mendelian randomization (MR) analysis to determine whether those associations are causal. We used 21, 126, 360, 39 single nucleotide polymorphisms (SNPs) as instrumental variables for number of cigarettes per day, lifetime smoking index, smoking initiation, and drinks per week, respectively. A total of 1115 cases with bladder cancer and 174 006 noncases from FinnGen consortium and 2883 cases with bladder cancer and 417 955 noncases from UK Biobank study were obtained. Genetic predisposition to cigarettes per day, lifetime smoking index and smoking initiation were positively associated with an increased risk of bladder cancer in both the FinnGen and UK Biobank consortium. The summary odds ratio (OR) of bladder cancer was 1.79 (95% confidence interval [CI], 1.31-2.45; P = .0002), 2.38 (95% CI, 1.45-3.88; P = .0005) and 1.91 (95% CI, 1.46-2.50; P = 1.59 × 10-06 ) for one SD increase in the number of cigarettes per day, lifetime smoking index and smoking initiation, respectively. The genetically instrumented number of drinks per week was not associated with bladder cancer (OR = 0.69; 95% CI, 0.44-1.10; P = .1237). Estimates were consistent in multivariable MR analyses by the adjustments of body mass index and education. Our study suggests a causal potential of the association of smoking but not alcohol consumption with bladder cancer according to current evidence.

Comparative transcriptome and DNA methylation analysis in temperature-sensitive genic male sterile wheat BS366.

BACKGROUND: Known as the prerequisite component for the heterosis breeding system, the male sterile line determines the hybrid yield and seed purity. Therefore, a deep understanding of the mechanism and gene network that leads to male sterility is crucial. BS366, a temperature-sensitive genic male sterile (TGMS) line, is male sterile under cold conditions (12 °C with 12 h of daylight) but fertile under normal temperature (20 °C with 12 h of daylight). RESULTS: During meiosis, BS366 was defective in forming tetrads and dyads due to the abnormal cell plate. During pollen development, unusual vacuolated pollen that could not accumulate starch grains at the binucleate stage was also observed. Transcriptome analysis revealed that genes involved in the meiotic process, such as sister chromatid segregation and microtubule-based movement, were repressed, while genes involved in DNA and histone methylation were induced in BS366 under cold conditions. MethylRAD was used for reduced DNA methylation sequencing of BS366 spikes under both cold and control conditions. The differentially methylated sites (DMSs) located in the gene region were mainly involved in carbohydrate and fatty acid metabolism, lipid metabolism, and transport. Differentially expressed and methylated genes were mainly involved in cell division. CONCLUSIONS: These results indicated that the methylation of genes involved in carbon metabolism or fatty acid metabolism might contribute to male sterility in BS366 spikes, providing novel insight into the molecular mechanism of wheat male sterility.

Comparison on the Efficacy and Safety of Different Surgical Treatments for Benign Prostatic Hyperplasia With Volume >60 mL: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.

The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A systematic literature review and network meta-analysis of randomized controlled trials (RCTs) within a Bayesian framework was performed. A total of 52 parallel-group RCTs included, reporting on 6,947 participants, comparing open prostatectomy (OP), monopolar/bipolar transurethral resection of prostate (monopolar/ bipolar TURP), thulium, holmium and diode laser enucleation of prostate (LEP), bipolar enucleation of prostate, potassium titanyl phosphate laser vaporization of prostate (KTP LVP), bipolar vaporization of prostate (bipolar VP), and laparoscopic simple prostatectomy (laparoscope SP). Compared with OP, laparoscope SP identified better maximal flow rate (Qmax; mean differences [MDs] = 2.89 mL/s) at the 24th month, but bipolar VP demonstrated worse Qmax (MD = -3.20 mL/s) and International Prostate Symptom Score (IPSS; MD = 2.60) at the 12th month. Holmium LEP (MD = 1.37) demonstrated better International Index of Erectile Function-5 at the 12th month compared with OP. However, compared with OP, KTP LVP demonstrated worse postvoid residual volume (PVR) at the sixth (MD = 10.42 mL) and 12th month (MD = 5.89 mL) and monopolar TURP (MD = 6.9 mL) demonstrated worse PVR at the 12th month. Eight new surgical methods for BPH with volume >60 mL appeared to be superior in safety compared with OP and monopolar TURP due to fewer complications. Bipolar VP and KTP LVP maybe not suitable for prostates more than 60 mL due to short- and middle-term worse Qmax, IPSS, and PVR than OP.

Analysis of the Status and Trends of Chinese Clinical Practice Guideline Development Between 2010 and 2020: A Systematic Review.

Objective: This study aimed to systematically review the status and trends of Chinese clinical practice guidelines (CPGs) during the time period 2010-2020 and explore their methodological characteristics. Then, based on the strengths and weaknesses in development, offer several recommendations for the quality improvement which will serve as a reference for the users and developers of CPG. Introduction: With the development of evidence-based medicine (EBM), the CPGs play an increasingly important role in healthcare decision-making both in China and worldwide. Inclusion criteria: The CPGs that have been used to help the health professionals in the healthcare decision-making were included. Methodology: The China National Knowledge Infrastructure (CNKI) and WanFang databases were searched from 2010 to 2020 for the studies describing the general and methodological characteristics of Chinese CPGs. Comparisons of the methodological characteristics between the groups were conducted using the chi-square test or Fisher's exact test. The M-K test was adopted to identify the monotonically increasing or decreasing trends of methodological characteristics over the timespan. Results: A total of 2,654 CPGs fulfilled the inclusion criteria. The quantity and quality of the guidelines developed in China have improved over the time span. From 2010 to 2020,the guidelines had differing characteristics and covered a wide range of subjects. In total, 2,318(87.34%) guidelines focused on Western Medicine. Eight (0.30%) had been developed for patient versions of guidelines, 10(0.38%) were tentative guidelines, and 16(0.60%) were rapid advice guidelines. Medical specialty societies (including their branches) (71.1%) were the main guideline makers. The most addressed diseases were neoplasms (14.43%). The target population is mainly adults (84.97%). The methodological quality of consensus-based (CB)-CPGs was obviously lower than evidence-based (EB)-CPGs. Except for the item, "recommendations were based on evidence of systematic reviews," there were statistical differences in all other methodological items between the EB-CPGS and CB-CPGS (P < 0.01). Higher methodological quality has been observed in EB-CPGs. All the data relating to the methodological characteristics indicated that higher methodological quality was present in the guidelines using GRADE (P < 0.01). Conclusion: The quantity and quality of the guidelines developed in China have improved between 2010 and 2020. CB-CPGs have also paid attention to the methodology quality, but obviously, this is lower than that in the EB-CPGs.

Utility of process capability indices in assessment of quality control processes at a clinical laboratory chain.

BACKGROUND: To evaluate the utility of the process capability indices Cp and Cpk for assessing the quality control processes at chain laboratory facilities. METHODS: In April 2020, the minimum Cp and Cpk values for 33 assays of a laboratory chain with 19 facilities were collected for further analysis and a total of 627 datasets (Cp and Cpk ) were compared. In addition, standard values for Cp and Cpk , defined as the lowest of the top 20%, were obtained for comparison and the indices were used to determine whether precision or trueness improvements were required for the corresponding assay. RESULTS: A total of 627 datasets of 33 assays from 19 laboratory facilities were collected for further analysis. Based on the Cp results, 329 (52.5%), 211 (33.7%), 65 (10.3%), and 22 (3.5%) were rated as excellent, good, marginal, and poor, respectively. While the corresponding results for Cpk were 300 (47.8%), 216 (34.4%), 79 (12.6%), and 32 (5.1%). In addition, it was noteworthy that eight (Cp criteria) and six assays (Cpk criteria) were rated as excellent or good at all 19 facilities. Comparison of the process capability indices at the Jinan KingMed Center with the standard values revealed that total protein, albumin, and urea showed trueness individual improvement, precision individual improvement, and precision common improvement, respectively, while the results of other assays were stable. CONCLUSION: Process capability indices are useful for evaluating the quality control procedures in laboratory facilities and can help improve the precision and trueness of laboratory tests.

Association of Insulin Glargine Treatment with Bone Mineral Density in Patients with Type 2 Diabetes Mellitus.

PURPOSE: To assess the association of type 2 diabetes mellitus (T2DM) and insulin glargine treatment with bone mineral density (BMD) in Chinese people. METHODS: This retrospective study included 50 subjects with T2DM: 25 received oral glucose-lowering medication (ORL group), and 25 received oral glucose-lowering medication in combination with insulin glargine injection (CGI group). Thirty non-diabetic control subjects were also included. BMD was measured at lumbar vertebrae 1-4 (L1-L4), spine bone mineral density (sBMD) results summary (L2-L4), femoral neck and trochanter by dual-energy x-ray absorptiometry. RESULTS: Compared with non-diabetic controls, people with T2DM had significantly lower mean BMD at L2 (1.073±0.120 vs 0.984±0.158), L3 (1.094±0.129 vs 0.991±0.163) and L4 (1.089±0.130 vs 0.982±0.165) (all P<0.05), significantly lower levels of serum calcium (2.02±0.22 vs 2.27±0.17 mmol/L, P<0.05), PTH (24.19±9.71 vs 31.52±8.96 pg/mL, P<0.05), and higher serum phosphate levels (1.43±0.37 vs 1.20±0.15 mmol/L, P<0.05). The CGI group had higher L2, L3 and L4 BMD and sBMD (L2-L4) (P<0.05), higher serum calcium levels (2.19±0.11 vs 1.98±0.20 mmol/L, P<0.05) and lower serum phosphate levels (1.28±0.20 vs 1.58±0.43 mmol/L, P<0.05) versus the ORL group. BMD and serum calcium levels were associated with the application of insulin glargine. CONCLUSION: These results suggest that insulin glargine may affect bone metabolism in patients diagnosed with T2DM. The study has implications for the selection of hypoglycemic agents for diabetic patients at risk of osteoporosis.

Genome-wide identification and transcriptional characterization of DNA methyltransferases conferring temperature-sensitive male sterility in wheat.

BACKGROUND: DNA methyltransferase (DMT) genes contribute to plant stress responses and development by de novo establishment and subsequent maintenance of DNA methylation during replication. The photoperiod and/or temperature-sensitive genic male sterile (P/TGMS) lines play an important role in hybrid seed production of wheat. However, only a few studies have reported on the effect of DMT genes on temperature-sensitive male sterility of wheat. Although DMT genes have been investigated in some plant species, the identification and analysis of DMT genes in wheat (Triticum aestivum L.) based on genome-wide levels have not been reported. RESULTS: In this study, a detailed overview of phylogeny of 52 wheat DMT (TaDMT) genes was presented. Homoeolog retention for TaDMT genes was significantly above the average retention rate for whole-wheat genes, indicating the functional importance of many DMT homoeologs. We found that the strikingly high number of TaDMT genes resulted mainly from the significant expansion of the TaDRM subfamily. Intriguingly, all 5 paralogs belonged to the wheat DRM subfamily, and we speculated that tandem duplications might play a crucial role in the TaDRM subfamily expansion. Through the transcriptional analysis of TaDMT genes in a TGMS line BS366 and its hybrids with the other six fertile lines under sterile and fertile conditions, we concluded that TaCMT-D2, TaMET1-B1, and TaDRM-U6 might be involved in male sterility in BS366. Furthermore, a correlation analysis showed that TaMET1-B1 might negatively regulate the expression of TaRAFTIN1A, an important gene for pollen development, so we speculated regarding an epigenetic regulatory mechanism underlying the male sterility of BS366 via the interaction between TaMET1-B1 and TaRAFTIN1A. CONCLUSIONS: Our findings presented a detailed phylogenic overview of the DMT genes and could provide novel insights into the effects of DMT genes on TGMS wheat.

Secular trends in severe periodontitis incidence, prevalence and disability-adjusted life years in five Asian countries: A comparative study from 1990 to 2017.

AIMS: To investigate secular trends in severe periodontitis incidence, prevalence and disability-adjusted life year (DALY) rates in China, India, Japan, South Korea and Thailand from 1990 to 2017. MATERIALS AND METHODS: Data were obtained from the "Global Burden of Disease Study" 2017. The annual percentage change and average annual percentage change were calculated using Joinpoint regression analysis. The independent age, period and cohort effects were estimated by age-period-cohort analysis. RESULTS: From 1990 to 2017, the overall age-standardized incidence, prevalence and DALY rates increased in China, Japan and India, while decreasing in South Korea and Thailand. The highest incidence, prevalence and DALY rates were in India. By APC analysis, the age effect presented increase in 20-59 years in China, Japan and South Korea, 20-54 years in India and 20-64 years in Thailand; the period effect showed progressive increases in five countries, with the most significant increase shown in China; the cohort effect showed monotonic decreases with birth cohort in five countries. CONCLUSIONS: Severe periodontitis poses a serious burden in Asian countries, especially China and India. We suggest raising people's awareness of periodontal health and providing professional interventions in these countries, especially for high-risk groups, such as younger people aged ≤65 years.

Immortal time bias exaggerates the effect of metformin on the risk of gastric cancer: A meta-analysis.

High heterogeneity has been reported among epidemiological studies exploring the relationship between metformin and the risk of gastric cancer. Immortal time bias might be one of the vital factors causing heterogeneity because of its widespread existence in pharmacological observational studies and it could severely exaggerate the drug's effectiveness. Immortal time bias could occur in an observational study if exposure status is determined based on a measurement or event that occurs after baseline. In this study, we aimed to assess whether immortal time bias is responsible for the false assumption that metformin reduces the risk of gastric cancer. We searched PubMed, Embase, Web of Science and Cochrane Library databases for relevant studies from the inception to August 9, 2020. The strength of the relationship was assessed using pooled relative risks (RRs) with corresponding 95% confidence intervals (95% CIs). Statistical analyses were carried out using a random-effects model. Pooled RR from 6 cohort studies with immortal time bias found a clear 33% reduced risk associated with metformin use (RR = 0.67, 95% CI = 0.59, 0.77; P < 0.001; I2 = 48.5%). However, pooled RR from 8 cohort studies without immortal time bias indicated no association between the use of metformin and gastric cancer risk (RR = 0.95, 95% CI = 0.85, 1.05; P = 0.317; I2 = 64.5%). From a univariate meta-regression model, the presence of immortal time bias was associated with a significant reduction of 29% in the effect estimate of metformin on gastric cancer risk (ratio of RR = 0.71, 95% CI = 0.58, 0.86; P = 0.002). This meta-analysis indicates that metformin use has no protective effect on gastric cancer risk. The relationship between metformin use and gastric cancer risk has been exaggerated as a result of the presence of immortal time bias. Further studies are required to confirm the results by controlling for immortal time bias based on appropriate study designs and statistical methods.

Causal Association Between Periodontitis and Type 2 Diabetes: A Bidirectional Two-Sample Mendelian Randomization Analysis.

Background: Previous observational studies have reported a bidirectional association between periodontitis and type 2 diabetes, but the causality of these relationships remains unestablished. We clarified the bidirectional causal association through two-sample Mendelian randomization (MR). Methods: We obtained summary-level data for periodontitis and type 2 diabetes from several published large-scale genome-wide association studies (GWAS) of individuals of European ancestry. For the casual effect of periodontitis on type 2 diabetes, we used five independent single-nucleotide polymorphisms (SNPs) specific to periodontitis from three GWAS. The summary statistics for the associations of exposure-related SNPs with type 2 diabetes were drawn from the GWAS in the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) consortium and the FinnGen consortium R5 release, respectively. For the reversed causal inference, 132 and 49 SNPs associated with type 2 diabetes from the DIAGRAM consortium and the FinnGen consortium R5 release were included, and the summary-level statistics were obtained from the Gene-Lifestyle Interactions in Dental Endpoints consortium. Multiple approaches of MR were carried out. Results: Periodontitis was not causally related with the risk of type 2 diabetes (all p > 0.05). No causal effect of type 2 diabetes on periodontitis was found (all p > 0.05). Estimates were consistent across multiple MR analyses. Conclusion: This study based on genetic data does not support a bidirectional causal association between periodontitis and type 2 diabetes.

Prucalopride inhibits the glioma cells proliferation and induces autophagy via AKT-mTOR pathway.

BACKGROUNDS: Glioma is the most fatal primary brain glioma in central nervous system mainly attributed to its high invasion. Prucalopride, a Serotonin-4 (5-HT4) receptor agonist, has been reported to regulate neurodevelopment. This study aimed to investigate the influence of the Prucalopride on glioma cells and unveil underlying mechanism. METHODS: In this study, glioma cells proliferation was evaluated by Cell counting kit-8 (CCK8). Wound healing and transwell assay were used to test cellular migration and invasion. Flow cytometry was utilized to determine cellular apoptosis rate. Apoptosis related markers, autophagy markers, and protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway key molecules were detected using western blot assay. RESULTS: As a result, the proliferation, migration and invasiveness of glioma cells were impaired by Prucalopride treatment, the apoptosis rate of glioma cells was enhanced by Prucalopride stimulation, accompanied by the increased pro-apoptosis proteins Bax and Cleaved caspase-3 and decreased anti-apoptosis protein Bcl-2. Prucalopride significantly promoted autophagy by increased expression level of Beclin 1 and LC3-II, while decreased expression level of p62. Prucalopride administration resulted in obvious inhibitions of key molecules of AKT-mTOR pathway, including phosphorylated- (p-) AKT, p-mTOR and phosphorylated-ribosomal p70S6 kinase (p-P70S6K). CONCLUSIONS: Taking together, these results indicate that Prucalopride may be likely to play an anti-tumor role in glioma cells, which suggests potential implications for glioma promising therapy alternation in the further clinics.

Transcriptome analysis of wheat seedling and spike tissues in the hybrid Jingmai 8 uncovered genes involved in heterosis.

MAIN CONCLUSION: Transcriptome analysis was carried out for wheat seedlings and spikes from hybrid Jingmai 8 and both inbred lines to unravel mechanisms underlying heterosis. Heterosis, known as one of the most successful strategies for increasing crop yield, has been widely exploited in plant breeding systems. Despite its great importance, the molecular mechanism underlying heterosis remains elusive. In the present study, RNA sequencing (RNA-seq) was performed on the seedling and spike tissues of the wheat (Triticum aestivum) hybrid Jingmai 8 (JM8) and its homozygous parents to unravel the underlying mechanisms of wheat heterosis. In total, 1686 and 2334 genes were identified as differentially expressed genes (DEGs) between the hybrid and the two inbred lines in seedling and spike tissues, respectively. Gene Ontology analysis revealed that DEGs from seedling tissues were significantly enriched in processes involved in photosynthesis and carbon fixation, and the majority of these DEGs expressed at a higher level in JM8 compared to both inbred lines. In addition, cell wall biogenesis and protein biosynthesis-related pathways were also significantly represented. These results confirmed that a combination of different pathways could contribute to heterosis. The DEGs between the hybrid and the two inbred progenitors from the spike tissues were significantly enriched in biological processes related to transcription, RNA biosynthesis and molecular function categories related to transcription factor activities. Furthermore, transcription factors such as NAC, ERF, and TIF-IIA were highly expressed in the hybrid JM8. These results may provide valuable insights into the molecular mechanisms underlying wheat heterosis.