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Abstract Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis.

Abstract Car wheels are crucial to automobile safety, requiring a rigorous test before production. A 90° impact test simulates the frontal impact and its influences on the wheel structure, replicating dynamic driving conditions. A novel modelling approach is illustrated for the 90° impact test simulation and investigates the feasibility of excluding the tyre. Firstly, the test performs and validates five impact simulations, with the maximum deformation error being 7.04%. Subsequently, with additional tests, the effectiveness of the modelling approach is evaluated. Lastly, the effect of tyres has been analysed from an energy perspective. The results indicate that the tyre significantly influences the simulation results and should be included in the finite element (FE) model, which differs from the 13° impact test.

A central goal of cancer genomics is to identify, in each patient, all the cancer-driving mutations. Among them, point mutations are referred to as cancer-driving nucleotides (CDNs), which recur in cancers. The companion study shows that the probability of i recurrent hits in n patients would decrease exponentially with i; hence, any mutation with i ≥ 3 hits in The Cancer Genome Atlas (TCGA) database is a high-probability CDN. This study characterizes the 50–150 CDNs identifiable for each cancer type of TCGA (while anticipating 10 times more undiscovered ones) as follows: (i) CDNs tend to code for amino acids of divergent chemical properties. (ii) At the genic level, far more CDNs (more than fivefold) fall on noncanonical than canonical cancer-driving genes (CDGs). Most undiscovered CDNs are expected to be on unknown CDGs. (iii) CDNs tend to be more widely shared among cancer types than canonical CDGs, mainly because of the higher resolution at the nucleotide than the whole-gene level. (iv) Most important, among the 50–100 coding region mutations carried by a cancer patient, 5–8 CDNs are expected but only 0–2 CDNs have been identified at present. This low level of identification has hampered functional test and gene-targeted therapy. We show that, by expanding the sample size to 105, most CDNs can be identified. Full CDN identification will then facilitate the design of patient-specific targeting against multiple CDN-harboring genes.

Tumorigenesis, like most complex genetic traits, is driven by the joint actions of many mutations. At the nucleotide level, such mutations are cancer-driving nucleotides (CDNs). The full sets of CDNs are necessary, and perhaps even sufficient, for the understanding and treatment of each cancer patient. Currently, only a small fraction of CDNs is known as most mutations accrued in tumors are not drivers. We now develop the theory of CDNs on the basis that cancer evolution is massively repeated in millions of individuals. Hence, any advantageous mutation should recur frequently and, conversely, any mutation that does not is either a passenger or deleterious mutation. In the TCGA cancer database (sample size n=300–1000), point mutations may recur in i out of n patients. This study explores a wide range of mutation characteristics to determine the limit of recurrences (i*) driven solely by neutral evolution. Since no neutral mutation can reach i*=3, all mutations recurring at i≥3 are CDNs. The theory shows the feasibility of identifying almost all CDNs if n increases to 100,000 for each cancer type. At present, only

Abstract Background This study aims to analyze breast cancer burden attributable to high body mass index (BMI) and high fasting plasma glucose (FPG) in China from 1990 to 2019. Methods Data were obtained from the Global Burden of Disease (GBD) study 2019. Deaths and disability‐adjusted life years (DALYs) were used for attributable burden, and age‐period‐cohort (APC) model was used to evaluate the independent effects of age, period and birth cohort. Results In 2019, the age‐standardized mortality and DALY rates of breast cancer attributable to high BMI were 1.107 (95% UI: 0.311, 2.327) and 29.990 (8.384, 60.713) per 100 000, and mortality and DALY rates attributable to high FPG were 0.519 (0.095, 1.226) and 13.662 (2.482, 32.425) per 100 000. From 1990 to 2019, the age‐standardized mortality and DALY rates of breast cancer attributable to high BMI increased by 1.192% and 1.180%, and the trends of high FPG were not statistically significant. The APC results showed that the age effects of high BMI and high FPG‐mortality and DALY rates increased, with the highest rates in the age group over 80 years. The birth cohort effects of high BMI showed “inverted V” shapes, while high FPG showed downward trends. Conclusions Age was the main reason for the increase of attributable burden, and postmenopausal women were the high‐risk groups. Therefore, targeted prevention measures should be developed to improve postmenopausal women's awareness and effectively reduce the prevalence of obesity and diabetes, thereby reducing the breast cancer burden caused by metabolic factors in China.

Abstract Background Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. Methods The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. Results P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. Conclusion P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Abstract Background The rising burden of thyroid cancer (TC) is a public health problem in Asia. Predicting the future burden of TC in Asian countries is essential for disease prevention. Methods Data were obtained from the Global Burden of Disease 2019 for five Asian countries. We applied Bayesian age‐period‐cohort models to predict morbidity and mortality to 2035 and calculated age‐standardized incidence rate (ASIR) and age‐standardized mortality rate (ASMR). Furthermore, the estimated annual percentage change was calculated to evaluate the variation of ASIR and ASMR. Results By 2035, predictions suggest that cases of TC will reach 75.56 × 103 in China, 70.22 × 103 in India, 15.78 × 103 in the Republic of Korea, 9.01 × 103 in Japan and 5.55 × 103 in Thailand, respectively. Except Japan, a significant upward trend of ASIR of TC will be observed in five Asian countries. The deaths from TC will increase in five countries and India will become the highest reaching 14.07 × 103. The ASMR will rise to 0.83/100 000 in India and 1.06/100 000 in the Republic of Korea, while it will drop to 0.35/100 000 in China, 0.43/100 000 in Japan and 0.50/100 000 in Thailand. In further predictions projected by sex, the growth rate of ASIR is reported higher in males than in females among most countries. ASMR of male will exceed that of females in China and Thailand by 2035. Conclusion The disease burden caused by TC will further increase in five Asian countries, especially for men. It is necessary to develop more rational and timely disease prevention and manage strategies facing this disease trend.

Electrostatic charging of powders becomes important, when particles become smaller, especially for fine powders at micron or sub-micron size. Charging of powders causes strong particle adhesion and consequently difficulties in processes such as blending or mixing, and sieving, etc. Not only does the charge of powders influence the process and the quality of the products, but also the discharge creates risks of dust explosion. Assessing powder charge and the hazards in manufacturing can be difficult. One of the major challenges is to evaluate the charge levels and polarity in the powders but this requires a significant number of tests to detect charge tendency and distributions in bulk materials, which is time-consuming. In this paper, electrostatic charging of powders in material handling processes and the associated hazards are briefly reviewed. For an assessment, the challenges for sensing electrostatic charges of particulate solids, particularly for fine powders, are discussed. It was revealed that sensing the charge polarity for representative samples of powders can be the main challenge because of the difficulty in separation of the charged particles. The inductive charge sensor showed great potential to measure charge levels and polarity distributions in powders. Experimental trials for several fine powders showed that the inductive charge sensor can be used for rapidly assessing chargeability and charge polarity distribution of powders.

Textile polymer composite is made of structured fibre matrix using textile technologies in fabrication, and gains benefits from strong mechanical properties with extra light weight. However, erosion behaviours and associated wear mechanisms of the composites may be influenced by the fibre structures due to heterogeneous composition and complex architectural topologies. Understanding the erosive mechanisms of the structured composites can be important, not only for preventing surface damage and loss of mechanical strength but also for improving design and fabrication of the composites. This paper presents an experimental study of erosive wear under sand blasting on 3D woven carbon-fibre-reinforced textile composites with epoxy. The architectural topology methods of the composites include non-crimped bidirectional, tufted bidirectional, 3D layer-to-layer and 3D orthogonal textile methods. The erosion tests were conducted on four impact angles (20°, 30°, 45° and 90°) under one impact velocity at 40 m/s. The study results show that the erosive mechanism of the textile composites is different from that of the neat substrate material. The observations from this study also reveal the different erosive behaviours between the composites with different fibre structures. It concludes that architectural structures can influence the erosion of a textile composite but will not result in significant differences in the wear resistance of the composites (

Abstract Background Studies had shown many diseases affect the stability of human microbiota, but how this relates to benign prostatic hyperplasia (BPH) has not been well understood. Hence, this study aimed to investigate the regulation of BPH on gut microbiota composition and metabonomics. Methods We analyzed gut samples from rats with BPH and healthy control rats, the gut microbiota composition and metabonomics were detected by 16S rDNA sequencing and liquid chromatography tandem mass spectrometry (LC–MS/MS). Results High-throughput sequencing results showed that gut microbiota beta-diversity increased (P 0.05), Bacteroidetes (46.54% vs. 41.64%, P > 0.05), Clostridia (50.89% vs. 54.66%, P > 0.05), Ruminococcaceae (25.67% vs. 20.56%, P > 0.05). LC–MS/MS of intestinal contents revealed that differential metabolites were mainly involved in cellular processes, environmental information processing, metabolism and organismal systems. The most important pathways were global and overview maps, lipid metabolism, amino acid metabolism, digestive system and endocrine system. Through enrichment analysis, we found that the differential metabolites were significantly enriched in metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, biosynthesis of unsaturated fatty acids and bile secretion. Pearson correlation analysis (R = 0.94) showed that there was a strong correlation between Prevotellaceae, Corynebacteriaceae, Turicibacteraceae, Bifidobacteriaceae and differential metabolites. Conclusion Our findings suggested an association between the gut microbiota and BPH, but the causal relationship between the two groups is unclear. Thus, further studies are warranted to elucidate the potential mechanisms and causal relationships between BPH and gut microbiota.

Abstract Background To investigate the burden of thyroid cancer and its attributable risk factors in 204 countries and territories during 30 years. Methods We extracted data from the Global Burden of Disease (GBD) 2019 database, including incidence, mortality, disability‐adjusted life‐years (DALYs), and the attributable risk factors of thyroid cancer from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age‐standardized incidence rate (ASIR), age‐standardized mortality rate (ASMR), and age‐standardized DALYs rate (ASDR). We also examined the associations between cancer burden and the sociodemographic index (SDI). Results The global new cases, death, and DALYs of thyroid cancer in 2019 were 233 847 (95% UI: 211 637–252 807), 45 576 (95% UI: 41 290‐48 775), and 1 231 841 (95% UI: 1 113 585–1 327 064), respectively. From 1990 to 2019, the ASIR of thyroid cancer showed an upward trend (EAPC = 1.25), but ASMR (EAPC = −0.15) and ASDR (EAPC = −0.14) decreased. The burden of thyroid cancer varied at regional and national levels, but the association between ASIR and SDI was positive. We found that the burden of thyroid cancer was mainly concentrated in females and that the age of onset tended to be younger. The proportion of DALYs from thyroid cancer attributable to high body‐mass index was higher in high SDI regions, especially in males. Conclusions The global incidence of thyroid cancer has continued to increase in the past three decades. The high body‐mass index as an important risk factor for thyroid cancer deserves greater attention, especially in high SDI regions.

Abstract Nicotinamide adenine dinucleotide phosphate (NADPH), as a well-known cofactor, is widely used in the most of enzymatic redox reactions, playing an important role in industrial catalysis. However, the absence of a comparable method for efficient NADP+ to NADPH cofactor regeneration radically impairs efficient green chemical synthesis. Alcohol dehydrogenase (ADH) enzymes, allowing the in situ regeneration of the redox cofactor NADPH with high specific activity and easy by-product separation process, are provided with great industrial application potential and research attention. Accordingly, herein a NADP+-specific ADH from Clostridium beijerinckii was selected to be engineered for cofactor recycle, using an automated algorithm named Protein Repair One-stop Shop (PROSS). The mutant CbADH-6M (S24P/G182A/G196A/H222D/S250E/S254R) exhibited a favorable soluble and highly active expression with an activity of 46.3 U/mL, which was 16 times higher than the wild type (2.9 U/mL), and a more stable protein conformation with an enhanced thermal stability: Δ $${T}_{1/2}^{60\mathrm{min}}$$ T 1 / 2 60 min = + 3.6 °C (temperature of 50% inactivation after incubation for 60 min). Furthermore, the activity of CbADH-6M was up-graded to 2401.8 U/mL by high cell density fermentation strategy using recombinant Escherichia coli, demonstrating its industrial potential. Finally, the superb efficiency for NADPH regeneration of the mutant enzyme was testified in the synthesis of some fine chiral aromatic alcohols coupling with another ADH from Lactobacillus kefir (LkADH).

Abstract Background CPGs are not uniformly successful in improving care and several instances of implementation failure have been reported. Performing a comprehensive assessment of the barriers and enablers is key to developing an informed implementation strategy. Our objective was to investigate determinants of guideline implementation and explore associations of self-reported adherence to guidelines with characteristics of participants in China. Methods This is a cross-sectional survey, using multi-stage stratified typical sampling based on China's economic regional divisions (the East, the Middle, the West and the Northeast). 2–5 provinces were selected from each region. 2–3 cities were selected in each province, and secondary and tertiary hospitals from each city were included. We developed a questionnaire underpinned by recommended methods for the design and conduct of self-administered surveys and based on conceptual framework of guideline use, in-depth related literature analysis, guideline development manuals, related behavior change theory. Finally, multivariate analyses were performed using logistic regression to produce adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Results The questionnaire consisted of four sections: knowledge of methodology for developing guidelines; barriers to accessing guideline; barriers to guideline implementation; and methods for improving guideline implementation. There were 1732 participants (87.3% response rate) from 51 hospitals. Of these, 77.2% reported to have used guidelines frequently or very frequently. The key barriers to guideline use were lack of education or training (46.2%), and overly simplistic wording or overly broad scope of recommendations (43.8%). Level of adherence to guidelines was associated with geographical regions (the northeast P

ObjectivesPeriodontitis affects the progression of many diseases, while its detailed mechanism remains unclear. This study hopes to provide new ideas for exploring its mechanism by analyzing the gut microbiota and fecal metabolic characteristics of experimental periodontitis rats.MethodsA total of 10 rats were randomly divided into ligature-induced experimental periodontitis (EP) group and healthy control group. After 4 weeks of the experiment, the feces of all rats were collected for sequencing through 16S ribosomal DNA (rDNA) sequencing technology and liquid chromatography–mass spectrometry (LC–MS).Results16S rDNA sequencing results showed that the β-diversity of gut microbiota was significantly different between the EP and control group, and the levels of dominant genera were different. Compared with the control group, Ruminococcus, Escherichia, and Roseburia were significantly enriched in EP, and Coprococcus, Turicibacter, Lachnospira were significantly decreased. Correlation analysis showed that Roseburia exhibited the highest correlation within the genus. Of 3,488 qualitative metabolites, 164 metabolites were upregulated and 362 metabolites were downregulated in EP. Enrichment analysis showed that periodontitis significantly changed 45 positive/negative ion metabolic pathways. Five KEGG pathways, protein digestion and absorption, tyrosine metabolism, glycolysis/gluconeogenesis, niacin and nicotinamide metabolism, and oxidative phosphorylation, are enriched in both the microbiome and metabolome. Correlation analysis showed that the genera with significant differences in periodontitis were usually significantly correlated with more metabolites, such as Roseburia, Lachnospira, Escherichia, Turicibacter, and Ruminococcus. The genera with the same changing trend tended to have a similar correlation with some certain metabolites. In addition, vitamin D2 and protoporphyrin IX have the most significant correlations with microorganisms.ConclusionOur study reveals that periodontitis alters gut microbiota and fecal metabolites. The correlation analysis of microbiota and metabolome provides a deeper understanding of periodontitis, and also provides a direction for the study of periodontitis affecting other diseases.

Abstract The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued “A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)”; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Abstract Background Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers. Methods This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured. Results Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms. Conclusion The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.

Abstract In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

In this study, the degradation of wood pellets and dry roasted coffee beans in a pneumatic conveyor was evaluated for high-speed impacts. The change in particle size and generation of fine particles were used as an indicating parameter for the degradation. A four-bends industrial scale conveying system was used for the degradation study in lean phase pneumatic conveying. The effects of operating parameters on the degradation were investigated, including the conveying velocity of particles and particle concentration. The experimental results showed that the degradation and the fines generation increased with an increase in particle velocity. An opposite trend was observed with an increased solid concentration in the pipeline. It was found that the two types of wood pellets traveled at different particle velocities with the same operating conditions, which resulted in significant differences in the degradation. Compared to the wood pellets, roasted coffee beans were found to travel at air velocity. In conclusion, the degradation in a pneumatic conveying system is complex and challenging to evaluate because there are many influential factors, such as the type of materials, equipment, and operation conditions. Early assessments in a laboratory will be beneficial to evaluate the degradation at all controlled operative conditions.

Abstract Background Bladder cancer (BC) has become a major worldwide public health issue, especially non-muscle-invasive bladder cancer (NMIBC). A flood of related clinical practice guidelines (CPGs) have emerged; however, the quality and recommendations of the guidelines are controversial. We aimed to appraise the quality of the CPGs for NMIBC within the past 5 years and compare the similarities and differences between recommendations for therapies. Methods A systematic search to identify CPGs for NMIBC was performed using electronic databases (including PubMed, Embase, Web of Science), guideline development organizations, and professional societies from January 12, 2014 to January 12, 2019. The Appraisal of Guidelines Research & Evaluation (AGREE) II instrument was used to evaluate the quality of the guidelines. Intraclass correlation coefficient (ICC) analysis was performed to assess the overall agreement among reviewers. Results Nine CPGs were included. The overall agreement among reviewers was excellent. The interquartile range (IQR) of scores for each domain were as follows: scope and purpose 69.44% (35.42, 85.42%); stakeholder involvement 41.67% (30.56, 75.00%); rigour of development 48.96% (27.08, 65.63%); clarity and presentation 80.56% (75.00, 86.11%); applicability 34.38% (22.92, 40.63%) and editorial independence 70.83% (35.42, 85.42%). The NICE, AUA, EAU and CRHA/CPAM clinical practice guidelines consistently scored well in most domains. It was generally accepted that the transurethral resection of bladder tumour (TURBT) and intravesical chemotherapy should be performed in the management of bladder cancer. The application of chemotherapy was highly controversial in high risk NMIBC. The courses of BCG maintenance were similar and included 3 years of therapy at full maintenance doses. Conclusions The quality of NMIBC guidelines within the past 5 years varied, especially regarding stakeholders, rigour and applicability. Despite many similarities, the recommendations had some inconsistencies in the details.

Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights.

Measurement of particle’s charge in the pneumatic conveying systems can be used to monitor the flow behaviour (stable or unstable) in dilute phase pneumatic conveying. The particle’s charge can be measured by inductive electrostatic sensors and converted into a time-domain signal, which is called an electrostatic signal. However, with popular ring-shaped sensors, limited information can be obtained on electrostatic signals. Arc-shaped electrostatic sensors have some advantages on measuring particle’s charge at different locations such as the top or bottom of the pipe. To get enough information about the flow behaviour, the electrostatic signal needs to be processed by using different data analysis techniques.In this study, electrostatic signals are recorded at the top and bottom section of the pipe at varied conveying air velocity and at a constant solid feed rate. These different air velocities result in a stable dilute flow and unstable dune flow in the pipeline. The electrostatic signals of stable and unstable flows are analysed by using Fast Fourier Transform (FFT) and Hilbert-Huang Transform (HHT) techniques for real-time monitoring of flow behaviour in a pilot pneumatic conveyor.The results show that HHT analysis is far better than FFT for distinguishing between stable dilute and unstable dune flow. Where FFT only capture the difference in the flow behaviour with only top electrostatic sensor’s signal but HHT work with both top and bottom sensor’s signals. HHT does not only distinguish between stable and unstable flows but also shows the consistency in the results of the 80 ​s, 10 ​s and 5 ​s of the data analysis, which is the main requirement for any technique to be used for real-time monitoring systems. This clearly represents a huge benefit for control and monitoring in the pneumatic conveying systems.

ObjectiveThe quality and rationality of many recently registered clinical studies related to coronavirus disease 2019 (COVID-19) needs to be assessed. Hence, this study aims to evaluate the current status of COVID-19 related registered clinical trial.MethodsWe did an electronic search of COVID-19 related clinical studies registered between December 1, 2019 and February 21, 2020 (updated to May 28, 2020) from the ClinicalTrials.gov, and collected registration information, study details, recruitment status, characteristics of the subjects, and relevant information about the trial implementation process.ResultsA total of 1,706 studies were included 10.0% of which (n=171) were from France, 943 (55.3%) used an interventional design, and 600 (35.2%) used an observational design. Most of studies (73.6%) aimed to recruit fewer than 500 people. Interferon was the main prevention program, and antiviral drugs were the main treatment program. Hydroxychloroquine and chloroquine (230/943, 24.4%) were widely studied. Some registered clinical trials are incomplete in content, and 37.4% of the 1,706 studies may have had insufficient sample size.ConclusionThe quality of COVID-19 related studies needs to be improved by strengthening the registration process and improving the quality of clinical study protocols so that these clinical studies can provide high-quality clinical evidence related to COVID-19.

Recently WHO has characterized COVID-19 as a pandemic. Diagnosing the disease accurately and decreasing misdiagnoses and missed diagnoses is very important for management. Therefore, we have analyzed the seven versions of China's national guidelines to examine how the diagnostic criteria roadmap has developed and evolved, in order to share our experience worldwide. In this article, we present the developments from the first to seventh versions, involving changes of case classification, changes to “suspected case,” changes in “confirmed case,” changes in clinical classifications, changes in “severe case,” and unchanged criteria. We have also discussed the reasons and implications for these changes and are looking forward to providing suggestions for worldwide understanding and management of this pandemic. A nucleic acid test is currently accepted as the gold standard method to confirm diagnosis. In addition, imaging examination and epidemiological history should also be considered as auxiliary diagnosis methods.

ObjectiveTo systematically evaluate the quality of clinical practice guidelines (CPG) for medically treating benign prostatic hyperplasia (BPH), and to compare the context of recommendations in order to provide references for clinical application.MethodsWe searched databases of National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization (WHO), PubMed, Embase, CNKI, VIP, WanFang Data, CBM, and Medlive from their establishment to October 13, 2019, to collect evidence-based guidelines and/or consensus on BPH. Method quality of included guidelines was assessed according to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, and differences and similarities among recommendations were compared.ResultsA total of 22 guidelines were included, of which eight were updated versions. According to the AGREE II instrument, the median score of scope and purpose, stakeholder involvement, rigor of formulate, clarity of presentation, applicability, and editorial independence was 71.5%, 41%, 25%, 64%, 18%, and 28%, respectively. Based on recommendations for medical treatment, almost all guidelines recommended α1-blockers and 5α-reductase inhibitors, and most guidelines also recommended muscarinic receptor antagonists. In terms of drug combination therapy, most guidelines recommended “α1 blockers and 5α-reductase inhibitors”, and some guidelines also recommended “α1 blockers and muscarinic receptor antagonists”.ConclusionThe recommendations from different guidelines were basically similar, only showing conflicts in some areas. The quality of included guidelines remains to be unified, and their context can provide valuable implications for development or improvement.

The objective of this study was to evaluate association between body mass index (BMI) and prostate volume (PV), international prostate symptom scores (IPSS), maximum urinary flow rate ( Q max ), and post-void residual (PVR) of Chinese benign prostatic hyperplasia (BPH) patients. All newly diagnosed BPH patients between September 2016 and August 2018 were selected and 788 patients were included. According to BMI, the patients were categorized into four groups, while according to PV, IPSS, Q max , and PVR, they were categorized into two groups based on clinical significant cutoffs. Univariable and multivariable logistic regressions and a restricted cubic spline (RCS) were applied to explore the relationship of BMI with categorical PV, IPSS, Q max , and PVR. Compared with normal BMI, obesity presented significant association with increased risk of larger PV (>80 ml) in both unadjusted and adjusted models (unadjusted odds ratio [OR] = 1.772, 95% CI [1.201, 2.614], p = .004; adjusted OR = 1.912, 95% CI [1.212, 3.017], p = .005); however, underweight or overweight did not present a significant connection with such risk. No significant effect was identified for BMI on IPSS, Q max , or PVR in either unadjusted or adjusted model. Nonlinear test including BMI using RCS and adjusting for confounders showed no significance ( p > .05); however, a significant linear relationship was ascertained between BMI and the risk of larger PV ( p < .001). In conclusion, there was a significant linear association between BMI and the risk of larger PV in BPH patients. Hence, this suggests urologists should consider both BMI and PV when providing surgical treatment for BPH patients.

Objective: The current study is aimed at exploring the relationship between chronic periodontitis and serotonin transporter (5-HTT) gene polymorphisms (rs6354 and rs12449783) in the Chinese Han population.Methods: This study included a total of 120 patients with chronic periodontitis and 125 healthy control subjects. The 5-HTT gene (rs6354 and rs12449783) was genotyped using oral mucosal tissue with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium was examined using Haploview. Genotype and allele frequencies were compared between the cases and controls using a χ2 test.Results: Genotype distribution of the 5-HTT gene polymorphisms rs6354 and rs12449783 in the control group conformed to Hardy–Weinberg equilibrium. The frequency of the AC genotype, the AC + CC genotype and C allele of the 5-HTT rs6354 polymorphism was higher in cases (P < 0.05) vs. the healthy control. The adjusted odds ratio (OR) was 1.910 (95%CI = 1.049–3.476) for the AC genotype, 2.026 (95%CI = 1.115–3.680) for the AC+CC genotype, and 1.875 for the C allele (95%CI = 1.089–3.228. Such an association was particularly strong in women for the AC genotype (OR = 2.167, 95%CI = 1.034–4.542). The genotype and allele frequencies of rs12449783 did not differ between the cases and controls. Haplotype C-C (rs6354-rs12449783) was also more frequent in the cases (OR = 2.372, 95%CI = 1.154–4.875, P = 0.016).Conclusion: Chronic periodontitis is associated with the 5-HTT gene rs6354 polymorphism, as well as rs6354/rs12449783 interaction.

Background: In recent decades, research on drug therapy for ventilator-associated pneumonia (VAP) remains one of the major hot-spots in the field of critical care medicine, but relevant data are not satisfactory. Our aim was to assess the status and trends of the most cited articles on drug therapy for VAP through bibliometric approaches.Methods: The Institute for Scientific Information (ISI) Web of Science core collection database was searched for the VAP-related articles. The time period for retrieval was from the beginning of the database to September 30, 2018. The top 100 most cited articles were selected to obtain their information on the authors, title, publication, number of citations, author’s affiliations, country, etc. These general information and bibliometric data were collected for analysis. VOSviewer software was used to generate a term co-occurrence graph that visualized a reference pattern for different terms in the 100 articles.Results: The number of citations for the 100 selected articles ranged from 142 to 3,218. These articles were published in 31 different journals. The top three journals in terms of the number of our selected articles they published were “Critical Care Medicine” (17 articles), “American Journal of Respiratory and Critical Care Medicine” (11 articles) and “Clinical Infectious Diseases” (10 articles). The most frequently nominated author was Marin H. Kollef from the University of Washington, and of the top 100 articles, 16 listed his name. These top 100 articles were published after the year of 2000. The most common type of article in the top 100 was an original article (53%). The United States and France were the countries that contributed the most articles to the top 100. Gram-negative bacilli, pseudomonas aeruginosa, antibiotics, risk factors and other terms appeared more frequently, suggesting that attentions on this issue currently focused on the rational application and management of antibiotics.Conclusion: This study analyzed the 100 most cited articles on drug-treated VAP, and provided insights into the historical developments and characteristics of the most cited articles in the field of VAP.