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Genome‐wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID‐19) cases and outbreaks. We performed whole‐genome sequencing of 27 SARS‐CoV‐2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real‐time reverse‐transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19–6.38). The integration of sequencing and epidemiological data suggests that SARS‐CoV‐2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID‐19 prevention and control in Vietnam. [ABSTRACT FROM AUTHOR]

Background: Acute traumatic spinal cord injury (SCI) induces a systemic immune response involving circulating white blood cells (WBCs). How this response is influenced by overall trauma severity, the neurological level of injury and/or correlates with patient outcomes is poorly understood. The objective of this study was to identify relationships between early changes in circulating WBCs, injury characteristics and long‐term patient outcomes in individuals with traumatic SCI. Methods: We retrospectively analysed data from 161 SCI patients admitted to Brisbane's Princess Alexandra Hospital (exploration cohort). Logistic regression models in conjunction with receiver operating characteristic (ROC) analyses were used to assess the strength of specific links between the WBC response, respiratory infection incidence and neurological outcomes (American Spinal Injury Association Impairment Scale (AIS) grade conversion). An independent validation cohort from the Trauma Hospital Berlin, Germany (n = 49) was then probed to assess the robustness of effects and disentangle centre effects. Results: We find that the extent of acute neutrophilia in human SCI patients is positively correlated with New Injury Severity Scores but inversely with the neurological outcome (AIS grade). Multivariate analysis demonstrated that acute SCI‐induced neutrophilia is an independent predictor of AIS grade conversion failure, with an odds ratio (OR) of 4.16 and ROC area under curve (AUC) of 0.82 (P < 0.0001). SCI‐induced lymphopenia was separately identified as an independent predictor of better recovery (OR = 24.15; ROC AUC = 0.85, P < 0.0001). Acute neutrophilia and increased neutrophil‐lymphocyte ratios were otherwise significantly associated with respiratory infection presentation in both patient cohorts. Conclusions: Our findings demonstrate the prognostic value of modelling early circulating neutrophil and lymphocyte counts with patient characteristics for predicting the longer term recovery after SCI. [ABSTRACT FROM AUTHOR]

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS‐CoV‐2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human‐to‐human transmission of SARS‐CoV‐2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi‐morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies. Highlights: Transmission of SARS‐CoV‐2 is a global public health and clinical concern.This report describes clinical features, virus isolation, and complete genome sequences from the first two SARS‐CoV‐2 infections in Vietnam.Epidemiological and phylogenetic analysis suggested evidence of human‐to‐human transmission of SARS‐CoV‐2. Comparison of SARS‐CoV‐2 strains isolated from these two patients with those from Wuhan showed high similarities.Nonsynonymous substitutions existed in the ORF1ab region of the viral sequence.Compared with mild clinical and virological manifestations in the younger patient, the elderly suffered from pneumonia, prolonged viral shedding, and residual lung damage. [ABSTRACT FROM AUTHOR]

The Vietnamese Mekong Delta (VMD) is one of the most examined deltas in the world given its dynamics, complexity, and vulnerability. In the past decades, the VMD has changed rapidly, especially the land use in relation with the socioeconomic development. National policy has profoundly influenced these changes and the changes have significantly affected local livelihoods. However, these changes are not well reported systematically. In this study, we investigate land‐use changes based on institutional analyses across multiple scales, that is, from national, provincial, to local livelihood based on institutional and sustainability analysis. The results show a strong relationship between legal settings over the last 30 years on land use and livelihood transitions. In addition, the constraints of implementing national legal frameworks at provincial level in practice were identified including effects to local livelihoods. We offer some recommendations for sustainable livelihoods in the VMD, with a focus on increasing socioecological resilience. [ABSTRACT FROM AUTHOR]

The SAR target recognition based on optimised GPU parallel algorithm is proposed here. In general, with the rapid increment of the data dimension and the amount of data of SAR images, the traditional CPU-based target recognition algorithm cannot meet the requirements of real-time processing. Here, the target recognition algorithm which includes feature extraction and the classification is investigated and then parallel decomposed and optimised. First, the algorithms are investigated and parallel decomposed, including the principal component analysis, linear discriminant analysis, and non-negative matrix factorisation feature extraction technologies, and the support vector machines classifier. Then, the three feature extraction methods and sequential minimal optimisation algorithm are realised. Finally, the causes of compute unified device architecture programme running speed in target recognition algorithm are deeply analysed, and the algorithm is optimised from three aspects: communication, access, and instruction flow. According to the experiments, the optimised GPU-based parallel implementation of the target recognition algorithm has been optimised to obtain about 25–30 times performance upgrade [ABSTRACT FROM AUTHOR]

Summary: Biological invasions are determined by interactions between resident plant communities and exotic plants. Time of invasion and species diversity of resident plant communities may greatly affect exotic plant invasions. We assembled low‐ and high‐diversity resident plant communities by sowing seeds of four and eight grassland species, respectively, and at each of three time periods (1, 4 and 7 weeks after sowing), the resident communities were invaded by Hydrocotyle vulgaris or not. We also constructed a plant community with H. vulgaris alone. Presence of H. vulgaris had no effect on biomass of the resident communities or biomass of each component species. Community age significantly affected biomass and evenness of the resident communities, and their competition with H. vulgaris, but the priority effect of the resident communities was slight. Increasing species richness did not change the interaction between H. vulgaris and the resident plant communities. These findings suggest a weaker competitive exclusionary effect of H. vulgaris on the resident communities with early germination, and H. vulgaris tended to have no significant impact on intact resident terrestrial plant communities. Thus, the potential risk of H. vulgaris invasion is low, especially in the communities with young age. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of hydrophilic dental resin monomers, triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA), on the polarization of a human monocyte cell line (THP‐1). Methodology: THP‐1 cells were treated with resin monomers at noncytotoxic concentrations for 48 h and were analysed for CD86 and CD206 expressions using flow cytometry. The cells were stimulated for polarization in the presence of resin monomers (co‐treatment) or after treatment with monomers (pre‐treatment). CD86 and CD206 mRNA in co‐treated cells was evaluated using quantitative real‐time polymerase chain reaction. The release of TNF‐α and TGF‐β by pre‐treated and co‐treated cells was assessed using enzyme‐linked immunosorbent assay. Morphological changes of macrophages during polarization were observed using bright‐field microscopy. One‐way analysis of variance was used for statistical analysis. Results: TEGDMA (1 mmol L−1) and HEMA (2 mmol L−1) did not induce CD86 and CD206 expressions in THP‐1 cells but rather inhibited their expressions in the co‐treated cells. The inhibitory effects also appeared at the transcription level. However, the expression of surface markers was not affected by pre‐treatment with resin monomers. The release of TNF‐α and TGF‐β by M1‐ and M2‐stimulated cells, respectively, was suppressed by co‐treatment (P < 0.05). Microscopic studies revealed that co‐treatment with resin monomers suppressed polarization‐associated morphological changes such as cell volume increase. Conclusions: TEGDMA and HEMA inhibited macrophage polarization to both M1 and M2 at the transcription level, and the inhibitory effects disappeared upon the removal of resin monomers from the cell culture. [ABSTRACT FROM AUTHOR]

Background: Delay discounting refers to the devaluation of a reward given increasing delays to delivery. Similarly, effort discounting refers to the devaluation of a reward given increasing effort required to obtain it. Individuals with substance use disorder show higher rates of delay discounting, exacerbating short‐term positive reinforcement at the expense of long‐term consequences. This study explores how effort discounting compares to delay discounting behavior among alcohol users as well as how these preferences change between monetary and alcohol rewards. Methods: A total of 100 participants completed an online survey through Amazon Mechanical Turk. Participant alcohol use was evaluated using DSM‐5 and the Alcohol Use Disorders Identification Test criteria. All participants completed 4 randomized discounting tasks involving delay or effort discounting, in which the reward was money or alcohol. A follow‐up experiment (n = 423) added the alcohol purchase task to assess alcohol valuation. Results: Individuals with greater alcohol use disorder (AUD) severity discounted future money and alcohol significantly more than those with less AUD. However, individuals meeting more DSM‐5 criteria were only willing to perform more effort for alcohol. The follow‐up experiment replicated these findings and demonstrated that individuals with greater AUD also showed an increased valuation of alcohol and alcohol value‐mediated effort discounting. Conclusions: These results suggest that individuals with greater AUD were less willing to wait for money or alcohol. While all participants were willing to work for money regardless of AUD severity, individuals with greater AUD showed increased valuation of alcohol drinks and were willing to exert more effort to obtain alcohol. Together, these results paint a picture of individuals with increased AUD as both more impulsive and willing to work to obtain alcohol, contributing to our understanding of decision making among individuals who abuse substances. [ABSTRACT FROM AUTHOR]

Introduction Mean platelet volume (MPV) and platelet (PLT) count are the two major parameters that reflect the functions and activities of PLTs. The associations of MPV and PLT count with the occurrence and prognosis of stroke have not been fully clarified. This study aimed to investigate the association of MPV and PLT count with the development and prognosis of first-ever ischemic and hemorrhagic stroke in order to provide evidence for early diagnosis and treatment of both strokes. Methods This study included 281 first-ever ischemic stroke and 164 first-ever hemorrhagic stroke patients between 2010 and 2012. All participants received routine blood tests within 2 h after admission and were categorized into good or poor prognosis group based on the Modified Rankin Scale (mRS) score. MPV and PLT counts were transformed into categorical variables and their association with the occurrence and prognosis of both strokes was evaluated by multivariate logistic regression. Results The risk of ischemic and hemorrhagic stroke in MPV group (>13 fL) was 22.17 and 5.21 times higher compared with normal MPV group. The PLT count was positively correlated with the risk of ischemic stroke, but negatively correlated with the risk of hemorrhagic stroke. MPV and PLT count was not correlated with the prognosis of either stroke. Conclusions Increased MPV is an independent risk factor for both strokes. Elevated PLT count increases the risk for ischemic stroke, but decreases the risk for hemorrhagic stroke. However, neither MPV nor PLT count has significant association with the prognosis of either stroke. [ABSTRACT FROM AUTHOR]

The skeletal and immune systems share a multitude of regulatory molecules, including cytokines, receptors, signaling molecules, and signaling transducers, thereby mutually influencing each other. In recent years, several novel insights have been attained that have enhanced our current understanding of the detailed mechanisms of osteoimmunology. In orthodontic tooth movement, immune responses mediated by periodontal tissue under mechanical force induce the generation of inflammatory responses with consequent alveolar bone resorption, and many regulators are involved in this process. In this review, we take a closer look at the cellular/molecular mechanisms and signaling involved in osteoimmunology and at relevant research progress in the context of the field of orthodontic tooth movement. [ABSTRACT FROM AUTHOR]

Aims Rates of diabetes mellitus in the young have not been quantified on a population level, particularly in South Asian and Chinese populations, which bear high rates of diabetes. We determined the incidence of diabetes (Type 2 diabetes and diabetes using insulin only) and rates of hospitalizations among South Asian, Chinese and White people aged 5-29 years with newly diagnosed diabetes. Methods People with newly diagnosed diabetes (1997-2006) in British Columbia, Canada were identified using population-based administrative data and pharmacy databases. Age-standardized incidence rates were calculated for people with diabetes prescribed insulin only and those with Type 2 diabetes. They were followed for up to 8 years for all hospitalizations and diabetes-related complications. Results There were 712 South Asians, 498 Chinese and 6176 White people aged 5-29 years with diabetes. Most youth with diabetes had Type 2 diabetes (South Asian 86.4%; Chinese 87.1% and White 61.8%). The incidence of diabetes on insulin only was highest in White people compared with the other groups. The incidence of Type 2 diabetes was highest in South Asians, particularly in 20-29-year-olds, with rates 2.2 times that of White people and 3.1 times that of Chinese people. Hospitalization and diabetes-related complications were uncommon in all groups. Conclusion The incidence of Type 2 diabetes is higher than previously estimated among youth and is now surpassing diabetes on insulin only. Significant reductions in Type 2 diabetes screening ages in South Asians need to be considered and prevention efforts are urgently required in childhood and adolescence. Global estimates need to consider the epidemic of Type 2 diabetes in the young. [ABSTRACT FROM AUTHOR]

Aim To determine the prescribing of and adherence to oral hypoglycaemic agents, insulin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and statin therapy among South-Asian, Chinese and white people with newly diagnosed diabetes. Methods The present study was a population-based cohort study using administrative and pharmacy databases to include all South-Asian, Chinese and white people aged ≥ 35 years with diabetes living in British Columbia, Canada (1997-2006). Adherence to each class of medication was measured using proportion of days covered over 1 year with optimum adherence defined as ≥ 80%. Results The study population included 9529 South-Asian, 14 084 Chinese and 143 630 white people with diabetes. The proportion of people who were prescribed angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin or oral hypoglycaemic agents was ≤ 50% for all groups. South-Asian and Chinese people had significantly lower adherence for all medications than white people, with the lowest adherence to angiotensin-converting enzyme inhibitor treatment (South-Asian people: adjusted odds ratio 0.37, 95% CI 0.34-0.39; P<0.0001; Chinese people: adjusted odds ratio 0.50, 95% CI 0.47-0.54; P<0.0001) and statin therapy (South-Asian people: adjusted odds ratio 0.47, 95% CI 0.41 - 0.53, P < 0.0001; Chinese people: adjusted odds ratio 0.72, 95% CI 0.67 - 0.77; P<0.0001) compared with white people. Conclusion Adherence to evidence-based pharmacotherapy was substantially worse among the South-Asian and Chinese populations. Care providers need to be alerted to the high levels of non-adherence in these groups and the underlying causes need to be investigated. [ABSTRACT FROM AUTHOR]

During intrauterine life, genome interacts with maternal signals to influence the mRNA expression levels of specific genes persistently by regulating DNA methylation status. The objective of this study was to examine the responses of glucocorticoid receptor (GR), peroxisome proliferator-activated receptor alpha and gamma (PPARα and PPARγ) promoter methylation, mRNA expression of genes involved in energy metabolism and metabolite concentrations of intrauterine growth-retarded (IUGR) piglets to dietary folic acid supplementation. According to a 2 × 2 factorial arrangement, 16 IUGR and 16 normal birth weight (NBW) piglets were fed a basal diet or a basal diet supplemented with 5 mg/kg of folic acid from weaning (day 14) to day 35 of age. Triglycerides in hepatic tissue and plasma were significantly elevated in control diets-fed IUGR piglets compared with NBW piglets but were decreased by dietary folic acid supplementation. Hepatic mRNA expression levels of GR, PPARα, PPARγ, fatty acid synthase and phosphoenolpyruvate carboxykinase (PEPCK) in IUGR piglets fed a control diet were significantly higher than that in NBW piglets, and promoter methylation status of GR, PPARα and PPARγ in IUGR piglets was reduced significantly compared with NBW piglets. However, the changes in gene expression and DNA methylation status of IUGR piglets were reversed by dietary folic acid supplementation. Hepatic DNA methyltransferase activity was greater with dietary folic acid supplementation regardless of birth weight. Taken together, these results demonstrated that folic acid supplementation during early period of life could prevent the changes of promoter methylation status and gene expressions in the liver of IUGR piglets. [ABSTRACT FROM AUTHOR]

Introduction: The Candida albicans THI13 gene was identified by its homology to the Candida tropicalis CtNMT1 gene, which is involved in pyrimidine precursor biosynthesis. Methods: Disruption of THI13 revealed that this gene played a minor role in thiamin biosynthesis in C. albicans. Purified human monocytes were incubated with C. albicans at the optimal Candida: monocyte ratio of 0.5 and cytokines in the supernatants were measured by enzyme-linked immunosorbent assay. Results and discussion: This experiment showed that the wild-type strain significantly induced interleukin-10 (IL-10) production but had little effect on IL-12 production, and that THI13 mutants had no significant effect on IL-10 production, though the IL-12 level was increased in the supernatants. These results suggest that THI13 is involved in the host effective immune response by regulating IL-10 and IL-12 production. [ABSTRACT FROM AUTHOR]

Summary Background : Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclo-oxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. Aim : To assess the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib vs. non-selective non-steroidal anti-inflammatory drugs. Methods : Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric/duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. Results : In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of ≥ 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of ≥ 5 mm. Conclusions : The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds. [ABSTRACT FROM AUTHOR]

Background:Highly selective inhibitors of the inducible cyclooxygenase-2 enzyme (coxibs) have been associated with less gastrotoxicity than nonselective NSAIDs in clinical studies. Aim:To evaluate the influence of risk factors for NSAID-induced gastrotoxicity on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen. Methods:We analysed pooled data from two identical double-blind, randomized, 12-week endoscopy studies which compared the gastroduodenal toxicity of placebo (n=371), rofecoxib 25 mg (n=390), rofecoxib 50 mg (n=379), and ibuprofen 2400 mg daily (n=376) in patients with osteoarthritis. The potential risk factors evaluated were: age (< 65, ≥ 65 years), sex, race (white, nonwhite), Helicobacter pylori status, presence of gastroduodenal erosions at baseline, a history of upper gastrointestinal disease, prior NSAID use within 30 days of study entry, and smoking. We also evaluated these factors for possible association with the development of clinically-evident gastrointestinal perforations, ulcers or bleeds over 12 weeks. Results:Across all treatment groups, the likelihood of detecting endoscopic ulcers, or of clinical presentation with a bleed, over 12 weeks was increased approximately 4–5-fold in patients with previous upper gastrointestinal disease (relative risk [95% confidence interval] of 4.2 [2.5, 7.1] for endoscopic ulcers; 3.8 [1.4, 10.6] for bleeds), or those with gastroduodenal erosions at baseline endoscopy (relative risk of 4.4 [2.6, 7.5] for endoscopic ulcers; 5.0 [1.9, 13.5] for bleeds). H. pylori infection did not increase the risk of endoscopic ulcers or bleeds (relative risk of 1.1 [0.8, 1.6] for endoscopic ulcers; 0.3 [0.1, 0.9] for bleeds). The risk factor sub-group effects were constant across all treatment groups, and the significantly higher incidence of ulcers with ibuprofen as compared to rofecoxib and placebo was maintained in all risk factor subgroups. Conclusions:Gastroduodenal erosions at... [ABSTRACT FROM AUTHOR]

Background : Compared with currently available NSAIDs (which inhibit COX-1 and COX-2 isoforms of cyclooxy- genase), MK-0966 (a specific COX-2 inhibitor) is expected to cause less gastrointestinal toxicity. Aim : To compare the effect on the upper gastrointestinal mucosae of a high dose of MK-0966 with that of conventional doses of ibuprofen and aspirin. Methods Healthy subjects (n = 170; age range 18–54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK-0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7-day, double-blind, parallel-group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end-point was the percentage of subjects who developed a mucosal score ≥ 2 (i.e. the development of one or more erosions). To evaluate COX-1 activity, serum thromboxane B2 levels were determined in a subset of the population. Results The percentage of subjects who developed a mucosal score ≥ 2 in the MK-0966 group (12%) was significantly lower (P < 0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated. Conclusions In this acute short-term endoscopic study, MK-0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard. [ABSTRACT FROM AUTHOR]

Background. The potential role of finasteride in treating androgen related skin disorders was investigated. Methods. Pooled human dermal fibroblasts were used to assess the effect of finasteride on the 5α-reductase activity in skin tissue. Vmax and Km were estimated in the presence of 0, 10, and 200 nM finasteride. Results. Vmax values remain constant near 1.20 pmol/mg protein/h in the presence of increasing concentrations of finasteride; however, apparent Km increases from 0.27 nM at 0 nM finasteride to 0.31 nM and 0.44 nM at 10 nM and 200 nM finasteride, respectively. This suggests that finasteride competes with testosterone and has a high affinity for same binding site of the 5α-reductase enzyme. Apparent K was estimated at 282 nM, indicating that a high concentration of finasteride is required to significantly suppress the enzyme activity. Conclusions. This study confirms that finasteride inhibits the conversion of testosterone to dihydrotestosterone in human reticular dermal fibroblasts. Finasteride may have therapeutic potential in treating skin disorders influenced by the action of dihydrotestosterone. [ABSTRACT FROM AUTHOR]

Azelaic acid (AZA) is a naturally occurring saturated nine-carbon dicarboxylic acid. It possesses a variety of biological actions both in vitro and in vivo. Interest in the biological activity of AZA arose originally out of studies of skin surface lipids and the pathogenesis of hypochromia in pityriasis versicolor infection. At 10-100 millimeter concentrations AZA was shown to exhibit time and concentration dependent antiproliferative effects in vitro in human and murine malignant melanoma, mainly by inhibiting DNA synthesis.

Aims: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S)., Materials and Methods: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months., Results: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A 1c (HbA 1c ) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years., Conclusions: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally., (© 2024 John Wiley & Sons Ltd.)

Background: Many studies have recently highlighted the role of photobiomodulation (PBM) in neuropathic pain (NP) relief after spinal cord injury (SCI), suggesting that it may be an effective way to relieve NP after SCI. However, the underlying mechanisms remain unclear. This study aimed to determine the potential mechanisms of PBM in NP relief after SCI., Methods: We performed systematic observations and investigated the mechanism of PBM intervention in NP in rats after SCI. Using transcriptome sequencing, we screened CXCL10 as a possible target molecule for PBM intervention and validated the results in rat tissues using reverse transcription-polymerase chain reaction and western blotting. Using immunofluorescence co-labeling, astrocytes and microglia were identified as the cells responsible for CXCL10 expression. The involvement of the NF-κB pathway in CXCL10 expression was verified using inhibitor pyrrolidine dithiocarbamate (PDTC) and agonist phorbol-12-myristate-13-acetate (PMA), which were further validated by an in vivo injection experiment., Results: Here, we demonstrated that PBM therapy led to an improvement in NP relative behaviors post-SCI, inhibited the activation of microglia and astrocytes, and decreased the expression level of CXCL10 in glial cells, which was accompanied by mediation of the NF-κB signaling pathway. Photobiomodulation inhibit the activation of the NF-κB pathway and reduce downstream CXCL10 expression. The NF-κB pathway inhibitor PDTC had the same effect as PBM on improving pain in animals with SCI, and the NF-κB pathway promoter PMA could reverse the beneficial effect of PBM., Conclusions: Our results provide new insights into the mechanisms by which PBM alleviates NP after SCI. We demonstrated that PBM significantly inhibited the activation of microglia and astrocytes and decreased the expression level of CXCL10. These effects appear to be related to the NF-κB signaling pathway. Taken together, our study provides evidence that PBM could be a potentially effective therapy for NP after SCI, CXCL10 and NF-kB signaling pathways might be critical factors in pain relief mediated by PBM after SCI., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Ciliary neurotrophic factor is a member of the interleukin-6 family of cytokines. Ciliary neurotrophic factor drives many cells for their development. However, its effects on Leydig cell development remain unclear., Methods: In the current study, we used three-dimensional seminiferous tubule culture system to induce the proliferation and differentiation of tubule-associated stem Leydig cells and primary progenitor Leydig cells culture to address the effects of ciliary neurotrophic factor., Results: We found that ciliary neurotrophic factor stimulated the proliferation of stem Leydig cells but inhibited their development into the Leydig cell lineage. The ciliary neurotrophic factor-mediated effects can be reversed by signal transducer and activator 3 inhibitor S3I-201 and phosphatidylinositol 3-kinase inhibitor wortmannin, indicating that ciliary neurotrophic factor acts via signal transducer and activator 3-phosphatidylinositol 3-kinase signaling pathways to increase stem/progenitor Leydig cell proliferation. Ciliary neurotrophic factor at 1 and 10 ng/mL significantly decreased androgen production by progenitor Leydig cells. Microarray analysis of ciliary neurotrophic factor-treated progenitor Leydig cells showed that ciliary neurotrophic factor blocked steroidogenic pathways by downregulating Scarb1, Star, and Hsd3b1, possibly by downregulating the transcription factor Nr5a1 expression., Conclusion: Ciliary neurotrophic factor stimulates proliferation but blocks the differentiation of stem/progenitor Leydig cells., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background Nonpharmacologic interventions that modify lifestyle can lower blood pressure (BP) and have been assessed in numerous randomized controlled trials and pairwise meta-analyses. It is still unclear which intervention would be most efficacious. Methods and Results Bayesian network meta-analyses were performed to estimate the comparative effectiveness of different interventions for lowering BP. From 60 166 potentially relevant articles, 120 eligible articles (14 923 participants) with a median follow-up of 12 weeks, assessing 22 nonpharmacologic interventions, were included. According to the surface under the cumulative ranking probabilities and Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality of evidence, for adults with prehypertension to established hypertension, high-quality evidence indicated that the Dietary Approach to Stop Hypertension (DASH) was superior to usual care and all other nonpharmacologic interventions in lowering systolic BP (weighted mean difference, 6.97 mm Hg; 95% credible interval, 4.50-9.47) and diastolic BP (weighted mean difference, 3.54 mm Hg; 95% credible interval, 1.80-5.28). Compared with usual care, moderate- to high-quality evidence indicated that aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, breathing-control, and meditation could lower systolic BP and diastolic BP. For patients with hypertension, moderate- to high-quality evidence suggested that the interventions listed (except comprehensive lifestyle modification) were associated with greater systolic BP and diastolic BP reduction than usual care; salt restriction was also effective in lowering both systolic BP and diastolic BP. Among overweight and obese participants, low-calorie diet and low-calorie diet plus exercise could lower more BP than exercise. Conclusions DASH might be the most effective intervention in lowering BP for adults with prehypertension to established hypertension. Aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, salt restriction, breathing-control, meditation and low-calorie diet also have obvious effects on BP reduction.

Background: Non-coding RNAs play a critical role in the occurrence and development of oral cancer. The present study is aimed to identify long non-coding RNA (lncRNA) that might be novel effective targets for the treatments of oral cancer and the underlying mechanism., Methods: The microarray profiling and RNA-sequencing analysis were performed to identify lncRNAs related to oral cancer development, and lncRNA DNM3OS was selected. DNM3OS knockdown was generated in cancer cell lines, and the specific effects of DNM3OS knockdown on cell phenotype were examined. DNM3OS targeted miRNA and miRNA targeted downstream mRNA were selected, the predicted bindings were verified, and the specific effects of miRNA on oral cancer cells were examined. Finally, the dynamic effects of DNM3OS and miRNA on target mRNA expression and oral cancer cell phenotype were examined., Results: DNM3OS was upregulated in oral cancer tissues and cells. DNM3OS knockdown in CAL27 and SCC-9 cells inhibited cell viability and migration. DNM3OS targeted miR-204-5p to inhibit miR-204-5p expression. miR-204-5p overexpression suppressed oral cancer cell aggressiveness. miR-204-5p targeted HIP1 to inhibit HIP1 expression. HIP1 knockdown inhibited oral cancer cell viability and migration. The effects of DNM3OS knockdown were significantly reversed by miR-204-5p inhibition. Within oral carcinoma tissue samples, expression of DNM3OS and HIP1 was increased whereas the miR-204-5p expression was downregulated; miR-204-5p had a negative correlation with DNM3OS and HIP1, respectively, while DNM3OS and HIP1 were positively correlated with each other., Conclusion: Long non-coding RNA DNM3OS, miR-204-5p, and HIP1 form an axis that modulates oral cancer cell viability and migration., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mirabilis himalaica is an endangered medicinal plant species in the Tibetan Plateau. The two genes respectively encoding chalcone synthase (MhCHS) and chalcone isomerase (MhCHI) were isolated and characterized from M. himalaica. The sequence analysis revealed that the two genes were similar with their corresponding homologous genes in other plants. The tissue profiles showed that both MhCHS and MhCHI had higher expression levels in roots than in stems and leaves. Transgenic hairy root cultures respectively with overexpressing MhCHS and MhCHI were established. The genomic PCR detection confirmed the authority of transgenic hairy root lines, in which either MhCHS or MhCHI expression levels were much higher than that in non-transgenic hairy root line. Finally, the HPLC detection results demonstrated that the rotenoid contents in MhCHS/MhCHI-transformed hairy root lines were enhanced. This study provided two candidate genes that could be used to genetic engineering rotenoid biosynthesis in M. himalaica and an alternative method to produce rotenoid using transgenic hairy root cultures., (© 2015 International Union of Biochemistry and Molecular Biology, Inc.)

Background/aims: Administrative databases could be useful in studying the epidemiology of primary sclerosing cholangitis (PSC); however, there is no information regarding the validity of the diagnostic code in administrative databases. The aims of this study were to determine the validity of administrative data for a diagnosis of PSC and generate algorithms for the identification of PSC patients., Methods: The sensitivity (Se) and positive predictive value (PPV) of a PSC diagnosis based on administrative data from 2000 to 2003 were determined through chart review data. Algorithms were developed by considering variables associated with PSC and coding details. A logistic regression model was constructed using covariates associated with PSC. Based on this model, each subject was assigned a probability of having PSC. A cutoff value was selected that maximized the Se and specificity (Sp) of correctly predicting PSC cases., Results: In the administrative data, the initial Se and PPV were 83.7 and 7.2% respectively. The optimal algorithm included one PSC code and one inflammatory bowel disease code and had Se 56% and PPV 59%. Overall, the algorithms yielded inadequate PPV and Se estimates to identify a cohort of true PSC cases. The predictive model was constructed using six covariates. For this model, the area under the receiver operating characteristic curve was 93.5%. A cutoff of 0.0729 was used, which maximized the Se 81.9% and Sp 90.7%; however, the PPV was 41.0%., Conclusion: An algorithm for the identification of true PSC cases from administrative data was not possible. We recommend that PSC receives a distinct ICD code from ascending cholangitis., (© 2011 John Wiley & Sons A/S.)

Objective: This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design)., Methods: Seven hundred seventy-five patients with osteoarthritis were randomized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibuprofen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assessed by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks, respectively., Results: Ulcers were significantly less common (P < 0.001) following treatment with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3% and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 46.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence., Conclusion: At 2-4 times the therapeutically effective dose, rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen. Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied prespecified criteria for equivalence to placebo.

Objectives: Several published articles have described the importance of exposing medical trainees to the 'new paradigm' of evidence-based medicine (EBM). Recognizing this, we sought to develop and objectively evaluate a mini-course in EBM for third-year medical students., Design: We developed a mini-course consisting of four sessions in which students learn to derive sequentially focused questions, search MEDLINE, review articles critically and apply information from the literature to specific clinical questions. To evaluate the teaching intervention, we performed a controlled educational study. Students at the intervention site (n=34) attended the EBM mini-course, while students at the control site (n=26) received more 'traditional' didactic teaching on various clinical topics. Intervention and control students were surveyed immediately before and after the mini-course to assess changes in reading and literature searching skills, as well as a tendency to use the literature to answer clinical questions., Setting: Boston University School of Medicine., Subjects: Third-year medical students., Results: The intervention was associated with significant changes in students' self-assessed skills and attitudes. MEDLINE and critical appraisal skills increased significantly in the intervention group relative to the control group (significance of between group differences: P=0.002 for MEDLINE and P=0.0002 for critical appraisal), as did students' tendency to use MEDLINE and original research articles to solve clinical problems (significance of between group differences: P=0.002 and P=0.0008, respectively)., Conclusions: We conclude that this brief teaching intervention in EBM has had a positive impact on student skills and attitudes at our medical school. We believe that the key elements of this intervention are (1) active student involvement, (2), clinical relevance of exercises and (3) integrated teaching targeting each of the component skills of EBM.