A review of long non-coding RNAs in ankylosing spondylitis: pathogenesis, clinical assessment, and therapeutic targets.

Ankylosing spondylitis (AS) is a chronic immune-mediated type of inflammatory arthritis characterized by inflammation, bone erosion, and stiffness of the spine and sacroiliac joints. Despite great efforts put into the investigation of the disease, the pathogenesis of AS remains unclear, posing challenges in identifying ideal targets for diagnosis and treatment. To enhance our understanding of AS, an increasing number of studies have been conducted. Some of these studies reveal that long non-coding RNAs (lncRNAs) play crucial roles in the etiology of AS. Some certain lncRNAs influence the development of AS by regulating inflammatory responses, autophagy, apoptosis, and adipogenesis, as well as the proliferation and differentiation of cells. Additionally, some lncRNAs demonstrate potential as biomarkers, aiding in monitoring disease progression and predicting prognosis. In this review, we summarize recent studies concerning lncRNAs in AS to elucidate the underlying mechanisms in which lncRNAs are involved and their potential values as biomarkers for disease assessment and druggable targets for therapy.

Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis.

Ischemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. Our study utilizes nonhuman primates (NHPs) to provide a detailed exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month postmiddle cerebral artery occlusion (MCAO) and then stabilized. This pattern was strongly correlated to notable changes in motor function and working memory performance. Using diffusion tensor imaging (DTI), we detected significant alterations in fractional anisotropy (FA) and mean diffusivity (MD) values, signaling microstructural changes in the brain. These alterations closely correlated with the neurological and cognitive deficits that we observed, highlighting the sensitivity of DTI metrics in stroke assessment. Behaviorally, the monkeys exhibited a reliance on their unaffected limb for compensatory movements, a common response to stroke impairment. This adaptation, along with consistent DTI findings, suggests a significant impact of stroke on motor function and spatial perception. Proteomic analysis through MS/MS functional enrichment identified two distinct groups of proteins with significant changes post-MCAO. Notably, MMP9, THBS1, MB, PFN1, and YWHAZ were identified as potential biomarkers and therapeutic targets for ischemic stroke. Our results underscore the complex nature of stroke and advocate for an integrated approach, combining neuroimaging, behavioral studies, and proteomics, for advancing our understanding and treatment of this condition.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

The effect of controlling person's illegalities on stock price returns: Evidence from Elman neural network model.

Controlling persons are the ultimate decision-makers of listed companies. Their illegalities have impacts on investors' wealth, firm development, and capital market's quality. Against this backdrop, we provide a quantitative analysis of the short-term stock price reaction to the criminal detention announcements of controlling persons throughout 2007-2019. We applied the Elman neural network (ENN) model into the classical event study methodology and demonstrated that the combination of them helps to improve the estimation accuracy of the stock price reaction. The results show that the stock price has a significant negative reaction to the criminal detention announcements of listed companies' controlling persons on the announcement day, and the average reaction level is -6.67%. Additionally, the crisis communication measures of the firms could diminish the negative impact of such mandatory disclosure information on their stock price, but the effect is limited. Finally, the 31 companies in our sample cause a total loss of RMB 21.1 billion in market capitalization on the announcement day alone. The above results indicate that the impact of listed companies' controlling persons on the capital market is tremendous, although the number of this group is small. Our work enriches the listed companies' illegalities research and provides a reference for investors' investment choices and follow-up decision making of regulatory authorities. It also provides some guidance for most of the researchers to further explore the application of data mining techniques in nonlinear problems.

Boosting the green total factor energy efficiency in urban China: Does low-carbon city policy matter?

Low-carbon city (LCC) pilot is a strategic policy to deal with global climate change and energy poverty. Using the city-level data from 2006 to 2019, this paper applies a multiple difference-in-difference (DID) analysis to explore the impact of LCC policy on urban green total factor energy efficiency(GTFEE) and its potential mechanism. The results show that the LCC pilot policy can significantly improve urban GTFEE, and the finding remains robust with various tests. Secondly, we shed light on the mechanism of the LCC policy and explore the possible channels through green innovation and structural upgrading to improve the urban GTFEE. Third, the policy effect is affected by different levels of urban economic development, urban development scale, and urban development types. In cities with higher levels of economic development, super-large resource-based cities, the pilot policy has a more significant improvement effect on GTFEE. On the other hand, in the less developed regions, pilot policies will hinder the improvement of GTFEE.

Does FDI improve green total factor energy efficiency under heterogeneous environmental regulation? Evidence from China.

Green development is a strategy for China's sustainable economic growth, and improving green total factor energy efficiency (GTFEE) is the key to achieving the dual goals of energy conservation, emission reduction, and economic development. This paper takes panel data of 267 prefecture-level cities in China from 2004 to 2019 as samples to explore how heterogeneous environmental regulation can have the effects of FDI on GTFEE. The results show that, first, except for environmental regulation and FDI independently affecting GTFEE, there is a synergistic effect between environmental regulation and FDI, and their interaction can also significantly affect GTFEE. Secondly, FDI has no significant impact on GTFEE when environmental regulation is low, but FDI can significantly improve GTFEE when environmental regulation is high. Thirdly, market-based environmental regulations (MER) have a better improvement effect on GTFEE than command-based environmental regulations (CER). Therefore, it is necessary to pay attention to the benign interaction between FDI and environmental regulation, especially giving full play to the role of market-based environmental regulation and further improving the design of command-based environmental regulation.

Dynamic environmental regulation threshold effect of technical progress on green total factor energy efficiency: evidence from China.

Sustainability is a strategic choice for the transition to a green economy in China. Improving green total factor energy efficiency (GTFEE) is the key to realizing the dual targets of energy-saving and economic growth. This paper empirically tests the nonlinear effects of environmental regulation on technical innovation affecting GTFEE by using panel data of 271 prefecture-level cities in China from 2004 to 2019. Meanwhile, a system GMM approach is used to verify the channels through which technical innovation affects GTFEE. Finally, the spatial and temporal characteristics of technical innovation affecting GTFEE are analyzed from the perspective of environmental regulation. The empirical results are as follows: (1) Technical innovation can significantly improve GTFEE. However, this improvement effect is a threshold characteristic; when environmental regulation is above the threshold value, technical innovation has a greater improvement effect on GTFEE. (2) Besides directly influencing GTFEE, technical innovation can also indirectly influence GTFEE via channels such as economic growth effect, industrial structure upgrading effect, and foreign investment effect. Meanwhile, indirect influence channels also show environmental regulation heterogeneity. (3) The number of cities crossing the threshold of environmental regulation in China increases year by year, which helps technical innovation play a role in improving GTFEE. However, there are still a small number of cities that do not cross the threshold during the sample period, which should attract the attention of local governments.

Research on multiple bubbles in China's multi-level stock market.

Financial bubbles have always been a topic of long-term concern for economists. Understanding bubble phenomenon and dating the period of bubbles in real time can provide an early warning diagnosis for financial bubbles and help regulatory authorities to control it and maintain market order. The generalized sup ADF (GSADF) and backward sup ADF (BSADF) tests with flexible window width can effectively detect and date periodically collapsing bubbles in real time. Based on the financial present value model, this paper applies right-tail recursive ADF test to test multiple bubbles in China's multi-level stock market. Unlike the other researches in China, the ratios of the real stock prices' natural logarithm to the real dividends' natural logarithm are used for our testing instead of stock price index. Empirical results show that there are 8 bubbles in the Main-Board Market, 6 bubbles in the Small and Medium Enterprises Board (SMEs), and 4 bubbles in the Growth Enterprise Market (GEM). These bubbles are liquidity-driven and presuppose a loose credit cycle, with the exception of bubbles in 2014-2015. The frequent emergence of bubbles in a short time indicates that China's stock market is still emerging market. In addition, frequent fluctuations imply there is a serious "herd effect" and a lack of monitoring mechanism for bubble risk. This study not only enrich the real-time dynamic research on periodical bubbles of China's stock market, but also provide an empirical reference for investors' investment choices, financial decisions of listed companies and warning mechanism of regulatory authorities.

Tableting model assessment of porosity and tensile strength using a continuous wet granulation route.

This paper presents a comprehensive assessment of the most widely used tablet compaction models in a continuous wet granulation tableting process. The porosity models, tensile strength models and lubricant models are reviewed from the literature and classified based on their formulations i.e. empirical or theoretical and applications, i.e. batch or continuous. The majority of these models are empirical and were initially developed for batch tabletting process. To ascertain their effectiveness and serviceability in the continuous tableting process, a continuous powder processing line of Diamond Pilot Plant (DiPP) installed at The University of Sheffield was used to provide the quantitative data for tablet model assessment. Magnesium stearate (MgSt) is used as a lubricant to investigate its influence on the tensile strength. Whilst satisfactory predictions from the tablet models can be produced, a compromise between the model fidelity and model simplicity needs to be made for a suitable model selection. The Sonnergaard model outperforms amongst the porosity models whilst the Reynolds model produces the best goodness of fitting for two parameters fitting porosity models. An improved tensile strength model is proposed to consider the influence of powder size and porosity in the continuous tableting process.

Cross-cultural adaptation and psychometric assessment of the statement format Decisional Conflict Scale for Mandarin version.

BACKGROUND: The statement format of the Decisional Conflict Scale (sf-DCS) is designed and widely used to assess patients' state of uncertainty during health related decision making. As yet no Mandarin version of the sf-DCS has been produced. This study aims to produce the first Mandarin version of the sf-DCS and test its validity and reliability in mainland China. METHODS: The translation and cross-cultural adaptation of the original English version of the sf-DCS into Mandarin was carried out in accordance with previously published guidelines. The psychometric properties of sf-DCS were assessed in two hypothesized decision-making contexts through online surveys. RESULTS: In the online survey designed to test scale validity and reliability, 437 people responded to the influenza immunization survey and 238 responded to the breast cancer screening survey. The results confirm that the Mandarin version of sf-DCS has good criteria validity and the exploratory factor analysis suggested a fitted revised five factors model by removing three items. Respondents who were "unsure" about their decisions/intentions, had read less information, and reported lower self-perceived prior knowledge level scored higher on sf-DCS. The Cronbach's alpha for the sf-DCS total score was 0.963 and that for each subscale ranged from 0.784 to 0.937 in both decision making contexts, and the test-retest correlation coefficient was 0.528. CONCLUSIONS: The Mandarin version of sf-DCS has good criteria validity and its internal consistency is satisfactory. Our analysis suggests a refinement of the original sf-DCS's factor structure is needed.

Assessment of clinical sepsis-associated biomarkers in a septic mouse model.

Objective Clinical sepsis-associated biomarkers were utilized in a cecal ligation and puncture (CLP) septic mouse model to provide a reference for investigating pathophysiological mechanisms and evaluating novel therapeutic interventions for sepsis. Methods Sepsis in mice was induced by CLP, and clinical biomarkers were evaluated (survival rate, blood physiological and biochemical indices, cytokines, hepatorenal function parameters, and blood coagulation). Results The mortality rate was >70%. The body temperature, blood pressure, and heart rate decreased within 48 h. Low lactic acid was found at 8 h. The CLP mice showed typical inflammatory symptoms with decreased white blood cells and procalcitonin and increased levels of soluble triggering receptor expressed on myeloid cells-1, interleukin (IL)-6, IL-10, tumor necrosis factor-α, macrophage inflammatory protein (MIP)-1α, MIP-1ß, and MIP-2. The platelet count and activated partial thromboplastin time significantly decreased, and the prothrombin time and prothrombin time-international normalized ratio markedly increased. Phenotypes of multiple organ dysfunction were found in the CLP model, including increased liver alanine aminotransferase and aspartate transaminase; significantly reduced total protein, globulin, and serum albumin; increased blood urea nitrogen and creatinine; and decreased blood glucose. Conclusion The clinical features of the CLP mouse model were similar to those of human patients with sepsis.

Prehypertension and socioeconomic status: A cross-sectional study in Chongqing, China.

BACKGROUND: A large amount of research is available on the relationship between socioeconomic status (SES) and hypertension. However, the relationship between SES and prehypertension remains complex and unclear. Prehypertension is defined as a systolic blood pressure (SBP) between 120 and 139 mmHg or diastolic blood pressure (DBP) 80 and 89 mmHg. This paper focuses on the impact of SES on the prevalence of prehypertension and provides suggestions for the prevention and control measures of prehypertension and health resource allocation. METHOD: Using multistage random sampling, 11,773 subjects were selected. Subjects aged above 15 years old and subjects who had been living in the eight selected districts for more than 6 months were analyzed using a multivariable logistical model. RESULTS: The prevalence of prehypertension at the present time reaches 55.17%, with it being higher among men than that among women (63.15% vs. 47.19%, p < 0.05). After adjustment for other factors such as age and gender, a logistic regression showed that a higher education level and a history of marital status were significantly associated with prehypertension. CONCLUSIONS: People of different SES indicate different working and living conditions. They also face different risk factors for prehypertension. Lower education and a history of marital status were associated with a higher risk of prehypertension among residents in Chongqing, China.

Assessment of gray and white matter structural alterations in migraineurs without aura.

BACKGROUND: Migraine constitute a disorder characterized by recurrent headaches, and have a high prevalence, a high socio-economic burden and severe effects on quality of life. Our previous fMRI study demonstrated that some brain regions are functional alterations in migraineurs. As the function of the human brain is related to its structure, we further investigated white and gray matter structural alterations in migraineurs. METHODS: In current study, we used surface-based morphometry, voxel-based morphometry and diffusion tensor imaging analyses to detect structural alterations of the white matter and gray matter in 32 migraineurs without aura compared with 32 age- and gender-matched healthy controls. RESULTS: We found that migraineurs without aura exhibited significantly increased gray matter volume in the bilateral cerebellar culmen, increased cortical thickness in the lateral occipital-temporal cortex, decreased cortical thickness in the right insula, increased gyrification index in left postcentral gyrus, superior parietal lobule and right lateral occipital cortex, and decreased gyrification index in the left rostral middle frontal gyrus compared with controls. No significant change in white matter microstructure was found in DTI analyses. CONCLUSION: The significantly altered gray matter brain regions were known to be associated with sensory discrimination of pain, multi-sensory integration and nociceptive information processing and were consistent with our previous fMRI study, and may be involved in the pathological mechanism of migraine without aura.

Dietary exposure to aluminium in the popular Chinese fried bread youtiao.

Youtiao is a typical, traditional and widely consumed fried food in China. Fermentation of youtiao involves the use of aluminium potassium sulphate (alum). There are health concerns related to the levels of aluminium in food; therefore, we aimed to determine the aluminium concentrations of youtiao from various locations, and to estimate the dietary exposure by different age groups in southern and northern China. The aluminium content of youtiao samples varied considerably (range = 4.46-852.69 mg kg-1). Both the mean and median aluminium contents of youtiao exceeded 100 mg kg-1, which is the China National Standard (GB) 2760-2014 National Food Safety for Standards for food additives. However, the median and 97.5th percentile of weekly dietary exposure to aluminium from youtiao, estimated using Monte Carlo simulation, did not exceed the provisional tolerable weekly intake (PTWI) set by the joint FAO/WHO Expert Committee on Food Additives (JECFA) for children, adolescents, adults and seniors. The weekly dietary exposure to aluminium would exceed the PTWI if children, adolescents, adults and seniors consumed 134.47, 260.98, 327.10 or 320.41 g of youtiao per week, respectively.

Epidemiology Characteristics, Methodological Assessment and Reporting of Statistical Analysis of Network Meta-Analyses in the Field of Cancer.

Because of the methodological complexity of network meta-analyses (NMAs), NMAs may be more vulnerable to methodological risks than conventional pair-wise meta-analysis. Our study aims to investigate epidemiology characteristics, conduction of literature search, methodological quality and reporting of statistical analysis process in the field of cancer based on PRISMA extension statement and modified AMSTAR checklist. We identified and included 102 NMAs in the field of cancer. 61 NMAs were conducted using a Bayesian framework. Of them, more than half of NMAs did not report assessment of convergence (60.66%). Inconsistency was assessed in 27.87% of NMAs. Assessment of heterogeneity in traditional meta-analyses was more common (42.62%) than in NMAs (6.56%). Most of NMAs did not report assessment of similarity (86.89%) and did not used GRADE tool to assess quality of evidence (95.08%). 43 NMAs were adjusted indirect comparisons, the methods used were described in 53.49% NMAs. Only 4.65% NMAs described the details of handling of multi group trials and 6.98% described the methods of similarity assessment. The median total AMSTAR-score was 8.00 (IQR: 6.00-8.25). Methodological quality and reporting of statistical analysis did not substantially differ by selected general characteristics. Overall, the quality of NMAs in the field of cancer was generally acceptable.

The prevalence, incidence, management and risks of atrial fibrillation in an elderly Chinese population: a prospective study.

BACKGROUND: There is limited information on prevalent and incident atrial fibrillation in Chinese. We aimed to investigate the prevalence, incidence, management and risks of atrial fibrillation in an elderly Chinese population. METHODS: In a population--based prospective study in elderly (≥ 60 years) Chinese, we performed cardiovascular health examinations including a 12-lead electrocardiogram at baseline in 3,922 participants and biennially during follow-up in 2,017 participants. We collected information on vital status during the whole follow-up period. RESULTS: The baseline prevalence of atrial fibrillation was 2.0 % (n = 34) in 1718 men and 1.6 % (n = 36) in 2204 women. During a median 3.8 years of follow-up, the incidence rate of atrial fibrillation (n = 34) was 4.9 per 1000 person-years (95 % confidence interval [CI], 3.4-6.9). In univariate analysis, both the prevalence and incidence of atrial fibrillation were higher with age advancing (P < 0.0001) and in the presence of coronary heart disease (P ≤ 0.02). Of the 104 prevalent and incident cases of atrial fibrillation, only 1 (1.0 %) received anticoagulant therapy (warfarin). These patients with atrial fibrillation, compared with those with sinus rhythm, had significantly higher risks of all-cause (n = 261, hazard ratio [HR] 1.87, 95 % CI, 1.09-3.20, P = 0.02), cardiovascular (n = 136, HR 3.78, 95 % CI 2.17-6.58, P < 0.0001) and stroke mortality (n = 44, HR 6.31, 95 % CI 2.81-14.19, P = 0.0003). CONCLUSIONS: Atrial fibrillation was relatively frequent in elderly Chinese, poorly managed and associated with higher risks of mortality.

Cash incentives improve participation rate in a face-to-face survey: an intervention study.

OBJECTIVES: Our study examined the effect of a ChinaYuan (CNY) 10 cash incentive on the participation rate in a face-to-face health survey among the general Chinese population. STUDY DESIGN AND SETTING: Subjects older than 15 years of age and had been living in the two selected districts for more than 6 months were selected using multistage random sampling. Participants from only one district received a cash incentive (CNY 10) for completing the survey. RESULTS: The participation rates in the nonincentive and incentive groups were 39.9% and 61.2%, respectively, P < 0.01. In the nonincentive group, the 65-74 years age group had the highest participation rate (54.4%); no significant difference was found between men (39.4%) and women (40.5%), P = 0.59. In the incentive group, the highest participation rate was observed in the ≥75 years (78.1%) age group. The cost for a completed interview was CNY 34.5 in the incentive group and CNY 35.8 in the nonincentive group. CONCLUSION: Cash incentives might increase participation rates in face-to-face surveys in China. The absolute cost was higher for the incentive group, whereas cost for a completed interview was actually the lowest. Furthermore, participation rate did not differ between men and women, but elders were more likely to participate in health surveys.

Early postnatal nutrition determines adult physical activity and energy expenditure in female mice.

Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1 (P1), mice were fostered in control (C) or small litters (SL). SL mice had increased body weight and adiposity at weaning (P21), which persisted to adulthood (P180). Detailed metabolic studies indicated that female adult SL mice have decreased physical activity and energy expenditure but not increased food intake. Genome-scale DNA methylation profiling identified extensive changes in hypothalamic DNA methylation during the suckling period, suggesting that it is a critical period for developmental epigenetics in the mouse hypothalamus. Indeed, SL mice exhibited subtle and sex-specific changes in hypothalamic DNA methylation that persisted from early life to adulthood, providing a potential mechanistic basis for the sustained physiological effects. Expression profiling in adult hypothalamus likewise provided evidence of widespread sex-specific alterations in gene expression. Together, our data indicate that early postnatal overnutrition leads to a reduction in spontaneous physical activity and energy expenditure in females and suggest that early postnatal life is a critical period during which nutrition can affect hypothalamic developmental epigenetics.

Ask the experts: future of the pharmaceutical industry. Interview by Future Medicinal Chemistry.

The pharmaceutical industry is facing numerous, well-documented challenges - from the effects of patent expirations to high attrition rates in the drug-development pipeline. Future Medicinal Chemistry has invited a group of leaders from academia and industry to express their views on where the industry is heading and speculate as to what role medicinal chemists will play in the future.

[Study on the change of urinary iodine of different salt concentrations among the target population in an intervention trial].

OBJECTIVE: To analyze the change of urinary iodine in a cohort of intervention trial and to observe the role of different doses on salt iodization and related impact factors on nutritional condition of iodine. METHODS: Multistage cluster sampling was used to sample three townships in two counties for community intervention with different doses (15 ± 5, 25 ± 5, 35 ± 5) mg/kg. RESULTS: Compared to the (35 ± 5) mg/kg group, the urine iodine levels of three experimental townships were gradually declining in county B when time went on, and the (15 ± 5) mg/kg group showed an obvious results, at 6, 12, 18 and 24 months, with the urine iodine level as 180.00, 186.10, 150.04, 191.28 µg/L respectively, which were in accordance with the WHO standard and reached to appropriate range (187.96 µg/L) at the 18 month. The townships at county Y under intervention had declined slightly, but the urine iodine levels did not reach the WHO standard. The thyroid volume declined from 3.65 ml to 3.40 ml in two counties and the difference between them was statistically significant. CONCLUSION: To some extent, reducing the iodine concentration in salt, had a role of lowering the urine iodine level and reducing the strumous rate.