Comparison of Efficacy of Baricitinib and Dupilumab in the Treatment of Chinese Moderate-To-Severe Atopic Dermatitis: A Retrospective Study.

INTRODUCTION: The treatment of atopic dermatitis (AD) patients with insufficient response or intolerance to topical medication remains clinical challenges, and there is a paucity of head-to-head trials comparing the efficacy of novel biological agents such as JAK inhibitor and antibody. METHODS: To compare the efficacy of selective JAK1/JAK2 inhibitor baricitinib and interleukin-4 monoclonal antibody dupilumab in the treatment of patients with moderate-to-severe AD, a retrospective cohort study method was adopted. Clinical data from June 2020 to April 2022 were systematically reviewed. Eligible patients who received baricitinib or dupilumab were screened according to the following inclusion criteria: (1) age ≥ 18 years; (2) moderate-to-severe AD: baseline investigator global assessment (IGA) score ≥ 3, baseline eczema area and severity index (EASI) score ≥ 16; (3) poor response or intolerance to at least one topical drug in the past 6 months; (4) no topical glucocorticoids were used in the past 2 weeks and no systematic treatment was given in the past 4 weeks. Patients of the baricitinib group were treated with oral baricitinib in doses of 2 mg per day for 16 weeks, and patients of the dupilumab group were treated with standardized use of dupilumab for 16 weeks, with the initial 600 mg subcutaneous injection and the following 300 mg subcutaneous injection every 2 weeks. The clinical efficacy score indexes including the IGA score, EASI score, and Itch Numeric Rating Scale (NRS) score. These scores at 0, 2, 4, 8, 12, and 16 weeks after the start of treatment were collected. RESULTS: A total of 54/45 patients treated with baricitinib/dupilumab were included. There was no significant difference in the decrease of all scores between the two groups at the 4th week (p > 0.05). There was no difference in the EASI score and Itch NRS score (p > 0.05), but the IGA score of the baricitinib group was lower at the 16th week (Z = 4.284, p < 0.001). Within the first 4 weeks, the Itch NRS score of the baricitinib group decreased rapidly, but with the prolongation of treatment time, there was no significant difference between the two groups at the 16th week (Z = 1.721, p = 0.085). CONCLUSIONS: The efficacy of baricitinib at a dose of 2 mg daily was similar to dupilumab, and the improvement in pruritus was significantly faster in the early stage of treatment (the first 4 weeks) than that of dupilumab.

Impact of Omalizumab on Anaphylaxis in Patients Treated for Chronic Urticaria.

BACKGROUND: Anaphylaxis is a life-threatening systemic allergic reaction. Omalizumab (OMA) is an established treatment in chronic urticaria (CU), but experience in anaphylaxis is limited. OBJECTIVES: The objective was to evaluate the efficacy and safety of OMA on anaphylaxis in patients with CU who are resistant to antihistamine therapy and have a history of anaphylaxis. METHOD: Patients with antihistamine-resistant CU and a history of anaphylaxis were eligible. OMA was given 300 mg/150 mg every 4 weeks. Urticaria control test (UCT) scores, the episodes of anaphylaxis, and adverse events were recorded during the OMA treatment. RESULTS: A total of 7 adults were included. After starting OMA, all of them achieved a complete control (UCT = 16) after 3 months of OMA treatment; 6 of them did not suffer any attack of anaphylaxis in the follow-up periods (5 patients for more than 12 months and 1 patient for 4 months). No adverse events were observed. CONCLUSION: The study indicated the efficacy and safety of OMA for antihistamine-resistant CU patients with a history of anaphylaxis and its potential as a prevention option for anaphylaxis.

Knowledge, attitude, and practice regarding sarcopenia: a survey between orthopedic and geriatric professionals in China.

BACKGROUND: In elderly patients with fractures, sarcopenia impairs recovery and even increases mortality. Both orthopedic and geriatric professionals are at the forefront of treating sarcopenic patients with fractures. However, it is not clear to what extent they have knowledge and skills to diagnose and treat sarcopenia. AIMS: This study aimed to analyze and compare knowledge, attitude, and practice regarding sarcopenia between orthopedic and geriatric professionals. METHODS: An online cross-sectional survey was conducted in June 2022 targeting professionals in orthopedic and geriatric departments in two largest tertiary general hospitals in Taizhou, southeastern China. Results on knowledge, attitude, and practice of sarcopenia were analyzed. Variables with significance were then included in a stepwise multiple linear regression analysis. RESULTS: A total of 220 professionals, 176 from orthopedic departments and 44 from geriatric departments, participated in this study. Orthopedic professionals scored lower than geriatrics in knowledge, attitude and practice (P < 0.001). The attitude score was high in both orthopedic and geriatric professionals. Stepwise multiple linear regression analysis showed that participants who had contact with sarcopenia patients had higher knowledge score (ß = 1.941, P < 0.001); participants who had attended sarcopenia training in the past 6 months (ß = 4.305, P < 0.001) had higher practice score. DISCUSSION: Orthopedic professionals have deficiencies in the screening and diagnosis of sarcopenia. Improving the knowledge and training of professionals can strengthen practice. It is necessary to formulate diagnostic criteria and improve practice of sarcopenia through training. CONCLUSION: Orthopedic professionals had limited knowledge and practice regarding sarcopenia compared with geriatric professionals. To improve sarcopenia practice, the use of diagnostic tools to formally diagnose sarcopenia and regular training on sarcopenia should be encouraged.

Is spinal sagittal alignment of diffuse idiopathic skeletal hyperostosis relevant to thoracolumbar pain? A controlled study.

OBJECTIVES: The extension of diffuse idiopathic skeletal hyperostosis (DISH) from the low thoracic spine to the lumbar spine result in adjustment of spinal sagittal alignment in surgical patients. The aim of this study was to investigate changes in sagittal alignment and back pain in the thoracolumbar spine in nonsurgical DISH and control participants selected from a radiological database. METHODS: Participants in the DISH and the control group were selected by searching for "DISH or degenerative changes in the thoracic spine" in the radiology database of Taizhou Hospital between 2018 and 2021 using Resnick and Niwayama's criteria. The subjects with spinal tumors, previous spinal surgery, vertebral fractures, inflammatory diseases, poor-quality radiographs, or loss of follow-up were excluded. Demographic and clinical characteristics were recorded retrospectively via the hospital information system and telephone follow-up. Segmental disc angles (SDAs), lumbar lordosis (LL), and bridge scores were analyzed using images of three-dimensional CT. RESULTS: The final participants consisted of 51 individuals with DISH (DISH group) and 102 individuals without DISH (control group). Depending on the presence of thoracolumbar pain, the DISH group was divided into the DISH group with thoracolumbar pain (DISH+Pain) and the DISH group without thoracolumbar pain (DISH-Pain). The LL and SDAs of T11-T12 and T12-L1 were significantly greater in the DISH group than in the control group. In addition, the SDA of L1-L2 was significantly smaller in the DISH+Pain group than in the DISH-Pain group, whereas there was no significant difference in lumbar lordosis between the DISH+Pain group and the DISH-Pain group. The bridge scores in DISH+Pain group was larger in T10-T11 (p = 0.01) and L1-L2 (p < 0.01) spine segments than those in DISH-Pain group. CONCLUSION: The extension of DISH from thoracic to lumbar spine may increase lumbar lordosis and SDAs in the thoracolumbar spine. The DISH patients with more bony bridging and small L1-L2 SDA may be more likely have thoracolumbar pain. Adjustment of sagittal alignment of the spine in the development of DISH may be of clinical importance.

Yangonin treats inflammatory osteoporosis by inhibiting the secretion of inflammatory factors and RANKL expression.

OBJECTIVES: As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors. METHODS: We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining, Western blotting and quantitative real-time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin-eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo. RESULTS: Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis. CONCLUSION: Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.

A High-Fidelity Electrochemical Platform Based on Au-Se Interface for Biological Detection.

Gold (Au) electrodes are one of the most ideal electrodes and are extensively used to construct electrochemical biological detection platforms. The electrode-molecule interface between the Au electrode and biomolecules is critical to the stability and efficiency of the detection platform. However, traditional Au-sulfur (Au-S) interfaces experience distortion due to high levels of glutathione (GSH) and other biological thiols in biological samples as well as a high charge barrier when electrons are injected into the biomolecule from the Au electrode. In view of the higher bonding energy of Au-selenium (Au-Se) bonds than those of Au-S bonds and the elevated Fermi energy of the Au electrodes when Au-Se bonds are formed instead of Au-S bonds at the interface between the electrodes and molecules, we establish a new type of electrochemical platform based on the Au-Se interface (Au-Se electrochemical platform) for high-fidelity biological detection. Compared with that of the electrochemical platform based on the Au-S interface (Au-S electrochemical platform), the Au-Se electrochemical platform shows a higher charge transfer rate and excellent stability in millimolar levels of GSH. The Au-Se electrochemical platform supplies an ideal solution for accurate biological detection and has great potential in biomedical detection applications.

Quantitative evaluation of the medicine innovation policy in China: based on the PMC-Index model.

Introduction: Medicine innovation is crucial in promoting the sustainable development of medicine undertakings, which has significant economic and social benefits. China is the main force in global medicine consumption, with a huge demand for innovative medicines. Thus, the Chinese government releases a series of policies aimed at providing scientific and reasonable guidance for medicine innovation. However, there is inadequate quantitative evaluation and comparison of various medicine innovation policies in the existing studies. Methods: This paper adopts the approach of text mining and the Policy Modeling Consistency Index (PMC-Index) model to construct an evaluation system and then quantitatively evaluates and compares the traditional Chinese medicine innovation policies (TCMIPs), the biological medicine innovation policies (BMIPs), and the multiple medicine innovation policies (MMIPs) in China. Results: The results indicate that: (1) The three types of drug innovation policies have similarities in content and goal through comparative analysis of high-frequency words, while they also have their own characteristics. (2) The average PMC-Index of 29 TCMIPs is 5.77, which has the highest policy bad rate (21%); the average PMC-Index of 12 BMIPs is 6.21, which has the highest policy good rate (92%); moreover, the average PMC-Index of 35 MMIPs is 6.06, which has the highest policy excellence rate (26%). (3) The BMIPs, MMIPs, and TCMIPs have similar scores on policy object, policy orientation, policy timeliness, policy evaluation, and policy accessibility, while they differ significantly mainly on policy nature, incentive method, policy function, policy issuing agency, and policy instrument. Discussion: This study contributes to a comprehensive understanding of medicine innovation policies in China, in order to provide theoretical support for future policy formulation and optimization in the medicine industry. Moreover, we expand the application scenarios of policy diffusion theory.

The relationship between health insurance and economic performance: an empirical study based on meta-analysis.

Health insurance stands as a pivotal facet of social wellbeing, with profound implications for the overarching landscape of economic development. The existing research, however, lacks consensus on the relationship between health insurance and economic performance and provides no evidence about the magnitude of the correlation. This lack of information seriously impedes the high-quality development of the healthcare system. Therefore, to scientifically elucidate the relationship between the two, this study involved a meta-analysis, analyzing 479 effect values derived from 34 independent research samples. The results reveal a strongly positive correlation between health insurance and economic performance [r = 0.429, 95% CI = (0.381, 0.475)]. Findings show that health insurance in developed countries more effectively fosters economic performance than in developing countries. Moreover, public health insurance exerts a stronger promoting effect on economic performance than commercial health insurance. The relationship between health insurance and economic performance is moderated by data type, research method, country of sample origin, literature type, journal impact factor, publication year, type of health insurance, and the research populations. Based on meta-analysis, this study not only scientifically responds to the controversy of the relationship between health insurance and economic performance, and the magnitude of a correlation, but also further reveals the inner conduction mechanism between the two. Our research findings are meaningful for policymakers to choose an appropriate healthcare strategy according to their unique attributes, propelling sustainable economic development.

Construction of PCR-SERS Method for Detection of Vibrio parahaemolyticus.

A paper-based surface enhancement of a Raman scattering substrate consisting of silver-nanowires stacked on glass-fiber filter paper was prepared. At the same time, the DNA-embedding molecule Eva Green was introduced as a signaling molecule for surface-enhanced Raman scattering (SERS) detection. Polymerase chain reaction (PCR) was used to amplify target genes and the method was developed into a rapid molecular diagnostic system. The total detection time of the developed detection method was 40 min, including 30 min of PCR amplification and 10 min of SERS measurement. After 30 PCR cycles, bacterial DNA with an initial concentration of 20 fg/µL and a bacterial suspension with an initial concentration of 7.2 × 101 CFUs/mL could be detected. When the enrichment culture time was 4 h, target bacteria with an initial contamination inoculation volume of 1.5 CFUs/mL could be detected in artificially contaminated samples. The method is fast and highly sensitive, and has not been applied to the detection of V. parahaemolyticus.

Artificial Intelligence in Liver Diseases: Recent Advances.

Liver diseases cause a significant burden on public health worldwide. In spite of great advances during recent years, there are still many challenges in the diagnosis and treatment of liver diseases. During recent years, artificial intelligence (AI) has been widely used for the diagnosis, risk stratification, and prognostic prediction of various diseases based on clinical datasets and medical images. Accumulative studies have shown its performance for diagnosing patients with nonalcoholic fatty liver disease and liver fibrosis and assessing their severity, and for predicting treatment response and recurrence of hepatocellular carcinoma, outcomes of liver transplantation recipients, and risk of drug-induced liver injury. Herein, we aim to comprehensively summarize the current evidence regarding diagnostic, prognostic, and/or therapeutic role of AI in these common liver diseases.

Development and validation of modified Liaoning score for predicting the prognosis of liver cirrhosis: a retrospective, international multicenter, observational study.

BACKGROUND: Liaoning score has been developed and validated to predict the risk of esophageal varices in liver cirrhosis. This study aimed to further modify the Liaoning score by combining clinical and laboratory parameters to predict the long-term outcome of cirrhotic patients. METHODS: First, 474 cirrhotic patients were retrospectively enrolled from Shenyang, China as the training cohort. Independent predictors for death were identified by competing risk analyses, and then a new prognostic model, called as modified Liaoning score, was developed. Its performance was externally validated at three centers from Fuzhou, China (n = 1944), Jinan, China (n = 485), and São Paulo, Brazil (n = 221). RESULTS: Age, total bilirubin (TBIL), albumin (ALB), serum creatinine (SCr), and Liaoning score were independently associated with death in the training cohort. Modified Liaoning score = 0.159×Liaoning score + 0.010×TBIL(µmol/L)+0.029×age(years)+0.011×SCr(µmol/L)-0.037×ALB(g/L). The area under curve of modified Liaoning score was 0.714 (95%CI = 0.655-0.773), which was higher than that of Child-Pugh score (0.707, 95%CI = 0.645-0.770), MELD score (0.687, 95%CI = 0.623-0.751), and Liaoning score (0.583, 95%CI = 0.513-0.654). A modified Liaoning score of ≥ 1.296 suggested a higher cumulative incidence of death in liver cirrhosis (p < 0.001). Modified Liaoning score still had the highest prognostic performance in Chinese and Brazilian validation cohorts. CONCLUSIONS: Modified Liaoning score can be considered for predicting the long-term outcome of cirrhotic patients.

The Relationship between Health Insurance and Pharmaceutical Innovation: An Empirical Study Based on Meta-Analysis.

The growing research interest in the relationship between health insurance and pharmaceutical innovation is driven by their significant impact on healthcare optimization and pharmaceutical development. The existing literature, however, lacks consensus on this relationship and provides no evidence of the magnitude of a correlation. In this context, this study employs meta-analysis to explore the extent to which health insurance affects pharmaceutical innovation. It analyzes 202 observations from 14 independent research samples, using the regression coefficient of health insurance on pharmaceutical innovation as the effect size. The results reveal that there is a strong positive correlation between health insurance and pharmaceutical innovation (r = 0.367, 95% CI = [0.294, 0.436]). Public health insurance exhibits a stronger promoting effect on pharmaceutical innovation than commercial health insurance. The relationship between health insurance and pharmaceutical innovation is moderated by the country of sample origin, data range, journal type, journal impact factor, type of health insurance, and research perspective. Our research findings further elucidate the relationship mechanism between health insurance and pharmaceutical innovation, providing a valuable reference for future explorations in pharmaceutical fields.

The Role and Potential Mechanism of Complement Factor D in Fibromyalgia Development.

Purpose: Fibromyalgia (FM) is a syndrome characterized by chronic musculoskeletal pain. Its clinical symptoms include both somatic and psychiatric symptoms, making the treatment of FM extremely challenging. The cause of FM is still unknown, and some patients do not improve their symptoms even after long-term active treatment. Thus, the development of new targeted therapies is important to reduce pain and improve quality of life for FM patients. Methods: In this study, we screened genes and secreted factors that play key roles in FM through bioinformatics and big data analysis. Furthermore, we performed CCK-8, qRT-PCR, glucose, ATP and lactate content testing, dual luciferase reporter gene assay to investigate the potential mechanism of complement factor D in fibromyalgia development. Results: In bioinformatics and big data analysis, we identified CFD was negatively correlated with the pro-inflammatory factor IL-6 and positively correlated with the anti-inflammatory factor IL-4, which suggested that CFD may be an anti-inflammatory factor. Through cellular assays, we verified that CFD reversed the decrease in IL-4 expression and the increase in IL-6 expression in BV2 cells caused by ATP. Conclusion: In summary, based on bioinformatic methods and big data mining we obtained a new target CFD for FM, and further experiments verified that CFD has significant inhibition of ATP-induced neuropathic pain. These findings provide a new theoretical basis for the clinical translation of CFD.

LC-Q-TOF/MS-based Fragmentation Behavior Study and In vitro Metabolites Identification of Nine Benzodiazepines.

BACKGROUND: Benzodiazepines (BZDs) are compounds that contain one diazepine ring and two benzene rings, and are widely used to treat central nervous system diseases. However, drug abuse and BZDs' illegal addition may affect normal life and even lead to grave social harm. As BZDs may be metabolized and eliminated quickly, it is of great theoretical and practical significance to clarify their metabolic profile. OBJECTIVE: In this paper, LC-Q-TOF/MS-based fragmentation behavior has been investigated for nine benzodiazepine drugs available and widely used in clinical treatment (diazepam, nitrazepam, clonazepam, oxazepam, lorazepam, alprazolam, estazolam, triazolam, and midazolam), and their metabolic profile has been studied by using in vitro human liver microsomal incubation. METHODS: A regular human liver microsomal system was used to investigate the potential biotransformation of the nine benzodiazepines in vitro, and an LC-Q/TOF-MS was used to perform fragmentation behavior studies and metabolite identification. RESULTS: As a result, characteristic fragmentation pathway and diagnostic fragment ions of the nine BZDs were analyzed, and 19 metabolites of the 9 benzodiazepines were found and identified, with glucuronidation and hydroxylation considered as their most important metabolic pathways. CONCLUSION: These experimental data add to our knowledge of the nine benzodiazepine drugs and their metabolism study, which could provide useful information and evidence of their in vivo metabolic profile prediction and help promote their monitoring in both clinical use and social/illegal abuse.