The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound ...directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFα-TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis.
There were few studies that investigated health-related quality of life (HRQoL) of the general population in China, and many of them reported limitations in sampling.
To investigate the relationship ...between lifestyles and HRQoL in the Chinese population in both individual and family levels.
Online questionnaires were distributed across China to collect demographic information and participants' HRQoL using EuroQoL 5 Dimension scales. The EuroQoL Group's 5 Dimension scale (EQ-5D) index and EuroQoL Group's visual analog scale (EQ VAS) score were calculated to evaluate the HRQoL.
A total of 1305 valid questionnaires were included. Higher HRQoL was found in people with intend to lower oil intake, intend to lower salt intake, intend to lower sugar intake, balanced diet, moderate sports every week, a sport hobby and joining a fitness organization (all p<.05). HRQoL was higher among male (female as reference), healthy weight (unhealthy weight as reference) (both p<.05). Negative correlation was found between HRQoL and clinical medical history and drinking history. Small families (1-2 persons, 83.19 ± 20.14) had poorer HRQoL (EQ VAS score) than big families (≥3 persons, 85.00 ± 17.96, p <.05).
In China, people with healthy dietary habits, regular sports habits, healthy weight and male groups tended to have better HRQoL. Clinical medical history and drinking history were negatively related to HRQoL. Small families tend to have poorer HRQoL than big families. The finding implicated influence of the number of family members on people's perception of health and provided scientific evidence for the current policies to encourage birth in China. For a better HRQoL, we suggest people live in big families and take measures to lower salt/sugar/oil intake and exercise regularly in daily life.
ObjectivesAssessing the knowledge, attitude and practices (KAP) regarding health self-management among patients with osteogenesis imperfecta (OI) in China.DesignAn online cross-sectional ...survey.SettingA structured questionnaire was distributed online through China-Dolls Center for Rare Disorders (CCRD), a non-governmental charity in China.ParticipantsParticipants were all patients with OI from CCRD. After stratified sampling according to the economic level of residential city, 901 patients were proportionally selected and 869 patients completed the survey (response rate: 96.4%).Main outcome measuresDemographic characteristics and KAP information were gathered using a 5-point Likert scale. The score of each dimension of KAP was the sum of the scores of all included items. Χ2 test or Fisher’s exact test was used to compare scores of different items. Ordinal regression was employed to determine the significant factors influencing KAP.ResultsA total of 802 questionnaires were included for analysis. Male respondents accounted for 57.1%, and 29.1% of respondents were of 26~30 years. More than half (50~60%) of patients knew the main symptoms of OI and the treatment of OI-related complications. Almost 80% of patients showed positive attitude. Nearly 60~70% of the patients were relatively able to take appropriate practice regarding OI management. There was a significant correlation between scores of knowledge and attitude, attitude and practice, as well as knowledge and practice. Patients aged 26~30 years, from urban areas and big cities, had higher KAP scores. Male patients showed better performance in knowledge, and highly educated patients perform better in practice.ConclusionsPatients with OI did not have sufficient knowledge on disease care and up-to-date caring guidelines, and their practice regarding health self-management also needs to be improved. Gender, age, educational level and economic level of residence can affect the level of KAP for patients, thus developing targeted and tailored programmes for patients with OI is highly recommended.
Background
Improving the health self-management level of patients with tuberculosis (TB) is significant for reducing drug resistance, improving the cure rate, and controlling the prevalence of TB. ...Mobile health (mHealth) interventions based on behavioral science theories may be promising to achieve this goal.
Objective
This study aims to explore and conduct an mHealth intervention based on the Integrated Theory of Health Behavior Change (ITHBC) in patients with pulmonary TB to increase their ability of self-care management.
Methods
A prospective randomized controlled study was conducted from May to November 2020. A total of 114 patients who were admitted consecutively to the TB clinic of Harbin Chest Hospital, China from May 2020 to August 2020 were recruited by convenience sampling. Patients were divided into the control group and intervention group, and all received a 3-month intervention. Patients in the intervention group and the control group received routine medical and nursing care in the TB clinic, including the supervision of their medications. In addition, pharmacist-assisted mHealth (WeChat) intervention based on the ITHBC theory about TB management was provided to the intervention group. The primary outcome was self-management behavior, while the secondary outcomes were TB awareness, self-efficacy, social support, and degree of satisfaction with health education. The outcomes were measured using web-based self-designed and standard questionnaires administered at baseline and at the end point of the study. Intergroup data were assessed using the Mann-Whitney U test, whereas intragroup data were assessed with the Wilcoxon test (for paired samples).
Results
A total of 112 patients (59 in intervention group and 53 in control group) completed the study. After the intervention, a statistically significant increase was noted in the scores of each item of self-care management behaviors compared with the scores at the baseline (P<.001) in the intervention group. The scores of all self-care management behaviors of the control group were lower than those of all self-care management behaviors in the intervention group (all P<.05), except for the item “cover your mouth and nose when coughing or sneezing” (P=.23) and item “wash hands properly” (P=.60), which had no statistically significant difference from those in the intervention group. Compared with those at baseline, TB knowledge awareness, self-efficacy, social support, and degree of satisfaction with health education in the intervention group increased significantly (P<.001), and the intervention group had significantly higher scores than the control group (P<.001).
Conclusions
mHealth intervention for TB self-management based on ITHBC could deepen the understanding of patients with TB about their disease and improve their objective initiative and self-care management behaviors, which were beneficial for promoting compliance behavior and quality of prevention and control for pulmonary TB.
Trial Registration
Chinese Clinical Trial Registry ChiCTR2200055557; https://tinyurl.com/4ray3xnw
Purpose
Prescription refills are long-term prescriptions for chronic patients in stable status, which varies from country to country. A well-established prescription refill system is beneficial for ...chronic patients’ medication management and facilitates the efficacy of clinical care. Therefore, we carried out a bibliometric analysis to examine the development of this field.
Summary
Publications on prescription refills from 1970 to 2021 were collected in the Web of Science Core Collection (WoSCC). Search strategy TS = “prescri* refill*” OR “medi* refill*” OR “repeat prescri*” OR “repeat dispens*” OR TI = refill* was used for search. VOSviewer was applied to visualize the bibliometric analysis. A total of 319 publications were found in WoSCC. Study attention on prescription refills has shown a steady rise but is still low in recent years. The United States was the most productive country, which had the highest total citations, average citations per publication, and the highest H-index, and participated in international collaboration most frequently. The University of California system was the most productive institution. The U.S. Department of Veterans Affairs was the institution with the most citations, most average citation, and highest H-index. Sundell was the most productive author, and Steiner J. F. was the most influential author. “Adherence,” “medication,” and “therapy” were the most prominent keywords.
Conclusion
Publications on prescription refills have increased rapidly and continue to grow. The United States had the leading position in the area. It is recommended to pay closer attention to the latest hotspots, such as “Opioids,” “Surgery,” “Differentiated care,” and “HIV.”
Delta/Notch-like EGF-related receptor (DNER) has been reported to act as a Notch ligand, despite lacking a Delta/Serrate/Lag (DSL) binding domain common to all other known ligands. The established ...Notch ligand Delta-like 1 (DLL1), but not DNER, activated Notch1 in a luciferase assay, prevented the differentiation of myoblasts through Notch signaling, and bound Notch-fc in a cell-based assay. DNER is not a Notch ligand and its true function remains unknown.
Dulaglutide (glucagon like peptide-1/IgG-Fc fusion protein, GLP-1-Fc) is a long lasting GLP-1 agonist, which consists of two arms of GLP-1 moieties fused to IgG Fc fragment. Dulaglutide is a safe and ...effective medication for type 2 diabetes. In an attempt to develop a biosimilar version of dulaglutide, we found that up to 75% of GLP-1-Fc displayed
N
-terminal truncations in one or both GLP-1 arms. We proposed that the
N
-terminal heterogeneity was caused by mis-cleavage of signal peptide and solved this problem through signal peptide optimization. Murine immunoglobulin kappa light chain signal peptide (KASP) significantly improves GLP-1-Fc
N
-terminal integrity and homogeneity. 92.8–95.7% of GLP-1-Fc molecules directed by KASP contain intact
N
-terminus. The productivity of GLP-1-Fc could reach 2.2 g/L in shaking flask fed batch culture. KASP is an optimal signal peptide for GLP-1-Fc expression in Chinese hamster ovary (CHO) cells.
Protein aggregation is a major challenge in the development of therapeutic monoclonal antibodies (mAbs). Several stressors can cause protein aggregation, including temperature shifts, mechanical ...forces, freezing-thawing cycles, oxidants, reductants, and extreme pH. When antibodies are exposed to low pH conditions, aggregation increases dramatically. However, low pH treatment is widely used in protein A affinity chromatography and low pH viral inactivation procedures. In the development of an IgG4 subclass antibody, mAb1-IgG4 showed a strong tendency to aggregate when temporarily exposed to low pH conditions. Our findings showed that the aggregation of mAb1-IgG4 under low pH conditions is determined by the stability of the Fc. The CH2 domain is the least stable domain in mAb1-IgG4. The L309E, Q311D, and Q311E mutations in the CH2 domain significantly reduced the aggregation propensity, which could be attributed to a reduction in the hydrophobicity of the CH2 domain. Protein stabilizers, such as sucrose and mannose, could also attenuate low pH-induced mAb1-IgG4 aggregation by shielding hydrophobic areas and increasing protein stability. Our findings provide valuable strategies for managing the aggregation of protein therapeutics with a human IgG4 backbone.
•In this paper, we report a 1,8-naphthalimide/ triphenylamine-based fluorescent probe (TPA-NI-NO2) for the specific detection of 4‑methoxy-thiophenol (MTP) with good selectivity among the ...thiophenols.•The probe can “turn on” detect MTP with the limit of detection (LOD) of 80 nM and no obvious response to relevant analytes and homologues.•The sensing mechanism was explored by HPLC experiment and the PET process was determined by density functional theory (DFT) calculations.•The Gibbs free energy (DG) analysis for the reaction between the probe and different thiophenols were obtained by the theoretical calculations to study the specificity of the probe.•The probe was successfully applied to monitor the MTP in Hela cells.
Thiophenols as a series of industrial products are widely used and high toxicity to the organisms and the environment. The fluorescent probe technique offers important insights into thiophenols convenient sensing. Herein, we report a 1,8-naphthalimide/ triphenylamine-based fluorescent probe (TPA-NI-NO2) for the specific detection of 4‑methoxy-thiophenol (MTP). The probe can “turn on” specific detect MTP with the limit of detection (LOD) of 80 nM among various relevant analytes and homologues (p-Cl-C6H4SH, p-NO2-C6H4SH, C6H5SH and o-CH3-C6H5SH). The sensing mechanism was explored by the HPLC experiment and the PET process was determined by density functional theory (DFT) calculations. In addition, the specificity of the probe was also studied by the Gibbs free energy (ΔG) analysis of the reaction between the probe and different thiophenols. The reaction between probe and MTP gives the minimum of the ΔG value (∼ -9.7280 kcal/mol) and that of other thiophenols-mediated is -2.5283 to -5.8911 kcal/mol, which proves the thermodynamic chemical equilibrium can optimize the design of reaction-based fluorescent probes with excellent specificity. At last, TPA-NI-NO2 was successfully applied to Hela cells imaging.
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The anti-Tr immune response is associated with paraneoplastic cerebellar degeneration and Hodgkin lymphoma (HL). One case series has reported that the Delta/notch-like epidermal growth factor-related ...receptor (DNER) is the actual target for anti-Tr antibodies, but this result has not been replicated.
To describe a patient with anti-Tr and confirm that DNER is the autoantigen for a series of patients with anti-Tr.
Observational study and analysis of biological samples for antibodies to DNER at the hospital of the University of Pennsylvania. We examined a cerebrospinal fluid sample from 1 patient with anti-Tr and serum and/or cerebrospinal fluid samples from 5 other patients with anti-Tr.
Transfection of HEK293T and Hela cells to express DNER coupled to an enhanced green fluorescent protein tag using a plasmid previously used to detect human DNER antibodies.
A man in his 30s with paraneoplastic cerebellar degeneration and anti-Tr underwent treatment with corticosteroids and intravenous immunoglobulin, resulting in clinical improvement before chemotherapy. Despite close oncologic follow-up, a biopsy, positron emission tomography, and computed tomography, he was not diagnosed as having HL until 6 months after symptom onset. The cerebrospinal fluid sample from this patient reacted with cells transfected to express DNER, as did cerebrospinal fluid and/or serum samples from 5 other patients with paraneoplastic cerebellar degeneration, HL, and anti-Tr. Only 4 of the 5 serum samples reacted to permeabilized cells enough to be distinguished from background, but all 5 serum samples convincingly labeled live cells, which had considerably less background. All 6 control serum samples and 1 serum sample from a patient previously diagnosed as having anti-Tr (but without HL or cerebellitis) did not recognize DNER.
This case demonstrates the importance of testing for the anti-Tr immune response in patients with cerebellar degeneration. The strong association of anti-Tr with HL requires careful surveillance for this tumor. We also confirm that DNER is the target antigen of the anti-Tr immune response. Screening for DNER antibodies against living transfected cells may offer an improved signal-to-noise characteristic compared with immunostaining of fixed, permeabilized cells.
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