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Background: Immunomodulatory agents, such as tocilizumab (TCZ), exert promising effects against SARS-CoV-2 infection. However, growing evidence indicates that using TCZ may carry higher risks of secondary bloodstream infection (sBSI). This study determined whether TCZ is associated with an increased risk of sBSI. Methods: We retrospectively collected the demographic and clinical data of hospitalized patients with SARS-CoV-2 infection from two Taiwanese hospitals. The time-to-incident sBSI in the TCZ users and nonusers was compared using the log-rank test. A multivariate Cox proportional hazards model was performed to identify independent risk factors for sBSI. Results: Between May 1 and August 31, 2021, among 453 patients enrolled, 12 (2.65 %) developed sBSI. These patients were in hospital for longer duration (44.2 ± 31.4 vs. 17.6 ± 14.3 days, p = 0.014). Despite sBSI being more prevalent among the TCZ users (7.1 % vs. 1.6 %, p = 0.005), Kaplan–Meier survival analysis and multivariate Cox proportional hazards model both revealed no significant difference in risks of sBSI between the TCZ users and nonusers [adjusted HR (aHR) = 1.32 (95 % confidence interval (CI) = 0.29–6.05), p = 0.724]. Female sex [aHR = 7.00 (95 % CI = 1.45–33.92), p = 0.016], heavy drinking [aHR = 5.39 (95 % CI = 1.01–28.89), p = 0.049], and mechanical ventilation [aHR = 5.65 (95 % CI = 1.67–19.30), p = 0.006] were independently associated with a higher sBSI risk. Conclusion: This real-world evidence indicates that in hospitalized patients with SARS-CoV-2 infection, TCZ does not significantly increase the risk of sBSI.

Abstract Background CTLA4Ig is a dimeric fusion protein of the extracellular domain of cytotoxic T-lymphocyte protein 4 (CTLA4) and an Fc (Ig) fragment of human IgG1 that is approved for treating rheumatoid arthritis. However, CTLA4Ig may induce adverse effects. Developing a lesion-selective variant of CTLA4Ig may improve safety while maintaining the efficacy of the treatment. Methods We linked albumin to the N-terminus of CTLA4Ig (termed Alb-CTLA4Ig) via a substrate sequence of matrix metalloproteinase (MMP). The binding activities and the biological activities of Alb-CTLA4Ig before and after MMP digestion were analyzed by a cell-based ELISA and an in vitro Jurkat T cell activation assay. The efficacy and safety of Alb-CTLA4Ig in treating joint inflammation were tested in mouse collagen-induced arthritis. Results Alb-CTLA4Ig is stable and inactive under physiological conditions but can be fully activated by MMPs. The binding activity of nondigested Alb-CTLA4Ig was at least 10,000-fold weaker than that of MMP-digested Alb-CTLA4Ig. Nondigested Alb-CTLA4Ig was unable to inhibit Jurkat T cell activation, whereas MMP-digested Alb-CTLA4Ig was as potent as conventional CTLA4Ig in inhibiting the T cells. Alb-CTLA4Ig was converted to CTLA4Ig in the inflamed joints to treat mouse collagen-induced arthritis, showing similar efficacy to that of conventional CTLA4Ig. In contrast to conventional CTLA4Ig, Alb-CTLA4Ig did not inhibit the antimicrobial responses in the spleens of the treated mice. Conclusions Our study indicates that Alb-CTLA4Ig can be activated by MMPs to suppress tissue inflammation in situ. Thus, Alb-CTLA4Ig is a safe and effective treatment for collagen-induced arthritis in mice.

Engineering quantum states requires precise manipulations at the atomic level. Here, the authors use deep reinforcement learning to manipulate Ag adatoms on Ag surfaces, which combined with path planning algorithms enables autonomous atomic assembly.

Abstract Background Humanization of mouse monoclonal antibodies (mAbs) is crucial for reducing their immunogenicity in humans. However, humanized mAbs often lose their binding affinities. Therefore, an in silico humanization method that can prevent the loss of the binding affinity of mAbs is needed. Methods We developed an in silico V(D)J recombination platform in which we used V(D)J human germline gene sequences to design five humanized candidates of anti-tumor necrosis factor (TNF)-α mAbs (C1–C5) by using different human germline templates. The candidates were subjected to molecular dynamics simulation. In addition, the structural similarities of their complementarity-determining regions (CDRs) to those of original mouse mAbs were estimated to derive the weighted interatomic root mean squared deviation (wRMSDi) value. Subsequently, the correlation of the derived wRMSDi value with the half maximal effective concentration (EC50) and the binding affinity (KD) of the humanized anti-TNF-α candidates was examined. To confirm whether our in silico estimation method can be used for other humanized mAbs, we tested our method using the anti-epidermal growth factor receptor (EGFR) a4.6.1, anti-glypican-3 (GPC3) YP9.1 and anti-α4β1 integrin HP1/2L mAbs. Results The R2 value for the correlation between the wRMSDi and log(EC50) of the recombinant Remicade and those of the humanized anti-TNF-α candidates was 0.901, and the R2 value for the correlation between wRMSDi and log(KD) was 0.9921. The results indicated that our in silico V(D)J recombination platform could predict the binding affinity of humanized candidates and successfully identify the high-affinity humanized anti-TNF-α antibody (Ab) C1 with a binding affinity similar to that of the parental chimeric mAb (5.13 × 10−10). For the anti-EGFR a4.6.1, anti-GPC3 YP9.1, and anti-α4β1 integrin HP1/2L mAbs, the wRMSDi and log(EC50) exhibited strong correlations (R2 = 0.9908, 0.9999, and 0.8907, respectively). Conclusions Our in silico V(D)J recombination platform can facilitate the development of humanized mAbs with low immunogenicity and high binding affinities. This platform can directly transform numerous mAbs with therapeutic potential to humanized or even human therapeutic Abs for clinical use. Graphical Abstract

Globally, obesity is a major health problem and can markedly increase the risk of various diseases, including type 2 diabetes mellitus, hypertension (HTN), dyslipidemia, and chronic kidney disease (CKD). The association of obesity-related parameters, such as lipid parameters and their ratio, with CKD in clinical settings is not well understood. This study aimed to investigate the association of obesity-related parameters with CKD in the middle-aged and elderly population in Taiwan. This cross-sectional, community-based study recruited 400 participants (141 males and 259 females) aged 50 years or over from a community health promotion project at the Linkou Chang Gung Memorial Hospital (Guishan District, Taoyuan City) in 2014. Each participant completed a questionnaire including personal information and medical history during a face-to-face interview. Laboratory data were obtained from blood and urine sampling. The data were analyzed using t-test, chi-square test, Pearson's correlation test, multivariate logistic regression, and receiver operating characteristic (ROC) analysis. A total of 81 participants were identified as having CKD [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urine albumin/creatinine ratio ≥30 mg/g], and their mean triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio was 3.37 ± 2.72. The mean TG/HDL-C ratio of the 319 participants without CKD was 2.35 ± 1.66. After adjusting for age, TG/HDL-C was significantly positively correlated with blood pressure, body mass index, waist circumference, and fasting plasma glucose but not low-density lipoprotein cholesterol. There was a negative correlation between TG/HDL-C and eGFR. Multiple logistic regression model analysis showed that TG/HDL-C was still significantly associated with CKD (OR: 1.17, 95% CI: 1.01–1.36, p = 0.04) after adjusting for multiple covariates. The cut-off point of TG/HDL-C as a predictor of CKD was 2.54 with an area under the ROC curve of 0.61 (95% CI: 0.53–0.68). There was a significant positive correlation between TG/HDL-C and several cardiovascular disease risk factors, including obesity indices. The TG/HDL-C ratio was significantly associated with the risk of CKD and demonstrated predictive ability for CKD in the middle-aged and elderly population. Further studies on its application in clinical settings are warranted.

BackgroundTraditional risk factors for chronic kidney disease (CKD) include diabetes mellitus (DM), hypertension (HTN), and metabolic syndrome, which are health conditions related to obesity. We aimed to investigate which of the three obesity indices has the strongest association with CKD and to explore whether there are gender differences in these relationships in the middle-aged and elderly Taiwanese population.MethodsThis was a cross-sectional, community-based study. It included 400 residents (141 males and 259 females, age 50–90 years) residing in a community in northern Taiwan. Each participant was asked to fill a questionnaire that collected personal information, medical history, medication use, and anthropometric measurements. The laboratory data were obtained by testing the blood and urine samples. The baseline characteristics were compared, and the obesity indices included body mass index (BMI), waist circumference (WC), and visceral adiposity index (VAI). CKD was defined as the presence of renal dysfunction (urine albumin-creatinine ratio ≥ 30 mg/g) or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. We used a multiple logistic regression model to evaluate the association between each obesity index and CKD for both genders. Further, we used the area under the receiver operating characteristic (ROC) curve (AUC) to examine the best obesity indices to predict CKD in different genders.ResultsThe average age of the subjects was 64.47 ± 8.45 years, and men were significantly older. CKD was found in 31 (22.0%) males and 50 (19.3%) females. In men, there was no significant difference between the CKD and non-CKD groups among the three obesity indices. However, in women, only VAI was significantly higher in subjects with CKD (1.9 [1.1, 3.4]) than in subjects without CKD (1.5 [1.0, 2.2]) (p-value = 0.03). The multivariate logistic regression revealed that even after adjusting for possible confounding factors, VAI was found to be an independent risk factor for CKD in women (OR: 1.32, 95% CI: 1.04-1.69, p = 0.02), but not in men (OR: 1.20, 95% CI: 0.85-1.69, p = 0.30). The AUC of VAI had a significant ability to predict CKD in women but not in men.ConclusionOur results showed that among the three obesity indices, VAI had the strongest association with CKD compared to BMI and WC in women. In addition, VAI in women should be given more importance in the screening for CKD among the middle-aged and elderly Taiwanese population.

Fibrinogen-like protein 1 (FGL1) was recently identified as a major ligand of lymphocyte-activation gene-3 (LAG-3) on activated T cells and serves as an immune suppressive molecule for regulation of immune homeostasis. However, whether FGL1 has therapeutic potential for use in the T cell-induced the autoimmune disease, rheumatoid arthritis (RA), is still unknown. Here, we attempted to evaluate the effect of FGL1 protein on arthritis progression. We also evaluated potential adverse events in a collagen-induced arthritis (CIA) mouse model. We first confirmed that soluble Fgl1 protein could specifically bind to surface Lag-3 receptor on 3T3-Lag-3 cells and further inhibit interleukin (IL-2) and interferon gamma (IFNγ) secretion from activated primary mouse T cells by 95% and 43%, respectively. Intraperitoneal administration of Fgl1 protein significantly decreased the inflammatory cytokine level (i.e., IL-1β and IL-6) in local paw tissue, and prevented joint inflammation, cellular infiltration, bone deformation and attenuated collagen-induced arthritis progression in vivo. We further demonstrated that exogenous Fgl1 does not cause obvious adverse events during treatment by monitoring body weight and liver weight, and assessing the morphology of several organs (i.e., heart, liver, spleen, lung and kidney) by pathological studies. We expect that Fgl1 protein may be suitable to serve as a potential therapeutic agent for treatment of RA or even other types of T cell-induced autoimmune or inflammatory diseases in the future.

Abstract Background Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG × HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger intensity. Result We used a one-step formulation to rapidly modify the nanoprobes with mPEG × HER2 and optimized the modified ratio of BsAbs on several PEG-NPs (Lipo-DiR, SPIO, Qdot and AuNP). The αHER2/PEG-NPs could specifically target MCF7/HER2 cells (HER2++) but not MCF7/neo1 cells (HER2+/−). The αHER2/Lipo-DiR and αHER2/SPIO could enhance the sensitivity of untargeted PEG-NPs on MCF7/HER2 (HER2++). In in vivo imaging, αHER2/Lipo-DiR and αHER2/SPIO increased the specific targeting and enhanced PEG-NPs accumulation at 175% and 187% on 24 h, respectively, in HER2-overexpressing tumors. Conclusion mPEG × HER2, therefore, provided a simple one-step formulation to confer HER2-specific targeting and enhanced sensitivity and contrast intensity on HER2 positive tumors for multimodality imaging.

Background: This study aimed to quantify the proportion of participants with chronic kidney disease (CKD) and associated metabolic risk factors in a middle-aged and elderly population in Guishan District, Taoyuan City, Taiwan.Methods: This cross-sectional study enrolled residents aged 50–90 years living in one community. All participants received a standardized personal interview, including a structured questionnaire, anthropometric measurements, and blood samples collected for laboratory testing. CKD was defined as the presence of kidney damage (urine albumin-creatinine ratio ≥30 mg/g) or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Multiple logistic regression models were used to evaluate the risk factors associated with CKD.Results: A total of 400 participants were enrolled. The overall proportion of participants with CKD was 20.5% (95% confidence interval [CI]: 16.54–24.46%). The proportions of participants with CKD among those aged 50–64, 65–74, and 75 years and over were 17.7, 18.8, and 35.7%, respectively (p = 0.01). Multiple logistic regression model revealed that elevated blood pressure (odds ratio [OR] = 2.23, 95% CI: 1.16–4.30), hyperglycemia (OR = 2.87, 95% CI: 1.64–5.00), hyperuricemia (OR = 1.38, 95% CI: 1.14–1.69), and metabolic syndrome (OR = 2.30, 95% CI: 1.31–4.06) were significantly associated with CKD.Conclusions: The prevalence of CKD in the study population was high. Hypertension, hyperglycemia, hyperuricemia, and metabolic syndrome are significantly associated with CKD in a middle-aged and elderly population in Taiwan.

Antecedentes/Objetivo: El bienestar emocional afecta el rendimiento escolar de los ni˜nos de Educación Primaria. Las mediciones de la calidad de vida (QoL) son indicativas del bienestar emocional. Sin embargo, el desarrollo de herramientas de evaluación adecuadas para medir la calidad de vida de ni˜nos de Educación Primaria ha recibido escasa atención y, por lo tanto, se requiere la creación de herramientas de evaluación confiables para medir la calidad de vida en esta población. Método: Se empleraron métodos de investigación cualitativa y cuantitativa para desarrollar y validar una escala de QoL para ni˜nos de Primaria en Taiwán. Se utilizó un muestreo aleatorio por grupos para reclutar a 711 estudiantes de Quinto y Sexto Grado, de 10 a 12 a˜nos, de 14 escuelas primarias. Resultados: La escala agrupa seis factores (Función escolar, Función familiar, Vida ambiental, Vitalidad para la vida, Capacidad de aprendizaje y Relaciones entre compa˜neros) que explican el 44% de la varianza. El instrumento de QoL (ESQoL) de 21 ítems tiene alta fiabilidad de consistencia interna y validez satisfactoria. Conclusiones: El instrumento ESQoL puede facilitar la evaluación de factores asociados con el bienestar emocional de los escolares. Se requieren estudios adicionales utilizando el instrumento ESQoL para evaluar su aplicabilidad en el análisis de las relaciones entre QoL y rendimiento escolar, y otras áreas del ámbito escolar.

Traditional Chinese medicine (TCM; 中醫 zhōng yī) syndrome groups are based on the symptoms of human diseases and guide the use of Chinese herbs. The aim of this study was to examine the effects of TCM syndrome groups on biochemical characteristics and quality of life (QOL) in women with metabolic syndrome (MS). Among the 1080 registered female patients screened at our outpatient clinic, a total of 322 women aged between 18 and 65 years and meeting the requirements of MS were enrolled. All the patients were asked to fill out a questionnaire on metabolic TCM syndrome groups and a questionnaire on the QOL, the Medical Outcomes Study (MOS) Short Form-12 (SF-12). Data of biochemical characteristics were collected at the same time. The present study showed MS women in TCM syndrome groups had significantly lower physical and mental component scores in SF-12 compared with those not in TCM syndrome groups. We also found MS patients in TCM syndrome groups, except Kidney Deficiency syndrome, showed higher body mass indexes, waist circumference, and hip circumference. However, there was almost no difference in most biochemical characteristics between TCM syndrome groups. The MS patients diagnosed as belonging to TCM syndrome groups had poor QOL.

During rheumatoid arthritis (RA) treatment, long-term injection of antitumor necrosis factor α antibodies (anti-TNFα Abs) may induce on-target toxicities, including severe infections (tuberculosis [TB] or septic arthritis) and malignancy. Here, we used an immunoglobulin G1 (IgG1) hinge as an Ab lock to cover the TNFα-binding site of Infliximab by linking it with matrix metalloproteinase (MMP) -2/9 substrate to generate pro-Infliximab that can be specifically activated in the RA region to enhance the selectivity and safety of treatment. The Ab lock significantly inhibits the TNFα binding and reduces the anti-idiotypic (anti-Id) Ab binding to pro-Infliximab by 395-fold, 108-fold compared with Infliximab, respectively, and MMP-2/9 can completely restore the TNFα neutralizing ability of pro-Infliximab to block TNFα downstream signaling. Pro-Infliximab was only selectively activated in the disease site (mouse paws) and presented similar pharmacokinetics (PKs) and bio-distribution to Infliximab. Furthermore, pro-Infliximab not only provided equivalent therapeutic efficacy to Infliximab but also maintained mouse immunity against Listeria infection in the RA mouse model, leading to a significantly higher survival rate (71%) than that of the Infliximab treatment group (0%). The high-selectivity pro-Infliximab maintains host immunity and keeps the original therapeutic efficiency, providing a novel strategy for RA therapy.

The ageing population is a powerful and transformative demographic force. The World Health Organization (WHO) has encouraged the development of an age-friendly hospital (AFH) network. However, no specific implementation strategies or best practices of AFH standards have been produced. This study sought to apply Kotter's change model to the elements included in a successful AFH certification process and to evaluate the changes in employees' knowledge of ageing and their attitudes toward the elderly. This was an observational study that utilized a pre- and posttest design, before and after an age-friendly hospital certification process was implemented. Participants were 163 hospital employees in Taiwan, who completed both pre- and postquestionnaires. The self-administered online questionnaire consisted of three sections: The Facts on Ageing Quiz, the Geriatric Attitudes Scale, and a demographic questionnaire. Following introduction of the intervention, the change process began, and later Kotter's model was brought in as a descriptive framework. The results showed that Kotter's eight-step framework is a good choice for thinking about how to change practice and make healthcare more age-friendly. Employee knowledge of ageing and their attitudes toward the elderly improved after this certification process. Appointing a chief executive officer, forming a steering committee, obtaining interdepartmental and interdisciplinary cooperation, and "soliciting support" for new policies from all employees, were identified as key factors influencing the success of age-friendly hospital (AFH) certification. This is the first study to apply Kotter's eight-step framework of organizational change to an AFH certification process.

Objective . Numerous studies have investigated the efficacy of mindfulness meditation (MM) in managing quality of life (QoL) in cancer populations, yet only a few have studied the Asian population. The aim of this exploratory study is to evaluate the effect of a MM program on the QoL outcomes in Taiwanese cancer outpatients. Methods . Patients with various cancer diagnoses were enrolled and assigned to the MM group and usual care (UC) group. The meditation intervention consisted of 3 sessions held monthly. The outcomes of the whole intervention were measured using the World Health Organization Quality of Life (WHOQOL-BREF) instrument. Results . A total of 35 participants in the MM group and 34 in the UC group completed the study. The results showed that the postintervention scores were significantly higher than the preintervention scores in the MM group. In the UC group, there was no significant difference between preintervention and postintervention scores, except for the lower environment domain scores. There was no significant difference between the follow-up scores and postintervention scores in the MM group, indicating that improvement can be maintained for 3 months after completing the MM course. Conclusions . The present study provides preliminary outcomes of the effects on the QoL in Taiwanese cancer patients. The results suggest that MM may serve as an effective mind–body intervention for cancer patients to improve their QoL, and the benefits can persist over a 3-month follow-up period. This occurred in a diverse cancer population with various cancer diagnoses, strengthening the possibility of general use.

The aim of this study is to explore the correlation of laboratory data, hormone peptides, and quality of life with different traditional Chinese medicine (TCM) syndrome groups in type 2 diabetes patients. Of 513 registered patients, 179 subjects aged between 20 and 65 years and having type 2 diabetes mellitus (T2DM) for more than 1 year were enrolled in the study. All the participants were asked to fill out a questionnaire on diabetic TCM syndrome groups, which was designed by professional TCM doctors, and two questionnaires on the quality of life (QOL), WHOQOL-BREF Taiwan version and Medical Outcomes Study (MOS) Short Form-12 (SF-12). The biochemical characteristics and hormone peptide levels were collected at the same time. The patients in any one of the six TCM syndrome groups had the trend to have worse QOL. Especially, patients with qi deficiency had worse life quality on every aspect compared to those without qi deficiency and were fatter than others. We also found that the subjects who had qi deficiency, qi stagnation, and yin deficiency at the same time had worsened condition. We consider that patients with qi deficiency may also be at a higher risk of developing other complications. They need more advanced health care than others. This self-reported questionnaire will be a reference for health care workers screening those T2DM patients who have a higher possibility of developing other complications. Especially in remote areas, where there is a lack of medical resources, an easy-to-use tool such as the one in the present study for detecting and evaluating disease conditions is needed.

Molecular weight markers that can tolerate denaturing conditions and be auto-detected by secondary antibodies offer great efficacy and convenience for Western Blotting. Here, we describe M&R LE protein markers which contain linear epitopes derived from the heavy chain constant regions of mouse and rabbit immunoglobulin G (IgG Fc LE). These markers can be directly recognized and stained by a wide range of anti-mouse and anti-rabbit secondary antibodies. We selected three mouse (M1, M2 and M3) linear IgG1 and three rabbit (R1, R2 and R3) linear IgG heavy chain epitope candidates based on their respective crystal structures. Western blot analysis indicated that M2 and R2 linear epitopes are effectively recognized by anti-mouse and anti-rabbit secondary antibodies, respectively. We fused the M2 and R2 epitopes (M&R LE) and incorporated the polypeptide in a range of 15-120 kDa auto-detecting markers (M&R LE protein marker). The M&R LE protein marker can be auto-detected by anti-mouse and anti-rabbit IgG secondary antibodies in standard immunoblots. Linear regression analysis of the M&R LE protein marker plotted as gel mobility versus the log of the marker molecular weights revealed good linearity with a correlation coefficient R2 value of 0.9965, indicating that the M&R LE protein marker displays high accuracy for determining protein molecular weights. This accurate, regular and auto-detected M&R LE protein marker may provide a simple, efficient and economical tool for protein analysis.

BACKGROUND:Growing evidence shows that sense of coherence (SOC) is related to health promotion. Knowledge of SOC among older adults in Taiwan is limited. The present study aimed to investigate SOC status and its relationship to personal and environmental factors among older adult residents of long-term care facilities (LTCFs) in northeastern Taiwan. METHODS:This cross-sectional study was performed in Yilan, Taiwan. With face-to-face interviews, we obtained data from 104 LTCF residents (aged 65 years and older) using the Chinese version of Antonovsky's short 13-item SOC scale. We also collected the information on personal characteristics, physical and social environmental resources. Multiple linear regression was used to analyze factors potentially influencing SOC. RESULTS:Of the participants, the mean score (±standard deviation) of SOC was 58.3 (±8.8), while scores on SOC subscales (comprehensibility, manageability, and meaningfulness) were 23.4 ±4.5, 17.9 ±3.8, and 17.0 ±3.2, respectively. Education level, activities of daily living and number of LTCF staff were found to be independently associated with SOC status after adjusting for demographic characteristics, health status, and environmental resources. In addition, interactions between personal and environmental factors had a crucial influence on SOC status. CONCLUSIONS:Participants in this study had relatively low SOC scores compared to their counterparts in Western countries. In addition to personal factors, environmental factors can play a significant role in SOC status among older adult LTCF residents. Comprehensive evaluation of SOC status should consider person-environment interaction effects.

The aim of this study was to explore the relationship between obesity-related hormone peptides and quality of life in obese women among different traditional Chinese medicine (TCM) syndrome groups (證型 zhèng xíng). 260 obese women met with age between 20 and 65 years old and body mass index (BMI) ≧ 27 kg/m2, were recruited. The participants filled out a questionnaire on obese TCM syndrome groups, which was designed by professional TCM doctors, and two questionnaires on quality of life (QOL), WHOQOL-BREF Taiwan version and MOS Short Form-12 (SF-12). Data of biochemical characteristics and obesity-related hormone peptides were collected at the same time. According to the responses provided, the obese subjects were classified into spleen deficiency with dampness encumbrance syndrome (脾虛濕阻證 pí xū shī zǔ zhèng; SDD), stomach heat with dampness encumbrance syndrome (胃熱濕阻證 wèi rè shī zǔ zhèng; SHD), liver depression and qi stagnation syndrome (肝鬱氣滯證 gān yù qì zhì zhèng; LDQ), dual spleen-kidney deficiency syndrome (脾腎兩虛證 pí shèn liǎng xū zhèng; SKD), yin deficiency with internal heat syndrome (陰虛內熱證 yīn xū nèi rè zhèng; YDI) and a control group. For physical conditions, SDD group had significantly higher means in weight and BMI compared with the control group. The insulin and leptin levels in SHD group were significantly higher than those in the control group. The LDQ group showed marked decrease in mental condition scores compared with the control group. This study found that obese women in the SDD group were fatter than those in the control group. SHD group might have greater influence on the regulation of obesity-related hormone peptides. The LDQ group had poor QOL than the control group. Analysis of TCM syndrome groups among obese women merits further investigation.

Febrile convulsion (FC) is the most common neurological disease in children. Cases with seizures that persist for more than 15 minutes or recurrent seizures within the same febrile illness are considered to be atypical and may have a different prognosis. Neuropeptide Y (NPY), an endogenous anticonvulsant that is widely distributed throughout the central nervous system, including the hippocampus, is known to prevent seizures by increasing the seizure threshold. Based on our previously finding that patients with atypical FC have lower concentrations of NPY, we hypothesized that the concentration of NPY may play a role in the development of atypical FC. To investigate this hypothesis, we used a radioimmunoassay to measure the plasma NPY concentration of 60 children with FC (typical FC, n = 46; atypical FC, n = 14) and 56 age-matched controls. The atypical FC group had significantly lower concentrations of NPY than children with typical FC and controls (66.47 ± 19.11 pmol/L vs. 88.68 ± 28.50 pmol/L and 86.82 ± 22.66 pmol/L, respectively). Very low NPY levels were found in two patients; one patient (NPY level: 44.75 pmol/L) experienced prolonged seizures lasting for up to 1 hour and the other had recurrent seizures (three seizures) during the same febrile illness (NPY level: 33.53 pmol/L). These results suggest that patients with inadequate NPY inhibitory activity are more susceptible to atypical FC.

UnlabelledThe aim of this study is to investigate the effect of green tea extract on patients with type 2 diabetes mellitus and lipid abnormalities on glycemic and lipid profiles, and hormone peptides by a double-blinded, randomized and placebo-controlled clinical trial. This trial enrolled 92 subjects with type 2 diabetes mellitus and lipid abnormalities randomized into 2 arms, each arm comprising 46 participants. Of the participants, 39 in therapeutic arm took 500 mg green tea extract, three times a day, while 38 in control arm took cellulose with the same dose and frequency to complete the 16-week study. Anthropometrics measurements, glycemic and lipid profiles, safety parameters, and obesity-related hormone peptides were analyzed at screening and after 16-week course. Within-group comparisons showed that green tea extract caused a significant decrease in triglyceride and homeostasis model assessment of insulin resistance index after 16 weeks. Green tea extract also increased significantly high density lipoprotein cholesterol. The HOMA-IR index decreased from 5.4±3.9 to 3.5±2.0 in therapeutic arm only. Adiponectin, apolipoprotein A1, and apolipoprotein B100 increased significantly in both arms, but only glucagon-like peptide 1 increased in the therapeutic arm. However, only decreasing trend in triglyceride was found in between-group comparison. Our study suggested that green tea extract significantly improved insulin resistance and increased glucagon-like peptide 1 only in within-group comparison. The potential effects of green tea extract on insulin resistance and glucagon-like peptide 1 warrant further investigation.Trial registrationClinicalTrials.gov NCT01360567.

Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+) in the Arabidopsis (Arabidopsis thaliana) AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collectively accounted for a tertiary trisomy 2. Morphologic, cytogenetic and genetic analyses of aur2-1 progeny showed impaired male and female gametogenesis to various degrees and a tight association of the aur2-1 allele with the tertiary trisomy that was preferentially inherited. Transcriptome analysis showed overlapping and distinct gene expression profiles between primary and tertiary trisomy 2 plants, particularly genes involved in response to stress and various types of external and internal stimuli. Additionally, transcriptome and gene ontology analyses revealed an overrepresentation of nuclear-encoded organelle-related genes functionally involved in plastids, mitochondria and peroxisomes that were differentially expressed in at least three if not all Arabidopsis trisomics. These observations support a previous hypothesis that aneuploid cells have higher energy requirement to overcome the detrimental effects of an unbalanced genome. Moreover, our findings extend the knowledge of the complex nature of the T-DNA insertion event influencing plant genomic integrity by creating high-grade trisomy. Finally, gene expression profiling results provide useful information for future research to compare primary and tertiary trisomics for the effects of aneuploidy on plant cell physiology.

Abstract Background PEGylated nanoparticles (PEG-NPs) are not effective for hematologic malignancies as they lack the enhanced permeability and retention effect (EPR effect). Tumor-targeted PEG-NPs can systemically track lymphoma and actively internalize into cancer cells to enhance therapeutic efficacy. We generated an anti-PEG bispecific antibody (BsAb; mPEG × CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent αCD20-armed liposomes. This αCD20-armed liposome was able to crosslink CD20 on lymphoma cells to enhance cellular internalization and the anti-cancer efficacy of the liposomes to lymphoma. We generated mPEG × CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation. Results αCD20-armed PLD (αCD20/PLD) specifically targeted CD20+ Raji cells and enhanced PLD internalization 56-fold after 24 h. αCD20/PLD also increased cytotoxicity to Raji cells by 15.2-fold in comparison with PLD and control mPEG × DNS-modified PLD (αDNS/PLD). mPEG × CD20 significantly enhanced the tumor accumulation 2.8-fold in comparison with mPEG × DNS-conjugated PEGylated liposomal DiD in Raji tumors. Moreover, αCD20/PLD had significantly greater therapeutic efficacy as compared to αDNS/PLD (P