Accelerated discovery and miniaturization of novel single-stranded cytidine deaminases.

Cytidine base editors (CBEs) hold significant potential in genetic disease treatment and in breeding superior traits into animals. However, their large protein sizes limit their delivery by adeno-associated virus (AAV), given its packing capacity of <4.7 kb. To overcome this, we employed a web-based fast generic discovery (WFG) strategy, identifying several small ssDNA deaminases (Sdds) and constructing multiple Sdd-CBE 1.0 versions. SflSdd-CBE 1.0 demonstrated high C-to-T editing efficiency, comparable to AncBE4max, while SviSdd-CBE 1.0 exhibited moderate C-to-T editing efficiency with a narrow editing window (C3 to C5). Utilizing AlphaFold2, we devised a one-step miniaturization strategy, reducing the size of Sdds while preserving their efficiency. Notably, we administered AAV8 expressing PCSK9 targeted sgRNA and SflSdd-CBEs (nSaCas9) 2.0 into mice, leading to gene-editing events (with editing efficiency up to 15%) and reduced serum cholesterol levels, underscoring the potential of Sdds in gene therapy. These findings offer new single-stranded editing tools for the treatment of rare genetic diseases.

Surface Engineering and Programmed Self-Assembly of Silica Nanoparticles with Controllable Polystyrene/Poly(4-vinybenzyl azide) Patches.

The programmed self-assembly of patchy nanoparticles (NPs) through a bottom-up approach is an efficient strategy for producing highly organized materials with a predetermined architecture. Herein, we report the preparation of di- and trivalent silica NPs with polystyrene (PS)/poly(4-vinylbenzyl azide) (PVBA) patches and assemble them in a THF mixture by lowering the solvent quality. Silica-PS/PVBA colloidal hybrid clusters were synthesized through the seeded growth emulsion copolymerization of styrene and 4-vinylbenzyl azide (VBA) in varying ratios. Subsequently, macromolecules on silica NPs originating from the copolymerization of growing PS or PVBA chains with the surface-grafted MMS compatibilizer are engineered by fine-tuning of polymer compositions or adjustment of solvent qualities. Moreover, multistage silica regrowth of tripod and tetrapod allowed a fine control of the patch-to-particle size ratio ranging from 0.69 to 1.54. Intriguingly, patchy silica NPs (1-, 2-, 3-PSNs) rather than hybrid clusters are successfully used as templates for multistep regrowth experiments, leading to the formation of silica NPs with a new morphology and size controllable PVBA/PS patches. Last but not least, combined with mesoscale dynamics simulations, the self-assembly kinetics of 2-PSN and 3-PSN into linear colloidal polymers and honeycomb-like lattices are studied. This work paves a new avenue for constructing colloidal polymers with a well-defined sequence and colloidal crystals with a predetermined architecture.

Association between polypharmacy and 2-year outcomes among Chinese older inpatients: a multi-center cohort study.

BACKGROUND: The escalating global prevalence of polypharmacy presents a growing challenge to public health. In light of this issue, the primary objective of our study was to investigate the status of polypharmacy and its association with clinical outcomes in a large sample of hospitalized older patients aged 65 years and over. METHODS: A two-year prospective cohort study was carried out at six tertiary-level hospitals in China. Polypharmacy was defined as the prescription of 5 or more different medications daily, including over-the-counter and non-prescription medications. Baseline polypharmacy, multimorbidity, and other variables were collected when at admission, and 2-year outcomes were recorded by telephone follow-up. We used multivariate logistic regression analysis to examine the associations between polypharmacy and 2-year outcomes. RESULTS: The overall response rate was 87.2% and 8713 participants were included in the final analysis. The mean age was 72.40 years (SD = 5.72), and women accounted for 42.2%. The prevalence of polypharmacy among older Chinese inpatients is 23.6%. After adjusting for age, sex, education, marriage status, body mass index, baseline frailty, handgrip strength, cognitive impairment, and the Charlson comorbidity index, polypharmacy is significantly associated with frailty aggravation (OR 1.432, 95% CI 1.258-1.631) and mortality (OR 1.365, 95% CI 1.174-1.592), while inversely associated with readmission (OR 0.870, 95% CI 0.764-0.989). Polypharmacy was associated with a 35.6% increase in the risk of falls (1.356, 95%CI 1.064-1.716). This association weakened after adjustment for multimorbidity to 27.3% (OR 1.273, 95%CI 0.992-1.622). CONCLUSIONS: Polypharmacy was prevalent among older inpatients and was a risk factor for 2-year frailty aggravation and mortality. These results highlight the importance of optimizing medication use in older adults to minimize the risks associated with polypharmacy. Further research and implementing strategies are warranted to enhance the quality of care and safety for older individuals exposed to polypharmacy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017682, registered 09/08/2018.

Motion states identification of underwater glider based on complex networks and graph convolutional networks.

Underwater glider (UG) plays an important role in ocean observation and exploration for a more efficient and deeper understanding of complex ocean environment. Timely identifying the motion states of UG is conducive for timely attitude adjustment and detection of potential anomalies, thereby improving the working reliability of UG. Combining limited penetrable visibility graph (LPVG) and graph convolutional networks (GCN) with self-attention mechanisms, we propose a novel method for motion states identification of UG, which is called as visibility graph and self-attention mechanism-based graph convolutional network (VGSA-GCN). Based on the actual sea trial data of UG, we chose the attitude angle signals of motion states related sensors collected by the control system of UG as the research object and constructed complex networks based on the LPVG method from pitch angle, roll angle, and heading angle data in diving and climbing states. Then, we build a self-attention mechanism-based GCN framework and classify the graphs under different motion states constructed by a complex network. Compared with support vector machines, convolutional neural network, and GCN without self-attention pooling layer, the proposed VGSA-GCN method can more accurately distinguish the diving and climbing states of UG. Subsequently, we analyze the variation of the transitivity coefficient corresponding to these two motion states. The results suggest that the coordination of the various sensors in the attitude adjustment unit during diving becomes closer and more efficient, which corresponds to the higher network measure of the diving state compared to the climbing state.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: A multicentre observational study.

Co-infection in patients with severe fever with thrombocytopenia syndrome (SFTS) has been reported, posing a serious threat to survival and treatment. We aimed to systematically investigate the SFTS associated pulmonary infection, particularly invasive pulmonary fungal infection (IPFI). During April 2019 to October 2021, we conducted a multicentre observational study on adult hospitalized patients confirmed with SFTS from three tertiary hospital in central China. Demographic, clinical and laboratory data of patients were collected and re-assessed. A total of 443 patients (51.7% were male sex) were included for analysis with median age of 65-year-old. Among them, 190 (42.9%) patients met the criteria for pulmonary infection. Pulmonary infection was associated with shorter survival time (p < 0.0001 by log-rank test), and adjusted hazard ratio was 1.729 [95% confidence interval, 1.076-2.780] (p = 0.024). Age (odds ratio (OR) 1.040 [1.019-1.062], p < 0.001), time from onset to admission (OR 1.163 [1.070-1.264], p < 0.001), having severe status (OR 3.166 [2.020-4.962], p < 0.001) and symptoms of skin change (OR 2.361 [1.049-5.316], p < 0.001) at admission and receiving intravenous immunoglobin (OR 2.185 [1.337-3.569], p = 0.002) were independent risk factors for the occurrence of pulmonary infection. A total of 70 (15.8%) patients were defined as IPFI. Multivariate analysis showed that time from onset to admission (OR 1.117 [1.016-1.229], p = 0.022), severe status (OR 5.737 [3.054-10.779], p < 0.001), having smoking history (OR 3.178 [1.251-8.070], p = 0.015) and autoimmunity disease (OR 7.855 [1.632-37.796], p = 0.010), receiving intravenous immunoglobin (OR 3.270 [1.424-7.508], p = 0.005) were independent risk factors for the occurrence of IPFI. In SFTS patients with pulmonary infection, white blood count <2.09 × 109 per L (OR 11.064 [3.708-33.012], p < 0.001) and CD3+ CD4+ T cell count <104.0 per µL (OR 10.429 [3.395-32.038], p < 0.001) could independently predict IPFI. This study showed the high prevalence and poor outcomes of pulmonary infection and IPFI in patients with SFTS. These findings highlighted the need for active surveillance of fungal pathogens and early antifungal treatment in patients with SFTS.

Imparting pH and temperature dual-responsiveness in a micellar solution of cationic surfactants by introducing a hydrotrope.

Over the recent years, intelligent, multi-responsive micelles have received considerable attention due to their promising application in a variety of fields, including biomedical technology, drug delivery, separation, and catalysis. However, the design of such systems with controlled self-assembly is challenging both experimentally and theoretically and is still in the nascent stage. In this study, a novel dual-stimuli triggered wormlike micellar solution is prepared by mixing cationic surfactants 3-hexadecyloxy-2-hydroxypropyltrimethylammonium bromide (R16HTAB) and sodium hydrogen phthalate (SHP). The viscoelasticity, aggregate morphology, and pH- and thermo-responsive behavior of the micellar solution are examined by rheological measurements, cryogenic-transmission electron microscopy (cryo-TEM), nuclear magnetic resonance (1H NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The dual-sensitive fluid can be switched between a water-like state and a gel-like state by adjusting the pH and temperature. The variations in the flowing behavior are ascribed to the microstructural transition between wormlike micelles, short cylindrical micelles, and spherical micelles. Furthermore, based on the experimental results, dual-responsive behavior of the mixed solution is attributed to the different binding modes between SHP and the surfactant with the variation in the pH and temperature. We hope that the proposed system provides a new route for developing multi-stimuli-responsive materials that are capable of adapting to local environmental variations.

Association between Frailty and 90-Day Outcomes amongst the Chinese Population: A Hospital-Based Multicentre Cohort Study.

INTRODUCTION: Frailty has gained increasing attention as it is by far the most prevalent geriatric condition amongst older patients which heavily impacts chronic health status. However, the relationship between frailty and adverse health outcomes in China is far from clear. This study explored the relation between frailty and a panel of adverse health outcomes. METHODS: We performed a multicentre cohort study of older inpatients at 6 large hospitals in China, with two-stage cluster sampling, from October 2018 to April 2019. Frailty was measured according to the FRAIL scale and categorized into robust, pre-frail, and frail. A multivariable logistic regression model and multilevel multivariable negative binomial regression model were used to analyse the relationship between frailty and adverse outcomes. Outcomes were length of hospitalization, as well as falls, readmission, and mortality at 30 and 90 days after enrolment. All regression models were adjusted for age, sex, BMI, surgery, and hospital ward. RESULTS: We included 9,996 inpatients (median age 72 years and 57.8% male). The overall mortality at 30 and 90 days was 1.23 and 1.88%, respectively. At 30 days, frailty was an independent predictor of falls (odds ratio [OR] 3.19; 95% CI 1.59-6.38), readmission (OR 1.45; 95% CI 1.25-1.67), and mortality (OR 3.54; 95% confidence interval [CI] 2.10-5.96), adjusted for age, sex, BMI, surgery, and hospital ward clustering effect. At 90 days, frailty had a strong predictive effect on falls (OR 2.10; 95% CI 1.09-4.01), readmission (OR 1.38; 95% CI 1.21-1.57), and mortality (OR 6.50; 95% CI 4.00-7.97), adjusted for age, sex, BMI, surgery, and hospital ward clustering effect. There seemed to be a dose-response association between frailty categories and fall or mortality, except for readmission. CONCLUSIONS: Frailty is closely related to falls, readmission, and mortality at 30 or 90 days. Early identification and intervention for frailty amongst older inpatients should be conducted to prevent adverse outcomes.

A pH, thermal and light triple-stimuli responsive micellar solution formed by a cationic surfactant and trans-o-hydroxycinnamic acid.

Controlling the viscoelastic characteristics of wormlike micelles is of great significance to both basic theory and practical applications. In this article, a novel multi-stimuli responsive wormlike micellar solution was prepared by mixing cationic surfactant 3-hexadecyloxy-2-hydroxypropyltrimethylammonium bromide (R16HTAB) with trans-o-hydroxycinnamic acid (OHCA). Rheological studies, nuclear magnetic resonance (1H-NMR) spectroscopy, UV-vis spectroscopy, and cryogenic-transmission electron microscopy (cryo-TEM) were utilized to investigate the wormlike micellar system's multi-responsive activity. The results showed that the self-assembled structure and viscoelasticity of the mixed system could be regulated by pH, temperature, and light irradiation. With the increasing trans-OHCA concentration, η0 of the mixed solution increases first and then decreases and the turning point is presented at 30 mM trans-OHCA, indicating the transformation of spherical micelles to wormlike micelles, and then to short micelles. The microstructure of the mixed systems could be reversibly altered by adjusting the pH between 6.41 and 3.90, which was ascertained by cryogenic-transmission electron microscopy (cryo-TEM). The relationship of temperature and η0 obeys the Arrhenius law, attributed to the decreasing micellar contour length. η0 of a 40 mM R16HTAB/15 mM OHCA solution sharply increases after UV irradiation, mainly because the cis-isomer could insert into the micelle more easily, and the transition mechanism was studied by UV-vis and 1H NMR. The multi-responsive self-assembled system may open a new vista for building multi-functional aggregates to adapt to various environmental changes.

Cytidine deaminase 435C>T polymorphism relates to gemcitabine-platinum efficacy and hematological toxicity in Chinese non-small-cell lung cancer patients.

CDA 435C>T is reported as a functional SNP but there is no relevant research on the efficacy/hematological toxicity of gemcitabine-platinum treatment in Chinese non-small-cell lung cancer (NSCLC) patients. In this study, 63 patients who received radical resection (stage IB or IIIA) and 100 advanced NSCLC (stage IIIB or IV) patients have been collected, and all were treated with gemcitabine-platinum regimens from February of 2017 to February 2019. CDA 435C>T polymorphisms have been detected by PCR and direct sequencing. CT scan results and blood routine examinations have been collected to evaluate the efficacy and hematological toxicity. Then the relationships have been analyzed about CDA 435C>T. We found that T allele carriers have better therapy response (p<0.05). Patients carrying CDA 435C/T or T/T genotypes are statistically associated with a better efficacy (p<0.05) but are more prone to leukopenia (p<0.05). Although there is no difference in grade III-IV hematologic toxicity of 163 patients (p>0.05), in the case of 100 stage IIIB-IV patients, the CDA 435C/T and T/T have an increased risk (p<0.05). Regarding the CDA 435C>T polymorphism in the Chinese population, in patients with the mutant T allele, gemcitabine is more effective, but they are more prone to suffering from hematological toxicity, especially the late-stage patients.

An early predictive model of frailty for older inpatients according to nutritional risk: protocol for a cohort study in China.

BACKGROUND: Previous reports suggest that the attributes of frailty are multidimensional and include nutrition, cognition, mentality, and other aspects. We aim to develop an early warning model of frailty based on nutritional risk screening and apply the frailty early warning model in the clinic to screen high-risk patients and provide corresponding intervention target information. METHODS: The proposed study includes two stages. In the first stage, we aim to develop a prediction model of frailty among older inpatients with nutritional risk. Study data were collected from a population-based aging cohort study in China. A prospective cohort study design will be used in the second stage of the study. We will recruit 266 older inpatients (age 65 years or older) with nutritional risk, and we will apply the frailty model in the clinic to explore the predictive ability of the model in participants, assess patients' health outcomes with implementation of the frailty model, and compare the model with existing frailty assessment tools. Patients' health outcomes will be measured at admission and at 30-day follow-up. DISCUSSION: This project is the first to develop an early prediction model of frailty for older inpatients according to nutritional risk in a nationally representative sample of Chinese older inpatients of tertiary hospitals. The results will hopefully help to promote the development of more detailed frailty assessment tools according to nutritional risk, which may ultimately lead to reduced health care costs and improvement in independence and quality of life among geriatric patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017682 , registered August 9, 2018; and ChiCTR2100044148 , registered March 11, 2021.

Prevalence of cognitive impairment in Chinese older inpatients and its relationship with 1-year adverse health outcomes: a multi-center cohort study.

BACKGROUND: Previous studies on the relationship between cognitive impairment and adverse outcomes among geriatric inpatients are not representative of older inpatients in China because of insufficient sample sizes or single-center study designs. The purpose of our study was to examine the prevalence of cognitive impairment and the relationship between cognitive impairment and 1-year adverse health outcomes in older inpatients. METHODS: This study was a large-scale multi-center cohort study conducted from October 2018 to February 2020. Six tertiary hospitals across China were selected using a two-stage cluster sampling method, and eligible older inpatients were selected for the baseline survey and follow-up. The Mini Cognitive Scale and the FRAIL scale were used to screen for cognitive impairment and frailty, respectively. The EuroQol-5 Dimension-5 Level questionnaire was used to assess health-related quality of life (HRQoL). We used a generalized estimating model to evaluate the relationship between cognitive impairment and adverse outcomes. RESULTS: The study included 5008 men (58.02%) and 3623 women (41.98%), and 70.64% were aged 65-75 years, and 26.27% were aged 75-85 years. Cognitive impairment was observed in 1756 patients (20.35%). There were significant differences between participants with cognitive impairment and those with normal cognitive function for age, gender, surgery status, frailty, depression, handgrip strength and so on. After adjusting for multiple covariates, compared with patients with normal cognitive function, the odds ratio for 1-year mortality was 1.216 (95% confidence interval [CI]: 1.076-1.375) and for 1-year incidence of frailty was 1.195 (95% CI: 1.037-1.376) in patients with cognitive impairment. Similarly, the regression coefficient of 1-year HRQoL was - 0.013 (95% CI: - 0.024-- 0.002). In the stratified analysis, risk of adverse outcome within 1 year was higher in older patients with cognitive impairment aged over 75 years than those aged 65-74 years. CONCLUSIONS: We revealed that cognitive impairment was highly correlated with occurrence of 1-year adverse health outcomes (death, frailty, and decreased HRQoL) in older inpatients, which provides a basis for formulating effective intervention measures. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017682 , registered 09 August 2018.

Prevalence and associated factors for frailty among elder patients in China: a multicentre cross-sectional study.

BACKGROUND: To date, most previous studies of frailty among hospitalized elderly Chinese patients have been conducted based on small samples, which cannot represent the elderly patient population. The aim of this study was to identify the prevalence of and risk factors for frailty among elderly patients in China. STUDY DESIGN AND SETTING: This cross-sectional study surveyed 9996 elderly patients from 6 tertiary-level hospitals in China. The prevalence of frailty among patients from selected wards was surveyed by trained investigators. A mixed-effects Poisson regression model was used to analyse the factors associated with frailty among elderly patients. RESULTS: The mean age of all subjects was 72.47 ± 5.77 years. The prevalence rate of frailty in this study was 18.02%. After adjustments were made for the confounding effect of the clustering of hospital wards, a mixed-effects Poisson regression model showed that the associated factors of frailty included the following: age (OR: 1.016, 95% CI: 1.012-1.020), BMI < 18.5 (OR: 1.248, 95% CI: 1.171-1.330), female gender (OR: 1.058, 95% CI: 1.004-1.115), ethnic minority (OR: 1.152, 95% CI: 1.073-1.236), admission to hospital by the emergency department (OR: 1.104, 95% CI: 1.030-1.184), transit from another hospital (OR: 1.159, 95% CI: 1.049-1.279), former alcohol use (OR: 1.094, 95% CI: 1.022-1.171), fall history in the past 12 months (OR: 1.257, 95% CI: 1.194-1.323), vision dysfunction (OR: 1.144, 95% CI: 1.080-1.211), cognition impairment (OR: 1.182, 95% CI: 1.130-1.237), sleeping dysfunction (OR: 1.215, 95% CI: 1.215-1.318), urinary dysfunction (OR: 1.175, 95% CI: 1.104-1.251), and defecation dysfunction (OR: 1.286, 95% CI: 1.217-1.358). The results also showed some of the following protective effects: BMI > 28 (OR: 0.897, 95% CI: 0.856-0.940); higher education level, including middle school (OR: 0.915, 95% CI: 0.857, 0.977) and diploma and above (OR: 0.891, 95% CI: 0.821, 0.966); and current alcohol use (OR: 0.869, 95% CI: 0.815, 0.927). CONCLUSION: We identified a relatively high prevalence of frailty among elderly patients, and there are several associated factors among the population derived from this investigation of a large-scale, multicentre, nationally representative Chinese elderly inpatient population. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017682, registered 09 August 2018.

Potential associated factors of functional disability in Chinese older inpatients: a multicenter cross-sectional study.

BACKGROUND: There is still controversy about the relationship between aging and changes in functional ability. This study aims to describe the level of basic activities of daily living (ADL) and higher-level instrumental activities of daily living (IADL) in different age groups and explore the factors associated with functional disability in Chinese older inpatients. METHODS: This cross-sectional study surveyed 9996 older inpatients aged 65 years and older from six tertiary hospitals in China from October 2018 to February 2019. The levels of ADL and IADL were measured by scores of the Barthel index and Instrumental Activities of Daily Living Scale. A mixed-effect generalized linear model was used to examine the association between functional disability and covariates. RESULTS: The average ADL score was 89.51 ± 19.29 and the mean IADL score 6.76 ± 2.01 for all participants. There was a trend of decreasing scores along with aging, and significant differences between age groups were also observed (P < 0.001). The most affected ADL and IADL was stair climbing and shopping, respectively. Sociodemographic characteristics (such as age), physical health variables (frailty, emaciation, hearing dysfunction, urinary dysfunction, defecation dysfunction, falling accidents in the past 12 months), and mental health variables (cognitive dysfunction, depression) were associated with functional disability. Patients from the emergency department or transferred from other hospitals and former alcohol drinkers are at risk of ADL disability. Former smoking is a risk factor for IADL disability, whereas current drinking, higher-level education, and residing in a building without elevators were likely to maintain a better IADL performance. CONCLUSIONS: Functional ability declines with aging, older inpatients are low dependency upon ADL and IADL. There are several associated factors among the participants derived from this investigation of a large-scale, multicenter, nationally representative Chinese older inpatient population. These findings potentially have major importance for the planning of hospital services, discharge planning, and post-discharge care. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017682 , registered August 9, 2018.

Predictive factors associated with glycaemic response to exenatide in Chinese patients with type 2 diabetes mellitus.

WHAT IS KNOWN AND OBJECTIVE: Exenatide is widely used in the treatment of type 2 diabetes mellitus (T2DM) because of its established effect on lowering glucose and promotion of weight loss. However, therapeutic response to exenatide varies considerably among patients with T2DM. The purpose of this study was to determine which variables can predict the response to exenatide and to individualize specific therapies for patients with T2DM who need treatment with exenatide. METHODS: This is a retrospective cohort study of patients with T2DM who were treated with exenatide twice daily as a part of their diabetes care for at least 12 months. Patients were categorized into two cohorts based on glycaemic response to exenatide use: responders and non-responders. RESULTS AND DISCUSSION: One hundred forty-eight patients met the inclusion criteria; among them, 92 responded with an HbA1C reduction ≥1.0% from baseline HbA1C and 56 did not respond to exenatide after 6 months of exenatide treatment. Binary logistic regression analysis revealed that baseline HbA1C and duration of diabetes were identified as predictors of HbA1C reduction ≥1% at 6 months (P < .05). Linear regression analysis further identified that patients with a higher baseline HbA1C (≥7.4%) and shorter duration of diabetes (≤15.0 years) were likely to respond to exenatide, whereas those with a lower baseline HbA1C (<7.4%) and longer duration of diabetes (>15.0 years) were not likely to respond to exenatide. WHAT IS NEW AND CONCLUSION: Our data indicate that T2DM patients with a higher baseline HbA1C and a shorter duration of diabetes are more likely to have a glycaemic response to exenatide than those with a lower baseline HbA1C and a longer duration of diabetes. The identification of predictors of therapeutic response to exenatide can provide clinically useful information for characterizing the patients who could receive the greatest benefit from exenatide.

Magnetic Multiarm Scaffold for the One-Step Purification of Epitope-Specific Neutralizing Antibodies.

Epitope-specific neutralizing antibodies (EsAbs) are of prime importance in the diagnosis and treatment of various serious diseases. However, obtaining EsAbs by the monoclonal antibody technique involves time-consuming and sophisticated multistep procedures, and the epitopes of the resulting antibodies are often not explicit. It is also very challenging to isolate EsAbs from numerous kinds of total immunoglobulins because of nonspecific adsorption and low separation efficiency. Herein, a magnetic core@multiarm shell-epitope (M@A-E) bioconjugate was fabricated to enrich and isolate EsAbs from immune serums. This robust multiarm scaffold exhibits outstanding binding capacity and good resistance to nontarget adsorption and serves as a reservoir for the release and reloading of EsAbs for repeatable applications. The EsAbs yield per milligram of the M@A-E was about 30 µg, which was approximately twice that of commercially available beads (16 µg). After 10 cycles of loading and release in glycine buffer (0.1 M, pH 2.5), the M@A-E bioconjugates still showed relatively high specificity and capture capacity (20 µg) superior to the same amount of new, unused conventional ones. This strategy provides a promising platform for enriching and isolating substantial quantities of EsAbs, which have great potential for applications in the detection and treatment of critical illness.

Effects of additives on the viscoelastic responses of cationic gemini surfactant solutions.

Several additives, including inorganic (NaCl) and organic salts (derivatives of benzoate), were added into aqueous solutions of a gemini cationic surfactant, 2-hydroxypropyl-1,3-bis (myristyldimethylammonium chloride) (abbreviated as 14-3(OH)-14(2Cl)). The mixed systems were investigated using rheological measurement, cryo-TEM and 1H NMR analysis. The results showed that addition of salts induced rich aggregate morphologies in the 14-3(OH)-14(2Cl)/salt systems. The influence of an inorganic salt on the viscoelasticity of 14-3(OH)-14(2Cl) solutions is much weaker than that of organic salts. Furthermore, the ability of three organic salts in enhancing the viscoelasticity of 14-3(OH)-14(2Cl) solutions is in the order sodium m-hydroxybenzoate > sodium o-hydroxybenzoate > sodium p-hydroxybenzoate. The different roles of these organic salt isomers arise from the different types of hydrogen bonding formed between 14-3(OH)-14(2Cl) and the organic counter ions.

Neuroprotection of rhGLP-1 in diabetic rats with cerebral ischemia/reperfusion injury via regulation of oxidative stress, EAAT2, and apoptosis.

Preclinical Research & Development The purpose of the present study is to evaluate the neuroprotective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) as well as to explore corresponding mechanisms in diabetic rats with cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion (MCAO). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The rats were pretreated with rhGLP-1 (20 µg/kg intraperitoneally, thrice a day) for 14 days. Thereafter, the rats were subjected to MCAO 90 min/reperfusion 24 hr. At 2 and 24 hr of reperfusion, the rats were assessed for neurological deficits and subsequently executed for the evaluation of cerebral infarct volume, oxidative stress parameters, and the expression of excitatory amino acid transporter 2 (EAAT2) and apoptotic markers. Results indicate that rhGLP-1 significantly ameliorated neurological deficits and reduced cerebral infarct volume in diabetic MCAO rats. In addition, oxidative stress parameters in ischemic penumbra were significantly alleviated in rhGLP-1-pretreated diabetic MCAO rats. rhGLP-1 significantly upregulated the ratio of Bcl-2/Bax and EAAT2 expression and downregulated cleaved caspase-3 expression in ischemic penumbra of diabetic MCAO rats. Our results suggest that rhGLP-1 could significantly ameliorate neurological deficits and reduce cerebral infarct volume in diabetic MCAO rats, which may be due to the inhibition of oxidative stress and apoptosis and the promotion of EAAT2 expression.

A variant of GRK5 is associated with the therapeutic efficacy of repaglinide in Chinese Han patients with type 2 diabetes mellitus.

Post-Market Research We aimed to investigate the impact of G protein-coupled receptor kinase 5 (GRK5) rs10886471 polymorphism on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 300 T2DM patients and 210 healthy controls were genotyped for GRK5 rs10886471 on a three-dimensional polyacrylamide gel-based DNA microarray. Eighty-five patients with the same genotypes of cytochrome P450 (CYP) 2C8*3 139Arg and organic anion-transporting polypeptide 1B1 (OATP1B1) 521TT were randomly selected to orally take repaglinide for eight consecutive weeks. Then, the biochemical indicators and pharmacodynamic parameters were measured before and after repaglinide treatment. The T allelic frequency of GRK5 rs10886471 was higher in T2DM patients than in healthy subjects (p < .01). T2DM patients with genotypes CC and CT at GRK5 rs10886471 had a significant reduction in terms of fasting plasma glucose (FPG) compared with those with genotype TT (p < .01). In addition, the carriers of genotypes CC and CT at GRK5 rs10886471 had higher differential values of postprandial serum insulin (PINS) compared with genotype TT carriers (p < .05). These findings suggest that GRK5 rs10886471 polymorphism may influence the therapeutic efficacy of repaglinide in Chinese Han T2DM patients.

Impact of Menopause on Quality of Life in Community-based Women in China: 1 Year Follow-up.

Quality of life (QOL) throughout menopause has become an outcome variable requiring measurement in clinical care. Staff nurses can provide earlier nursing during the menopausal transition (MT) stage. The purpose of this study was to describe the changes of QOL in different stages of the MT according to The Stages of Reproductive Aging Workshop (STRAW) in Chinese women in community settings. Prospective longitudinal study design was used to analyze QOL of 327 community women age 30-65years old. They were followed up at 1-year. An instrument including the Chinese version of the Menopause-Specific Quality of Life Questionnaire was used to obtain data. A gradual decline in QOL was seen from premenopausal to menopausal transition (MT) and in postmenopausal women. Significant differences were observed in vasomotor, physical and sexual scores at baseline and follow-up (P<0.05). Significant differences in vasomotor scores were observed between baseline and follow-up for women in the premenopausal and Late MT stages (P<0.05). There were significant differences in psychosocial and physical scores between baseline and follow-up in the Late MT stage (P<0.05). Menopause might have a negative impact on QOL independent of age in community-based women in China. There seemed to be a potential model of the relationship of menopause status to change in QOL, but this needs supporting evidence from longer longitudinal studies.