Activation of the Epac/Rap1 signaling pathway alleviates blood-brain barrier disruption and brain damage following cerebral ischemia/reperfusion injury.

Blood brain barrier (BBB) destruction plays a key role in ischemia stroke, including promoting BBB leakage and brain edema, and leads to unfavorable patient prognosis. Epac/Rap1 signaling pathway is important in mediating endothelial cell barrier function. This study will investigate the regulatory role of Epac/Rap1 signaling pathway in BBB disruption after cerebral ischemia/reperfusion (CI/R) injury. CI/R model was induced by 90 min of transient middle cerebral artery occlusion (MCAO) in male C57BL/6J mice. Injection of Epac/Rap1 signaling pathway agonist was performed half an hour before the MCAO operation. The results showed that CI/R injured the tight connection of BBB and evoked the suppression of the Epac/Rap1 signaling pathway. Based on Epac activation with a cAMP analogue, 8-CPT could improve BBB disfunction by increasing the expression of tight junction protein and reducing the formation of stress fibers. In addition, 8-CPT could ameliorate neurobehavioral disorders, cerebral edema, and cerebral infarction volume in MCAO mice. Moreover, inhibition of Epac pathway with Rap1 inhibitor GGTI298 and Rac1 inhibitor NSC23766 could aggravate the damage of BBB and cerebral injury accordingly. Our results indicate that, the activation of Epac/Rap1 signaling pathway has neuroprotective effects on CI/R damaged brain, through the recovery of BBB.

Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer.

Background: The emergence of HER2 antibody-drug conjugates provides new treatment decisions for breast cancer patients, especially those with HER2-low expression. In order to explore the biological characteristics of breast cancer with HER2-low expression, the HER2-low category in primary breast cancer and residual tumor after neoadjuvant therapy was investigated to reflect the evolution of HER2 expression. Methods: HER2 was assessed according to the latest ASCO/CAP guidelines. The cut-off value for staining of HER2-positive cells was >10%. HER2-negative cases were divided into HER2-low (IHC=1+/2+ and no ISH amplification) and HER2-zero (IHC-0), and the clinicopathological characteristics of the cases were collected. Results: This study included 1140 patients with invasive breast cancer who received preoperative neoadjuvant therapy from 2018 to 2021, of which 365 patients achieved pCR and 775 were non-pCR. In the non-pCR cohort, HER2-low cases accounted for 59.61% of primary tumors and 55.36% of residual tumors. Among HER2-negative cases, HR-positive tumors had a higher incidence of low HER2 expression compared with triple-negative tumors (80.27% vs 60.00% in primary tumors and 72.68% vs 50.77% in residual tumors). The inconsistency rate of HER2 expression was 21.42%, mainly manifested as the conversion of HER2-low cases to HER2-zero (10.19%) and the conversion of HER2-zero to HER2-low (6.45%). Among the HER2-negative cases in the primary tumor, the HER2 discordance rate of HR-positive cases was lower than that of triple-negative cases (23.34% VS 36.92%). This difference was mainly caused by the case switching from HER2-low to HER2-zero. Compared with HER2-zero cases, there were statistically significant differences in RCB grade, MP grade and the number of metastatic lymph nodes in HER2-low cases. Patients with low HER2 expression had a lower pathological response rate and a higher number of metastatic lymph nodes. Conclusion: HER2-low breast cancer is highly unstable during disease evolution and has certain biological characteristics. HER2-low breast cancer is not only correlated with positive HR, but also has a certain correlation with positive AR. Re-detection of HER2 in breast cancer after neoadjuvant therapy may lead to new treatment opportunities for a certain proportion of patients.

Long-term exposure to ambient air pollutants and their interaction with physical activity on insomnia: A prospective cohort study.

Exposure to air pollution or lack of physical activity (PA) increases the risk of insomnia. However, evidence on joint exposure to air pollutants is limited, and the interaction of joint air pollutants and PA on insomnia is unknown. This prospective cohort study included 40,315 participants with related data from the UK Biobank, which recruited participants from 2006 to 2010. Insomnia was assessed by self-reported symptoms. The annual average air pollutant concentrations of particulate matter (PM2.5, PM10), nitrogen oxides (NO2, NOX), sulfur dioxide (SO2) and carbon monoxide (CO) were calculated based on participants' addresses. We applied a weighted Cox regression model to evaluate the correlation between air pollutants and insomnia and newly proposed an air pollution score to assess joint air pollutants effect using a weighted concentration summation after obtaining the weights of each pollutant in the Weighted-quantile sum regression. With a median follow-up of 8.7 years, 8511 participants developed insomnia. For each 10 µg/m³ increase in NO2, NOX, PM10, SO2, the average hazard ratios (AHRs) and 95% confidence interval (CI) of insomnia were 1.10 (1.06, 1.14), 1.06 (1.04, 1.08), 1.35 (1.25, 1.45) and 2.58 (2.31, 2.89), respectively; For each 5 µg/m³ increase in PM2.5 and each 1 mg/m³ increase in CO, the corresponding AHRs (95%CI) were 1.27 (1.21, 1.34) and 1.83 (1.10, 3.04), respectively. The AHR (95%CI) for insomnia associated with per interquartile range (IQR) increase in air pollution scores were 1.20 (1.15, 1.23). In addition, potential interactions were examined by setting cross-product terms of air pollution score with PA in the models. We observed an interaction between air pollution scores and PA (P = 0.032). The associations between joint air pollutants and insomnia were attenuated among participants with higher PA. Our study provides evidence on developing strategies for improving healthy sleep by promoting PA and reducing air pollution.

Comparative effectiveness of non-pharmacological interventions for frailty: a systematic review and network meta-analysis.

BACKGROUND: Frailty endangers the health of older adults. Furthermore, the prevalence of frailty continues to increase as the global population ageing. OBJECTIVE: To update evidence on the effectiveness of non-pharmacological interventions for frailty by conducting a network meta-analysis (NMA) of randomised controlled trials (RCTs). METHODS: Eight databases were searched from January 1, 2000, until September 24, 2021. RCTs of interventions for frailty among participants aged ≥60 years were considered eligible. The primary outcome was frailty. Pairwise meta-analysis and NMA were performed, with the pooled standardised mean difference (SMD) and 95% confidence interval (CI) being reported. RESULTS: A total of 69 RCTs were included after screening 16,058 retrieved citations. There were seven types of interventions (11 interventions) for frailty among the included RCTs. Physical activity (PA) (pooled SMD = 0.43, 95% CI: 0.34-0.51), multicomponent intervention (pooled SMD = 0.34, 95% CI: 0.23-0.45) and nutrition intervention (pooled SMD = 0.21, 95% CI: 0.06-0.35) were associated with reducing frailty compared to control, of which PA was the most effective type of intervention. In terms of specific types of PA, resistance training (pooled SMD = 0.58, 95% CI: 0.33-0.83), mind-body exercise (pooled SMD = 0.57, 95% CI: 0.24-0.90), mixed physical training (pooled SMD = 0.47, 95% CI: 0.37-0.57) and aerobic training (pooled SMD = 0.36, 95% CI: 0.09-0.62) were associated with a reduction in frailty compared to usual care. Resistance training was the most effective PA intervention. CONCLUSION: Resistance training has the best potential to reduce frailty in older adults. This finding might be useful to clinicians in selecting interventions for older adults with frailty.

Charge-dependent negative effects of polystyrene nanoplastics on Oryzias melastigma under ocean acidification conditions.

Marine nanoplastics (NPs) have attracted increasing global attentions because of their detrimental effects on marine environments. A co-existing major environmental concern is ocean acidification (OA). However, the effects of differentially charged NPs on marine organisms under OA conditions are poorly understood. We therefore investigated the effects of OA on the embryotoxicity of both positively and negatively charged polystyrene (PS) NPs to marine medaka (Oryzias melastigma). Positively charged PS-NH2 exhibited slighter aggregation under normal conditions and more aggregation under OA conditions than negatively charged PS-COOH. According to the integrated biomarker approach, OA reversed the toxicity of positively and negatively charged NPs towards embryos. Importantly, at environmental relevant concentrations, both types of PS-NPs could enter the embryos through chorionic pores and then transfer to the larvae. OA reversed the internalization of PS-NH2 and PS-COOH in O. melastigma. Overall, the reversed toxicity of PS-NH2 and PS-COOH associated with OA could be caused by the reversed bioavailability of NPs to O. melastigma, which was attributed to altered aggregation of the NPs in acidified seawater. This finding demonstrates the charge-dependent toxicity of NPs to marine fish and provides new insights into the potential hazard of NPs to marine environments under OA conditions that could be encountered in the near future.

Metal-Backboned Polymers with Well-Defined Lengths.

Constructing the backbones of polymers with metal atoms is an attractive strategy to develop new functional polymeric materials, but it has yet to be studied due to synthetic challenges. Here, metal atoms are interconnected as the backbones of polymers to yield metal-backboned polymers (MBPs). Rational design of multidentate ligands synthesized via an efficient iterative approach leads to the successful construction of a series of nickel-backboned polymers (NBPs) with well-defined lengths and up to 21 nickel atoms, whose structures are systematically confirmed. These NBPs exhibit strong and length-depended absorption with narrow band gaps, offering promising applications in optoelectronic devices and semiconductors. We also demonstrate the high thermal stability and solution processsability of such nickel-backboned polymers. Our results represent a new opportunity to design and synthesize a variety of new metal-backboned polymers for promising applications in the future.

Cimigenol depresses acute myeloid leukemia cells protected by breaking bone marrow stromal cells via CXCR4/SDF­1α.

The purpose of the present study was to evaluate cimigenol (Cim) treatment effects to cell proliferation by breaking bone marrow stromal cells (BMSCs) through C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor-1α (SDF-1α) pathway. MV-4-11 and U937 cell lines were used. The present study was divided into two parts. First, the cell lines were divided into normal control (NC), BMSC (cells co-cultured with BMSCs), BMSC + DMSO, BMSC + Low (treated with 5 mg/ml Cim), BMSC + Middle (treated with 10 mg/ml Cim), BMSC + High (treated with 20 mg/ml Cim). In the second step, the cell lines were divided into NC, BMSC, BMSC + BL8040 (treated with BL8040 which inhibits CXCR4), BMSC + Cim and BMSC + Cim + BL8040. EdU positive cell numbers were measured by EdU assay and apoptosis rate by flow cytometry and TUNEL assay. Relative gene and protein expression was measured by reverse transcription-quantitative PCR and western blotting assay. BMSCs were able to protect proliferation of cancer cells and decreased cell apoptosis compared with the NC group (P<0.001, respectively). With Cim supplement, the cell proliferation was decreased with cell apoptosis increasing compared with NC group (P<0.001 respectively). However, the anti-tumor effects of Cim were not significantly different from the BL8040 treated groups (P<0.001, respectively). In conclusion Cim decreased acute myeloid leukemia cells protected by BMSCs through the CXCR4/SDF-1α pathway.

Analysis of Floral Color Differences between Different Ecological Conditions of Clematis tangutica (Maxim.) Korsh.

The Clematis tangutica (Maxim.) Korsh. is a wild flowering plant that is most widely distributed on the Qinghai-Tibet Plateau, with beautiful, brightly colored flowers and good ornamental properties and adaptability. In diverse natural environments, the blossom color of C. tangutica (Maxim.) Korsh. varies greatly, although it is unclear what causes this diversity. It was examined using UPLC-MS/MS and transcriptome sequencing for the investigation of various compounds, differentially expressed genes (DEGs), and flavonoid biosynthesis-related pathways in two flowers in two ecological settings. The results showed that a total of 992 metabolites were detected, of which 425 were differential metabolites, mainly flavonoid metabolites associated with its floral color. The most abundant flavonoids, flavonols and anthocyanin metabolites in the G type were cynaroside, isoquercitrin and peonidin-3-O-glucoside, respectively. Flavonoids that differed in multiplicity in G type and N type were rhoifolin, naringin, delphinidin-3-O-rutinoside, chrysoeriol and catechin. Rhoifolin and chrysoeriol, produced in flavone and flavonol biosynthesis, two flavonoid compounds of C. tangutica (Maxim.) Korsh. with the largest difference in floral composition in two ecological environments. In two ecological environments of flower color components, combined transcriptome and metabolome analyses revealed that BZ1-1 and FG3-1 are key genes for delphinidin-3-O-rutinoside in anthocyanin biosynthesis, and HCT-5 and FG3-3 are key genes for rhoifolin and naringin in flavonoid biosynthesis and flavone and flavonol. Key genes for chlorogenic acid in flavonoid biosynthesis include HCT-6, CHS-1 and IF7MAT-1. In summary, differences in flavonoids and their content are the main factors responsible for the differences in the floral color composition of C. tangutica (Maxim.) Korsh. in the two ecological environments, and are associated with differential expression of genes related to flavonoid synthesis.

Ocean acidification and warming significantly affect coastal eutrophication and organic pollution: A case study in the Bohai Sea.

Most coastal ecosystems are faced with novel challenges associated with human activities and climate change such as ocean acidification, warming, eutrophication, and organic pollution. However, data on the independent or combined effects of ocean acidification and warming on coastal eutrophication and organic pollution at present are relatively limited. Here, we applied the generalized additive models (GAMs) to explore the dynamics of coastal eutrophication and organic pollution in response to future climate change in the Bohai Sea. The GAMs reflected the fact that acidification alone favors eutrophication and organic pollution, while warming alone inhibits these two variables. Differently, the interactions between acidification and warming in the future may further exacerbate the organic pollution but may mitigate the progress of eutrophication. These different responses of eutrophication and organic pollution to acidification and warming may be attributed to algae growth and microbial respiration, as well as some physical processes such as stratification.

Comparative authentication of Semiliquidambar cathayensis and its substituted species via macroscopic and microscopic features.

Objective: Ban Fenghe recorded in the Quality Standard of Yao Medicine of Guangxi Zhuang Autonomous Region (Volume 1) is derived from the dried stems and leaves of Semiliquidambar cathayensis. It is usually confused with medicinal herbs from Pterospermum heterophyllum and Dendropanax dentiger. However, they are very different in chemical composition, and should not be used as the same drug. To ensure their safety and efficacy, a method based on macroscopic and microscopic characteristics was developed to distinguish them. Methods: A total of 14 batches of Ban Fenghe samples from three species were collected from different producing areas in China. The macroscopic characteristics were examined by observing external traits. The tissue structures of transverse sections of stems and leaves, the leaf epidermis, and the powder were observed microscopically. Results: The branchlets and leaf surfaces of S. cathayensis and P. heterophyllum were hairy, especially the lower leaf surfaces of P. heterophyllum were densely covered with hairs, but those of D. dentiger were hairless. The pericyclic fibers of S. cathayensis stems were intermittently distributed in a circular shape and accompanied by stone cells, whereas those of P. heterophyllum and D. dentiger were bundled without stone cells. So stone cells and hairs were present in S. cathayensis powder, stone cells were not found in P. heterophyllum and D. dentiger powder, and hairs were not present in D. dentiger powder. The distribution sites, sizes and types of secretory tissues of these three species were also different in transverse sections of stems and leaves. Stomata on the lower epidermis of S. cathayensis leaves were paracytic, whereas those of P. heterophyllum and D. dentiger were anomocytic. Conclusion: Ban Fenghe drugs derived from S. cathayensis could readily be distinguished from those of P. heterophyllum and D. dentiger by macroscopic and microscopic features.

Pacemaker activity and ion channels in the sinoatrial node cells: MicroRNAs and arrhythmia.

The primary pacemaking activity of the heart is determined by a spontaneous action potential (AP) within sinoatrial node (SAN) cells. This unique AP generation relies on two mechanisms: membrane clocks and calcium clocks. Nonhomologous arrhythmias are caused by several functional and structural changes in the myocardium. MicroRNAs (miRNAs) are essential regulators of gene expression in cardiomyocytes. These miRNAs play a vital role in regulating the stability of cardiac conduction and in the remodeling process that leads to arrhythmias. Although it remains unclear how miRNAs regulate the expression and function of ion channels in the heart, these regulatory mechanisms may support the development of emerging therapies. This study discusses the spread and generation of AP in the SAN as well as the regulation of miRNAs and individual ion channels. Arrhythmogenicity studies on ion channels will provide a research basis for miRNA modulation as a new therapeutic target.

Diagnostic performance of adenosine deaminase for abdominal tuberculosis: A systematic review and meta-analysis.

Background and aim: Abdominal tuberculosis (TB) is a common type of extrapulmonary TB with an insidious onset and non-specific symptoms. Adenosine deaminase (ADA) levels increase rapidly in the early stages of abdominal TB. However, it remains unclear whether ADA serves as a diagnostic marker for abdominal TB. Methods: We performed a systematic literature search for relevant articles published in PubMed, Web of Science, Cochrane Library, and Embase up to April 2022. First, we used the Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2), to evaluate the quality of the included articles. Bivariate and hierarchical summary receiver operating characteristic (HSROC) models were then utilized to analyze pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC). In addition, we explored a subgroup analysis for potential heterogeneity and publication bias among the included literature. Results: Twenty-four articles (3,044 participants, 3,044 samples) which met the eligibility criteria were included in this study. The pooled sensitivity and specificity of ADA for abdominal TB detection were 93% [95% confidence interval (CI): 0.89-0.95] and 95% (95% CI: 0.93-0.96), respectively. PLR and NLR were 18.6 (95% CI: 14.0-24.6) and 0.08 (95% CI: 0.05-0.12), respectively. DOR and AUROC were 236 (95% CI: 134-415) and 0.98 (95% CI: 0.96-0.99), respectively. Furthermore, no heterogeneity or publication bias was found. Conclusions: Our meta-analysis found ADA to be of excellent diagnostic value for abdominal TB and could be used as an auxiliary diagnostic tool. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022297931.

Association of necrotizing enterocolitis with antimicrobial exposure in preterm infants <32 weeks gestational age:A multicenter prospective case-control study.

Objective: To assess the risk of necrotizing enterocolitis (NEC) and explore the relationship between antibiotic overexposure and disease occurrence in a large prospective birth cohort. Methods: Based on a prospective birth cohort, the study collected hospitalization data of very preterm infants (VPIs) having gestational age of less than 32 weeks from January 1, 2018, to June 30, 2021 via the China Northern Neonatal Network. Infants diagnosed with NEC ≥ stage II were included in the case group, and each case was matched for GA and birth weight for the control group. Furthermore, the risk factors for NEC were determined by statistical analyses. Results: A total of 6425 VPIs were included in this study, and 167 (2.6%) of these subjects were diagnosed with NEC ≥ stage II. The study also included 984 extremely preterm infants (gestational age <28 weeks), including 50 (5.1%) infants diagnosed with NEC ≥ stage II. In the matched case-control study, subjects had a total of antibiotic days-of-therapy for 9015 days, of which broad-spectrum antibiotics (BSAs) accounted for 77%. The antibiotic spectrum index per antibiotic day in the case group was significantly higher and was an independent risk factor for the occurrence of NEC (p = 0.001, OR = 1.13). Conclusion: The cohort of VPIs was overexposed to antiboitics. Unreasonable combination of antibiotics and overexposure to BSAs may increase the risk of NEC in preterm infants.

Influences of Antithrombotic Elastic Socks Combined with Air Pressure in Reducing Lower Extremity Deep Venous Thrombosis for Patients Undergoing Cardiothoracic Surgery.

This study was designed to investigate the application and therapeutic effect of antithrombotic elastic socks combined with air pressure in the prevention of lower extremity deep venous thrombosis in patients undergoing cardiothoracic surgery. Sixty patients in cardiothoracic surgery of our hospital from January 2019 to December 2020 were randomly divided into a study group and control group. The control group was treated with routine treatment intervention. Based on routine treatment intervention, the study group was treated with antithrombotic elastic socks combined with pneumatic treatment intervention. The activated partial thromboplastin time (APTT), thrombin time (TT), femoral venous blood flow velocity of both lower limbs, and the incidence of lower extremity deep venous thrombosis (LEDVT), postoperative lower extremity swelling, inflammatory factors, and satisfaction were measured. After intervention, APTT (31.74 ± 1.15 s) and TT (14.58 ± 0.24 s) in the study group were higher than those in the control group APTT (25.13 ± 1.14 s) and TT (12.14 ± 0.23 s) (P < 0.05). The left lower limb femoral vein blood flow velocity and the right lower limb femoral vein blood flow velocity in the study group were better than those in the control group (P < 0.05). The incidence of postoperative lower limb swelling and deep vein in the study group was lower than that in the control group (P < 0.05). Serum tumor necrosis factor alpha and interleukin-6 concentrations in the study group were lower than those in the control group (P < 0.05). The satisfaction rate of patients in the study group (93.33%) was significantly higher than that in the control group (70.00%) (P < 0.05). In conclusion, after cardiothoracic surgery, antithrombotic elastic socks combined with air pressure can significantly reduce the incidence of LEDVT by improving patients' coagulation function, reducing inflammatory reaction. It is worthy of popularization and application in relevant surgery.

Pathogen Distribution and Antimicrobial Resistance of Early Onset Sepsis in Very Premature Infants: A Real-World Study.

INTRODUCTION: Early onset sepsis (EOS) remains a potentially fatal newborn condition, especially in very preterm infants. Data on the pathogen distribution and antibiotic susceptibility patterns of EOS among very preterm infants are scarce but essential for the choice of empirical antibiotic administration. We sought to assess the epidemiologic characteristics and antibiotic susceptibility patterns of pathogens causing EOS among a cohort of very preterm infants in China. METHODS: This prospective, observational study included a cohort of infants born at a gestational age (GA) less than 32 weeks of 32 newborn intensive care units (NICUs) in China between January 1, 2018 and December 31, 2020. EOS was defined by isolation of pathogenic species from blood culture within 72 h of birth. RESULTS: A total of 108 EOS cases (18.4 per 1000 admissions) were identified among 5865 very preterm infants. Incidence of EOS increased with the decrease of GA and birthweight. Escherichia coli (n = 44, 40.7%) was the most common pathogen, followed by Klebsiella spp. (n = 10, 9.3%). The distribution and proportion of pathogenic bacteria varied significantly by GA. E. coli and Klebsiella spp. showed high resistance to ampicillin and third-generation cephalosporins, while they showed good susceptibility to carbapenem antibiotics and piperacillin-tazobactam. CONCLUSION: Our data demonstrated that pathogens causing neonatal EOS showed high rates of resistance to ampicillin and third-generation cephalosporins. This raised questions about the best empirical antibiotic choice for preterm infants suspected of having EOS in low- and middle-income countries (LMICs).

Prediction Models for Osteoporotic Fractures Risk: A Systematic Review and Critical Appraisal.

Osteoporotic fractures (OF) are a global public health problem currently. Many risk prediction models for OF have been developed, but their performance and methodological quality are unclear. We conducted this systematic review to summarize and critically appraise the OF risk prediction models. Three databases were searched until April 2021. Studies developing or validating multivariable models for OF risk prediction were considered eligible. Used the prediction model risk of bias assessment tool to appraise the risk of bias and applicability of included models. All results were narratively summarized and described. A total of 68 studies describing 70 newly developed prediction models and 138 external validations were included. Most models were explicitly developed (n=31, 44%) and validated (n=76, 55%) only for female. Only 22 developed models (31%) were externally validated. The most validated tool was Fracture Risk Assessment Tool. Overall, only a few models showed outstanding (n=3, 1%) or excellent (n=32, 15%) prediction discrimination. Calibration of developed models (n=25, 36%) or external validation models (n=33, 24%) were rarely assessed. No model was rated as low risk of bias, mostly because of an insufficient number of cases and inappropriate assessment of calibration. There are a certain number of OF risk prediction models. However, few models have been thoroughly internally validated or externally validated (with calibration being unassessed for most of the models), and all models showed methodological shortcomings. Instead of developing completely new models, future research is suggested to validate, improve, and analyze the impact of existing models.

Predictive models for the incidence of Parkinson's disease: systematic review and critical appraisal.

Numerous predictive models for Parkinson's disease (PD) incidence have been published recently. However, the model performance and methodological quality of those available models are yet needed to be summarized and assessed systematically. In this systematic review, we systematically reviewed the published predictive models for PD incidence and assessed their risk of bias and applicability. Three international databases were searched. Cohort or nested case-control studies that aimed to develop or validate a predictive model for PD incidence were considered eligible. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used for risk of bias and applicability assessment. Ten studies covering 10 predictive models were included. Among them, four studies focused on model development, covering eight models, while the remaining six studies focused on model external validation, covering two models. The discrimination of the eight new development models was generally poor, with only one model reported C index > 0.70. Four out of the six external validation studies showed excellent or outstanding discrimination. All included studies had high risk of bias. Three predictive models (the International Parkinson and Movement Disorder Society [MDS] prodromal PD criteria, the model developed by Karabayir et al. and models validated by Faust et al.) are recommended for clinical application by considering model performance and resource-demanding. In conclusion, the performance and methodological quality of most of the identified predictive models for PD incidence were unsatisfactory. The MDS prodromal PD criteria, model developed by Karabayir et al. and model validated by Faust et al. may be considered for clinical use.

Biomedical polymers: synthesis, properties, and applications.

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

Characteristics and Quality of Diagnostic and Risk Prediction Models for Frailty in Older Adults: A Systematic Review.

Several prediction models for frailty in older adults have been published, but their characteristics and methodological quality are unclear. This review aims to summarize and critically appraise the prediction models. Studies describing multivariable prediction models for frailty among older adults were included. PubMed, Embase, Web of Science, and PsycINFO were searched from outset to Feb 21, 2021. Methodological and reporting quality of included models were evaluated by PROBAST and TRIPOD, respectively. All results were descriptively summarized. Twenty articles including 39 models were identified. The included models showed good predictive discrimination with C indices ranging from 0.70 to 0.98. However, all studies except one were assessed as high risk of bias mainly due to inappropriate analysis; meanwhile, poor reporting quality was also frequently observed. Few mature prediction models can be used in practice. Researchers should pay more attention to external validation and improving the quality both in methodology and reporting.

Non-contact electrical stimulation as an effective means to promote wound healing.

Electrical stimulation has been demonstrated to have beneficial effects in skin tissue repair. However, most electrical stimulations are applied with percutaneous electrode, which is prone to causing serious trauma. Using non-contact electrical stimulation (NCES) is expected to reduce the potential risk. In this study, NCES was expediently exerted by a self-designed practical device. Electrode plates of 10-cm spacing with appropriate side lengths of 21 and 30 cm were selected by EF distribution analysis for applying NCES to cells and mice, respectively, and the real EF strengths were measured. The change of loading voltage which had no effect on the regular pattern of EF distribution could be used as a single factor to explore the effect of NCES on wound healing. It was subsequently demonstrated that 53 mV mm-1 NCES facilitated the migration and proliferation of HaCaT cells and HDFs in vitro, and the M2-type polarization of macrophages. Moreover, 54 and 84 mV mm-1 NCESs accelerated the wound healing rate of model mice from the perspective of reducing scarring, enhancing collagen synthesis and increasing angiogenesis in vivo. The promoting role of NCES in wound healing showed the potential to initiate new possibilities for the clinical treatment of skin tissue injuries.