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Xiao-Fang Dong,1 Qiang Zhang,2 Jia-Ning Wei,2 Qian-Yu Zhou,3 Fan-Jia-Yi Yang,2 Yan-Jin Liu,4 Yu-Sheng Li,5 Chang-Qing Sun2,3 1Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2School of Nursing and Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Epidemiology and Biostatistics, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Chang-Qing Sun, School of Nursing and Health, Zhengzhou University, NO. 101 Kexue Road, High-Tech Development Zone of District, Zhengzhou, Henan, People’s Republic of China, Email suncq@zzu.edu.cnObjective: Our research explores how leisure-time sedentary behavior (SB) correlates with stroke risk. Additionally, we utilize the isotemporal substitution model (ISM) to examine how replacing brief durations of leisure-time SB with light physical activity (LPA), moderate physical activity (MPA), vigorous physical activity (VPA), and sleep might influence the risk of stroke.Methods: This investigation tracked 478,198 participants from the UK Biobank. Data regarding individual leisure-time SB and PA were collected through a standardized questionnaire. A Cox proportional hazards model, alongside an isotemporal substitution model (ISM), was utilized.Results: We identified 10,003 cases of incident stroke over 12.7 years. When compared to participants who engaged in leisure-time SB for less than 4 hours per day, the hazard ratios (HRs) for stroke incidence increased with more prolonged leisure-time SB: HRs were 1.06 (95% CI: 1.01 to 1.11) for 4– 6 h/d, 1.16 (95% CI: 1.10 to 1.23) for 6– 8 h/d, and 1.24 (95% CI: 1.15 to 1.33) for over 8 h/d. According to the ISM analysis, substituting leisure-time SB with various forms of PA could markedly reduce stroke risk. For individuals sleeping ≤ 8h/d, replacing one hour of leisure-time SB with an equivalent duration of LPA, VPA, or sleep corresponded to a 3.0%, 7.0%, and 22.0% decrease in stroke risk, respectively. Meanwhile, for those already sleeping more than 8h/d, substituting one hour of leisure-time SB with an equivalent duration of LPA or VPA resulted in a notable decrease in the risk of stroke by 6.0% and 18.0%, respectively.Conclusion: The findings demonstrate that leisure-time SB and unhealthy sleep durations are confirmed risk factors for stroke. For individuals sleeping 8 hours or less per day, and for those who sleep more than 8 hours, substituting SB with an adequate amount of sleep or engaging in VPA, respectively, emerges as an effective strategy for reducing stroke risk.Keywords: stroke, isotemporal substitution model, physical activity, sedentary behavior, sleep

Catherine Q Sun, Tiffany A Chen, Michael S Deiner, Yvonne Ou Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USACorrespondence: Catherine Q SunUCSF F.I. Proctor Foundation, 490 Illinois Street, Floor 2, San Francisco, CA 94143, USAEmail catherine.sun@ucsf.eduBackground: There is limited long-term data comparing selective laser trabeculoplasty (SLT) to the newer micropulse laser trabeculoplasty (MLT) using a laser emitting at 532 nm. In this study, we determine the effectiveness and safety of MLT compared to SLT.Design: Retrospective comparative cohort study.Participants: A total of 85 consecutive eyes received SLT and 43 consecutive eyes received MLT.Methods: Patients with open-angle glaucoma receiving their first treatment of laser trabeculoplasty were included. Exclusion criteria are prior laser trabeculoplasty, laser cyclophotocoagulation or glaucoma surgery, and follow-up of less than 1 year.Main Outcome Measures: The primary outcome was success at 1 year, defined as a reduction in intraocular eye pressure (IOP) by ≥ 20% from baseline or met prespecified target IOP with no additional glaucoma medication or subsequent glaucoma intervention.Results: Baseline IOP was 18.0 mmHg (95% CI=16.4– 19.5) in the MLT group on an average of 1.8 (95% CI=1.4– 2.2) glaucoma medications compared to 18.2 mmHg (95% CI=17.2– 19.3) for the SLT group on an average of 2.0 (95% CI=1.6– 2.3) medications. At 1-hour post-laser, the SLT group had more transient IOP spikes (MLT 5% vs SLT 16%, P=0.10). There was a trend toward increased success in the SLT group compared to MLT at 1 year (relative risk=1.4, 95% CI=0.8– 2.5, P=0.30).Conclusion and Relevance: Eyes had similar success after MLT compared to SLT at 1 year. Laser trabeculoplasty with either method could be offered as treatment with consideration of MLT in those eyes where IOP spikes should be avoided.Keywords: micropulse laser trabeculoplasty, selective laser trabeculoplasty, open-angle glaucoma

Hepatocellular carcinoma (HCC) progression is facilitated by gene-silencing chromatin histone hypoacetylation due to histone deacetylase (HDAC) activation. However, inhibiting HDACs-an effective treatment for lymphomas-has shown limited success in solid tumors. We report the discovery of a class of HDAC inhibitors (HDACi) that demonstrates exquisite selective cytotoxicity against human HCC cells. The lead compound STR-V-53 ( 3 ) showed a favorable safety profile in mice and robustly suppressed tumor growth in orthotopic xenograft models of HCC. When combined with the anti-HCC drug sorafenib, STR-V-53 , showed greater in vivo efficacy. Moreover, STR-V-53 combined with anti-PD1 therapy increased the CD8 + to regulatory T-cell (Treg) ratio and survival in an orthotopic HCC model in immunocompetent mice. This combination therapy resulted in durable responses in 40% of the mice. Transcriptomic analysis revealed that STR-V-53 primed HCC cells to immunotherapy through HDAC inhibition, impaired glucose-regulated transcription, impaired DNA synthesis, upregulated apoptosis, and stimulated the immune response pathway. Collectively, our data demonstrate that the novel HDACi STR-V-53 is an effective anti-HCC agent that can induce profound responses when combined with standard immunotherapy., Competing Interests: The authors declare the following competing financial interest(s): Conflicts of Interest: A.K.O. is the founder of Sophia Bioscience, Inc. S.T. is the PI on 1R43CA224642, an NIH/NCI SBIR grant that funded part of this study at Sophia Bioscience, Inc. D.A.G. is interim CEO of Sophia Bioscience, Inc. J.A.P. is the sub-contract PI on 1R43CA224642. A.K.O. received consultant fees from Sophia Bioscience while D.G.D. received consultant fees from Innocoll Pharmaceuticals and research grants from Exelixis, Bayer, BMS, and Surface Oncology., (© 2024 The Authors. Published by American Chemical Society.)

Objective/purpose: Standardization of eye care data is important for clinical interoperability and research. We aimed to address gaps in the representations of glaucoma examination concepts within Systemized Nomenclature of Medicine - Clinical Terms (SNOMED-CT), the preferred terminology of the American Academy of Ophthalmology., Design: Study of data elements., Methods: Structured eye examination data fields from 2 electronic health records (EHR) systems (Epic Systems and Medisoft) were compared against existing SNOMED-CT codes for concepts representing glaucoma examination findings. Glaucoma specialists from multiple institutions were surveyed to identify high-priority gaps in representation, which were discussed among the SNOMED International Eye Care Clinical Reference Group. Proposals for new codes to address the gaps were formulated and submitted for inclusion in SNOMED-CT., Main Outcome Measures: Gaps in SNOMED-CT glaucoma examination concept representations., Results: We identified several gaps in SNOMED-CT regarding glaucoma examination concepts. A survey of glaucoma specialists identified high-priority data elements within the categories of tonometry and gonioscopy. For tonometry, there was consensus that we need to define new codes related to maximum intraocular pressure (IOP) and target IOP and delineate all methods of measuring IOP. These new codes were proposed and successfully added to SNOMED-CT for future use. Regarding gonioscopy, the current terminology did not include the ability to denote the gonioscopic grading system used (e.g., Shaffer or Spaeth), degree of angle pigmentation, iris configuration (except for plateau iris), and iris approach. There was also no ability to specify eye laterality or angle quadrant for gonioscopic findings. We proposed a framework for representing gonioscopic findings as observable entities in SNOMED-CT., Conclusion: There are existing gaps in the standardized representation of findings related to tonometry and gonioscopy within SNOMED-CT. These are important areas for evaluating clinical outcomes and enabling secondary use of EHR data for glaucoma research. This international multi-institutional collaborative process enabled identification of gaps, prioritization, and development of data standards to address these gaps. Addressing these gaps and augmenting SNOMED-CT coverage of glaucoma examination findings could enhance clinical documentation and future research efforts related to glaucoma., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024. Published by Elsevier Inc.)

Purpose To compare the quality of optic nerve photographs from three different handheld fundus cameras and to assess the reproducibility and agreement of vertical cup-to-disk ratio (VCDR) measurements from each camera. Methods Adult patients from a comprehensive ophthalmology clinic and an intravitreous injection clinic in northern Thailand were recruited for this cross-sectional study. Each participant had optic nerve photography performed with each of 3 handheld cameras: the Volk iNview, Volk Pictor Plus, and Peek Retina. Images were graded for VCDR in a masked fashion by two photo-graders and images with > 0.2 discrepancy in VCDR were assessed by a third photo-grader. Results A total of 355 eyes underwent imaging with three different handheld fundus cameras. Optic nerve images were judged ungradable in 130 (37%) eyes imaged with Peek Retina, compared to 36 (10%) and 55 (15%) eyes imaged with the iNview and Pictor Plus, respectively. For 193 eyes with gradable images from all 3 cameras, inter-rater reliability for VCDR measurements was poor or moderate for each of the cameras, with intraclass correlation coefficients ranging from 0.41 to 0.52. A VCDR ≥ 0.6 was found in 6 eyes on iNview images, 9 eyes on Pictor Plus images, and 3 eyes on Peek images, with poor agreement between cameras (e.g., no eyes graded as VCDR ≥ 0.6 on images from both the iNview and Pictor Plus). Conclusions Inter-rater reliability of VCDR grades from 3 handheld cameras was poor. Cameras did not agree on which eyes had large VCDRs.

Background: Japanese encephalitis (JE) is a serious health concern in China, with approximately 80 % of global infections occurring in China. To develop effective prevention and control strategies, this study explored the epidemiological characteristics of JE in China based on spatiotemporal data, to understand the patterns and trends of JE incidence in different regions and time periods., Method: The incidence and mortality rates of JE were extracted from the Public Health Data Center, the official website of the National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System from 2004 to 2019. Joinpoint regression was applied to examine the spatiotemporal patterns and annual percentage change in incidence and mortality of the JE., Results: From 2004 to 2019, a total of 43,569 cases of JE were diagnosed, including 2081 deaths. The annual incidence rate of JE decreased from 0.4171/100,000 in 2004 to 0.0298/100,000 in 2019, with an annual percentage change (APC) of -13.5 % (P < 0.001). The annual mortality rate of JE showed three stages of change, with inflection points in 2006 and 2014. The incidence and mortality rates of JE have declined in all provinces of China, and more cases were reported in 0-14 years of age, accounting for nearly 80 % of all patients., Conclusions: The morbidity and mortality rates of JE in China are generally on a downward trend, and emphasis should be placed on strengthening disease surveillance in special areas and populations, popularizing vaccination, and increasing publicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Electronic health records (EHRs) contain a vast amount of clinical data. Improved automated classification approaches have the potential to accurately and efficiently identify patient cohorts for research. We evaluated if a rule-based natural language processing (NLP) algorithm using clinical notes performed better for classifying proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) severity compared with International Classification of Diseases, ninth edition (ICD-9) or 10th edition (ICD-10) codes., Design: Cross-sectional study., Subjects: Deidentified EHR data from an academic medical center identified 2366 patients aged ≥18 years, with diabetes mellitus, diabetic retinopathy (DR), and available clinical notes., Methods: From these 2366 patients, 306 random patients (100 training set, 206 test set) underwent chart review by ophthalmologists to establish the gold standard. International Classification of Diseases codes were extracted from the EHR. The notes algorithm identified positive mention of PDR and NPDR severity from clinical notes. Proliferative diabetic retinopathy and NPDR severity classification by ICD codes and the notes algorithm were compared with the gold standard. The entire DR cohort (N = 2366) was then classified as having presence (or absence) of PDR using ICD codes and the notes algorithm., Main Outcome Measures: Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and F1 score for the notes algorithm compared with ICD codes using a gold standard of chart review., Results: For PDR classification of the test set patients, the notes algorithm performed better than ICD codes for all metrics. Specifically, the notes algorithm had significantly higher sensitivity (90.5% [95% confidence interval 85.7, 94.9] vs. 68.4% [60.4, 75.3]), but similar PPV (98.0% [95.4-100] vs. 94.7% [90.3, 98.3]) respectively. The F1 score was 0.941 [0.910, 0.966] for the notes algorithm compared with 0.794 [0.734, 0.842] for ICD codes. For PDR classification, ICD-10 codes performed better than ICD-9 codes (F1 score 0.836 [0.771, 0.878] vs. 0.596 [0.222, 0.692]). For NPDR severity classification, the notes algorithm performed similarly to ICD codes, but performance was limited by small sample size., Conclusions: The notes algorithm outperformed ICD codes for PDR classification. The findings demonstrate the significant potential of applying a rule-based NLP algorithm to clinical notes to increase the efficiency and accuracy of cohort selection for research., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management., (© 2023 Royal Entomological Society.)

Electron delocalization has an important impact on the physical properties of condensed materials. However, the L-electron delocalization in inorganic, especially nitrogen, compounds needs exploitation to improve the energy efficiency, safety, and environmental sustainability of high-energy-density materials (HEDMs). This Letter presents an intriguing N 8 molecule, ingeniously utilizing nitrogen's L-electron delocalization. The molecule, exhibiting a unique lollipop-shaped conformation, can fold at various angles with very low energy barriers, self-assembling into environmentally stable, all-nitrogen crystals. These crystals demonstrate unparalleled stability, high energy density, low mechanical sensitivity, and optimal electronic thermal conductivity, outperforming existing HEDMs. The remarkable properties of these designed materials are attributed to two distinct delocalized systems within nitrogen's L-shell: π- and lone pair σ-electrons, which not only stabilize the molecular structure but also facilitate interconnected 3D networks of intermolecular nonbonding interactions. This work might pave the way to the experimental synthesis of environmentally stable all-nitrogen solids.

Purpose: Use of the electronic health record (EHR) has motivated the need for data standardization. A gap in knowledge exists regarding variations in existing terminologies for defining diabetic retinopathy (DR) cohorts. This study aimed to review the literature and analyze variations regarding codified definitions of DR., Design: Literature review and quantitative analysis., Subjects: Published manuscripts., Methods: Four graders reviewed PubMed and Google Scholar for peer-reviewed studies. Studies were included if they used codified definitions of DR (e.g., billing codes). Data elements such as author names, publication year, purpose, data set type, and DR definitions were manually extracted. Each study was reviewed by ≥ 2 authors to validate inclusion eligibility. Quantitative analyses of the codified definitions were then performed to characterize the variation between DR cohort definitions., Main Outcome Measures: Number of studies included and numeric counts of billing codes used to define codified cohorts., Results: In total, 43 studies met the inclusion criteria. Half of the included studies used datasets based on structured EHR data (i.e., data registries, institutional EHR review), and half used claims data. All but 1 of the studies used billing codes such as the International Classification of Diseases 9th or 10th edition (ICD-9 or ICD-10), either alone or in addition to another terminology for defining disease. Of the 27 included studies that used ICD-9 and the 20 studies that used ICD-10 codes, the most common codes used pertained to the full spectrum of DR severity. Diabetic retinopathy complications (e.g., vitreous hemorrhage) were also used to define some DR cohorts., Conclusions: Substantial variations exist among codified definitions for DR cohorts within retrospective studies. Variable definitions may limit generalizability and reproducibility of retrospective studies. More work is needed to standardize disease cohorts., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Objective: To determine if baseline diabetic retinopathy (DR) severity mediates the relationship between health insurance status and DR progression., Design: Retrospective cohort study., Subjects: Seven hundred sixteen patients aged ≥ 18 years with a diagnosis of type 1 or 2 diabetes mellitus, and a diagnosis of nonproliferative DR (NPDR) were identified from the electronic health record of a tertiary academic center between June 2012 and February 2022., Methods: NPDR severity at baseline was the proposed mediator in the relationship between insurance status and proliferative DR (PDR) progression. Logistic regression was used to determine the association between insurance status and NPDR severity at baseline, and Cox proportional hazards regression was used to assess the association between insurance status and time to PDR progression. To analyze the mediation effect of NPDR severity at baseline, a counterfactual approach, which decomposes a total effect into a natural direct effect and a natural indirect effect was applied., Main Outcome Measures: Time to progression from first NPDR diagnosis to first PDR diagnosis., Results: Of the 716 patients, 581 (81%) had Medicare or private insurance, 107 (15%) had Medicaid, and 28 (4.0%) were uninsured at their baseline eye visit. Uninsured or Medicaid patients had a higher proportion of moderate or severe NPDR at their baseline eye visit and a higher proportion of progression to PDR. After adjusting for confounders and NPDR severity at baseline, patients who were uninsured had significantly greater risk of progression to PDR compared with that of patients with Medicare/private insurance (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.10-6.25). Patients with Medicaid also had an increased risk of progression to PDR compared with that of patients with Medicare/private insurance, although not statistically significant (HR: 1.53; 95% CI: 0.81-2.89). NPDR severity at baseline mediated 41% of the effect of insurance status (uninsured vs. Medicare/private insurance) on PDR progression., Conclusions: Patients who were uninsured were more likely to have an advanced stage of NPDR at their baseline eye visit and were at significantly greater risk of progression to PDR compared with patients who had Medicare or were privately insured. Mediation analysis revealed that differences in baseline NPDR severity by insurance explained a significant proportion of the relationship between insurance status and DR progression., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To describe 1-year secondary outcomes in the Tube Versus Trabeculectomy IRIS® (Intelligent Registry In Sight) Registry Study (TVT IRIS ), and to compare to the TVT randomized controlled trial (TVT RCT )., Design: TVT IRIS was a retrospective cohort study., Methods: The 2013-2017 IRIS Registry was used to identify eyes that received a tube shunt (tube) or trabeculectomy after a previous trabeculectomy and/or cataract surgery and had 1 year of follow-up. The TVT RCT compared a Baerveldt 350-mm 2 glaucoma implant to trabeculectomy in similar eyes., Results: In the TVT IRIS cohort, the tube (n = 236, 56.3%) and trabeculectomy (n = 183, 43.7%) groups had similar and significant reductions in intraocular pressure (IOP) from baseline to 1 year. In the tube group, IOP (mean ± SD) decreased from 26.6 ± 6.5 mm Hg at baseline to 14.3 ± 4.8 mm Hg at 1 year. In the trabeculectomy group, IOP decreased from 25.3 ± 6.4 mm Hg at baseline to 13.5 ± 5.2 mm Hg at 1 year. The trabeculectomy groups from both studies had similar 1-year IOP reduction (P = .18), although the TVT RCT cohort used fewer medications at all time points (P < .01). There were more pronounced differences in the mean IOP and medications between the tube groups in the 2 studies, presumably due to the inclusion of valved tubes in TVT IRIS . More reoperations occurred in TVT IRIS ., Conclusions: The TVT IRIS tube and trabeculectomy groups had comparable 1-year IOP reduction, although trabeculectomy eyes used fewer glaucoma medications. The trabeculectomy group in TVT IRIS and TVT RCT had similar IOP and medication reduction at 1 year. Randomized controlled trials and electronic health record data both provide invaluable insight into surgical outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study evaluated the clinical effectiveness of Ruyi Zhenbao Pills in the treatment of osteoarthritis, aiming to clarify its clinical advantages and promote rational drug use and related policy transformation. Following the relevant standards in Guidelines for the Comprehensive Evaluation of Drugs in Clinical Practice and Technical Specifications for the Clinical Comprehensive Evaluation of Chinese Patent Medicine, comprehensive research and related data on Ruyi Zhenbao Pills in the treatment of osteoarthritis were collected in the dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and traditional Chinese medicine(TCM) cha-racteristics(referred to as the &quot;6+1&quot; dimensions). Through evidence-based medicine, questionnaire surveys, health technology assessment, pharmacoeconomic evaluation, and other methods, a multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Ruyi Zhenbao Pills. Spontaneous reporting system data on adverse reactions and literature data indicate that the adverse reactions of Ruyi Zhenbao Pills are mostly general adverse reactions, with no reports of se-rious adverse reactions. The known risks are small, and its safety is rated as class A. It has been shown to effectively relieve joint pain and restore joint function in the treatment of osteoarthritis. However, more high-quality, large-sample randomized controlled trials are needed to further validate its effectiveness, which is rated as class B. There is evidence supporting its economic viability, and its economic is rated as class B. It demonstrates good clinical innovation, innovative enterprise service system, and industrial innovation, and innovation is rated as class A. Medical professionals and patients have a favorable perception of the suitability of Ruyi Zhenbao Pills, and further improvement can be made in terms of convenience of administration and promotion to facilitate rational drug use by healthcare professionals and patients. Suitability is rated as class B. The drug has a favorable price level, availability, and affordability, and accessibility is rated as class A. Ruyi Zhenbao Pills are a classic Tibetan medicinal prescription with excellent TCM theoretical characteristics. However, further research is needed on its use in human studies. TCM characteristics are rated as class B. Based on the evaluation results of the &quot;6+1&quot; dimensions, the comprehensive clinical evaluation is rated as grade B. Ruyi Zhenbao Pills have good clinical value in the treatment of osteoarthritis, and it is recommended to undergo the necessary procedures for conditional transformation into a policy for the management of essential clinical drugs.

Molecular interactions in energetic materials form the key not only to the "structure stability, energy storage, ignition, and detonation" dynamics but also to the sensitivity to the loading of perturbation and the power intensity of radiation for the energetic substance, with the nature of the interactions remaining elusive. With the aid of perturbative Raman spectroscopy and the pressure-resolved density functional theory, we uncovered that the H-N bond of the intermolecular O:H-N bonds for LLM-105 shares the same negative compressibility and thermal expansivity of the H-O bond for the coupling O:H-O bond of water [ Phys. Rep. 2023 , 998, 1-68]. In contrast, the dangling H-N bond vibrating at a 3440 cm -1 high frequency does otherwise due to the absence of coupling interaction and the undercoordination-driven bond contraction. These findings should deepen our insight into interactions involving electron lone pairs and offer an efficient means for discriminating the performance of individual bonds.

A large number of transcriptome studies generate important data and information for the study of pathogenic mechanisms of pathogens, including Vibrio cholerae. V. cholerae transcriptome data include RNA-seq and microarray: microarray data mainly include clinical human and environmental samples, and RNA-seq data mainly focus on laboratory processing conditions, including different stresses and experimental animals in vivo . In this study, we integrated the data sets of both platforms using Rank-in and the Limma R package normalized Between Arrays function, achieving the first cross-platform transcriptome data integration of V. cholerae. By integrating the entire transcriptome data, we obtained the profiles of the most active or silent genes. By transferring the integrated expression profiles into the weighted correlation network analysis (WGCNA) pipeline, we identified the important functional modules of V. cholerae in vitro stress treatment, gene manipulation, and in vitro culture as DNA transposon, chemotaxis and signaling, signal transduction, and secondary metabolic pathways, respectively. The analysis of functional module hub genes revealed the uniqueness of clinical human samples; however, under specific expression patterning, the Δ hns , Δ oxyR1 strains, and tobramycin treatment group showed high expression profile similarity with human samples. By constructing a protein-protein interaction (PPI) interaction network, we discovered several unreported novel protein interactions within transposon functional modules. IMPORTANCE We used two techniques to integrate RNA-seq data for laboratory studies with clinical microarray data for the first time. The interactions between V. cholerae genes were obtained from a global perspective, as well as comparing the similarity between clinical human samples and the current experimental conditions, and uncovering the functional modules that play a major role under different conditions. We believe that this data integration can provide us with some insight and basis for elucidating the pathogenesis and clinical control of V. cholerae., Competing Interests: The authors declare no conflict of interest.

To meet the demand for novel pest management strategies to combat the development of insecticide resistance, plant essential oils may be a promising alternative source. This study investigated the insecticidal activity of five essential oils from the Rutaceae plant family against Thrips flavus Schrank (Thysanoptera: Thripidae) under laboratory conditions. The plant essential oils were citrus oil ( Citrus reticulata Blanco), Chuan-shan pepper oil ( Zanthoxylum piasezkii Maxim.), zanthoxylum oil ( Zanthoxylum bungeanum Maxim.), pomelo peel oil ( Citrus maxima (Burm.) Merr.) and orange leaf oil ( Citrus sinensis (L.) Osbeck). Among the essential oils evaluated, orange leaf oil (LC 50 = 0.26 g/L), zanthoxylum oil (LC 50 = 0.27 g/L), and pomelo peel oil (LC 50 = 0.44 g/L) resulted in a higher gastric toxicity under laboratory conditions. The results of the pot experiment also showed that orange leaf oil (93.06 ± 3.67% at 540.00 g a.i.·hm -2 , 97.22 ± 1.39% at 720 g a.i.·hm -2 , 100.00% at 900.00 g a.i.·hm -2 ) zanthoxylum oil (98.73 ± 1.27% at 900 g a.i.·hm -2 ), and pomelo peel oil (100.00% at 900 g a.i.·hm -2 ) exhibited a higher control efficacy, being the most effective against T. flavus after 7 days of treatment. The essential oil components were then identified by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of orange leaf oil, pomelo peel oil, and zanthoxylum oil could be attributed to their main constituents, such as methyl jasmonate (50.92%), D-limonene (76.96%), and linalool (52.32%), respectively. In the olfactory test, adult T. flavus were attracted by zanthoxylum oil and Chuan-shan pepper oil. We speculated that linalool might be the key signaling compound that attracts T. flavus . These results showed that orange leaf oil, zanthoxylum oil, and pomelo peel oil exhibited insecticidal activities under controlled conditions. They can be implemented as effective and low-toxicity botanical insecticides and synergistic agents against T. flavus .

Purpose: To develop models for progression of nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and determine if incorporating updated information improves model performance., Design: Retrospective cohort study., Participants: Electronic health record (EHR) data from a tertiary academic center, University of California San Francisco (UCSF), and a safety-net hospital, Zuckerberg San Francisco General (ZSFG) Hospital were used to identify patients with a diagnosis of NPDR, age ≥ 18 years, a diagnosis of type 1 or 2 diabetes mellitus, ≥ 6 months of ophthalmology follow-up, and no prior diagnosis of PDR before the index date (date of first NPDR diagnosis in the EHR)., Methods: Four survival models were developed: Cox proportional hazards, Cox with backward selection, Cox with LASSO regression and Random Survival Forest. For each model, three variable sets were compared to determine the impact of including updated clinical information: Static 0 (data up to the index date), Static 6m (data updated 6 months after the index date), and Dynamic (data in Static 0 plus data change during the 6-month period). The UCSF data were split into 80% training and 20% testing (internal validation). The ZSFG data were used for external validation. Model performance was evaluated by the Harrell's concordance index (C-Index)., Main Outcome Measures: Time to PDR., Results: The UCSF cohort included 1130 patients and 92 (8.1%) patients progressed to PDR. The ZSFG cohort included 687 patients and 30 (4.4%) patients progressed to PDR. All models performed similarly (C-indices ∼ 0.70) in internal validation. The random survival forest with Static 6m set performed best in external validation (C-index 0.76). Insurance and age were selected or ranked as highly important by all models. Other key predictors were NPDR severity, diabetic neuropathy, number of strokes, mean Hemoglobin A1c, and number of hospital admissions., Conclusions: Our models for progression of NPDR to PDR achieved acceptable predictive performance and validated well in an external setting. Updating the baseline variables with new clinical information did not consistently improve the predictive performance., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2023 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

Importance: Telehealth in ophthalmology has traditionally focused on preventive disease screening with limited use in outpatient evaluation. The unique conditions of the COVID-19 pandemic afforded the opportunity to evaluate different implementations of teleophthalmology at scale, providing insight into expanding teleophthalmology care., Objective: To compare telehealth use in ophthalmology with other specialties and assess the feasibility of augmenting ophthalmic telehealth encounters with asynchronous testing during the COVID-19 pandemic., Design, Setting, and Participants: This quality improvement study evaluated retrospective, longitudinal, observational data from the first 18 months of the COVID-19 pandemic (January 1, 2020, through July 31, 2021) for 881 080 patients receiving care from outpatient primary care, cardiology, neurology, gastroenterology, surgery, neurosurgery, urology, orthopedic surgery, otolaryngology, obstetrics/gynecology, and ophthalmology clinics of the University of California, San Francisco. Asynchronous testing was evaluated for teleophthalmology encounters., Interventions: A hybrid care model wherein ophthalmic testing data were acquired asynchronously and used to augment telehealth encounters., Main Outcomes and Measures: Telehealth as a percentage of total volume of ambulatory care and use of asynchronous testing for ophthalmic conditions., Results: The volume of in-person outpatient visits dropped by 83.3% (39 488 of 47 390) across the evaluated specialties at the onset of shelter-in-place orders for the COVID-19 pandemic, and the initial use of telehealth increased for these specialties before stabilizing over the 18-month study period. In ophthalmology, telehealth use peaked at 488 of 1575 encounters (31.0%) early in the pandemic and returned to mostly in-person visits as COVID-19 restrictions lifted. Elective use of telehealth was highest in gastroenterology, urology, neurology, and neurosurgery and lowest in ophthalmology. Asynchronous testing was combined with 126 teleophthalmology encounters, resulting in change of clinical management for 32 patients (25.4%) and no change for 91 (72.2%)., Conclusions and Relevance: Telehealth increased across various specialties during the COVID-19 pandemic. Combining teleophthalmic visits with asynchronous testing suggested that this approach is feasible for subspecialty-level evaluation. Additional study is needed to evaluate whether asynchronous testing outside the same institution could provide an effective and lasting approach for expanding the reach of ophthalmic telehealth.

Perturbation Raman spectroscopy has underscored the hydrogen bond (O:H-O or HB) cooperativity and polarizability (HBCP) for water, which offers a proper parameter space for the performance of the HB and electrons in the energy-space-time domains. The OO repulsive coupling drives the O:H-O segmental length and energy to relax cooperatively upon perturbation. Mechanical compression shortens and stiffens the O:H nonbond while lengthens and softens the HO bond associated with polarization. However, electrification by an electric field or charge injection, or molecular undercoordination at a surface, relaxes the O:H-O in a contrasting way to the compression with derivation of the supersolid phase that is viscoelastic, less dense, thermally diffusive, and mechanically and thermally more stable. The HO bond exhibits negative thermal expansivity in the liquid and the ice-I phase while its length responds in proportional to temperature in the quasisolid phase. The O:H-O relaxation modifies the mass densities, phase boundaries, critical temperatures and the polarization endows the slipperiness of ice and superfluidity of water at the nanometer scale. Protons injection by acid solvation creates the H↔H anti-HB and introduction of electron lone pairs derives the O:⇔:O super-HB into the solutions of base or H 2 O 2 hydrogen-peroxide. The repulsive H↔H and O:⇔:O interactions lengthen the solvent HO bond while the solute HO bond contracts because its bond order loss. Differential phonon spectroscopy quantifies the abundance, structure order, and stiffness of the bonds transiting from the mode of pristine water to the perturbed states. The HBCP and the perturbative spectroscopy have enabled the dynamic potentials for the relaxing O:H-O bond. Findings not only amplified the power of the Raman spectroscopy but also substantiated the understanding of anomalies of water subjecting to perturbation., Competing Interests: Declaration of Competing Interest No conflicting interest is declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The objective of this study was to compare the sensitivity and specificity of handheld fundus cameras in detecting diabetic retinopathy (DR), diabetic macular edema (DME), and macular degeneration. Participants in the study, conducted at Maharaj Nakorn Hospital in Northern Thailand between September 2018 and May 2019, underwent an ophthalmologist examination as well as mydriatic fundus photography with three handheld fundus cameras (iNview, Peek Retina, Pictor Plus). Photographs were graded and adjudicated by masked ophthalmologists. Outcome measures included the sensitivity and specificity of each fundus camera for detecting DR, DME, and macular degeneration, relative to ophthalmologist examination. Fundus photographs of 355 eyes from 185 participants were captured with each of the three retinal cameras. Of the 355 eyes, 102 had DR, 71 had DME, and 89 had macular degeneration on ophthalmologist examination. The Pictor Plus was the most sensitive camera for each of the diseases (73-77%) and also achieved relatively high specificity (77-91%). The Peek Retina was the most specific (96-99%), although in part due to its low sensitivity (6-18%). The iNview had slightly lower estimates of sensitivity (55-72%) and specificity (86-90%) compared to the Pictor Plus. These findings demonstrated that the handheld cameras achieved high specificity but variable sensitivities in detecting DR, DME, and macular degeneration. The Pictor Plus, iNview, and Peek Retina would have distinct advantages and disadvantages when applied for utilization in tele-ophthalmology retinal screening programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, the critical quality attributes of Wuzhuyu Decoction reference sample were explored by using characteristic chromatogram, index component content and dry extract rate as indexes.The dissemination relationship of quantity value between medicinal materials-decoction pieces-reference sample was investigated to preliminarily formulate the quality standard of the reference sample.The characteristic chromatogram of 15 batches of Wuzhuyu Decoction was established by high performance liquid chromatography(HPLC) and the similarity analysis was conducted.Common peaks were demarcated and assigned to medicinal materials.Moreover, quantitative determination of limonin, evodiamine, rutaecarpine and ginsenoside Rb&#95;1 of Wuzhuyu Decoction were performed.The dissemination of quantity value was explored combined with dry extract rate, similarity of characteristic chromatogram and transfer rate of index component content.A total of 18 common peaks were identified in the corresponding materials of Wuzhuyu Decoction reference sample, with the similarity of characteristic chromatogram greater than 0.9, and Fructus Evodiae, Radix Ginseng, Rhizoma Zingiberis Recens and Fructus Jujubae contributed 9, 5, 8 and 2 chromatographic peaks, respectively.The index component content of corresponding materials and the transfer rates of medicinal materials-decoction pieces and decoction pieces-reference sample of different batches of Wuzhuyu Decoction reference sample were as follows: the content of limonin was 0.16%-0.51%, and the transfer rates were 83.66%-115.60% and 38.54%-54.58%, respectively; the content of evodiamine was 0.01%-0.11%, the transfer rated were 80.80%-116.15% and 3.23%-12.93%, respectively; the content of rutaecarpine was 0.01%-0.05%, the transfer rates were 84.33%-134.53% and 5.72%-21.24%, respectively; the content of ginsenoside Rb&#95;1 was 0.06%-0.11%, and the transfer rates were 90.00%-96.92% and 32.45%-67.24%, respectively.The dry extract rate of the whole prescription was 22.58%-29.89%.In this experiment, the dissemination of quantity value of Wuzhuyu Decoction reference sample was analyzed by the combination of characteristic chromatogram, index component content and dry extract rate.A scientific and stable quality evaluation method of the reference sample was preliminarily established, which provided basis for the subsequent development of Wuzhuyu Decoction and the quality control of related preparations.

In this study, the effect of corn oligopeptides (COPs) with liver protection activity on mice with hepatic fibrosis (HF) induced by carbon tetrachloride (CCl 4 ) was studied. It was proved that COPs can ameliorate the liver injury and inflammation caused by CCl 4 by histopathology and enzyme-linked immunosorbent assay in mice. The expression of Akt/NF-κB inflammatory pathway was determined by real-time polymerase chain reaction (RT-PCR) and western blotting (WB). The results showed that COPs inhibited the expression of key proteins in the inflammatory pathway. In conclusion, the results of this study suggested that COPs could improve CCl 4 -induced HF by improving liver injury, reducing the expression of inflammatory factors, and inhibiting the expression of inflammatory signaling pathways. PRACTICAL APPLICATIONS: The corns around the world are mainly used as animal feed, and the liver protective activity of corn oligopeptides (COPs) is rarely applied to the market. The development of COPs liver protective food can prevent the occurrence of liver-related diseases such as hepatic fibrosis to a certain extent. Developing COPs liver protecting food can improve the utilization value of corn. It is hoped that this study can provide experimental support for the application of COPs in liver protection food., (© 2022 Wiley Periodicals LLC.)

Background: Obesity is a complex, multifactorial condition in which genetic play an important role. Most of the systematic studies currently focuses on individual omics aspect and provide insightful yet limited knowledge about the comprehensive and complex crosstalk between various omics levels., Subjects and Methods: Therefore, we performed a most comprehensive trans-omics study with various omics data from 104 subjects, to identify interactions/networks and particularly causal regulatory relationships within and especially those between omic molecules with the purpose to discover molecular genetic mechanisms underlying obesity etiology in vivo in humans., Results: By applying differentially analysis, we identified 8 differentially expressed hub genes (DEHGs), 14 differentially methylated regions (DMRs) and 12 differentially accumulated metabolites (DAMs) for obesity individually. By integrating those multi-omics biomarkers using Mendelian Randomization (MR) and network MR analyses, we identified 18 causal pathways with mediation effect. For the 20 biomarkers involved in those 18 pairs, 17 biomarkers were implicated in the pathophysiology of obesity or related diseases., Conclusions: The integration of trans-omics and MR analyses may provide us a holistic understanding of the underlying functional mechanisms, molecular regulatory information flow and the interactive molecular systems among different omic molecules for obesity risk and other complex diseases/traits., (© 2022. The Author(s).)

Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans . In this study, C18 shows antifungal activity against C. albicans or non- albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 μg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC value of 8 or 16 μg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans , which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 10 7 to 5.62 × 10 4 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca 2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca 2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Peng, Yang, Jiao, Zhou, Tao, Zhu, Tian, Huang and Guo.)

Candida albicans is the most common human fungal pathogen in immunocompromised individuals. With the emergence of clinical fungal resistance, there is an urgent need to develop novel antifungal agents. AMP-17, a novel antimicrobial peptide from Musca domestica, has an antifungal effect against C. albicans, but its mechanism of antifungal action remains unclear. In the current study, we performed a proteomics analysis in C. albicans using TMT technique under the treatment of AMP-17. A total of 3931 proteins were identified, of which 3600 included quantitative information. With a 1.5-fold change threshold and a t-test p-value < 0.05 as standard, 423 differentially expressed proteins (DEPs) were up-regulated and 180 DEPs were down-regulated in the AMP-17/control. Notably, GO enrichment revealed that DEPs associated with the cell wall, RNA and oxidative stress were significantly up-regulated, while DEPs involved in ergosterol metabolism and membrane were significantly down-regulated in the AMP-17/control. KEGG pathway enrichment revealed that DEPs involved seven significant metabolic pathways, mainly involved oxidative phosphorylation, RNA degradation, propanoate metabolism and fatty acid metabolism. These results show that AMP-17 induces a complex organism response in C. albicans, indicating that AMP-17 may inhibit growth by affecting multiple targets in C. albicans cells. SIGNIFICANCE: Antimicrobial peptides (AMPs) are an important part of the innate immune system of organisms and having broad range of activity against fungi, bacteria and viruses. These AMPs are considered as probable candidate for forthcoming drugs, due to their broad range of activity, lesser toxicity and decreased resistance development by target cells. AMP-17, a novel antimicrobial peptide from M. domestica, has significant antifungal activity against C. albicans. It has been confirmed that AMP-17 can play an antifungal effect by destroying the cell wall and cell membrane of C. albicans in previous studies, but its mechanism of action at the protein level is currently unclear. In the current study, using the TMT-based quantitative proteomics method, 603 differentially expressed proteins were identified in the cells of C. albicans treated with AMP-17 for 12 h, and these DEPs were closely related to cell wall, cell membrane, RNA degradation and oxidative stress. The results provide new insights into the potential mechanism of action of AMP- 17 against C. albicans. Meanwhile, it provides certain technical support and theoretical basis for the research and development of novel peptide drugs., (Copyright © 2021. Published by Elsevier B.V.)

Background: The authors sought to evaluate visual outcomes in patients with varying etiologies of neovascular glaucoma (NVG), who were treated with glaucoma drainage devices (GDD)., Methods: This was a retrospective case series of patients at a large academic teaching institution who had surgical intervention for neovascular glaucoma between September 2011 and May 2019. Eyes were included if there was documented neovascularization of the iris/angle with an intraocular pressure (IOP) > 21 mmHg at presentation. Eyes must also have been treated with surgical intervention that included a GDD. Primary outcome measure was visual acuity at the 1-year post-operative visit. Secondary outcome measure was qualified success after surgery defined by: pressure criteria (5 mmHg < IOP ≤ 21 mmHg), no re-operation for elevated IOP, and no loss of LP vision., Results: One hundred twenty eyes met inclusion criteria. 61.7% had an etiology of proliferative diabetic retinopathy (PDR), 23.3% had retinal vein occlusions (RVO), and the remaining 15.0% suffered from other etiologies. Of patients treated with GDD, eyes with PDR had better vision compared to eyes with RVO at final evaluation (p = 0.041). There was a statistically significant difference (p = 0.027) in the mean number of glaucoma medications with Ahmed eyes (n = 70) requiring 1.9 medications and Baerveldt eyes (n = 46) requiring 1.3 medications at final evaluation., Conclusions: In our study, many patients with NVG achieved meaningful vision, as defined by World Health Organization (WHO) guidelines, and IOP control after GDD. Outcomes differed between patients with PDR and RVO in favor of the PDR group. Different GDD devices had similar performance profiles for VA and IOP outcomes. Direct prospective comparison of Baerveldt, Ahmed, and cyclophotocoagulation represents the next phase of discovery., (© 2021. The Author(s).)

The clinical comprehensive evaluation of drugs is an important basis for the return of clinical value, decision-making of medical and health authorities, and allocation of medical resources. In July 2021, the National Health Commission issued the Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), which required the evaluation to be implemented from the six dimensions(safety, effectiveness, economy, innovation, suitability, and accessibility), and made detailed arrangements for the clinical comprehensive evaluation of drugs. As Chinese patent medicine differs from chemical medicines in terms of effective components and action modes, the clinical comprehensive evaluation of Chinese patent medicine should highlight the characteristics and advantages of traditional Chinese medicine(TCM) on the basis of general requirements of comprehensive clinical evaluation of drugs. At present, in the clinical comprehensive evaluation of Chinese patent medicine, unified report standards have not yet been generated, resulting in the uneven quality of existing reports. To standardize the clinical comprehensive evaluation report of Chinese patent medicine and improve its quality, the editorial team, based on the relevant policy documents of clinical comprehensive evaluation of drugs, formulated the clinical comprehensive evaluation report standards for Chinese patent medicine in combination with the previous practice and expert opinions. The report standards, containing seven sections with 15 items determined, focus on data source, evaluation content, evidence synthesis, quality control, and evaluation results supported with detailed interpretations to help researchers better understand and apply the report standards for clinical comprehensive evaluation of Chinese patent medicine, improve the report quality, and provide references for the decision-making by the national medical management authorities.

Due to the profound theoretical rationale, perfect diagnosis and treatment system, and characteristic medicinal resources, Tibetan medicine has been passed down to the present day as one of the four traditional medicine systems all over the world. With the development of modern society and the change in people's concept of seeking medical services, Tibetan medicine has gradually attracted wide attention by virtue of its natural, green and safe diagnosis and treatment characteristics, which enables it to be vigo-rously developed and inherited. There are numerous ancient books on Tibetan medicine, covering a large number of ancient prescriptions, which has laid a solid foundation for later scholars to thoroughly investigate the diagnosis and treatment rules in Tibetan medicine and apply them to modern clinical practice. Screening the classic prescriptions that meet modern clinical needs from those numerous ancient books is a new direction in the inheritance and development of Tibetan medicine. On the basis of historical origin and current application status of ancient prescriptions in Tibetan medicine, this paper preliminarily elaborated the definition of classic prescriptions of Tibetan medicine and their general screening principles and precautions, and also discussed the modern inheritance paths of classic prescriptions in Tibetan medicine from basic research, post-marketing evaluation, and the development of novel preparations. Considering the shortcomings in the present study, the key technical issues mentioned need to be more deeply explored and analyzed in future studies.

Objective: To explore the clinical value of real-time shear wave ultrasonic elastography in diagnosing the depth of infiltrating muscularis of endometrial cancer., Methods: Seventy-one patients with stage I endometrial cancer infiltrating the myometrium and 37 patients with normal physical examination were enrolled and divided into three groups: endometrial cancer superficial muscle infiltration group, endometrial cancer deep muscle infiltration group, and normal control group. After completing 2-dimensional ultrasound examination, each patient switched to the real-time shear wave elastography mode to measure the elasticity values Emax, Emean, and Esd., Results: For control group, comparison of elastic modulus values between superficial muscular layer near the intimal surface and the deep muscular layer near the serosa surface showed no difference (P > 0.05). For endometrial cancer superficial muscular infiltration group, significant difference was found regarding the elastic modulus values of infiltrated muscular layer and uninfiltrated muscular layer (Emax and Emean) without difference for Esd (P > 0.05). A significant difference of elastic modulus was observed between control group and deep myometrial infiltration group (P < 0.05) without difference of Emean or Emax but with difference of Esd. The accuracy in diagnosing muscular layer infiltration was 78.9% for Emax cutoff and 82.5% for Emean cutoff. The rate of using Emax ≥32.22 kPa or Emean ≥27.54 kPa as the ultrasound standard for diagnosing myometrium infiltration was 92.9%. The accuracy for the diagnosis of muscular layer infiltration was 96.1% for Emax cutoff, 94.1% for Emean cutoff and 86.3% for Esd cutoff., Conclusion: Real-time shear wave elastography is helpful to determine the depth of infiltrating myometrium of endometrial cancer., (© 2020 American Institute of Ultrasound in Medicine.)

Nucleic acid testing and antibody testing data from 143 recovered COVID-19 patients during the convalescent phase were retrospectively analyzed. A total of 23 (16.1%) recovered patients re-tested positive for SARS-CoV-2 RNA by RT-PCR. Three months after symptom onset, 100% and 99.3% of the patients remained positive for total and IgG antibodies, and the antibody levels remained high. IgM antibodies declined rapidly, with a median time to seroconversion of 67 (95% CI: 59, 75) days after onset. Approximately 25% of patients were seronegative for IgA antibodies at three months after onset. There was no statistically significant difference in antibody kinetics between patients with and without re-positive RT-PCR results during the convalescent phase., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: To evaluate the agreement of a home vision screening test compared to standard in-office technician-measured Snellen visual acuity to allow for remote screening and triaging of patients., Patients and Methods: In this prospective study, English-speaking patients with in-office ophthalmology appointments from May to August 2020 and visual acuity better than 20/125 were asked to complete a home vision test one week before their scheduled in-office appointment. The home vision test was a modified ETDRS chart displayed in a PDF document that could be printed or viewed on a monitor. The primary outcome was the mean difference between office-based and home visual acuity., Results: Eighty-two eyes of 45 patients were included in the study with 45 study eyes analyzed. The mean difference between office-based and home visual acuity was -0.02 logMAR (SD 0.15, P =0.28) among study eyes. Of these eyes, 91% demonstrated agreement between the two methods within 0.2 logMAR of the mean difference, and 60% had agreement within 0.1 logMAR of the mean difference. There were no significant demographic or ocular risk factors leading to a greater difference between the tests., Conclusion: There was good agreement between the home and in-office Snellen tests for patients with vision better than 20/125. The home vision test can be used to remotely determine if there is a significant vision change of >0.2 logMAR or approximately 2 lines of visual acuity., Competing Interests: Dr Julie M Schallhorn reports personal fees from Zeiss, Allergan, Vanda, and Long Bridge Medical, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2021 Chen et al.)

The theoretical prediction of the catalytic activity is very beneficial for the design of highly efficient catalysts. At present, most theoretical descriptors focus on estimating the catalytic activity and understanding the enhancement mechanism of catalysts, while it is also quite important to find a factor to correlate the descriptors with preparation methods. In this work, a correlation factor, the d electron density of transition metal ions, was developed to correlate the d band center values of transition metal ions with the preparation methods of amorphization and Al introduction. According to the results of theoretical simulations, the correlation factor not only exhibited favorable linear relationships with the theoretical overpotentials of (CoFeAl x ) 3 O 4 and (CoFeAl x ) 3 O 4 + (CoFeAl x )OOH systems but also correlated with two preparation methods by altering the volume of systems. Based on theoretical guidance, the electrocatalytic activities of the prepared (CoFeAl x ) 3 O 4 specimens were gradually improved by the preparation methods of amorphization and Al introduction, and the Am-CoFeAl-2-10h specimen exhibited a low kinetic barrier of 268 mV, fast charge transfer rate, and stable electrocatalytic activity. This strategy could be applied to design highly efficient catalysts by adjusting the correlation factor of the active site with suitable preparation methods.

This study estimates causality of physical activity (PA) on bone mineral density (BMD) by conducting multivariable Mendelian randomization (MR). The findings suggest that habitual vigorous PA increases lumbar spine BMD, and higher overall acceleration average would improve forearm BMD. The results could promote PA intervention targeting individuals with optimized type., Introduction: Evidence from epidemiologic studies showed type, frequency, and duration of PA influenced BMD. However, these observational studies may be confounded by many factors, resulting in spurious associations. We aimed to conduct multivariable MR to estimate the causal effect of self-reported and device-measured PA on osteoporosis., Methods: Three self-reported and two device-measured PA-related traits were selected as exposures. Outcomes were BMD at different skeletal sites: femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD). Exposure datasets were obtained from UK Biobank with total 377,234 subjects. Outcome datasets were obtained from GEFOS consortium with 53,236 subjects. Standard MR analysis and multivariable MR were conducted to assess the total and direct causal effect of PA on BMD., Results: For self-reported PA, inverse-normalized moderate-to-vigorous had a direct causal effect on FN BMD independently (β = - 1.116 (95% confidence interval, 95%CI: - 2.210, - 0.023), P = 0.045); vigorous PA showed a direct effect (β = 3.592 (95%CI: 0.310, 6.874), P = 0.032) on LS BMD independently. While overall acceleration average and fraction of accelerations both had a direct causal effect on FA BMD independently., Conclusions: Habitual vigorous PA could increase LS BMD. Individuals with higher overall acceleration average would have a higher FA BMD.

Purpose: This study compared 1-year results for the composite treatment outcome from the Tube Versus Trabeculectomy (TVT) randomized controlled trial (RCT) to those from an IRIS Ⓡ (Intelligent Research In Sight) Registry cohort of analogous eyes., Design: Retrospective clinical study with comparison to an RCT., Methods: Subjects' eyes in the IRIS Registry received either a glaucoma drainage implant (tube) or underwent trabeculectomy after a previous trabeculectomy and/or cataract extraction and had data for 1-year follow-up analyses., Outcome: Eyes were classified as failing if they had hypotony (intraocular pressure (IOP) ≤5 mm Hg) or inadequate IOP control (IOP >21 mm Hg or not reduced at least 20% below baseline) on 2 consecutive follow-up visits after 3 months, a reoperation for glaucoma, or no light perception vision and as successful otherwise. Failure risk was compared by treatment, demographic, and clinical variables and was compared to analogous failure risks from the TVT RCT., Results: The TVT IRIS Registry cohort included 419 eyes, 236 tube eyes (56.3%) and 183 trabeculectomy eyes (43.7%). In this cohort, there was no significant failure risk difference (12.3% for tube eyes and 16.4% for trabeculectomy eyes, P = 0.231). Comparing the studies, there was a significantly greater risk of failure in the TVT IRIS Registry tube eyes than in the TVT RCT tube eyes (3.8%; P <.001). Reasons for treatment failure included reoperations for glaucoma (none in the TVT RCT at 1 year)., Conclusions: Our results were different from those in the TVT RCT. Possible reasons include non-Baerveldt tubes, greater severity among tube eyes, and practice patterns that reflect real-world data, which are different than those in RCTs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The prevalence of chronic non-communicable diseases (NCDs) challenges the Chinese health system reform. Little is known for the differences in catastrophic health expenditure (CHE) between urban and rural households with NCD patients. This study aims to measure the differences above and quantify the contribution of each variable in explaining the urban-rural differences., Methods: Unbalanced panel data were obtained from the China Family Panel Studies (CFPS) conducted between 2012 and 2018. The techniques of Fairlie nonlinear decomposition and Blinder-Oaxaca decomposition were employed to measure the contribution of each independent variable to the urban-rural differences., Results: The CHE incidence and intensity of households with NCD patients were significantly higher in rural areas than in urban areas. The urban-rural differences in CHE incidence increased from 8.07% in 2012 to 8.18% in 2018, while the urban-rural differences in CHE intensity decreased from 2.15% in 2012 to 2.05% in 2018. From 2012 to 2018, the disparity explained by household income and self-assessed health status of household head increased to some extent. During the same period, the contribution of education attainment to the urban-rural differences in CHE incidence decreased, while the contribution of education attainment to the urban-rural differences in CHE intensity increased slightly., Conclusions: Compared with urban households with NCD patients, rural households with NCD patients had higher risk of incurring CHE and heavier economic burden of diseases. There was no substantial change in urban-rural inequality in the incidence and intensity of CHE in 2018 compared to 2012. Policy interventions should give priority to improving the household income, education attainment and health awareness of rural patients with NCDs.

By adopting the extension approaches of Mendelian randomization, we successfully detected and prioritized the potential causal risk factors for BMD traits, which might provide us novel insights for treatment and intervention into bone-related complex traits and diseases., Introduction: Osteoporosis (OP) is a common metabolic skeletal disease characterized by reduced bone mineral density (BMD). The identified SNPs for BMD can only explain approximately 10% of the variability, and very few causal factors have been identified so far., Methods: The Mendelian randomization (MR) approach enables us to assess the potential causal effect of a risk factor on the outcome by using genetic IVs. By using extension methods of MR-multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA)-we intend to estimate the causal relationship between fifteen metabolic risk factors for BMD and try to prioritize the most potential causal risk factors for BMD., Results: Our analysis identified three risk factors T2D, FG, and HCadjBMI for FN BMD; four risk factors FI, T2D, HCadjBMI, and WCadjBMI for FA BMD; and three risk factors FI, T2D, and HDL cholesterol for LS BMD, and all risk factors were causally associated with heel BMD except for triglycerides and WCadjBMI. Consistent with the mvMR results, MR-BMA confirmed those risk factors as top risk factors for each BMD trait individually., Conclusions: By combining MR approaches, we identified the potential causal risk factors for FN, FA, LS, and heel BMD individually and we also prioritized and ranked the potential causal risk factors for BMD, which might provide us novel insights for treatment and intervention into bone-related complex traits and diseases.

Purpose: To assess the feasibility of replicating a randomized controlled trial (RCT) with a cohort of eyes, from IRIS® Registry data, analogous to the Tube Versus Trabeculectomy (TVT) RCT cohort and compare characteristics and follow-up., Design: Comparison of RCT and IRIS Registry cohorts and follow-up., Methods: We identified a cohort of IRIS Registry eyes (2013-2017) that received either a glaucoma drainage implant (tube) or trabeculectomy after a previous trabeculectomy and/or cataract extraction; extracted clinical and demographic characteristics for baseline surgery and follow-up visits through 1 year; and compared treatment groups in the IRIS Registry cohort and this cohort to the TVT RCT cohort., Results: The IRIS Registry cohort included 419 eyes: 183 (43.7%) trabeculectomy; 236 (56.3%) tube. There were significant differences between treatment groups, including race (White: trabeculectomy 61.8%, tube 44.9%; Black: trabeculectomy 20.8%, tube 35.6%; P = .003) and the percentage of follow-up visits completed (trabeculectomy 88.4%, tube 83.8%, P = .004). There were also significant differences between the TVT IRIS Registry cohort and the TVT RCT cohort in the percentage of follow-up visits completed (IRIS Registry 85.6%, RCT 96.1%, P < .001) and in the probability of having a 1-year follow-up visit (IRIS Registry 81.4%, RCT 89.2%, P = .011)., Conclusion: The TVT IRIS Registry cohort had several significant treatment group differences at baseline, whereas there had been none in the TVT RCT cohort. Follow-up in the TVT IRIS Registry cohort was inferior to that of the TVT RCT. Some data needed to refine the selection of eyes for the cohort were not available in the IRIS Registry., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The long-standing performance-stability contradiction issue of high energy density materials (HEDMs) is of extremely complex and multi-parameter nature. Herein, machine learning was employed to handle 28 feature descriptors and 5 properties of detonation and stability of 153 HEDMs, wherein all 21,648 data used were obtained through high-throughput crystal-level quantum mechanics calculations on supercomputers. Among five models, namely, extreme gradient boosting regression tree (XGBoost), adaptive boosting, random forest, multi-layer perceptron, and kernel ridge regression, were respectively trained and evaluated by stratified sampling and 5-fold cross-validation method. Among them, XGBoost model produced the best scoring metrics in predicting the detonation velocity, detonation pressure, heat of explosion, decomposition temperature, and lattice energy of HEDMs, and XGBoost predictions agreed best with the 1,383 experimental data collected from massive literatures. Feature importance analysis was conducted to obtain data-driven insight into the causality of the performance-stability contradiction and delivered the optimal range of key features for more efficient rational design of advanced HEDMs., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)