ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.
Humans ; Glioma/metabolism* ; Blood Platelets/physiology* ; Brain Neoplasms/pathology* ; Tumor Microenvironment

OBJECTIVE: To quantitatively evaluate the accuracy of data obtained from liquid-interference surfaces using an intraoral 3D scanner (IOS) integrated with a compressed airflow system, so as to provide clinical proof of accuracy for the application of the compressed airflow system-based scanning head in improving data quality on liquid-interference surfaces. METHODS: The study selected a standard model as the scanning object, adhering to the "YY/T 1818-2022 Dental Science Intraoral Digital Impression Scanner" guidelines, a standard that defined parameters for intraoral scanning. To establish a baseline for accuracy, the ATOS Q 12M scanner, known for its high precision, was used to generate true reference values. These true values served as the benchmark for evaluating the IOS performance. Building on the design of an existing scanner, a new scanning head was developed to integrate with a compressed airflow system. This new design aimed to help the IOS capture high-precision data on surfaces where liquid-interference, such as saliva, might otherwise degrade scanning accuracy. The traditional scanning method, without airflow assistance, was employed as a control group for comparison. The study included five groups in total, one control group and four experimental groups, to investigate the effects of scanning lens obstruction, airflow presence, liquid media, and the use of the new scanning head on scanning process and accuracy. Each group underwent 15 scans, generating ample data for a robust statistical comparison. By evaluating trueness and precision in each group, the study assessed the impact of the compressed airflow system on the accuracy of IOS data collected from liquid-interference surfaces. Additionally, we selected Elite and Primescan scanners as references for numerical accuracy values. RESULTS: The scanning accuracy on liquid-interference surfaces was significantly reduced in terms of both trueness and precision [Trueness: 18.5 (6.5) vs. 38.0 (6.7), P < 0.05; Precision: 19.1 (8.5) vs. 31.7 (15.0), P < 0.05]. The use of the new scanning head assisted by the compressed airflow system significantly improved the scanning accuracy [Trueness: 22.3(7.6) vs. 38.0 (6.7), P < 0.05; Precision: 25.8 (9.6) vs. 31.7 (15.0), P < 0.05]. CONCLUSION The scanning head based on the compressed airflow system can assist in improving the accuracy of data obtained from liquid-interference surfaces by the IOS.
Imaging, Three-Dimensional/methods* ; Humans ; Dental Impression Technique/instrumentation*

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:To identify a novel reassortant H3N2 avian influenza virus using nanopore sequencing technology and analyze its genetic characteristics.Methods:The positive samples of the H3N2 avian influenza virus, collected from the external environment in the farmers' market of Guangzhou, were cultured in chicken embryos. The whole genome was sequenced by targeted amplification and nanopore sequencing technology. The genetic characteristics were analyzed using bioinformatics software.Results:The phylogenetic trees showed that each gene fragment of the strain belonged to the Eurasian evolutionary branch, and the host source was of avian origin. The HA gene was closely related to the origin of the H3N6 virus. The NA gene was closely related to the H3N2 avian influenza virus from 2017 to 2020. The PB1 gene was closely related to the H5N6 avian influenza virus in Guangxi Zhuang Autonomous Region and Fujian Province from 2016 to 2022 and was not related to the PB1 gene of the H5N6 avian influenza epidemic strain in Guangzhou. The other internal gene fragments had complex sources with significant genetic diversity. Molecular characteristics indicated that the strain exhibited the molecular characteristics of a typical low pathogenic avian influenza virus and tended to bind to the receptors of avian origin. On important protein sites related to biological characteristics, this strain had mutations of PB2-L89V, PB1-L473V, NP-A184K, M1-N30D/T215A, and NS1-P42S/N205S.Conclusions:This study identified a novel reassortant H3N2 avian influenza virus by nanopore sequencing, with the PB1 gene derived from the H5N6 avian influenza virus. The virus had a low ability to spread across species, but further exploration was needed to determine whether its pathogenicity to the host was affected.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.