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Abstract Background Although mesenchymal stem cells (MSCs) have been proven to be appropriate candidates for the treatment of AKI-CKD, their efficacy is limited and variable. Astilbin (AST) had a protective effect on MSCs from oxidative stress via ROS-scavenging, however, whether it can improve MSCs’ renoprotection and the underlying mechanism need to be elucidated. Methods AST-pretreated MSCs were administered intravenously into the ischemia–reperfusion injury mice models and the renal function, pathological changes and inflammation. Were evaluated. In addition, DARTS, molecular docking, surface plasma resonance(SPR), dual-luciferase reporter gene assay and the ChIP-PCR were utilized to explore the potential signaling pathways through which AST exert renal protective effects on MSCs. Results AST-pretreated MSCs markedly improved kidney function, reduced kidney pathological injury and inflammation in AKI and AKI-CKD mice. RNA-seq results showed that PTGS2 related pathway was significantly up-regulated in MSCs after AST pretreatment. DARTS assay, molecular docking and SPR assay revealed that AST could bind with the transcriptional factor of Kruppel-Like Factor 4(KLF4) protein. The promoter of PTGS2 had the binding and transcriptional activation by KLF4. Furthermore, AST pretreatment promoted the secretion of PGE2 in MSCs. And then the westren blot results showed that the protein levels of CD163 and CD206 were upregulated after coculture in AST-pretreated MSCs, indicating that the polarization of RAW264.7 cells towards M2-like macrophages was induced. Knockdown of PTGS2 reversed the ability of AST-pretreated MSCs in converting macrophages to M2 phenotype and reducing their therapeutic effects on AKI-CKD mice. Conclusion AST pretreatment enhances the efficacy of MSCs on AKI and AKI-CKD mice by inducing of M2-like phenotype polarization in macrophages through the PTGS2-mediated pathway. This approach not only provides a novel strategy to strengthen the capability of MSCs but also helps elucidate the beneficial effects of the Chinese herbal medicine AST.

Abstract Background Although electronic alerts are being increasingly implemented in patients with acute kidney injury (AKI), their effect remains unclear. Therefore, we conducted this meta-analysis aiming at investigating their impact on the care and outcomes of AKI patients. Methods PubMed, Embase, Cochrane Library, and Clinical Trial Registries databases were systematically searched for relevant studies from inception to March 2024. Randomized controlled trials comparing electronic alerts with usual care in patients with AKI were selected. Results Six studies including 40,146 patients met the inclusion criteria. The pooled results showed that electronic alerts did not improve mortality rates (relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.97–1.08, P = 0.44) or reduce creatinine levels (mean difference (MD) = − 0.21, 95% CI = − 1.60–1.18, P = 0.77) and AKI progression (RR = 0.97, 95% CI = 0.90–1.04, P = 0.40). Instead, electronic alerts increased the odds of dialysis and AKI documentation (RR = 1.14, 95% CI = 1.05–1.25, P = 0.002; RR = 1.21, 95% CI = 1.01–1.44, P = 0.04, respectively), but the trial sequential analysis (TSA) could not confirm these results. No differences were observed in other care-centered outcomes including renal consults and investigations between the alert and usual care groups. Conclusions Electronic alerts increased the incidence of AKI and dialysis in AKI patients, which likely reflected improved recognition and early intervention. However, these changes did not improve the survival or kidney function of AKI patients. The findings warrant further research to comprehensively evaluate the impact of electronic alerts.

Cervical cancer is highly preventable through vaccination, early detection, and treatment, yet is the fourth most common cancer globally. HPV testing is superior to cytology for the detection of cervical pre-cancer, and jurisdictions around the world are implementing HPV primary screening, which offers the opportunity for self-screening, an important self-care intervention. Digital health solutions are also increasingly important components of self-care. In this study, we assessed the acceptability and completion of self-screening for cervical cancer offered through a digital platform within a low screening uptake region of British Columbia. The primary objective of this study was to evaluate the acceptability of self-screening for cervical cancer offered through a digital platform as measured by return rates of self-screening kits. Patients due or overdue for cervix screening were invited to participate. Eligible participants registered online to receive a self-screening kit, which included a device for vaginal self-screening, instructions, and a return envelope, sent to their home. After self-screening using the vaginal device, HPV testing was conducted. HPV-negative participants were returned to routine screening, and HPV-positive participants were recommended for cytology or colposcopy. Attendance rates at follow-up were evaluated. Participants were invited to complete an acceptability survey. From April 2019 to December 2023, 283 participants were sent kits, with 207 kits returned for a completion rate of 73%. Of valid samples (n = 202), 15 were HPV positive, and 93% attended follow-up care. Most respondents found the CervixCheck website easy to use, informative, and secure and were satisfied with receiving their results online. CervixCheck had a high completion rate among participants who were sent a self-screening kit. High compliance with recommended follow-up and high acceptability of self-screening for cervical cancer was observed. Most participants indicated they would self-screen again in the future. Innovative approaches to cervical screening, including self-screening and the use of digital health interventions, are ways to enhance equity and improve uptake of cervical screening.

Abstract Background High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. Methods The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. Results The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (β = − 0.036 and β = 0.028, respectively, P 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (β = − 0.026 and β = − 0.053, respectively, P

Objective At present, there is still no practical case of using CTCS 3 (Chinese Train Control System Level 3) in city railway in China. The application of CTCS-3 system in city railway should be explored to expand its application in urban railway. Method The characteristics of the existing city railway and the current status of CTCS application in city railway are analyzed. The technical scheme of CTCS-3 application in city railway is proposed, its applicability is analyzed, and the optimization proposal for its application scheme is put forward. Result & Conclusion Compared with the CTCS-2, the CTCS-3 (without CTCS-2 as backup) has better applicability in city railway in terms of its advantages in traction power supply system adaptability, protection section setting method, interconnection with other rail transit systems, and lower signalling engineering cost.

Single-beam-per-fraction (SBPF) treatment schedules facilitate FLASH-RT implementation, eliminating the impact of dose dispersion and beam-switching dead time in all-beam-per-fraction schedules. However, SBPF schedules lead to an increase in biological equivalent dose (BED α/β) to healthy tissues due to the loss of fractionation. This increase may potentially surpass the protection of FLASH effect. Recently, plans with non-uniform fractionation dose (non-UFD) demonstrated a lower BED α/β and dose to healthy tissues, while maintaining the same BED α/β prescription as the plan with uniform fractionation dose (UFD). Therefore, we developed a BED α/β based fractional dose optimization to explore the additional sparing of healthy tissues in transmission proton SBPF FLASH. Ten lung cancer patients were prescribed a BED 10Gy of 100 Gy, equivalent to a dose of 50 Gy uniformly delivered in 5 fractions. UFD plans using five 230-MeV-proton transmission beams were optimized through single field optimization, with each beam contributing a BED 10Gy of 20 Gy to target. Without altering the spot map and relative weight distribution of UFD plans, a BED-based fractional dose optimization was employed to generate the optimal non-UFD plan, where the BED 10Gy to target varied among beams. The BED distribution of UFD and non-UFD plans were normalized to ensure that 95% of target volume received a BED 10Gy of 100 Gy. The dose and BED 3Gy in healthy tissues were evaluated to compare the UFD and non-UFD schemes. The fractional dose of non-UFD plans ranges from 5.02 Gy to 21.60 Gy. With comparable target's D 2% and D 98% and same D 95% in BED 10Gy distributions, non-UFD plans lowered the D 95% in dose distribution dose by 7.4%, compared to UFD plans. Additionally, non-UFD plans reduced the D mean of lung by 7.0% and 11.5% in dose and BED 3Gy distributions, respectively. The lung's V 20Gy in dose distribution and V 46.7Gy in BED 3Gy distribution of non-UFD plans were reduced by 10.8% and 21.7%, respectively. Spatiotemporal fractionation schemes provide extra protection for healthy tissues, facilitating the clinical implementation of SBPF FLASH-RT. [ABSTRACT FROM AUTHOR]

The access methods for terminal communication on the distribution network side are diverse. However, due to the lack of complete interconnection among various communication methods, the reliability of communication is compromised. Therefore, it is of great significance to realize automatic switching of various communication access modes and multi-network integration of terminals to improve the reliability of distribution communication network. Based on the research on the wide application of mature technologies such as bidirectional forwarding detection (BFD) link bidirectional monitoring, single-pole double-throw isolation, Bypass technology and tunnel technology in communication networks, the key technologies and integration methods to improve the reliability of distribution network were put forward， and the feasibility of the proposed scheme was verified by building a physical simulation environment. The simulation results show that the proposed scheme can be well applied to the complex distribution network, so as to improve its self-healing ability, meet the requirements of physical isolation and service transmission delay, and improve the reliability of the entire distribution network.

Abstract Objective To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). Methods A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. Results The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p

Abstract The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2 −), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2 − production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

Maintaining metabolic homeostasis is crucial for cellular and organismal health throughout their lifespans. The intricate link between metabolism and inflammation through immunometabolism is pivotal in maintaining overall health and disease progression. The multifactorial nature of metabolic and inflammatory processes makes study of the relationship between them challenging. Homologs of Saccharomyces cerevisiae silent information regulator 2 protein, known as Sirtuins (SIRTs), have been demonstrated to promote longevity in various organisms. As nicotinamide adenine dinucleotide-dependent deacetylases, members of the Sirtuin family (SIRT1–7) regulate energy metabolism and inflammation. In this review, we provide an extensive analysis of SIRTs involved in regulating key metabolic pathways, including glucose, lipid, and amino acid metabolism. Furthermore, we systematically describe how the SIRTs influence inflammatory responses by modulating metabolic pathways, as well as inflammatory cells, mediators, and pathways. Current research findings on the preferential roles of different SIRTs in metabolic disorders and inflammation underscore the potential of SIRTs as viable pharmacological and therapeutic targets. Future research should focus on the development of promising compounds that target SIRTs, with the aim of enhancing their anti-inflammatory activity by influencing metabolic pathways within inflammatory cells.

Background In recent years, the incidence of spinal metastasis (SM) has been increasing steadily. In response to this serious public health problem, researchers have made progress by using the integration of traditional Chinese and Western medicine. However, considerable heterogeneity in the definition and measurement of outcomes across clinical research studies, along with the lack of uniform measurement standards for study data, makes it difficult for researchers to compare different treatments. Therefore, it is crucial to accurately evaluate clinical research on the integration of traditional Chinese and Western medicine for SM.Methods This study protocol outlines a comprehensive research programme based on the Core Outcome Set Standards Protocol Items. The study consists of four phases: a literature review, semistructured interviews, a two-round modified Delphi survey, a consensus meeting. Phase 1 involves a comprehensive literature review to extract outcomes used in current clinical studies of integrated traditional Chinese and Western medicine or Western medicine for the treatment of SM. A semistructured interview format will be used to survey patients and caregivers in phase 2 to collect suggestions from the patient perspective. Phase 3 involves a two-round modified Delphi survey to complete a prioritisation evaluation of outcomes to generate a candidate list for core outcome set (COS). Finally, phase 4 involves a face-to-face consensus meeting to review and establish the COS.Ethics and dissemination Conducted in response to the current dilemma of SM, the study was endorsed by the Spine Oncology Group of the Orthopaedic Surgeons Branch of the Chinese Physicians’ Association. It will be developed and reported through a rigorous process, with the results of the study to be published in a peer-reviewed journal.Registration: COMET Registry: COMET 2938; https://www.comet-initiative.org/Studies/Details/2938.