Exploration of registration and the risk of bias in acupuncture randomised controlled trials: a systematic review protocol.

BACKGROUND: Randomised controlled trials (RCTs) are the predominant type in acupuncture clinical research, and the publications have increased rapidly in recent years, but there is a prevalence of the high risk of bias and poor methodological design in acupuncture RCTs. Clinical trial registration can improve the transparency and credibility of studies by disclosing key information in advance. However, the registration in acupuncture RCTs is not satisfactory, as there is widespread of the under-registration, inconsistency with published studies and insufficient disclosure of key methodological information. Whether registration can reduce the risk of bias in acupuncture RCTs and improve data transparency has not been fully explored. Therefore, we constructed this study to investigate the association between registration and risk of bias and data sharing level in acupuncture RCTs. METHODS: Seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP databases will be systematically searched between 1 January 2014 and 31 March 2024, for acupuncture RCTs. Two reviewers will independently extract data using a predefined standardised format and perform secondary validation. The characteristics and data sharing level of the included studies will be summarised. The risk of bias of included RCTs will be assessed by the revised Cochrane risk-of-bias tool for randomised trials. The risk of bias and registration in acupuncture RCTs will be analysed by logistic or quantile regression analyses (depending on the number of minimum events). The data sharing level and registration will be analysed by quantile regression analyses. ETHICS AND DISSEMINATION: As the systematic review aims to consolidate info from published sources, ethical approval is not necessary for this study. The study's findings will be submitted to a peer-reviewed academic journal and disseminated via conference presentations. This protocol has been registered in Open Science Framework Registries.

Recent advances and progress on the design, fabrication and biomedical applications of Gallium liquid metals-based functional materials.

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.

Reporting and influencing factors of patient-reported outcomes in acupuncture randomised controlled trials: a cross-sectional study protocol.

INTRODUCTION: Patient-reported outcomes (PROs) are health reports that come directly from the patients themselves and represented the experience and insights of the patient's perspective on the impact of the intervention. PROs were increasingly emphasised in acupuncture randomised controlled trials (RCTs). However, the reporting quality of PROs in acupuncture RCTs has not been investigated to date. Therefore, we constructed this study to reveal the basic characteristics and reporting quality of PROs in acupuncture RCTs, and explore the relationship between concealment, blinding and RROs. We hope our findings can provide guidance for the reporting standards and future development of PROs in acupuncture RCTs in reverse. METHODS AND ANALYSIS: RCTs using acupuncture treatment as the intervention and PROs as primary outcomes or secondary outcomes will be systematically searched through seven databases MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP between 1 January 2012 and 15 October 2022. The basic characteristics, concealment, blinding design and the characteristics of PROs in included RCTs will be summarised. The reporting quality of PROs will be assessed based on the CONSORT PRO extension. Logistic analysis will be performed to identify the association between concealment, blinding and RROs. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework (OSF) Registries. The findings of this study will be submitted to a peer-reviewed academic journal.

The Fabrication, Drug Loading, and Release Behavior of Porous Mannitol.

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray-antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer-Peppas kinetic model. In summary, the co-spray-antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials.

[Current situation and development trend of digital traditional Chinese medicine pharmacy].

The 21st century is a highly information-driven era, and traditional Chinese medicine(TCM) pharmacy is also moving towards digitization and informatization. New technologies such as artificial intelligence and big data with information technology as the core are being integrated into various aspects of drug research, manufacturing, evaluation, and application, promoting interaction between these stages and improving the quality and efficiency of TCM preparations. This, in turn, provides better healthcare services to the general population. The deep integration of emerging technologies such as artificial intelligence, big data, and cloud computing with the TCM pharmaceutical industry will innovate TCM pharmaceutical technology, accelerate the research and industrialization process of TCM pharmacy, provide cutting-edge technological support to the global scientific community, boost the efficiency of the TCM industry, and promote economic and social development. Drawing from recent developments in TCM pharmacy in China, this paper discussed the current research status and future trends in digital TCM pharmacy, aiming to provide a reference for future research in this field.

Efficient catalyst-free N2 fixation by water radical cations under ambient conditions.

The growth and sustainable development of humanity is heavily dependent upon molecular nitrogen (N2) fixation. Herein we discover ambient catalyst-free disproportionation of N2 by water plasma which occurs via the distinctive HONH-HNOH+• intermediate to yield economically valuable nitroxyl (HNO) and hydroxylamine (NH2OH) products. Calculations suggest that the reaction is prompted by the coordination of electronically excited N2 with water dimer radical cation, (H2O)2+•, in its two-center-three-electron configuration. The reaction products are collected in a 76-needle array discharge reactor with product yields of 1.14 µg cm-2 h-1 for NH2OH and 0.37 µg cm-2 h-1 for HNO. Potential applications of these compounds are demonstrated to make ammonia (for NH2OH), as well as to chemically react and convert cysteine, and serve as a neuroprotective agent (for HNO). The conversion of N2 into HNO and NH2OH by water plasma could offer great profitability and reduction of polluting emissions, thus giving an entirely look and perspectives to the problem of green N2 fixation.

Development of an integrated and project-based laboratory course in upper-level biochemistry and molecular biology.

An integrated and projected-based laboratory course was described, integrating interconnected knowledge points and biochemistry and molecular biology techniques on a research project-based system. The program, which served as an essential extension of theoretical courses to practice, was conducted with a sophomore of basic medical science who had completed the course in medical biochemistry and molecular biology. This course engaged students in learning "genetic manipulation" and "recombinant DNA technology" to understand the target gene's role in disease mechanics, thus altering evaluation and treatment for clinical disease. Students could master applied and advanced techniques, such as cell culture, transfection, inducing exogenous fusion protein expression, purifying protein and its concentration assay, quantitative polymerase chain reaction, and western bot analysis. This laboratory exercise links laboratory practices with the methods of current basic research. Students need to complete the experimental design report and laboratory report, which could be advantageous for improving their ability to write lab summaries and scientific papers in the future. The reliability and validity analyses were conducted on the questionnaire, and we examined students' satisfaction with the course and their gains from the course. The student feedback was generally positive, indicating that the exercise helped consolidate theoretical knowledge, increase scientific research enthusiasm, and provide a powerful tool to be a better person and make informed decisions.

Evidence of Cross-Kingdom Gene Regulation by Plant MicroRNAs and Possible Reasons for Inconsistencies.

The debate on whether cross-kingdom gene regulation by orally acquired plant miRNAs is possible has been ongoing for nearly 10 years without a conclusive answer. In this study, we categorized plant miRNAs into different groups, namely, extracellular vesicle (EV)-borne plant miRNAs, extracted plant miRNAs, herbal decoction-borne plant miRNAs, synthetic plant miRNA mimics, and plant tissue/juice-borne plant miRNAs. This categorization aimed to simplify the analysis and address the question more specifically. Our evidence suggests that EV-borne plant miRNAs, extracted plant miRNAs, herbal decoction-borne plant miRNAs, and synthetic plant miRNA mimics consistently facilitate cross-kingdom gene regulation. However, the results regarding the cross-kingdom gene regulation by plant tissue- and juice-borne plant miRNAs are inconclusive. This inconsistency may be due to variations in study methods, a low absorption rate of miRNAs and the selective absorption of plant miRNAs in the gastrointestinal tract. Overall, it is deduced that cross-kingdom gene regulation by orally acquired plant miRNAs can occur under certain circumstances, depending on factors such as the types of plant miRNAs, the delivery mechanism, and their concentrations in the plant.

One-step synthesis of a dual-functional AIE-active probe for ClO- detection and photodynamic therapy.

An amphiphilic fluorescent probe (BHSMP) with aggregation-induced emission (AIE) features was synthesized via a one-step route. The probe showed high water dispersibility, low toxicity and the ability of selective and sensitive (limit of detection of 0.11 µM) detection of ClO- with fast-response (≤30 s) in aqueous solution and living organisms. Owing to the donor-acceptor (D-A) structure and existence of cationic groups, BHSMP could also generate reactive oxygen species under light-irradiation and potentially be utilized for photodynamic therapy. The strategy described in this work is of great significance for the design and synthesis of multifunctional AIE-active functional materials to facilitate their biomedical applications.

Identification of a novel MICB allele, MICB*014:02, by cloning and sequencing.

The novel MICB*014:02 allele differs from MICB*014:01:01 by one nucleotide change in exon 2.

A comprehensive study of Ephedra sinica Stapf-Schisandra chinensis (Turcz.) Baill herb pair on airway protection in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedra sinica Stapf (Mahuang) and Schisandra chinensis (Turcz.) Baill (Wuweizi) are commonly utilized in traditional Chinese medicine for the treatment of cough and asthma. The synergistic effect of Mahuang-Wuweizi herb pair enhances their efficacy in alleviating respiratory symptoms, making them extensively employed in the management of respiratory disorders. Although previous studies have demonstrated the therapeutic potential of Mahuang-Wuweizi in pulmonary fibrosis, the precise mechanism underlying their effectiveness against asthma remains elusive. AIM OF THE STUDY: The objective of this study is to investigate the mechanism underlying the preventive and therapeutic effects of Mahuang-Wuweizi herb pair on asthma progression, focusing on airway inflammation and airway remodeling. MATERIALS AND METHODS: The active constituents and potential mechanisms of Mahuang-Wuweizi in the management of asthma were elucidated through network pharmacology analysis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to detect the main components of Mahuang-Wuweizi decoction. A rat model of bronchial asthma was established, and the effects of Mahuang-Wuweizi were investigated using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) staining, enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The results of network pharmacological prediction showed that Mahuang had 22 active components and Wuweizi had 8 active components, with 225 potential targets. 1159 targets associated with asthma and 115 targets that overlap between drugs and diseases were identified. These include interleukin-6 (IL-6), tumor necrosis factor (TNF), Tumor Protein 53, interleukin-1ß (IL-1ß), as well as other essential targets. Additionally, there is a potential correlation between asthma and Phosphatidylinositol 3 kinase (PI3K)/Protein Kinase B (AKT) signaling pathway, calcium ion channels, nuclear factor-kappa B (NF-κB) signaling pathway, and other signaling pathways. The animal experiment results demonstrated that treatment with Mahuang and Wuweizi, in comparison to the model group, exhibited improvements in lung tissue pathological injury, reduction in collagen fiber accumulation around the airway and proliferation of airway smooth muscle, decrease in concentration levels of IL-6, TNF-α and IL-1ß in lung tissue, as well as alleviation of airway inflammation. Furthermore, Mahuang and Wuweizi suppressed the expression of phospholipase C (PLC), transient receptor potential channel 1 (TRPC1), myosin light chain kinase (MLCK), NF-κB P65 protein in ovalbumin (OVA)-sensitized rat lung tissue and downregulated the mRNA expression of PLC, TRPC1, PI3K, AKT, NF-κB P65 in asthmatic rats. These findings were consistent with network pharmacological analysis. CONCLUSION: The results show that the synergistic interaction between Mahuang and Wuweizi occur, and they can effectively reduce airway remodeling and airway inflammation induced by inhaling OVA in bronchial asthma rats by inhibiting the expression of PLC/TRPC1/PI3K/AKT/NF-κB signaling pathway. Therefore, Mahuang and Wuweizi may be potential drugs to treat asthma.

Pueraria thomsonii Radix Water Extract Alleviate Type 2 Diabetes Mellitus in db/db Mice through Comprehensive Regulation of Metabolism and Gut Microbiota.

Type 2 diabetes mellitus (T2DM) is an increasingly prevalent and serious health problem. Its onset is typically associated with metabolic disorders and disturbances in the gut microbiota. Previous studies have reported the anti-T2DM effects of Pueraria thomsonii Radix as a functional food. However, the mechanism of action is still unknown. In this study, rich polyphenols and polysaccharides from Pueraria Thomsonii Radix water extract (PTR) were quantitatively determined, and then the effects of PTR on db/db mice were evaluated by pharmacology, metabolomics, and 16S rRNA gene sequencing. The results showed that PTR could alleviate pancreatic tissue damage, significantly decrease fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), urinary glucose (UGLU), and urinary albumin/creatinine ratio (UACR). Metabolomics showed that the Diabetes Control (DM) group produced 109 differential metabolites, of which 74 could be regulated by PTR. In addition, 16S rRNA sequencing was performed in fecal samples and results showed that PTR could reduce the Firmicutes/Bacteroidetes(F/B) ratio and regulate three beneficial bacteria and one harmful bacterium. In conclusion, the results showed that PTR could ameliorate the T2DM symptoms, metabolic disorder, and gut microbiota imbalance of db/db mice, and it was superior to metformin in some aspects. We suggested for the first time that γ-aminobutyric acid (GABA) may be involved in the regulation of the microbiota-gut-brain axis (MGB) and thus affects the metabolic disorders associated with T2DM. This study will provide a scientific basis for the development of functional food with PTR.

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

A comprehensive study on the ecotoxicity of ivermectin to earthworms (Eisenia fetida).

Ivermectin (IVM) is a dewormer commonly utilized in animal farming. Nevertheless, there is a deficiency of research on the bioecotoxicity of IVM in soil. In this study, earthworms were utilized as test animals to investigate the ecotoxicological impacts of IVM. The experiment lasted 28 days and involved adding varied doses of IVM to a culture substrate of soil mixed with cow dung and feeding it to earthworms. The experiment entailed recording earthworm weight, number of earthworm cocoons, histological damage, oxidative stress indicators, and gene expression levels. The analysis results showed that earthworm growth and reproduction were hampered by IVM. Moreover, pathological damage to the earthworms increased with increasing IVM concentration, which caused increased oxidative damage to the earthworms. These findings offer a summary of the impact of IVM on earthworms and a reference point for future research examining the ecological implications of IVM.

[Pharmacokinetics, pharmacodynamics, and tissue distribution of oral co-loaded puerarin/daidzein mixed micelles in rats].

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.

[Current status, trends, and challenges of continuous manufacturing technology for oral traditional Chinese medicine solid preparations].

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.

[Research progress in gut-skin axis and its association with traditional Chinese medicine theory].

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.

Efficacy and safety of community-based moxibustion for primary hypertension: A randomized controlled trial with patient preference arms.

Moxibustion has been shown to have a potential antihypertensive effect, but its applicability for the primary care of hypertension is unclear. The authors conducted a multicenter randomized controlled trial (RCT) with patient preference arms to investigate the effect, safety, cost-effectiveness, and compliance of moxibustion in community patients with hypertension. Patients with primary hypertension were enrolled from seven communities randomly or nonrandomly assigned to receive self-administered moxibustion + the original hypertensive regimen or the original hypertensive regimen alone for 6 months. The authors mainly evaluated the effects of moxibustion on hypertensive outcomes and adverse events. As a result, a total of 160 and 240 patients were recruited into the randomized and nonrandomized arms, respectively, with 87.5% completing the follow-up. At month 6, there was a significantly greater reduction in systolic blood pressure (SBP) (difference: -10.57 mmHg), a higher proportion of responders (82.2% vs. 53.7%; odds ratio 4.00), and better improvements in hypertensive symptoms and quality of life (QoL) in the moxibustion group than in the control group in the randomized population, but there was no significant between-group difference in diastolic blood pressure (DBP). The nonrandomized findings showed the same effect direction for all outcomes, except for DBP. All moxibustion-related adverse events were mild. In conclusion, moxibustion can reduce SBP and improve hypertensive symptoms and QoL in community patients with hypertension, with good safety and low cost, although its effect on DBP remains uncertain. The findings suggest that moxibustion may be an appropriate technique for community primary care of hypertension.

Glycemic variability correlates with medial temporal lobe atrophy and decreased cognitive performance in patients with memory deficits.

Background: In the past, researchers have observed a significant link between glycemia and dementia. Medial temporal atrophy (MTA) is regarded as a common marker of dementia. The correlation between glycemic variability and MTA is unclear, and it has not been determined whether glycemic variability can be utilized as a biomarker of MTA and cognitive performance. Methods: The patients in a memory clinic who underwent brain MRI scans and cognitive assessments within the first week of their hospital visit, were enrolled. All participants underwent three fasting blood glucose and one HBA1c assessments on three self-selected days within 1 week of their first visit. The variability independent of the mean (VIM) was employed. Validated visual scales were used to rate the MTA results. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were employed to assess the cognitive functions of the participants. Spearman's correlation and regression models were used to examine the relationship between the MMSE and MoCA scales, and also determine the link between the MRI characteristics and cognitive status, where vascular risk factors, educational status, age, gender, and mean glucose parameters served as covariates. Results: Four hundred sixty-one subjects completed the MMSE scale, while 447 participants completed the MoCA scale. Data analysis revealed that 47.72% of the participants were men (220/461), and the median age of the patients was 69.87 ± 5.37 years. The findings of Spearman's correlation analysis exhibited a strong negative relationship between the VIM and MMSE score (r = -0.729, P < 0.01), and the MoCA score (r = -0.710, P < 0.01). The VIM was regarded as an independent risk factor for determining cognitive impairment in both the MMSE and MoCA assessments. The results were unaffected by sensitivity analysis. In addition, a non-linear relationship was observed between the VIM and MTA scores. Conclusion: The variability in the blood glucose levels, which was presented as VIM, was related to the reduced cognitive function, which was reflected by MMSE and MoCA scales. The relationship between the VIM and the MTA score was non-linear. The VIM was positively related to the MTA score when the VIM was less than 2.42.

Protective effects of lycopene against zearalenone-induced reproductive toxicity in early pregnancy through anti-inflammatory, antioxidant and anti-apoptotic effects.

Zearalenone is a mycotoxin that is widely present in feed and raw materials and can cause severe reproductive toxicity. Lycopene is a natural carotenoid with antioxidant and anti-inflammatory pharmacological effects, but the protective effects of lycopene against zearalenone-induced uterine damage have not been reported. The aim of this study was to investigate the protective effect of lycopene treatment in early pregnancy on zearalenone-induced uterine damage and pregnancy impairment and its mechanism. Reproductive toxicity was induced by consecutive gavages of zearalenone at 5 mg/kg body weight during gestational days (GDs) 0-10 and in the presence or absence of oral administration of lycopene (20 mg/kg BW). The results showed that lycopene may alleviate zearalenone-induced pathological uterine histological damage and disturbances in oestradiol (E2), follicle-stimulating hormone (FSH), progesterone (P) and luteinizing hormone (LH) secretion. Lycopene increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) production, providing protection against zearalenone-induced oxidative stress in the uterus. Additionally, lycopene significantly reduced levels of pro-inflammatory cytokines, including interleukin 1ß (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and elevated levels of the anti-inflammatory factor interleukin 10 (IL-10), inhibiting the zearalenone-induced inflammatory response. In addition, lycopene improved the homeostasis of uterine cell proliferation and death via the mitochondrial apoptosis pathway. These data provide strong evidence that lycopene can be further developed into a potential new drug for the prevention or treatment of zearalenone-induced reproductive toxicity.