Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

The pathological mechanisms and potential therapeutic drugs for myocardial ischemia reperfusion injury.

BACKGROUND: Cardiovascular disease is the main cause of death and disability, with myocardial ischemia being the predominant type that poses a significant threat to humans. Reperfusion, an essential therapeutic approach, promptly reinstates blood circulation to the ischemic myocardium and stands as the most efficacious clinical method for myocardial preservation. Nevertheless, the restoration of blood flow associated with this process can potentially induce myocardial ischemia-reperfusion injury (MIRI), thereby diminishing the effectiveness of reperfusion and impacting patient prognosis. Therefore, it is of great significance to prevent and treat MIRI. PURPOSE: MIRI is an important factor affecting the prognosis of patients, and there is no specific in-clinic treatment plan. In this review, we have endeavored to summarize its pathological mechanisms and therapeutic drugs to provide more powerful evidence for clinical application. METHODS: A comprehensive literature review was conducted using PubMed, Web of Science, Embase, Medline and Google Scholar with a core focus on the pathological mechanisms and potential therapeutic drugs of MIRI. RESULTS: Accumulated evidence revealed that oxidative stress, calcium overload, mitochondrial dysfunction, energy metabolism disorder, ferroptosis, inflammatory reaction, endoplasmic reticulum stress, pyroptosis and autophagy regulation have been shown to participate in the process, and that the occurrence and development of MIRI are related to plenty of signaling pathways. Currently, a range of chemical drugs, natural products, and traditional Chinese medicine (TCM) preparations have demonstrated the ability to mitigate MIRI by targeting various mechanisms. CONCLUSIONS: At present, most of the research focuses on animal and cell experiments, and the regulatory mechanisms of each signaling pathway are still unclear. The translation of experimental findings into clinical practice remains incomplete, necessitating further exploration through large-scale, multi-center randomized controlled trials. Given the absence of a specific drug for MIRI, the identification of therapeutic agents to reduce myocardial ischemia is of utmost significance. For the future, it is imperative to enhance our understanding of the pathological mechanism underlying MIRI, continuously investigate and develop novel pharmaceutical agents, expedite the clinical translation of these drugs, and foster innovative approaches that integrate TCM with Western medicine. These efforts will facilitate the emergence of fresh perspectives for the clinical management of MIRI.

The Tao Hong Si Wu Decoction ameliorates diabetes-associated cognitive dysfunction by inhibiting the formation of amyloid plaques.

OBJECTIVES: The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism. METHODS: Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35 mg/kg). DACD rats were gavaged with THSWD for 1 week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins. RESULTS: The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, ß-secretase, Aß1-40 , Aß1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon. CONCLUSIONS: THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.

From growth promotion to intestinal inflammation alleviation: Unraveling the potential role of Lactobacillus rhamnosus GCC-3 in juvenile grass carp (Ctenopharyngodon idella).

Lactobacillus rhamnosus is a probiotic, which not only promotes the growth of animals, but also has anti-inflammatory effects. However, the mechanism by which Lactobacillus rhamnosus regulates intestinal immunity is not well comprehended. Hence, the study aimed to research how Lactobacillus rhamnosus affects the intestinal immunity using juvenile grass carp (Ctenopharyngodon idella) as a model. We selected 1800 juvenile grass carp for testing. They were divided into six treatments and fed with six gradients of Lactobacillus rhamnosus GCC-3 (0.0, 0.5, 1.0, 1.5, 2.0, 2.5 g/kg) for 70 days. Enteritis was subsequently induced with dextroside sodium sulfate. Results indicated that dietary Lactobacillus rhamnosus GCC-3 addition improved growth performance. Meanwhile, appropriate levels of Lactobacillus rhamnosus GCC-3 alleviated excessive inflammatory response by down-regulating the expression of TLR4 and NOD receptors, up-regulating the expression of TOR, and then down-regulating the expression of NF-κB. Additionally, appropriate Lactobacillus rhamnosus GCC-3 improved intestinal immunity by reducing pyroptosis triggered by NLRP3 inflammasome and mediated by GSDME. Furthermore, 16 S rRNA sequencing showing appropriate levels of Lactobacillus rhamnosus GCC-3 increased Lactobacillus and Bifidobacterium abundance and decreased Aeromonas abundance. These results suggest that Lactobacillus rhamnosus GCC-3 can alleviate intestinal inflammation through down-regulating NF-κB and up-regulating TOR signaling pathways, as well as by inhibiting pyroptosis.

The comparative analysis of Lonicerae Japonicae Flos and Lonicerae Flos: A systematical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) were once used as the same herb in China, but they were distinguished by Chinese Pharmacopoeia in 2005 in terms of their medicinal history, plant morphology, medicinal properties and chemical constituents. However, their functions, flavor, and meridian tropism are the same according to the Chinese pharmacopoeia 2020 edition, making researchers and customers confused. AIM OF THE REVIEW: This review aimed to provide a comparative analysis of LJF and LF in order to provide a rational application in future research. MATERIALS AND METHODS: The information was gathered from China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations (all chosen articles were reviewed attentively from 1980.1 to 2023.8). RESULTS: Till now, 507 chemical compounds have been isolated and identified in LJF, while 223 ones (79 overlapped compounds) are found in LF, including organic acids and derivatives, flavonoids, triterpenoids, iridoids, and essential oil components, etc. In addition, the pharmacological activities of LJF and LF, especially for their anti-influenza efficacy and mechanism, and their difference in terms of pharmacokinetic parameters, toxicology, and clinical applications were also summarized. CONCLUSION: The current work offers comparative information between LJF and LF in terms of botany, traditional uses, phytochemistry, ethnopharmacology, pharmacokinetics, toxicology, and pharmacology, especially their anti-influenza activities. Despite the same clinical applications and similar chemical components in LJF and LF, differentiated components were still existed, resulting in differentiated pharmacological activities and pharmacokinetics parameters. Moreover, the research about anti-influenza mechanism and functional substances of LJF and LF is dramatically limited, restricting their clinical applications. In addition, few studies have investigated the metabolism feature of LF in vivo, which is one of the important bases for revealing the pharmacological mechanism of LF. At the same time, the toxicity of LJF and LF is not fully studied, and the toxic compounds of LJF and LF need to be screened out in order to standardize the drug use and improve their rational applications.

Effect of transcutaneous electrical acupoint stimulation on remifentanil dosage during craniotomy aneurysm clipping: a prospective, randomized controlled study.

BACKGROUND: Craniotomy aneurysm clipping is one of the main treatments for intracranial aneurysm (IA). Endotracheal intubation and intraoperative operation may induce dramatic hemodynamic fluctuations and increase the risk of aneurysm rupture. Intraoperative high-dose opioid use is the main measure to reduce the intraoperative stress response, but it increases the incidence of complications such as postoperative vomiting and delayed awakening. Transcutaneous electrical acupoint stimulation (TEAS) stimulates ß-endorphin expression levels and reduces opioid requirements. In this study, we aimed to assess the effects of TEAS on remifentanil dosage and oxidative stress (OS) in craniotomy aneurysm clipping. METHOD: Forty-two patients with craniotomy aneurysm clipping were randomized into two groups: the TEAS group (T group) and the sham TEAS group (S group). "Hegu" (LI4), "Neiguan" (PC6) and "Zusanli" points (ST36) were selected, and a "HANS" percutaneous acupoint electrical stimulator was used for intervention 30 min before anesthesia induction until the end of the operation. The primary outcome was intraoperative remifentanil dosage. The secondary outcomes were intraoperative propofol dosage, mean arterial pressure (MAP) and heart rate (HR) 5 min before the TEAS intervention (T0), 5 min before head holder pinning (T1), immediately after pinning (T2), 5 min before craniotomy (T3), immediately after craniotomy (T4), at craniotomy (T5), and at the end of surgery (T6), as well as serum ß-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100ß, superoxide dismutase (SOD) and malondialdehyde (MDA) levels at T1, T2 and 24 h after surgery (T7). RESULTS: The dosage of remifentanil in the T group was reduced compared to that in the S group (P < 0.05). At T2, T4 and T5, the MAP and HR in the T group were lower than those in the S group (P < 0.05). At T2 and T7, the levels of NSE, S100ß and MDA in group T were lower than those in group S (P < 0.05), while the SOD levels in group T were higher than those in group S (P < 0.05). CONCLUSIONS: The use of TEAS can reduce the dosage of remifentanil and reduce hemodynamic fluctuations during craniotomy aneurysm clipping. It reduces the occurrence of OS and central nervous system damage during surgery and has a certain brain protective effect. TRIAL REGISTRATION: ChiCTR2100052353. https://www.chictr.org.cn/about.html .

Multienzyme-Like Nanozyme Encapsulated Ocular Microneedles for Keratitis Treatment.

Keratitis, an inflammation of the cornea caused by bacterial or fungal infections, is one of the leading causes of severe visual disability and blindness. Keratitis treatment requires both the prevention of infection and the reduction of inflammation. However, owing to their limited therapeutic functions, in addition to the ocular barrier, existing conventional medications are characterized by poor efficacy and low bioavailability, requiring high dosages or frequent topical treatment, which represents a burden on patients and increases the risk of side effects. In this study, manganese oxide nanocluster-decorated graphdiyne nanosheets (MnOx /GDY) are developed as multienzyme-like nanozymes for the treatment of infectious keratitis and loaded into hyaluronic acid and polymethyl methacrylate-based ocular microneedles (MGMN). MGMN not only exhibits antimicrobial and anti-inflammatory effects owing to its multienzyme-like activities, including oxidase, peroxidase, catalase, and superoxide dismutase mimics but also crosses the ocular barrier and shows increased bioavailability via the microneedle system. Moreover, MGMN is demonstrated to eliminate pathogens, prevent biofilm formation, reduce inflammation, alleviate ocular hypoxia, and promote the repair of corneal epithelial damage in in vitro, ex vivo, and in vivo experiments, thus providing a better therapeutic effect than commercial ophthalmic voriconazole, with no obvious microbial resistance or cytotoxicity.

Another thread to uncover the aging mystery of white tea: Focusing on the natural nanoparticles in tea infusion.

Aged white tea (WT) has promising medicinal potential, but how to accurately identify aged white tea is still a difficult problem. Inspired by tea cream, the relationship between the characteristics of nanoparticles in tea infusion and aging time was studied. The results showed that with the increase of aging time, the particle size of white tea nanoparticles (WTNs) decreased gradually. Microscopic images showed that the surface structure of WTNs was changed in three aspects: the waxy layer, the cuticle layer and the palisade tissue. Additional in vitro modeling demonstrated a strong correlation between nanoparticle size and protein and tea polyphenol content. The correlation between nanoparticle sizes and aging time was further verified in aged Pu'er raw tea. Starting with the tea infusion's nanoparticles, this study showed that the aging time of WT would impact the nanoparticles' properties, offering a unique way to determine the aging period of WT.

Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for combating MRSA biofilms.

The resistance and immune escape of methicillin-resistant Staphylococcus aureus (MRSA) biofilms cause recalcitrant infections. Here, we design a targeting and synergizing cascade PDT with nutritional immunotherapy nanosystems (Arg-PCN@Gel) containing PCN-224 as PDT platform for providing reactive oxygen species (ROS), incorporating arginine (Arg) as nitric oxide (NO) donor to cascade with ROS to produce more lethal ONOO- and promote immune response, and coating with gelatin as targeting agent and persistent Arg provider. The nanosystems adhered to the autolysin of MRSA and inhibited Arg metabolism by down-regulating icdA and icaA. It suppressed polysaccharide intercellular adhesin and extracellular DNA synthesis to prevent biofilm formation. The NO broke mature biofilms and helped ROS and ONOO- penetrate into biofilms to inactivate internal MRSA. Arg-PCN@Gel drove Arg to enhance immunity via inducible NO synthase/NO axis and arginase/polyamine axis and achieve efficient target treatment in MRSA biofilm infections. The targeting and cascading PDT synergized with nutritional immunotherapy provide an effective promising strategy for biofilm-associated infections.

[The rules of acupoint selection of acupuncture and moxibustion for scrofula in ancient times].

Based on data mining technology, the rules of acupoint selection of acupuncture-moxibustion for scrofula in ancient times were analyzed. The relevant articles of acupuncture and moxibustion for scrofula were searched in the Chinese Medical Code, and the original article, acupoint name, acupoint characteristic, and acupoint meridian tropism, etc. were screened and extracted. The Microsoft Excel 2019 was used to establish a acupoint prescription database, and the frequency of acupoints as well as their meridian tropism and characteristics were analyzed. The SPSS21.0 was applied to perform cluster analysis of acupuncture prescriptions; the SPSS Modeler 18.0 was used to perform the association rules analysis of the neck and the chest-armpit acupoints, respectively. As a result, 314 acupuncture prescriptions were extracted, including 236 single-acupoint prescriptions and 78 multiple-acupoints prescriptions (53 for neck and 25 for chest-armpit). A total of 54 acupoints were involved, with a total frequency of 530. The top 3 commonly-used acupoints were Tianjing (TE 10), Zulinqi (GB 41) and Taichong (LR 3); the most commonly-used meridians were hand shaoyang meridian, foot shaoyang meridian, hand yangming meridian and foot yangming meridian; the most commonly-used special acupoints were he-sea points and shu-stream points. The cluster analysis obtained 6 clusters, and the association rule analysis obtained that the core prescriptions of the neck were Quchi (LI 11), Jianyu (LI 15), Tianjing (TE 10) and Jianjing (GB 21), while the core prescriptions of the chest-armpit were Daling (PC 7), Yanglingquan (GB 34), Danzhong (CV 17), Jianjing (GB 21), Waiguan (TE 5), Zhigou (TE 6), Yuanye (GB 22) and Zhangmen (LR 13). The core prescriptions obtained from association rule analysis by difference areas were basically consistent with those by cluster analysis of total prescriptions.

Mechanism of Wuyao-Ginseng Medicine Pair in the Prevention and Treatment of Diarrhea-Type Irritable Bowel Syndrome Based on Gene Expression Omnibus Chip Data.

Based on a Gene Expression Omnibus (GEO) chip analysis combined with network pharmacology and molecular docking technology, in this study we explored the molecular targets and mechanism of the wuyao-ginseng medicine pair in the prevention and treatment of diarrhea-type irritable bowel syndrome (IBS-D). The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search for the chemical constituents and targets of wuyao and ginseng. The UniProt database was used to search for the target gene name. In the GEO database, IBS was searched to obtain GSE36701 and GSE14841 microarray data. We imported the intersection targets into the STRING database to construct a protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (Go) pathway analyses were performed using the Metascape database. A total of 30 active ingredients of wuyao-ginseng, 171 drug targets, 1257 IBS differentially expressed genes, and 20 drug-disease intersection genes were obtained from the GEO data. We screened the results and obtained the core active ingredients beta-sitosterol, DMPEC, Boldine, etc.; the core targets NCOA2, EGFR, VEGFA, etc.; and the key pathways P13K-Akt, MAPK, etc. The wuyao-ginseng medicine pair may be involved in inflammation-related signaling pathways, acting on disease targets such as NCOA2, EGFR, and VEGFA as well as pathways such as P13K-Akt and MAPK, thereby playing a key role in the prevention and treatment of IBS-D.

Effects of virtual reality on physical, cognitive, and psychological outcomes in cancer rehabilitation: a systematic review and meta-analysis.

PURPOSE: To systematically examine and summarize the current evidence regarding the effects of virtual reality (VR) on physical, cognitive, and psychological outcomes in cancer rehabilitation. METHODS: Six bioscience and engineering databases were searched. Two independent reviewers screened the titles and abstracts of 2397 records and retrieved 25 full-text articles. Inclusion criteria included patients with a current or previous diagnosis of cancer; VR was used as an intervention for physical, cognitive, or psychological impairments and functional limitations; and clinical trials with at least two arms and with both pre- and post-intervention assessments. Reviewers assessed methodological quality using the Physiotherapy Evidence Database scale. RESULTS: Seventeen studies including 799 patients with cancer were identified. Within-group pooled analysis indicated that patients demonstrated significant improvement in pain (P < 0.001), fatigue (P < 0.001), anxiety (P < 0.001), upper extremity function (P < 0.001), and quality of life (P = 0.008) after VR intervention. Between-group pooled analysis indicated significant improvements with VR in pain (P = 0.004), anxiety (P < 0.001), and upper extremity function (P < 0.001) compared with the control. Three studies reported the positive effects of VR on cognition. CONCLUSIONS: VR demonstrates promising effects in physical, cognitive, and psychological aspects of patients with cancer. VR can be incorporated into a comprehensive cancer rehabilitation program to alleviate impairments and functional limitations.

Omega-3 polyunsaturated fatty acids inhibit cardiomyocyte apoptosis and attenuate sepsis-induced cardiomyopathy.

OBJECTIVES: Sepsis can cause myocardial injury, which is one of the leading causes of death in critically ill patients. Fish oil rich in omega-3 polyunsaturated fatty acids (PUFAs) in ultralong chains has immunomodulatory effects and can inhibit the production of various critically ill proinflammatory cytokines. Therefore, this study focused on whether ω-3 PUFAs have a protective effect on sepsis-induced cardiomyopathy (SIC). METHODS: Male 6-8 weeks old C57BL/6 mice were pretreated with 3% special fish oil supplement rat food for seven consecutive days prior to surgery. Cecal ligation and puncture (CLP) was perfromed to induce polymicrobial sepsis.The cardiac function was assessed by echocardiography, apoptosis of cardiomyocyte were detected by TUNEL assay and Western blotting, and the level of TNF-α, IL-6, and IL-1ß in plasma was determined 24h after CLP. RESULTS: Pretreatment with omega-3 PUFAs attenuated cardiomyocyte apoptosis, decreased the production of proinflammatory cytokines, attenuated the SIC, and improved the survival rate of septic mice induced by CLP. CONCLUSIONS: ω-3 PUFAs alleviate SIC through attenuating cardiomyocyte apoptosis, which provides a new direction for the prevention and treatment of SIC.

Effect of alkaline washing treatment on leaching behavior of municipal solid waste incineration bottom ash.

This study aimed to find an effective, inexpensive, and safe washing treatment for municipal solid waste incineration bottom ash (MSWIBA) in order to reduce its potential harmful effects in disposal and recycling. The washing solutions, namely tap water (TW), saturated lime water (SLW), and wastewater from concrete batching plant (WW) were used to wash MSWIBA at different liquid-solid (L/S) ratios and for different durations. Leaching behavior of some heavy metals, chloride, and sulfate from MSWIBA was tested and evaluated. From the TCLP leaching test, when the L/S ratio was above 5, WW was the most effective solution in reducing As, Cd, Se, and Sb emissions from MSWIBA. The calcium and iron ions present in the WW were essential for controlling the leaching of As, Cd, and Sb from MSWIBA due to the formation of stable crystalline pharmacosiderite, cadmium hydroxide sulfate, and hydromeite during the washing process. Using WW showed the best effect in removing sulfate from MSWIBA. At a L/S ratio of 10, about 83% of the sulfate could be removed from MSWIBA after 20 min of washing. The L/S ratio was most influential in removing chloride from MSWIBA. The three washing treatments chosen were effective in reducing the chloride level in MSWIBA to below the level of hazardous waste. Nevertheless, there were still substantial amounts of chloride remaining in the treated MSWIBA. Under the Dutch Building Materials Decree, the treated MSWIBA may be used as a building material in parts which allow isolation, control, and monitoring (ICM).

Smart Lattice Structures with Self-Sensing Functionalities via Hybrid Additive Manufacturing Technology.

Lattice structures are a group of cellular materials composed of regular repeating unit cells. Due to their extraordinary mechanical properties, such as specific mechanical strength, ultra-low density, negative Poisson's ratio, etc., lattice structures have been widely applied in the fields of aviation and aerospace, medical devices, architecture, and automobiles. Hybrid additive manufacturing (HAM), an integrated manufacturing technology of 3D printing processes and other complementary processes, is becoming a competent candidate for conveniently delivering lattice structures with multifunctionalities, not just mechanical aspects. This work proposes a HAM technology that combines vat photopolymerization (VPP) and electroless plating process to fabricate smart metal-coated lattice structures. VPP 3D printing process is applied to create a highly precise polymer lattice structure, and thereafter electroless plating is conducted to deposit a thin layer of metal, which could be used as a resistive sensor for monitoring the mechanical loading on the structure. Ni-P layer and copper layer were successfully obtained with the resistivity of 8.2×10-7Ω⋅m and 2.0 ×10-8 Ω⋅m, respectively. Smart lattice structures with force-loading self-sensing functionality are fabricated to prove the feasibility of this HAM technology for fabricating multifunctional polymer-metal lattice composites.

Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells.

Objective: Increasing studies reported that long noncoding RNAs are involved in regulating glioma progression. However, the specific roles and mechanisms of lncRNAs in glioma remain unclear. Here, we sought to explore the functions of HOXD-AS2 in glioma progression. Methods: Gene expressions of lncRNAs in 5 normal brain tissue specimens and 5 glioblastoma tissue specimens were detected by gene expression profile chip technology. Bioinformatic analysis was performed to see whether differential expression of lncRNAs played any significant role in glioma occurrence and progression. The relationship between HOXD-AS2 level and clinical prognosis of the patients was analyzed. HOXD-AS2 was specifically interfered with by siRNA technology to observe its effects on U251 cell growth, proliferation, apoptosis, and invasion. Results: The expression level of HOXD-AS2 gene in glioma was significantly higher than that in the normal brain tissue, which was related to the tumor grade. The level of HOXD-AS2 gene in patients with high-grade glioma was higher than that in patients with low-grade glioma. High expression of HOXD-AS2 gene was a risk factor for poor prognosis of glioma patients. Knocking down the expression of HOXD-AS2 in glioma cell line U251 arrested the cell cycle and reduced the cell proliferation. Furthermore, it could significantly reduce the migration ability of the cells but had no significant effect on the invasion. Conclusion: HOXD-AS2 is an oncogenic lncRNA associated with the poor prognosis of glioma. Knockdown of HOXD-AS2 may reduce the growth of glioma, which may provide a new avenue for treatment.

Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study.

BACKGROUND: Gestational diabetes mellitus (GDM) may lead to many adverse effects on women and their offspring. METHOD: 24,429 pregnant women were enrolled during early pregnancy from January 2018 to December 2021. The self-reported intake of folic acid supplements was assessed via a questionnaire. Oral glucose tolerance tests were used for the diagnosis of GDM. The association between intake or not, dose, and duration of folic acid and GDM risk was assessed. RESULTS: 6396 (26.18%) women were diagnosed with GDM. In the univariate models, folic acid was found to be correlated with total GDM risk (OR = 0.82, 95% CI: 0.70~0.95, p = 0.009). After adjusting for potential confounders, the association with total GDM risk was not significant, but the association of folic acid with 2-h PBG diagnosed GDM risk was consistently significant (OR = 0.75, 95% CI: 0.63~0.90, p = 0.002). No significant association between the dose and duration of folic acid supplementation and GDM risk was observed in the analyses. CONCLUSION: Folic acid supplementation might be a protective factor for the risk of GDM caused by the high level of postprandial blood glucose, but the dose or duration-related association between folic acid supplementation and GDM risk is not clear.

Longitudinal semen parameter assessments and live birth: variability and implications for treatment strategies.

OBJECTIVE: To examine whether semen parameters are associated with live birth among couples seeking infertility treatment after accounting for semen parameter variability. DESIGN: Folic Acid and Zinc Supplementation Trial (FAZST) prospective cohort. SETTING: Four US reproductive endocrinology and infertility care study centers, 2013-2017. PATIENT(S): Couples (n = 2,369) seeking fertility consultations at 4 US infertility care study centers. INTERVENTION(S): Semen volume, pH, sperm viability, morphology, progressive and total motility, concentration, count, and total and progressive motile count assessed at baseline and at 2, 4, and 6 months after enrollment. MAIN OUTCOME MEASURE(S): Log-binomial models stratified by fertility treatment received (in vitro fertilization [IVF], intrauterine insemination [IUI], ovulation induction [OI], or no treatment) estimated risk differences (RDs) between semen parameter quartiles and live birth and accounted for multiple semen assessments per person. We accounted for abstinence time, the biological interdependence of semen parameters, and potential selection bias because of loss to follow-up. RESULT(S): Among couples using OI only or no treatment, 39% had a live birth, and relative to the highest quartile, the lowest quartiles of morphology (RD, -19 [95% CI, -23 to -15] per 100 couples), motility (RD, -13 [95% CI, -17 to -9]), concentration (RD, -22 [95% CI, -26 to -19]), and total motile count (RD, -18 [95% CI, -22 to -14]) were associated with fewer live births. For IUI, 26% had a live birth, and the lowest quartiles of volume (RD, -6 [95% CI, -11 to -0.4]), concentration (RD, -6 [95% CI, -11 to -0.1]), count (RD, -10 [95% CI, -15 to -4]), and total motile count (RD, -7 [95% CI, -13 to -1]) were associated with fewer live births. For IVF, 61% had a live birth, and only morphology (Q1 RD, -7 [95% CI, -14 to 0.2]; Q2 RD, -10 [95% CI, -17 to -2.2]) was associated with live birth. CONCLUSION(S): Semen parameters are critical in couples undergoing OI/IUI. Only low morphology was important for live birth after IVF. Although data supporting the use of semen parameters are fragmented across differing populations, current findings are generalizable across the range of male fertility and couple fertility treatments, providing evidence about which semen parameters are most relevant in which settings. CLINICAL TRIAL REGISTRATION NUMBER: NCT#01857310.

Safety and efficacy of low-dose and long-course tirofiban in large hemispheric infarction.

Background: The clinical efficacy and safety of tirofiban in the treatment of large hemispheric infarction (LHI) remain controversial. Methods: This study prospectively enrolled patients with acute LHI who were admitted to Putuo Hospital affiliated with Shanghai University of Traditional Chinese Medicine from June 2021 to December 2021. The patients were randomly assigned to the tirofiban group [3-4 µg/(kg·h)] or control group (clopidogrel 75 mg/d). Results: A total of 71 patients with acute LHI were selected: 36 in the tirofiban group and 35 in the control group. The reduction of the NIHSS score in the tirofiban group was 2.92 ± 9.31 at discharge, and that of the control group was -3.23 ± 12.06 (p = 0.021, OR, 0.006; 95% CI, 0.004-0.008). Six patients (16.7%) in tirofiban group and 14 patients (40%) in control group died during hospitalization (p = 0.029, OR, 0.300; 95% CI, 0.099-0.908). There was significant difference in Modified Rankin Scale (mRS) 5-6 scores at 90 days between the two groups (p = 0.023, OR, 0.327; 95% CI, 0.124-0.867). However, there was no significant difference in mRS 0-1 (p = 0.321, OR, 0.972; 95% CI, 0.920-1.027), mRS 2 (p = 0.572, OR, 2.00; 95% CI, 0.173-23.109), mRS 3 (p = 0.225, OR, 2.214; 95% CI, 0.601-8.161), or mRS 4(p = 0.284, OR, 1.859; 95% CI, 0.593-5.825) scores between the two groups. There was no difference in symptomatic intracranial hemorrhage (p = 0.29, OR, 0.305; 95% CI, 0.030-3.081), asymptomatic intracranial hemorrhage (p = 0.123, OR, 0.284; 95% CI, 0.053-1.518). There was a significant difference in systemic bleeding events during hospitalization (p = 0.044, OR, 0.309; 95% CI, 0.096-1.000). Conclusions: Low-dose and long-course tirofiban treatment may significantly improve the early neurological function and reduce the in-hospital mortality in LHI patients. Meanwhile, tirofiban does not increase the risk of any type of bleeding events.

Therapeutic effects and mechanisms of N-(9,10-anthraquinone-2-ylcarbonyl) xanthine oxidase inhibitors on hyperuricemia.

Objective: To observe the antioxidative effects of N-(9,10-anthraquinone-2-ylcarbonyl) xanthine oxidase inhibitors (NAY) in vitro and in vivo models of hyperuricemia and explore the mechanism. Methods: A classical experimental method of acute toxicity and a chronic toxicity test were used to compare the toxic effects of different doses of NAY in mice. The hyperuricemia mouse model was established by gavage of potassium oxonate in vivo. After treatment with different doses of NAY (low dose: 10 mg/kg, medium dose: 20 mg/kg, and high dose: 40 mg/kg) and allopurinol (positive drug, 10 mg/kg), observe the levels of uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) in urine and serum, respectively, and detect the activities of xanthine oxidase in the liver. The hyperuricemia cell model was induced by adenosine and xanthine oxidase in vitro. The cells were given different doses of NAY (50, 100, and 200 µmol/L) and allopurinol (100 µmol/L). Then the culture supernatant UA level of the medium was measured. The next step was to detect the xanthine oxidase activity in the liver and AML12 cells, and the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammatory factors in the kidney and serum of mice. Western blot was used to detect xanthine oxidase protein expression in mouse liver tissue and AML12 cells, ASC, Caspase-1, NLRP3, GLUT9, OAT1, and OAT3 protein expression in mouse kidney tissue and HK-2 cells. Hematoxylin-eosin staining was used to stain the liver and kidney tissues of mice and observe the tissue lesions. Results: NAY had little effect on blood routine and biochemical indexes of mice, but significantly reduced the serum UA level. NAY significantly reduced the level of UA in hyperuricemia mice and cells by inhibiting xanthine oxidase activity and reduced the levels of TNF-α, IL-6, and other inflammatory factors in serum and kidney of mice. NAY can inhibit inflammation by inhibiting the NLRP3 pathway. In addition, NAY can downregulate GLUT9 protein expression and upregulate OAT1 and OAT3 protein expression to reduce the UA level by promoting UA excretion and inhibiting UA reabsorption. Conclusion: These findings suggested that NAY produced dual hypouricemic actions. On the one hand, it can inhibit the formation of UA by inhibiting xanthine oxidase inhibitors activity, and on the other hand, it can promote the excretion of UA by regulating the UA transporter. It provides new ideas for the development of hyperuricemia drugs in the future.