Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold.

OBJECTIVES: To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response (ABR) in adults using CE-Chirp to analyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold. METHODS: Subjects (aged 20-77 with a total of 100 ears) who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold, and pure tone air conduction hearing threshold tests were conducted at 0.5, 1.0, 2.0 and 4.0 kHz, respectively, to obtain pure tone listening threshold. The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups. The correlation, differences and statistical differences between the two tests at each frequency were analyzed for all subjects. The linear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established, and the feasibility of the equation was tested. RESULTS: There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold difference between different hearing level groups and different age groups (P>0.05). There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance (P<0.05), and linear regression analysis showed a significant linear correlation between the two (P<0.05). CONCLUSIONS: The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects' pure tone hearing threshold under certain conditions, and can be used as an audiological test method for forensic hearing impairment assessment.

Traditional Chinese medicine for gastric cancer: An evidence mapping.

As a complementary and alternative therapy, traditional Chinese medicine (TCM) has been playing a significant role in gastric cancer treatment. Data from individual systematic reviews have not been comprehensively summarized, and the relationship between certain interventions and outcomes are ill-defined. This study aimed to analyze the advantages of TCM interventions for gastric cancer by the method of evidence mapping. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Database for systematic reviews of TCM treating gastric cancer up to December 31, 2023. We used Excel, Endnote 20, and Python software for the analysis of incorporated studies. We assessed the quality of included SRs by AMSTAR-2 and performed evidence mapping including 89 SRs, 1648 RCTs and 122,902 patients, identifying 47 types of interventions and 39 types of outcomes. From a visual overview, we displayed that most SRs reported beneficial effects in improving short- and long-term survival, myelosuppression, and immune function, even though the quality of evidence was generally low. The benefits of Brucea javanica Oil Emulsion Injection, ShenQiFuZheng Injection, XiaoAiPing, Astragalus-Containing TCM and Guben Xiaoji Therapy were found the most solid in corresponding aspects. Our findings suggest that although more rigorous clinical trials and SRs are needed to identify the precise effectiveness, integrating such evidence into clinical care of gastric cancer is expected to be beneficial.

Rosmarinic acid mitigates acrylamide induced neurotoxicity via suppressing endoplasmic reticulum stress and inflammation in mouse hippocampus.

BACKGROUND: Acrylamide (ACR) is a widely used compound that is known to be neurotoxic to both experimental animals and humans, causing nerve damage. The widespread presence of ACR in the environment and food means that the toxic risk to human health can no longer be ignored. Rosmarinic acid (RA), a natural polyphenolic compound extracted from the perilla plant, exhibits anti-inflammatory, antioxidant, and other properties. It has also been demon strated to possess promising potential in neuroprotection. However, its role and potential mechanism in treating ACR induced neurotoxicity are still elusive. PURPOSE: This study explores whether RA can improve ACR induced neurotoxicity and its possible mechanism. METHODS: The behavioral method was used to study RA effect on ACR exposed mice's neurological function. We studied its potential mechanism through metabolomics, Nissl staining, HE staining, immunohistochemical analysis, and Western blot. RESULTS: RA pretreatment reversed the increase in mouse landing foot splay and decrease in spontaneous activity caused by 3 weeks of exposure to 50 mg/kg/d ACR. Further experiments demonstrated that RA could prevent ACR induced neuronal apoptosis, significantly downregulate nuclear factor-κB and tumor necrosis factor-α expression, and inhibit NOD-like receptor protein 3 inflammasome activation, thereby reducing inflammation as confirmed by metabolomics results. Additionally, RA treatment prevented endoplasmic reticulum stress (ERS) caused by ACR exposure, as evidenced by the reversal of significant P-IRE1α,TRAF2,CHOP expression increase. CONCLUSION: RA alleviates ACR induced neurotoxicity by inhibiting ERS and inflammation. These results provide a deeper understanding of the mechanism of ACR induced neurotoxicity and propose a potential new treatment method.

Research Progress of Natural Product Photosensitizers in Photodynamic Therapy.

Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell apoptosis. Although photosensitizers have shown efficacy in clinical practice, they are associated with certain disadvantages, such as a certain degree of toxicity and limited availability. Recent studies have shown that natural product photosensitizers offer promising options due to their low toxicity and potential therapeutic effects. In this review, we provide a summary and evaluation of the current clinical photosensitizers that are commonly used and delve into the anticancer potential of natural product photosensitizers like psoralens, quinonoids, chlorophyll derivatives, curcumin, chrysophanol, doxorubicin, tetracyclines, Leguminosae extracts, and Lonicera japonica extract. The emphasis is on their phototoxicity, pharmacological benefits, and effectiveness against different types of diseases. Novel and more effective natural product photosensitizers for future clinical application are yet to be explored in further research. In conclusion, natural product photosensitizers have potential in photodynamic therapy and represent a promising area of research for cancer treatment.

Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification.

BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

Eco-friendly bamboo pulp foam enabled by chitosan and phytic acid interfacial assembly of halloysite nanotubes: Toward flame retardancy, thermal insulation, and sound absorption.

Lightweight, porous cellulose foam is an attractive alternative to traditional petroleum-based products, but the intrinsic flammability impedes its use in construction. Herein, an environmentally friendly strategy for scalable fabrication of flame-retardant bamboo pulp foam (BPF) using a foam-forming technique followed by low-cost ambient drying is reported. In the process, a hierarchical structure of halloysite nanotubes (HNT) was decorated onto bamboo pulp fibers through layer-by-layer assembling of chitosan (CS) and phytic acid (PA). This modification retained the highly porous microcellular structure of the resultant BPF (92 %-98 %). It improved its compressive strength by 228.01 % at 50 % strain, endowing this foam with desired thermal insulation properties and sound absorption coefficient comparable to commercial products. More importantly, this foam possessed exceptional flame retardancy (47.05 % reduction in the total heat release and 95.24 % reduction in the total smoke production) in cone calorimetry, and it showed excellent extinguishing performance, indicating considerably enhanced fire safety. These encouraging results suggest that the flame retardant BPF has the potential to serve as a renewable and cost-effective alternative to traditional foam for applications in acoustic and thermal insulation.

Versatile CYP98A enzymes catalyse meta-hydroxylation reveals diversity of salvianolic acids biosynthesis.

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.

Molecular mechanism of angiogenesis for cerebral infarction rats by acupuncture intervention based on sonic hedgehog signaling pathway.

BACKGROUND: To study the factors of the Sonic Hedgehog (Shh) signaling pathway after permanent cerebral ischemic and the effects by acupuncture. METHODS: Male Wistar rats were divided into Electro-acupuncture (EA) group, Model Control (MC) group, and blank control (Control) group. EA and MC were divided into 9 phases, namely 1 h, 3 h, 6 h, 9 h, 12 h, 24 h, 3 d, 7 d, and 12 d after the operation. The neurological deficits and permanent cerebral ischemic volume were observed. The immunofluorescence method was used to examine the angiogenesis. (Polymerase Chain Reaction) PCR and (Immunohistochemistry) IHC were used to test the changes in Shh, Ptch, Smo, and Gli2 mRNA and proteins. RESULTS: The neurological severity scores (NSS) of the Control was 0, the score of the EA group was less than that of the MC. The cerebral permanent ischemic volume of the Control was 0 %, and the EA group's was smaller than that of the MC. The expression of copositive cells in the EA group was higher than the MC's from 12 h to 12 d, and the EA group had more peripheral blood vessels. The rat brain expressions of Shh, Ptch, Smo and Gli2 mRNA and proteins in the MC was higher than that of the Control, the rat brain expression of the EA group was higher than that of the MC. CONCLUSIONS: EA can upregulate the expression of the Shh signaling pathway factors, thereby promoting angiogenesis.

Anti-Nasopharyngeal carcinoma mechanism of sanguinarine based on network pharmacology and molecular docking.

BACKGROUND: The purpose of this study was to investigate the mechanism of sanguinarine (SAN) against nasopharyngeal carcinoma (NPC) by means of network pharmacology, molecular docking technique, and experimental verification. METHODS: The SAN action targets were predicted using the Swiss Target Prediction database, the related NPC targets were determined using the GEO database, and the intersection of drug and disease pathway targets were considered to be the potential targets of SAN against NPC. The target-protein interaction network map was constructed using the STRING database, and the core target genes of SAN against NPC were obtained via topological network analysis. "R" language gene ontology (GO) function and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analyses were used to dock the core target genes with SAN with the help of AutodockVina. Cell proliferation was detected using MTT and xCELLigence real-time cell analysis. Apoptosis was identified via Hoechst 33342 staining, JC-1 mitochondrial membrane staining, and annexin V-FITC/PI double fluorescence staining, while protein expression was quantified using western blotting. RESULTS: A total of 95 SAN against NPC targets were obtained using target intersection, and 8 core targets were obtained by topological analysis and included EGFR, TP53, F2, FN1, PLAU, MMP9, SERPINE1, and CDK1. Gene ontology enrichment analysis identified 530 items, and 42 items were obtained by Kyoto encyclopedia of genes and genome pathway enrichment analysis and were mainly related to the PI3K/AKT, MAPK, and p53 signaling pathways. Molecular docking results showed that SAN had good binding activity to the core target. SAN inhibited the proliferation of NPC cells, induced apoptosis, reduced the expression levels of survivin and Bcl2, and increased the expression levels of Bax and cleaved caspase-8. It also decreased the expression levels of the key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway in NPC cells. CONCLUSION: SAN inhibits the proliferation and induces the apoptosis of NPC cells through the MAPK/ERK signaling pathway.

[Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis].

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1ß, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Efficacy and safety of traditional Chinese medicine nursing intervention in postoperative patients after gastrectomy.

Gastrectomy is a technically demanding procedure for gastric cancer patients that is associated with different degrees of postoperative complications (POCs). Perioperative traditional Chinese medicine (TCM) nursing intervention presents benefits for improving the survival of patients with gastric cancer. However, the effects of TCM nursing intervention on POCs and the prognosis of patients with gastric cancer following surgery are far from clear. In the present study, the effects of TCM nursing intervention on POCs, postoperative physical capacity, metal status, long-term survival and recurrence were investigated in patients with gastric cancer after gastrectomy. In total, 1,032 patients with gastric cancer were included in the study. The patients underwent a gastrectomy and were randomly divided into two groups: The TCM nursing intervention group (TCM group; n=520) and the routine nursing intervention group (control group; n=512). Postoperative pain score, hospital stay, POCs, postoperative gastrointestinal function, frequency of postoperative symptoms, inflammatory index, quality of life, physical capacity, mental status, survival and recurrence were compared after gastrectomy in the TCM and control groups. The treatment-related adverse events of TCM in patients after gastrectomy were recorded in the TCM nursing intervention group. The outcomes showed that TCM nursing intervention decreased the postoperative pain score and hospital stay, improved gastrointestinal function, and decreased the POCs and the inflammation index compared with the control group. In addition, TCM nursing intervention improved physical capacity, quality of life, depression, anxiety, immune activity, long-term survival and recurrence in patients with gastric cancer after gastrectomy. Furthermore, TCM nursing intervention was only associated with a low number of adverse events. In conclusion, outcomes in this study indicate that perioperative TCM nursing intervention improves POCs, mental status, long-term survival and reduces the recurrence of patients with gastric cancer, suggesting that TCM nursing intervention is efficacious and safe with regard to improving the prognosis in these patients after gastrectomy (Retrospective clinical trial registration number, 2015001CW1; name of the register, The First Hospital of Harbin; date of registration, May 7, 2015).

Evaluation and control of Alternaria tenuissima causing leaf spots in blue honeysuckle in China.

Blue honeysuckle is emerging as a popular edible fruit and folk medicine. However, from June to August 2021, a serious leaf-spot disease affected the yield and quality of blue honeysuckle in Harbin, Heilongjiang Province, China; the species and characteristics of the pathogens responsible for the disease are unknown. In this study, 30 fungal isolates were obtained from infected blue honeysuckle leaves, identified as Alternaria tenuissima based on morphological and molecular characteristics and phylogenetic analyses. To the best of our knowledge, this is one of the first studies to identify A. tenuissima as the causal agent of blue honeysuckle leaf spots in China. Pathogenicity tests of the isolates revealed that most isolates exhibited moderately pathogenic. All blue honeysuckle cultivars tested were found to be susceptible to 30 A. tenuissima isolates. In addition, elder, Dahurian rose fruit, sea-buckthorn, rowan, hawthorn, bird cherry, and sorb could be infected by A. tenuissima isolates, while European cranberry bush and nanking cherry were not infected. A. tenuissima isolates were highly sensitive to prochloraz (EC50 ≤ 0.50 µg·ml-1) with 86.21% efficacy at 400 µg·ml-1 in the field trials. Therefore, the application of rotation and chemical fungicides are considered to control the disease-causing leaf spots in blue honeysuckle. These results provide a basis for controlling A. tenuissima in blue honeysuckle in China.

Effectiveness and safety of digital rectal stimulation and abdominal massage for neurogenic bowel dysfunction in stroke patients: a randomized controlled trial protocol.

BACKGROUND: Neurogenic bowel dysfunction (NBD) is a prevalent complication among stroke patients, significantly affecting their quality of life, duration of hospitalization, medical expenses, and even mortality. Although current guidelines suggest a conservative strategy for addressing bowel dysfunction, which includes techniques such as digital rectal stimulation (DRS) and abdominal massage, the availability of interventions remains limited in healthcare facilities. METHODS: This study follows a prospective randomized controlled parallel-group clinical trial design. The control group will receive standard care, while the intervention group will undergo a program that combines DRS and abdominal massage in addition to standard care. The duration of the intervention for both groups will be 6 weeks. The primary outcome measures will be the Wexner score. Furthermore, secondary outcomes measure will be assessed, including Bristol score, Patient Assessment of Constipation-Quality of Life (PAC-QoL), and Fecal Incontinence Quality of Life (FI-QoL). DISCUSSION: This study aims to evaluate the effectiveness and safety of a bowel rehabilitation program for stroke patients with NBD. The findings will provide information that can contribute to the formulation of bowel management strategies. TRIAL REGISTRATION: The study has been registered in the Chinese Clinical Registry under the number ChiCTR2300071709. This registration was completed on May 23, 2023. All items from the World Health Organization Trial Registration Data set are described in this manuscript.

Promising Subjective and Objective Benefits of Modified Mindfulness-Based Stress Reduction Training for Chinese Adults with Chronic Pain: A Pilot Randomized Control Study.

INTRODUCTION: Mindfulness-based stress reduction (MBSR) has demonstrated its effectiveness in reducing pain-related stress in adults with chronic pain. However, the implementation of MBSR needs modifications across cultures. This pilot study reports the findings of a randomized controlled trial that investigated the effects of a culturally adaptive MBSR program on self-report and neuroimaging outcomes for chronic pain adults in China. METHODS: Sixty-seven participants were randomly assigned to the treatment group (n = 40) or the treatment-as-usual group (n = 27) group at a ratio of 1.5:1. Participants completed self-report measures of pain severity, pain interference, depression, perceived stress, pain catastrophizing, mindfulness, and resilience at baseline assessment (T1), post-treatment (T2), and 3-month follow-up (T3) assessments. Functional magnetic resonance imaging (fMRI) scanning was also performed at T1 and T3 assessments. RESULTS: For the intention-to-treat sample, the results of the mixed-effect model indicated that Group × Time interaction was significant for pain catastrophizing only (F (2, 130) = 3.51, p = 0.033). Compared with the control group, those in the MBSR group reported greater reductions in pain catastrophizing at T2 (d = - 0.60), though this effect was not maintained at T3 (d = - 0.05). Additionally, the results of completer analyses found significant Group × Time interactions for pain interference (F (2, 88) = 4.40, p = 0.015) and perceived stress (F (2, 88) = 3.13, p = 0.048), but not for other measures. Finally, both groups exhibited decreased regional homogeneity (ReHo) in the frontal lobe, while increased ReHo in the cerebellum anterior lobe was unique to the MBSR group. CONCLUSIONS: The present findings suggest that the minor modified MBSR program improves certain pain-related outcomes for Chinese adults with chronic pain. Future studies with larger samples of Chinese chronic pain patients are needed to detect the small-to-moderate benefit of MBSR on fMRI and/or other objective methods.

Factors influencing the quality of acupuncture clinical trials: a qualitative interview of stakeholders.

OBJECTIVE: To investigate the influencing factors on the quality of acupuncture clinical trials from the stakeholders, and to provide references for improving the quality of acupuncture clinical trials. METHODS: A qualitative study based on semi-structured interviews was performed. Experts, acupuncturists, editors, and patients were interviewed. The interview results were thematically analyzed from transcribed audio recordings. RESULTS: A total of 38 stakeholders were interviewed, including 12 experts, 14 acupuncturists, 2 editors, and 10 patients. There were 25 tree nodes and 106 sub-nodes, with 1141 reference points. The key factors influencing the quality of acupuncture clinical trials could be divided into five core theme frameworks: a) trial design, b) trial conduction, c) research results reporting and publication, d) research evidence dissemination, and e) research evidence transformation and application. CONCLUSIONS: The results reveal that to improve the quality of acupuncture trials, it should consider each step of trial design, trial conduction, research results reporting and publication, research evidence dissemination, and research evidence transformation and application. A guideline for quality control of the whole process of acupuncture clinical trials is needed.

[Therapeutic effect and mechanism of Xiaoyao Kangai Jieyu Recipe on mice with breast cancer related depression through regulating COX pathway].

This study aimed to investigate the intervention effect and mechanism of Xiaoyao Kangai Jieyu Recipe(XKJR) on hip-pocampal microglia and neuronal damage in mice with breast cancer related depression. The mouse model of breast cancer related depression was established by inoculation of 4T1 breast cancer cells in axilla and subcutaneous injection of corticosterone(30 mg·kg~(-1)). The successfully modeled mice were randomly divided into a model group, a positive drug group(capecitabine 60 mg·kg~(-1)+fluoxetine 19.5 mg·kg~(-1)), and XKJR group(19.5 mg·kg~(-1) crude drug), with 6 in each group. Another 6 normal mice were taken as a normal group. The administration groups were given corresponding drugs by gavage, while the normal and model groups were given an equal volume of distilled water, once a day for 21 consecutive days. The depressive behavior of mice was assessed by glucose consumption test, open field test and novelty-suppressed feeding test. Hematoxylin and eosin(HE) staining and tumor suppression rate were used to evaluate the changes of axillary tumors. The mRNA expressions and the relative protein expressions of interleukin-1ß(IL-1ß), interleukin-18(IL-18), cyclooxyganese-2(COX-2) and glutamyl-prolyl-tRNA synthetase(EPRs) in the hippocampus of mice were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and immunohistochemistry, respectively. Immunofluorescence was performed to detect the mean fluorescence intensity of CD11b, a marker of hippocampal microglia activation. Nissler staining and transmission electron microscopy were employed to observe the morphological changes and the ultramorphological changes of hippocampal neurons, respectively. The experimental results indicated that compared with the normal group, the model group had reduced glucose consumption and lowered number of total activities in open field test(P<0.05, P<0.01), prolonged first feeding latency in no-velty-suppressed feeding test(P<0.01), and significant depression-like behavior; the contents of IL-1ß, IL-18, COX-2, and EPRs in hippocampus were increased(P<0.05, P<0.01), with hippocampal microglia activation and obvious neuronal damage. Compared with the model group, the positive drug group and the XKJR group presented an improvement in depressive behaviors, a decrease in the contents of IL-1ß, IL-18, COX-2 and EPRs in hippocampus, and an alleviation in the activation of hippocampal microglia and neuronal damage; the tumor suppression rates of positive drug and XKJR were 40.32% and 48.83%, respectively, suggesting a lower tumor growth rate than that of the model group. In summary, XKJR may improve hippocampal microglia activation and neuronal damage in mice with breast cancer related depression through activating COX signaling pathway.

Selenoproteins synergistically protect porcine skeletal muscle from oxidative damage via relieving mitochondrial dysfunction and endoplasmic reticulum stress.

BACKGROUND: The skeletal muscle of pigs is vulnerable to oxidative damage, resulting in growth retardation. Selenoproteins are important components of antioxidant systems for animals, which are generally regulated by dietary selenium (Se) level. Here, we developed the dietary oxidative stress (DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation. RESULTS: Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation, which is accompanied by mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and protein and lipid metabolism disorders. Supplementation with Se (0.3, 0.6 or 0.9 mg Se/kg) in form of hydroxy selenomethionine (OH-SeMet) linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins, which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle, and the mitigation of mitochondrial dysfunction and ER stress. What's more, selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle. However, several parameters such as the activity of GSH-Px and T-SOD, the protein abundance of JNK2, CLPP, SELENOS and SELENOF did not show dose-dependent changes. Notably, several key selenoproteins such as MSRB1, SELENOW, SELENOM, SELENON and SELENOS play the unique roles during this protection. CONCLUSIONS: Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress, recover protein and lipid biosynthesis, thus alleviate skeletal muscle growth retardation. Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.

Effectiveness of a Mindfulness Meditation App Based on an Electroencephalography-Based Brain-Computer Interface in Radiofrequency Catheter Ablation for Patients With Atrial Fibrillation: Pilot Randomized Controlled Trial.

BACKGROUND: Radiofrequency catheter ablation (RFCA) for patients with atrial fibrillation (AF) can generate considerable physical and psychological discomfort under conscious sedation. App-based mindfulness meditation combined with an electroencephalography (EEG)-based brain-computer interface (BCI) shows promise as effective and accessible adjuncts in medical practice. OBJECTIVE: This study aimed to investigate the effectiveness of a BCI-based mindfulness meditation app in improving the experience of patients with AF during RFCA. METHODS: This single-center pilot randomized controlled trial involved 84 eligible patients with AF scheduled for RFCA, who were randomized 1:1 to the intervention and control groups. Both groups received a standardized RFCA procedure and a conscious sedative regimen. Patients in the control group were administered conventional care, while those in the intervention group received BCI-based app-delivered mindfulness meditation from a research nurse. The primary outcomes were the changes in the numeric rating scale, State Anxiety Inventory, and Brief Fatigue Inventory scores. Secondary outcomes were the differences in hemodynamic parameters (heart rate, blood pressure, and peripheral oxygen saturation), adverse events, patient-reported pain, and the doses of sedative drugs used in ablation. RESULTS: BCI-based app-delivered mindfulness meditation, compared to conventional care, resulted in a significantly lower mean numeric rating scale (mean 4.6, SD 1.7 [app-based mindfulness meditation] vs mean 5.7, SD 2.1 [conventional care]; P=.008), State Anxiety Inventory (mean 36.7, SD 5.5 vs mean 42.3, SD 7.2; P<.001), and Brief Fatigue Inventory (mean 3.4, SD 2.3 vs mean 4.7, SD 2.2; P=.01) scores. No significant differences were observed in hemodynamic parameters or the amounts of parecoxib and dexmedetomidine used in RFCA between the 2 groups. The intervention group exhibited a significant decrease in fentanyl use compared to the control group, with a mean dose of 3.96 (SD 1.37) mcg/kg versus 4.85 (SD 1.25) mcg/kg in the control group (P=.003).The incidence of adverse events was lower in the intervention group (5/40) than in the control group (10/40), though this difference was not significant (P=.15). CONCLUSIONS: BCI-based app-delivered mindfulness meditation effectively relieved physical and psychological discomfort and may reduce the doses of sedative medication used in RFCA for patients with AF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306015; https://clinicaltrials.gov/ct2/show/NCT05306015.

Integrating metabonomics and metagenomics sequencing to study the anti-liver fibrosis effects of palmatine in Corydalis saxicola Bunting.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the main anti-liver fibrosis ingredients in CS are incompletely understood. AIM OF THE STUDY: To elucidate the main anti-liver fibrosis ingredients in CS and its underlying mechanism. MATERIAL AND METHODS: Firstly, spectrum-effect relationship (SER) strategy was applied to identify the major ingredients against liver fibrosis in CS. Subsequently, 1H NMR metabonomics and metagenomics sequencing techniques were used to clarify the intervention of palmatine (PAL) on liver fibrosis. Furthermore, the expression of tight junction proteins and the levels of liver inflammation factors were examined, the effect of PAL on microbiota was verified by FMT. RESULTS: The SER model revealed that PAL was the most important active ingredient in CS. 1H NMR fecal metabonomics showed that PAL could reserve the abnormal levels of gut microbial-mediated metabolites of liver fibrosis, such as isoleucine, taurine, butyrate, propionate, lactate, glucose, which mainly involved in amino acid metabolism, intestinal flora metabolism and energy metabolism. Metagenomics sequencing found that PAL could callback the abundance of s__Lactobacillus_murinus, s__Lactobacillus_reuteri, s__Lactobacillus_johnsonii, s__Lactobacillus_acidophilus and s__Faecalibaculum_rodentium to varying degree. Furthermore, the intestinal barrier function and the levels of hepatic inflammation factors were significantly ameliorated by PAL. FMT demonstrated that the therapeutic efficiency of PAL was closely associated with gut microbiota. CONCLUSION: The effects of CS on liver fibrosis were attributed in part to PAL by alleviating metabolic disorders and rebalancing gut microbiota. The SER strategy may be a useful method for the discovery of active constituents in natural plants.

Hydroxy-Selenomethionine Mitigated Chronic Heat Stress-Induced Porcine Splenic Damage via Activation of Nrf2/Keap1 Signal and Suppression of NFκb and STAT Signal.

Chronic heat stress (CHS) compromised the immunity and spleen immunological function of pigs, which may associate with antioxidant suppression and splenocyte apoptosis and splenic inflammation. Selenium (Se) exhibited antioxidant function and immunomodulatory through selenoprotein. Thus, this study aimed to investigate the protective effect of dietary hydroxy-selenomethionine (Selisso®, SeO) on chronic heat stress (CHS)-induced porcine splenic oxidative stress, apoptosis and inflammation. Growing pigs were raised in the thermoneutral environment (22 ± 2 °C) with the basal diet (BD), or raised in hyperthermal conditions (33 ± 2 °C) with BD supplied with 0.0, 0.2, 0.4 and 0.6 mg Se/kg SeO for 28 d, respectively. The results showed that dietary SeO supplementation recovered the spleen mass and enhanced the splenic antioxidant capacity of CHS growing pigs. Meanwhile, SeO activated the Nrf2/Keap1 signal, downregulated p38, caspase 3 and Bax, inhibited the activation of NFκb and STAT3, and enhanced the protein expression level of GPX1, GPX3, GPX4, SELENOS and SELENOF. In summary, SeO supplementation mitigates the CHS-induced splenic oxidative damages, apoptosis and inflammation in pigs, and the processes are associated with the activation of Nrf2/Keap1 signal and the suppression of NFκb, p38(MAPK) and STAT signal. It seems that the antioxidant-related selenoproteins (GPXs) and functional selenoproteins (SELENOS and SELENOF) play important roles in the alleviation processes.